Signs and Symptoms
Thyroid eye disease, Graves’ ophthalmopathy, dysthyroid ophthalmopathy, and Graves’ disease are all synonymous terms connoting a process clinically characterized by eyelid retraction, proptosis, conjunctival exposure, ocular injection, ocular chemosis, corneal compromise, extraocular muscle infiltration and fibrosis with the potential for compressive optic neuropathy. It is the most common cause of bilateral, symmetric proptosis in adults.
Interestingly, ocular findings may occur independently from dysthyroid function. Euthyroid Graves’ disease is a condition where the characteristic ophthalmic manifestations of thyroid eye disease exist in the presence of a clinically and biomedically normal thyroid gland.
Most patients with ocular Graves’ disease manifest systemic hyperthyroidism. Up to 80 percent of patients with systemic hyperthyroidism develop some eye signs. Systemic signs of hyperthyroidism include weight loss despite increased appetite, nervousness, palpitations, tachycardia while at rest, systemic hypertension, and hyperreflexia. Conversely, lethargy, bradycardia and weight gain despite decreased appetite are signs of hypometabolism and potential hypothyroidism.
In 1969, the American Thyroid Association adopted the formal classification of Ocular Graves’ disease, represented by the pneumonic NOSPECS. The disease process passes through 6 stages: (0) No signs or symptoms present, (I) Only symptoms of ocular irritation (dryness, tearing, foreign body sensation), (II) Soft tissue involvement (periorbital edema), (III) Proptosis, (IV) Extraocular muscle involvement (ophthalmoplegia), (V) Corneal involvement (dense punctate epitheliopathy, infiltration and ulceration), (VI) Sight loss with or without visual field compromise secondary to compressive optic neuropathy. However, because the disease is recognized as variable, the formal classification was revised in 1974 to range from no manifestations to mild, moderate or severe manifestations.
The common, clinically diagnostic eye signs include: von Graefe’s sign (superior lid lag upon down gaze), Dalrymple’s sign (eyelid retraction), Stellwag’s sign (infrequent blinking), and Ballet’s sign (palsy of one or more extraocular muscles).
Pathophysiology
Graves’ disease is a multisystem disorder of unknown etiology, characterized by one or more of the following three clinical entities: (1) hyperthyroidism associated with diffuse hyperplasia of the thyroid gland; (2) infiltrative ophthalmopathy; and (3) infiltrative dermopathy (pretibial myxedema).
The histopathologic features of the malady include an infiltration of the thyroid gland, skin, extraocular muscles and orbital fat by lymphocytes, macrophages, plasma cells, mast cells and mucopolysaccharides. These changes are characteristic of, but not limited to, an immunologically mediated mechanism.
Management
The diagnosis of Graves’ disease can often be made easily based on symmetrical exophthalmos (exophthalmometry >22mm or asymmetry greater than 3mm) and lid retraction in the
presence of known hyperthyroidism. If symptoms are present and a systemic etiology has not been investigated, consultation with an endocrinologist and laboratory testing for thyroid hormones T3 (triiodothyronine), T4 (tetra-iodothyronine) and TSH (thyroid stimulating hormone) are indicated. Neuroimaging of the orbits in patients with exophthalmos and positive forced duction testing allows clinicians to distinguish extraocular muscle infiltration from inflammatory or infectious myositis.
The systemic management of patients with ocular Graves’ disease lies in the domain of the endocrinologist. Agents that block the synthesis of thyroid hormone such as propylthiouracil (Tapazole) or decrease hypermetabolic symptoms such as propranolol (Inderal) have been proven effective. Systemic steroids, immunosuppressive agents like azathioprine, cyclosporin or cyclophosphamide in combination with orbital irradiation have shown promise in advanced cases. Today, surgical orbital decompression procedures are a last resort.
Since the primary concern proptosis and lid retraction presents is corneal exposure, ocular management is predominantly supportive. Typically, moistening the cornea with artificial tear drops and ointments is effective. Moisture shields that can be attached to the temples of spectacles help to preserve tears and retard tear evaporation. Punctal occlusion may be effective. Cases that involve moderate to severe keratopathy may require prophylactic topical antibiotics. Visual fields should be performed on patients with advanced stage disease, monitoring for the first sign of sight or field loss. Evaluation is usually every three to six months and is based upon severity.
Clinical Pearls
Since a variety of neuro-ophthalmic entities deserve consideration in diseases where there is proptosis or malposition of the eyelid (myasthenia gravis, illusory ptosis of the opposite eyelid, neoplasm, arteriovenous malformation, carotid cavernous fistula, infection, inflammation), forced duction testing (positive in Graves’) and neuroimaging (MRI or CT revealing enlarged EOM bellies with tendon sparing, diagnostic of Graves’) should be done. If myasthenia gravis is suspected, a Tensilon test should be ordered.
Beware of glaucoma in patients with Graves’ ophthalmopathy. The infiltrated muscles can cause globe compression with secondary IOP elevation as well as compressive optic neuropathy.
Showing posts with label EYE. Show all posts
Showing posts with label EYE. Show all posts
Monday, November 28, 2011
Hypertension
Signs and Symptoms
The patient with hypertension tends to be older and the prevalence of the disease increases with age. However, 2 percent of children have hypertension while another 5 percent are borderline. Black adults have a higher incidence of hypertension than Caucasian adults and typically a more severe form of the disease. Risk factors for the development of hypertension include a positive family history of hypertension or cardiovascular disease, diabetes, hypercholesterolemia, obesity, sedentary lifestyle, high sodium intake, high dietary fat intake, alcohol use, smoking, and a stressful lifestyle.
Hypertension is defined as systolic blood pressure (BP) exceeding 140mmHg and/or diastolic BP exceeding 90mmHg measured at least twice on separate days. About 90 percent of cases are due to essential hypertension, while the remaining cases are secondary to another disease, such as renal parenchymal disease or pheochromocytoma. There is also isolated systolic hypertension and isolated diastolic hypertension.
Hypertension is manifested within the eye as both hypertensive retinopathy and hypertensive ocular complications. Hypertensive ocular complications include retinal vessel occlusion, ocular ischemic syndrome, non-arteritic anterior ischemic optic neuropathy, internuclear ophthalmoplegia, cranial nerve palsy, nystagmus and midbrain syndrome, and amaurosis fugax and transient ischemic attack.
Pathophysiology
Essential hypertension develops from renal system dysfunction. The kidney is a filtering organ that retains vital blood components and excretes excess fluid. If too much fluid is retained, BP rises. If too little fluid is retained, BP decreases. Arterial pressure within the renal artery triggers a feedback loop. The kidneys excrete sodium, which osmotically draws fluid into the excretory system in a process called pressure diuresis. This causes a decrease in blood fluid volume and arterial pressure.
As pressure within the renal artery decreases, the kidneys reflexively secrete an enzyme called renin. This enzyme causes the formation of a protein called Angiotensin I. Angiotensin I directly stimulates the kidneys to retain sodium and fluid. Angiotensin I is converted in the lungs, via the enzyme angiotensin converting enzyme (ACE) to Angiotensin II. Angiotensin II is a potent vasoconstrictor which increases total peripheral vascular resistance and hence elevates BP.
As BP elevates, the whole system begins again with pressure diuresis. In healthy individuals, this feedback loop maintains a constant blood pressure with only minor fluctuations. In patients with essential hypertension, this feedback loop fails for undiscovered reasons. The result is a higher than normal level of pressure within the renal artery necessary for pressure diuresis to occur.
Hypertension plays a significant role in the development of arteriosclerosis and atherosclerosis. Hypertension reduces the elasticity of vessels allowing lipids to deposit in the form of atheromas, which in turn leads to thrombus formation and possible emboli formation. This impedes blood flow and leads to ischemic disease.
Coronary heart disease is the leading cause of death in hypertensive patients. Ventricular hypertrophy occurs as a result of increased cardiac output in the face of systemic vascular resistance. Eventually, the heart is unable to maintain this constant output and the hypertrophied muscle outstrips its oxygen supply.
Cerebrovascular disease is a serious complication of hypertension. Hypertension is the leading cause of stroke. Hypertension-mediated atherothrombotic lesions are the cause.
Hypertension-induced arteriosclerosis may also result in atrophy of the renal glomeruli and tubules. This results in a malignant form of hypertension, and renal failure is also a frequent cause of death.
Management
Reducing morbidity and mortality is the main goal in hypertension management. Blood pressure reduction is done in a step-wise approach, often beginning with non-pharmacologic methods that include weight loss, and dietary and lifestyle modifications.
Should non-pharmacological methods prove unsuccessful, there are four families of drugs from which to choose:
1. Diuretics (reduce blood volume by inhibiting sodium and water retention)
2. Beta blockers (decrease cardiac output)
3. Calcium antagonists (induce vasodilation)
4. ACE inhibitors (decrease peripheral vascular resistance)
Medications from each family may be combined in order to achieve the desired pressure reduction.
Clinical Pearls
Hypertensive complications are mediated through arteriosclerosis and atherosclerosis.
Weight reduction is the most potent non-pharmacological method of hypertension management.
The patient with hypertension tends to be older and the prevalence of the disease increases with age. However, 2 percent of children have hypertension while another 5 percent are borderline. Black adults have a higher incidence of hypertension than Caucasian adults and typically a more severe form of the disease. Risk factors for the development of hypertension include a positive family history of hypertension or cardiovascular disease, diabetes, hypercholesterolemia, obesity, sedentary lifestyle, high sodium intake, high dietary fat intake, alcohol use, smoking, and a stressful lifestyle.
Hypertension is defined as systolic blood pressure (BP) exceeding 140mmHg and/or diastolic BP exceeding 90mmHg measured at least twice on separate days. About 90 percent of cases are due to essential hypertension, while the remaining cases are secondary to another disease, such as renal parenchymal disease or pheochromocytoma. There is also isolated systolic hypertension and isolated diastolic hypertension.
Hypertension is manifested within the eye as both hypertensive retinopathy and hypertensive ocular complications. Hypertensive ocular complications include retinal vessel occlusion, ocular ischemic syndrome, non-arteritic anterior ischemic optic neuropathy, internuclear ophthalmoplegia, cranial nerve palsy, nystagmus and midbrain syndrome, and amaurosis fugax and transient ischemic attack.
Pathophysiology
Essential hypertension develops from renal system dysfunction. The kidney is a filtering organ that retains vital blood components and excretes excess fluid. If too much fluid is retained, BP rises. If too little fluid is retained, BP decreases. Arterial pressure within the renal artery triggers a feedback loop. The kidneys excrete sodium, which osmotically draws fluid into the excretory system in a process called pressure diuresis. This causes a decrease in blood fluid volume and arterial pressure.
As pressure within the renal artery decreases, the kidneys reflexively secrete an enzyme called renin. This enzyme causes the formation of a protein called Angiotensin I. Angiotensin I directly stimulates the kidneys to retain sodium and fluid. Angiotensin I is converted in the lungs, via the enzyme angiotensin converting enzyme (ACE) to Angiotensin II. Angiotensin II is a potent vasoconstrictor which increases total peripheral vascular resistance and hence elevates BP.
As BP elevates, the whole system begins again with pressure diuresis. In healthy individuals, this feedback loop maintains a constant blood pressure with only minor fluctuations. In patients with essential hypertension, this feedback loop fails for undiscovered reasons. The result is a higher than normal level of pressure within the renal artery necessary for pressure diuresis to occur.
Hypertension plays a significant role in the development of arteriosclerosis and atherosclerosis. Hypertension reduces the elasticity of vessels allowing lipids to deposit in the form of atheromas, which in turn leads to thrombus formation and possible emboli formation. This impedes blood flow and leads to ischemic disease.
Coronary heart disease is the leading cause of death in hypertensive patients. Ventricular hypertrophy occurs as a result of increased cardiac output in the face of systemic vascular resistance. Eventually, the heart is unable to maintain this constant output and the hypertrophied muscle outstrips its oxygen supply.
Cerebrovascular disease is a serious complication of hypertension. Hypertension is the leading cause of stroke. Hypertension-mediated atherothrombotic lesions are the cause.
Hypertension-induced arteriosclerosis may also result in atrophy of the renal glomeruli and tubules. This results in a malignant form of hypertension, and renal failure is also a frequent cause of death.
Management
Reducing morbidity and mortality is the main goal in hypertension management. Blood pressure reduction is done in a step-wise approach, often beginning with non-pharmacologic methods that include weight loss, and dietary and lifestyle modifications.
Should non-pharmacological methods prove unsuccessful, there are four families of drugs from which to choose:
1. Diuretics (reduce blood volume by inhibiting sodium and water retention)
2. Beta blockers (decrease cardiac output)
3. Calcium antagonists (induce vasodilation)
4. ACE inhibitors (decrease peripheral vascular resistance)
Medications from each family may be combined in order to achieve the desired pressure reduction.
Clinical Pearls
Hypertensive complications are mediated through arteriosclerosis and atherosclerosis.
Weight reduction is the most potent non-pharmacological method of hypertension management.
Diabetes Mellitus
Signs and Symptoms
Diabetes mellitus is the most common endocrine disorder, and is defined as a group of disorders that exhibit a defective or deficient insulin secretory process, glucose underutilization, and hyperglycemia. Possible systemic signs and symptoms include polyuria (increased frequency of urination), polydipsia (increased thirst), polyphagia (increased appetite), glycosuria, weakness, weight loss, neuropathy, and nephropathy. Ophthalmic signs and symptoms may include chronic conjunctival injection, changes in corneal curvature, large fluctuations in refraction, premature cataractogenesis, nonproliferative and proliferative retinopathy and cranial nerve III, IV or VI palsy.
Type 1 diabetes, formerly known as insulin-dependent diabetes (IDDM) is also referred to as juvenile-onset or ketose prone DM, usually begins by age 20 and is defined by a severe, absolute lack of insulin caused by a reduction in the beta-cell mass of the pancreas. This may be the result of autoimmune processes and may involve genetic susceptibility.
Type 2 diabetes, formerly known as non-insulin-dependent diabetes (NIDDM), sometimes referred to as adult-onset DM, usually begins after age 40 as a multifactorial disease that may involve improper insulin secretion, malfunctioning insulin and/or insulin resistance in peripheral tissues. Approximately 10 percent of diabetic cases are type 1 and approximately 90 percent are Type 2.
Pathophysiology
The pancreas plays a primary role in the metabolism of glucose by secreting the hormones insulin and glucagon. The Islets of Langerhans secrete insulin and glucagon directly into the blood. Inadequate secretion of insulin, inadequate structure or function of insulin or its receptors results in impaired metabolism of glucose, carbohydrates, proteins and fats, characterized by hyperglycemia and glycosuria. Hyperglycemia is the most frequently observed sign of diabetes and is considered the etiologic source of diabetic complications both in the body and in the eye.
Glucagon is a hormone that opposes the action of insulin. It is secreted when blood glucose levels fall. Glucagon increases blood glucose concentration partly by breaking down glycogen in the liver. Following a meal, glucose is absorbed into the blood. In response to increased blood glucose levels, insulin is secreted causing rapid uptake, storage, or use of glucose by the tissues of the body. Unused glucose is stored as glycogen in the liver. Between meals, when blood glucose is at minimal levels, tissues continue to require an energy source to function properly. Stored glycogen, via glucagon, is converted to glucose by a pathway known as glycogenolysis. Gluconeogenesis is the production of glucose in the liver from noncarbohydrate precursors such as glycogenic amino acids.
Elevated glucose levels result in the formation of sorbitol (a sugar alcohol) via the aldose reductase pathway. Since sorbitol cannot readily diffuse through cell membranes, cell edema and changes in function can ensue. With respect to the eye, this contributes to the evolution of premature cataractogenesis (nuclear sclerotic, senile and snowflake posterior subcapsular cataracts) and sight threatening diabetic retinopathy (compromising the pericytes that line capillary walls).
An additional complication of hyperglycemia is nonenzymatic glycosylation. Nonenzymatic glycosylation is the binding of excess glucose to the amino group of proteins in the tissues. As a possible result, at the level of the capillary membranes, altered cell function may lead to the development of microaneurysms, vascular loops, and vessel dilation, allowing blood leakage. Platelet aggregation secondary to these changes initiates tissue hypoxia. These changes result in the system wide accumulation of edema and in the eye, increase the potential for retinal sequelae.
Glycemic control over the course of the disease has been shown to reduce the risk of developing debilitating organ disease and retinopathy. Blood glucose levels are of even greater importance in diabetic pregnant women, as hyperglycemia during pregnancy may initiate swift and severe progression of diabetic retinopathy. Other concurrent systemic variables that may potentiate the onset of diabetic retinopathy include hypertension, nephropathy, cardiac disease, autonomic neuropathy and ocular findings such as elevated intraocular pressure and myopia.
Management
The easiest method of treating Type 2 diabetes is with diet control. Dietary regulation is set by basing the caloric intake on the patient’s ideal body weight, selecting adequate sources of protein and carbohydrate, while maintaining a reasonable distribution of foods. When hyperglycemia persists despite dietary changes, oral hypoglycemic agents become necessary. These agents can be prescribed in small doses, adjusting the dosage to larger levels to achieve tighter control, as necessary.
Insulin is always required for Type 1 and is an option for recalcitrant cases involving Type 2 diabetes. Conventional therapy involves the administration of an intermediate-acting insulin (NPH or lente), once or twice a day, with or without small amounts of regular insulin.
Clinical Pearls
Large changes in refraction may be the first sign of diabetic disease. Often, myopic or hyperopic shifts are created as the lens swells, secondary to sorbitol effects, resulting in large refractive changes, in what were otherwise noted as "stable eyes."
Diabetes mellitus is the most common endocrine disorder, and is defined as a group of disorders that exhibit a defective or deficient insulin secretory process, glucose underutilization, and hyperglycemia. Possible systemic signs and symptoms include polyuria (increased frequency of urination), polydipsia (increased thirst), polyphagia (increased appetite), glycosuria, weakness, weight loss, neuropathy, and nephropathy. Ophthalmic signs and symptoms may include chronic conjunctival injection, changes in corneal curvature, large fluctuations in refraction, premature cataractogenesis, nonproliferative and proliferative retinopathy and cranial nerve III, IV or VI palsy.
Type 1 diabetes, formerly known as insulin-dependent diabetes (IDDM) is also referred to as juvenile-onset or ketose prone DM, usually begins by age 20 and is defined by a severe, absolute lack of insulin caused by a reduction in the beta-cell mass of the pancreas. This may be the result of autoimmune processes and may involve genetic susceptibility.
Type 2 diabetes, formerly known as non-insulin-dependent diabetes (NIDDM), sometimes referred to as adult-onset DM, usually begins after age 40 as a multifactorial disease that may involve improper insulin secretion, malfunctioning insulin and/or insulin resistance in peripheral tissues. Approximately 10 percent of diabetic cases are type 1 and approximately 90 percent are Type 2.
Pathophysiology
The pancreas plays a primary role in the metabolism of glucose by secreting the hormones insulin and glucagon. The Islets of Langerhans secrete insulin and glucagon directly into the blood. Inadequate secretion of insulin, inadequate structure or function of insulin or its receptors results in impaired metabolism of glucose, carbohydrates, proteins and fats, characterized by hyperglycemia and glycosuria. Hyperglycemia is the most frequently observed sign of diabetes and is considered the etiologic source of diabetic complications both in the body and in the eye.
Glucagon is a hormone that opposes the action of insulin. It is secreted when blood glucose levels fall. Glucagon increases blood glucose concentration partly by breaking down glycogen in the liver. Following a meal, glucose is absorbed into the blood. In response to increased blood glucose levels, insulin is secreted causing rapid uptake, storage, or use of glucose by the tissues of the body. Unused glucose is stored as glycogen in the liver. Between meals, when blood glucose is at minimal levels, tissues continue to require an energy source to function properly. Stored glycogen, via glucagon, is converted to glucose by a pathway known as glycogenolysis. Gluconeogenesis is the production of glucose in the liver from noncarbohydrate precursors such as glycogenic amino acids.
Elevated glucose levels result in the formation of sorbitol (a sugar alcohol) via the aldose reductase pathway. Since sorbitol cannot readily diffuse through cell membranes, cell edema and changes in function can ensue. With respect to the eye, this contributes to the evolution of premature cataractogenesis (nuclear sclerotic, senile and snowflake posterior subcapsular cataracts) and sight threatening diabetic retinopathy (compromising the pericytes that line capillary walls).
An additional complication of hyperglycemia is nonenzymatic glycosylation. Nonenzymatic glycosylation is the binding of excess glucose to the amino group of proteins in the tissues. As a possible result, at the level of the capillary membranes, altered cell function may lead to the development of microaneurysms, vascular loops, and vessel dilation, allowing blood leakage. Platelet aggregation secondary to these changes initiates tissue hypoxia. These changes result in the system wide accumulation of edema and in the eye, increase the potential for retinal sequelae.
Glycemic control over the course of the disease has been shown to reduce the risk of developing debilitating organ disease and retinopathy. Blood glucose levels are of even greater importance in diabetic pregnant women, as hyperglycemia during pregnancy may initiate swift and severe progression of diabetic retinopathy. Other concurrent systemic variables that may potentiate the onset of diabetic retinopathy include hypertension, nephropathy, cardiac disease, autonomic neuropathy and ocular findings such as elevated intraocular pressure and myopia.
Management
The easiest method of treating Type 2 diabetes is with diet control. Dietary regulation is set by basing the caloric intake on the patient’s ideal body weight, selecting adequate sources of protein and carbohydrate, while maintaining a reasonable distribution of foods. When hyperglycemia persists despite dietary changes, oral hypoglycemic agents become necessary. These agents can be prescribed in small doses, adjusting the dosage to larger levels to achieve tighter control, as necessary.
Insulin is always required for Type 1 and is an option for recalcitrant cases involving Type 2 diabetes. Conventional therapy involves the administration of an intermediate-acting insulin (NPH or lente), once or twice a day, with or without small amounts of regular insulin.
Clinical Pearls
Large changes in refraction may be the first sign of diabetic disease. Often, myopic or hyperopic shifts are created as the lens swells, secondary to sorbitol effects, resulting in large refractive changes, in what were otherwise noted as "stable eyes."
Albinism
Signs and Symptoms
Albinism affects approximately 1 in 20,000 individuals, producing pigmentary deficiency, abnormal crossings of the temporal fibers in the optic chiasm, nystagmus, photophobia, variable visual acuity and, frequently, strabismus. The main subdivisions of albinism include oculocutaneous, ocular, and albinoidism (absence of pigment in localized areas; the pigment in the skin, hair and eyes is less than normal but does not affect the individual as severely as the oculocutaneous or ocular types). The literature reports as many as 20 variants of oculocutaneous albinism alone.
Oculocutaneous as well as ocular albinos exhibit similar ocular and visual dysfunction. The oculocutaneous albino patient manifests reduced acuity, photophobia, strabismus, significant refractive error with astigmatism, transillumination of the iris and globe, nystagmus, blonde fundus with visible choroidal vasculature, and macular hypoplasia. A super-normal EOG and ERG is also present.
Transillumination of the iris and globe results from insufficient uveal pigmentation and poor development of the retinal pigment epithelium. This leads to a funduscopic picture of a blond fundus with extensive areas of hypopigmentation and clearly visible underlying choroidal vasculature. The pigment of the RPE acts as a sink for incoming light. When the RPE is underdeveloped, light scatters within the eye, producing the subjective complaint of photophobia.
The level of visual acuity varies among albino patients according to the amount of ocular pigmentation present and the concomitant level of macular development. Ocular albinos have variable amounts of uveal pigmentation and the potential to have the best acuity (20/25 to 20/300) among albinos. Oculocutaneous albinos exhibits less pigmentation than their ocular albino counterparts and tend to have lower acuity levels (20/80 to 20/400).
Systemically, albino patients may exhibit difficulties with healing and infection, as well as bleeding (Chédiak-Higashi syndrome and Hermansky-Pudlak respectively). Clinicians should ask questions in the history regarding bruising, nosebleeding and healing.
Pathophysiology
Albinism is a disorder of amino acid metabolism that results in a congenital hypopigmentation of ocular and systemic tissues. Cellular pigmentation is dependant upon a cell’s ability to manufacture and sequester the pigment melanin. This is accomplished within organelles called melanosomes which reside inside cells called melanocytes. The melanocytes that originate in the neural crest provide pigment for the skin (including eyelids), hair, uvea, conjunctiva, stroma of the iris, ciliary body and choroid. The melanocytes that supply pigment for the retinal pigment epithelium (RPE) are derived from neuroectoderm. Inside the melanosome, melanin is synthesized from the amino acid tyrosine through the actions of the enzyme tyrosinase. On the basis of the results of either the tyrosine hair bulb test or electron microscopy of the hair bulb or skin, oculocutaneous albinos are classified as tyrosinase-positive or tyrosinase-negative.
Tyrosinase-positive and -negative oculocutaneous albinos possess an autosomal recessive inheritance pattern. Oculocutaneous albinism results from incomplete melanization of the cellular melanosomes. In tyrosinase-negative oculocutaneous albinism, the congenital inactivity of the enzyme tyrosinase prevents the cell’s use of tyrosine in the formation of the pigment melanin. In tyrosinase-positive oculocutaneous albinism, tyrosinase activity is normal, but there is an inability of the cells to sequester the synthesized melanin into the melanosomes.
An autosomal recessive subtype of tyrosinase positive oculocutaneous albinism commonly seen in Puerto Rico is the Hermansky-Pudlak syndrome. Here, patients exhibit hemorrhagic diathesis (a tendency toward easy bruising and bleeding) due to a platelet dysfunction along with normal tyrosinase activity.
Another autosomal recessive subtype of oculocutaneous albinism is the Chédiak-Higashi syndrome. Here, patients may have a silvery sheen to their skin, and blue to brown irides. Normal tyrosinase activity within hair bulbs shows increased susceptibility to infection, hepatosplenomegaly, lymphadenopathy and a predisposition to development of a lymphoma-like condition.
Ocular albinism, in contrast to oculocutaneous albinism, exhibits pigmentary dilution due to abnormalities in melanosome synthesis rather than inadequate melanization. Ocular albinism is transmitted through either an X-linked or autosomal recessive mode. The hair and skin of the ocular albino tends to show a much greater pigmentation than that of the oculocutaneous albino, often falling into a normal pigmentation range. The uveal pigmentation of the ocular albino is variable and may range from very hypopigmented to a nearly normal pigmentation level.
Both ocular and oculocutaneous albinism exhibit a hypoplastic macula. Orderly retinal morphogenesis depends on the organizing influence of the adjacent retinal pigment epithelium. The insufficient uveal pigmentation and poor development of the RPE in the albinotic patient provides a developmentally unstable substrate for normal retinal organization. Hence, the albinotic macula is always hypoplastic and the albinotic patient has secondarily reduced acuity. This maldevelopment of the macula explains the pendular nystagmus of the albino patient, as the albino eye constantly searches for a clear image.
Albinism affects approximately 1 in 20,000 individuals, producing pigmentary deficiency, abnormal crossings of the temporal fibers in the optic chiasm, nystagmus, photophobia, variable visual acuity and, frequently, strabismus. The main subdivisions of albinism include oculocutaneous, ocular, and albinoidism (absence of pigment in localized areas; the pigment in the skin, hair and eyes is less than normal but does not affect the individual as severely as the oculocutaneous or ocular types). The literature reports as many as 20 variants of oculocutaneous albinism alone.
Oculocutaneous as well as ocular albinos exhibit similar ocular and visual dysfunction. The oculocutaneous albino patient manifests reduced acuity, photophobia, strabismus, significant refractive error with astigmatism, transillumination of the iris and globe, nystagmus, blonde fundus with visible choroidal vasculature, and macular hypoplasia. A super-normal EOG and ERG is also present.
Transillumination of the iris and globe results from insufficient uveal pigmentation and poor development of the retinal pigment epithelium. This leads to a funduscopic picture of a blond fundus with extensive areas of hypopigmentation and clearly visible underlying choroidal vasculature. The pigment of the RPE acts as a sink for incoming light. When the RPE is underdeveloped, light scatters within the eye, producing the subjective complaint of photophobia.
The level of visual acuity varies among albino patients according to the amount of ocular pigmentation present and the concomitant level of macular development. Ocular albinos have variable amounts of uveal pigmentation and the potential to have the best acuity (20/25 to 20/300) among albinos. Oculocutaneous albinos exhibits less pigmentation than their ocular albino counterparts and tend to have lower acuity levels (20/80 to 20/400).
Systemically, albino patients may exhibit difficulties with healing and infection, as well as bleeding (Chédiak-Higashi syndrome and Hermansky-Pudlak respectively). Clinicians should ask questions in the history regarding bruising, nosebleeding and healing.
Pathophysiology
Albinism is a disorder of amino acid metabolism that results in a congenital hypopigmentation of ocular and systemic tissues. Cellular pigmentation is dependant upon a cell’s ability to manufacture and sequester the pigment melanin. This is accomplished within organelles called melanosomes which reside inside cells called melanocytes. The melanocytes that originate in the neural crest provide pigment for the skin (including eyelids), hair, uvea, conjunctiva, stroma of the iris, ciliary body and choroid. The melanocytes that supply pigment for the retinal pigment epithelium (RPE) are derived from neuroectoderm. Inside the melanosome, melanin is synthesized from the amino acid tyrosine through the actions of the enzyme tyrosinase. On the basis of the results of either the tyrosine hair bulb test or electron microscopy of the hair bulb or skin, oculocutaneous albinos are classified as tyrosinase-positive or tyrosinase-negative.
Tyrosinase-positive and -negative oculocutaneous albinos possess an autosomal recessive inheritance pattern. Oculocutaneous albinism results from incomplete melanization of the cellular melanosomes. In tyrosinase-negative oculocutaneous albinism, the congenital inactivity of the enzyme tyrosinase prevents the cell’s use of tyrosine in the formation of the pigment melanin. In tyrosinase-positive oculocutaneous albinism, tyrosinase activity is normal, but there is an inability of the cells to sequester the synthesized melanin into the melanosomes.
An autosomal recessive subtype of tyrosinase positive oculocutaneous albinism commonly seen in Puerto Rico is the Hermansky-Pudlak syndrome. Here, patients exhibit hemorrhagic diathesis (a tendency toward easy bruising and bleeding) due to a platelet dysfunction along with normal tyrosinase activity.
Another autosomal recessive subtype of oculocutaneous albinism is the Chédiak-Higashi syndrome. Here, patients may have a silvery sheen to their skin, and blue to brown irides. Normal tyrosinase activity within hair bulbs shows increased susceptibility to infection, hepatosplenomegaly, lymphadenopathy and a predisposition to development of a lymphoma-like condition.
Ocular albinism, in contrast to oculocutaneous albinism, exhibits pigmentary dilution due to abnormalities in melanosome synthesis rather than inadequate melanization. Ocular albinism is transmitted through either an X-linked or autosomal recessive mode. The hair and skin of the ocular albino tends to show a much greater pigmentation than that of the oculocutaneous albino, often falling into a normal pigmentation range. The uveal pigmentation of the ocular albino is variable and may range from very hypopigmented to a nearly normal pigmentation level.
Both ocular and oculocutaneous albinism exhibit a hypoplastic macula. Orderly retinal morphogenesis depends on the organizing influence of the adjacent retinal pigment epithelium. The insufficient uveal pigmentation and poor development of the RPE in the albinotic patient provides a developmentally unstable substrate for normal retinal organization. Hence, the albinotic macula is always hypoplastic and the albinotic patient has secondarily reduced acuity. This maldevelopment of the macula explains the pendular nystagmus of the albino patient, as the albino eye constantly searches for a clear image.
SYPHILIS
SIGNS AND SYMPTOMS
Syphilis is a multi-system, multi-symptom disorder that occurs primarily through sexual transmission, though the disease can be spread through blood transfusion and direct contact with an infected lesion. Patients tend to be younger, with a history of unprotected sex. Elderly patients may manifest late-stage syphilis left untreated many years before.
In cases of congenital syphilis, the patient may manifest Hutchinson's triad (interstitial keratitis, deafness and malformed teeth), osteochondritis (inflammation of both bone and cartilage), chorioretinitis, hepatosplenomegaly (enlargement of the liver and spleen), and anorexia.
In the primary stage of acquired syphilis, the patient develops a painless chancre at the site of inoculation, as well as regional lymphadenopathy. While primarily genital, chancres may develop on the eyelid and conjunctiva. Other ocular signs in the primary stage include conjunctivitis, blepharitis, and alopecia.
In the secondary stage of acquired syphilis, the patient will develop malaise, lymphadenopathy, fever, maculopapular skin lesions on the palms and soles, joint pain, headache, and loss of appetite. Ocular signs are most common in secondary syphilis and include episcleritis, anterior uveitis, uveitic glaucoma, neuroretinitis, chorioretinitis, ischemic retinal vasculopathy, and infectious optic neuropathy.
In the third stage of acquired syphilis, focal endarteritis causes the formation of gummas (granulomatous lesions), which can involve the eye and adnexa, and the central nervous and cardiovascular systems. At this stage, neurosyphilis can manifest with acute meningitis, cranial neuropathies, optic atrophy, pupil abnormalities, paresis, and tabes dorsalis (degeneration of the dorsal columns of the spinal cord resulting in loss of coordination, reflexes and sensation, and ataxic gait).
PATHOPHYSIOLOGY
Syphilis is caused by the spirochete bacteria, Treponema pallidum. It is transmitted through mucous membranes or open skin-to-skin contact, primarily through sexual intercourse. Transmission can also occur through blood transfusion.
After infection, a period of incubation ensues. The organism enters the lymphatic system and bloodstream and disseminates soon after contact. Shortly after infection, a chancre forms at the site of inoculation. The chancres spontaneously heal after two to eight weeks, and the patient enters the secondary stage of syphilis. In individuals with an intact immune system, the disease enters a period of latency. Inflammation and regional vasculopathy account for the signs and symptoms.
After a period of latency (which may extend four or more years in an untreated or undertreated individual), the patient enters the tertiary stage. Focal granulomatous lesions known as gummas develop and can affect virtually any organ system. The resultant dysfunction caused by these gummas accounts for the dysfunction seen in tertiary syphilis. Approximately 10 percent of untreated patients develop neurosyphilis. Since the organism has a predilection for the dorsal spinal cord and intercalated neurons, these patients can develop an ataxic gait and loss of sensation from the lower limbs, and light-near dissociated pupils, which are often miotic (Argyll Robertson pupils). If left untreated, dysfunction of the central nervous and cardiovascular systems can lead to progressive dementia and death.
MANAGEMENT
Serologic testing to detect host antibodies is the mainstay of diagnosis. Tests that detect cardiolipin-lecithin-cholesterol antibodies but are non-specific for Treponema pallidum include the venereal disease research laboratory (VDRL) and rapid plasma reagin (RPR) which indicate current activity of disease. False-positive results are possible on these tests.
Tests specific for antibodies to Treponema pallidum include the fluorescent treponemal antibody absorption (FTA-ABS) and microhemagglutination assay for Treponemal pallidum (MHA-TP). These tests indicate whether or not antibodies are present from a previous syphilitic infection, but do not indicate current disease activity. There is a lower incidence of false-positive results with these specific tests. When you suspect syphilis, order both a specific and a non-specific test. In cases where serologic results are uncertain, these tests can be performed using cerebrospinal fluid.
Treatment of syphilis involves systemic IV or IM penicillin. Alternatives for penicillin-sensitive patients include doxycyline, tetracycline, ceftriaxone, and chloramphenicol. In neurosyphilis, there is no acceptable substitute, and patients must be desensitized to penicillin prior to treatment.
CLINICAL PEARLS
Syphilis is a great mimic. Always keep this condition in mind when encountering patients with cranial neuropathies, optic neuropathies, anterior uveitis, chorioretinitis, retinal vascular occlusion, and chronic anterior segment inflammation.
Manifestations of syphilis can be complicated by concurrent HIV infection. Always consider HIV infection in patients with syphilis. Further, concurrent infections with gonorrhea and chlamydia frequently occur, and should also be investigated.
Nearly 45 percent of males manifesting bilateral tonic pupils will test positive for syphilis.
Lyme disease, another spirochetal disease, is also a great mimic and behaves very similar to syphilis. In fact, Lyme disease can cause false-positive readings on both specific and non-specific tests for syphilis.
Syphilis is a multi-system, multi-symptom disorder that occurs primarily through sexual transmission, though the disease can be spread through blood transfusion and direct contact with an infected lesion. Patients tend to be younger, with a history of unprotected sex. Elderly patients may manifest late-stage syphilis left untreated many years before.
In cases of congenital syphilis, the patient may manifest Hutchinson's triad (interstitial keratitis, deafness and malformed teeth), osteochondritis (inflammation of both bone and cartilage), chorioretinitis, hepatosplenomegaly (enlargement of the liver and spleen), and anorexia.
In the primary stage of acquired syphilis, the patient develops a painless chancre at the site of inoculation, as well as regional lymphadenopathy. While primarily genital, chancres may develop on the eyelid and conjunctiva. Other ocular signs in the primary stage include conjunctivitis, blepharitis, and alopecia.
In the secondary stage of acquired syphilis, the patient will develop malaise, lymphadenopathy, fever, maculopapular skin lesions on the palms and soles, joint pain, headache, and loss of appetite. Ocular signs are most common in secondary syphilis and include episcleritis, anterior uveitis, uveitic glaucoma, neuroretinitis, chorioretinitis, ischemic retinal vasculopathy, and infectious optic neuropathy.
In the third stage of acquired syphilis, focal endarteritis causes the formation of gummas (granulomatous lesions), which can involve the eye and adnexa, and the central nervous and cardiovascular systems. At this stage, neurosyphilis can manifest with acute meningitis, cranial neuropathies, optic atrophy, pupil abnormalities, paresis, and tabes dorsalis (degeneration of the dorsal columns of the spinal cord resulting in loss of coordination, reflexes and sensation, and ataxic gait).
PATHOPHYSIOLOGY
Syphilis is caused by the spirochete bacteria, Treponema pallidum. It is transmitted through mucous membranes or open skin-to-skin contact, primarily through sexual intercourse. Transmission can also occur through blood transfusion.
After infection, a period of incubation ensues. The organism enters the lymphatic system and bloodstream and disseminates soon after contact. Shortly after infection, a chancre forms at the site of inoculation. The chancres spontaneously heal after two to eight weeks, and the patient enters the secondary stage of syphilis. In individuals with an intact immune system, the disease enters a period of latency. Inflammation and regional vasculopathy account for the signs and symptoms.
After a period of latency (which may extend four or more years in an untreated or undertreated individual), the patient enters the tertiary stage. Focal granulomatous lesions known as gummas develop and can affect virtually any organ system. The resultant dysfunction caused by these gummas accounts for the dysfunction seen in tertiary syphilis. Approximately 10 percent of untreated patients develop neurosyphilis. Since the organism has a predilection for the dorsal spinal cord and intercalated neurons, these patients can develop an ataxic gait and loss of sensation from the lower limbs, and light-near dissociated pupils, which are often miotic (Argyll Robertson pupils). If left untreated, dysfunction of the central nervous and cardiovascular systems can lead to progressive dementia and death.
MANAGEMENT
Serologic testing to detect host antibodies is the mainstay of diagnosis. Tests that detect cardiolipin-lecithin-cholesterol antibodies but are non-specific for Treponema pallidum include the venereal disease research laboratory (VDRL) and rapid plasma reagin (RPR) which indicate current activity of disease. False-positive results are possible on these tests.
Tests specific for antibodies to Treponema pallidum include the fluorescent treponemal antibody absorption (FTA-ABS) and microhemagglutination assay for Treponemal pallidum (MHA-TP). These tests indicate whether or not antibodies are present from a previous syphilitic infection, but do not indicate current disease activity. There is a lower incidence of false-positive results with these specific tests. When you suspect syphilis, order both a specific and a non-specific test. In cases where serologic results are uncertain, these tests can be performed using cerebrospinal fluid.
Treatment of syphilis involves systemic IV or IM penicillin. Alternatives for penicillin-sensitive patients include doxycyline, tetracycline, ceftriaxone, and chloramphenicol. In neurosyphilis, there is no acceptable substitute, and patients must be desensitized to penicillin prior to treatment.
CLINICAL PEARLS
Syphilis is a great mimic. Always keep this condition in mind when encountering patients with cranial neuropathies, optic neuropathies, anterior uveitis, chorioretinitis, retinal vascular occlusion, and chronic anterior segment inflammation.
Manifestations of syphilis can be complicated by concurrent HIV infection. Always consider HIV infection in patients with syphilis. Further, concurrent infections with gonorrhea and chlamydia frequently occur, and should also be investigated.
Nearly 45 percent of males manifesting bilateral tonic pupils will test positive for syphilis.
Lyme disease, another spirochetal disease, is also a great mimic and behaves very similar to syphilis. In fact, Lyme disease can cause false-positive readings on both specific and non-specific tests for syphilis.
SICKLE CELL DISEASE
SIGNS AND SYMPTOMS
Ocular symptoms are uncommon in the early stages of the disease. Systemically, symptoms include painful crises of abdominal and musculoskeletal discomfort.
Ocular signs include comma-shaped vessels in the bulbar conjunctiva, iris atrophy, iris neovascularization, dull-gray fundus appearance, retinal venous tortuosity, nonproliferative retinal hemorrhages in the subretinal, intraretinal or preretinal position. Further signs include black sunbursts (retinal pigment epithelial hyperplasia secondary to deep retinal vascular occlusions), glistening refractile deposits in the retinal periphery (hemosiderin-laden macrophages), salmon patch hemorrhages (orange-pink-colored intraretinal hemorrhage), angioid streaks (breaks in Bruch's membrane radiating from the optic nerve), venous occlusion, artery occlusion, peripheral neovascularization (seafan retinopathy) with subsequent vitreous hemorrhage and tractional retinal detachment.
PATHOPHYSIOLOGY
Hemoglobinopathies are among the more commonly inherited diseases in humans. Hemoglobinopathies result when there is altered structure, function or production of hemoglobin. Hemoglobin is the principle protein of the erythrocyte, responsible for binding and facilitating oxygen transmission to tissues. In the four variations of sickle cell disease, systemic and ocular tissues become deprived of oxygen and undergo pathologic changes.
Normal erythrocytes, containing normal hemoglobin, appear as flexible, pliable, biconcave discs. Erythrocytes affected by sickling disease lose their biconcave shape and their ability to efficiently move through the circulatory system. The "sickled" cells become rigid, restrict blood flow, produce clots and cause tissues to become hypoxic.
Variations in the alteration of the amino acid sequence on the globin chain produce variations in the disease's expression. The four forms of the disease are often referred to by their genotype: sickle cell trait (AS), sickle cell anemia (SS), sickle cell disease (SC) and sickle cell thalasemia (SThal).
Systemically, the sickle cell anemia variation (SS) produces the most symptoms. With respect to the eye, the sickle cell disease mutation (SC) produces the most effects. Overall, the sickle cell trait expression (AS) produces the fewest complications.
MANAGEMENT
The treatment goal for sickle cell retinopathy is to reduce the risk of, prevent or eliminate retinal neovascularization. Follow patients with asymptomatic sickle cell disease biannually with ocular examinations and dilated retinal evaluation. Since visual loss can result from both nonproliferative (subretinal neovascularization secondary to angioid streaks) and proliferative retinal disease, refer the patient to the retinologist when you see these retinal findings. Treat proliferative disease with fluorescein angiography and panretinal photocoagulation. Cryotherapy has not been proven to be efficacious and is associated with high complication rates.
CLINICAL PEARLS
Proliferative sickle cell retinopathy breaks down into five stages:
Stage 1: peripheral retinal arteriolar occlusions
Stage 2: peripheral arterio-venous anastamoses
Stage 3: neovascular fronds known as sea fans
Stage 4: vitreous hemorrhage as tractional forces and vitreous collapse tear fragile neovascular membranes
Stage 5: advanced disease, identified by severe vitreous traction and retinal detachment
Other causes of peripheral neovascularization include sarcoidosis, diabetes, retinal venous occlusion, Eales' disease, leukemia and ocular ischemic syndrome. However, the characteristic sea fan frond is diagnostic of sickle retinopathy.
For patients with suspicious findings, laboratory tests for sickle cell disease include the Sickledex, Sickle Prep and plasma hemoglobin electrophoresis.
Oral carbonic anhydrase inhibitors should be avoided. They may exacerbate the sickling of blood cells.
Ocular symptoms are uncommon in the early stages of the disease. Systemically, symptoms include painful crises of abdominal and musculoskeletal discomfort.
Ocular signs include comma-shaped vessels in the bulbar conjunctiva, iris atrophy, iris neovascularization, dull-gray fundus appearance, retinal venous tortuosity, nonproliferative retinal hemorrhages in the subretinal, intraretinal or preretinal position. Further signs include black sunbursts (retinal pigment epithelial hyperplasia secondary to deep retinal vascular occlusions), glistening refractile deposits in the retinal periphery (hemosiderin-laden macrophages), salmon patch hemorrhages (orange-pink-colored intraretinal hemorrhage), angioid streaks (breaks in Bruch's membrane radiating from the optic nerve), venous occlusion, artery occlusion, peripheral neovascularization (seafan retinopathy) with subsequent vitreous hemorrhage and tractional retinal detachment.
PATHOPHYSIOLOGY
Hemoglobinopathies are among the more commonly inherited diseases in humans. Hemoglobinopathies result when there is altered structure, function or production of hemoglobin. Hemoglobin is the principle protein of the erythrocyte, responsible for binding and facilitating oxygen transmission to tissues. In the four variations of sickle cell disease, systemic and ocular tissues become deprived of oxygen and undergo pathologic changes.
Normal erythrocytes, containing normal hemoglobin, appear as flexible, pliable, biconcave discs. Erythrocytes affected by sickling disease lose their biconcave shape and their ability to efficiently move through the circulatory system. The "sickled" cells become rigid, restrict blood flow, produce clots and cause tissues to become hypoxic.
Variations in the alteration of the amino acid sequence on the globin chain produce variations in the disease's expression. The four forms of the disease are often referred to by their genotype: sickle cell trait (AS), sickle cell anemia (SS), sickle cell disease (SC) and sickle cell thalasemia (SThal).
Systemically, the sickle cell anemia variation (SS) produces the most symptoms. With respect to the eye, the sickle cell disease mutation (SC) produces the most effects. Overall, the sickle cell trait expression (AS) produces the fewest complications.
MANAGEMENT
The treatment goal for sickle cell retinopathy is to reduce the risk of, prevent or eliminate retinal neovascularization. Follow patients with asymptomatic sickle cell disease biannually with ocular examinations and dilated retinal evaluation. Since visual loss can result from both nonproliferative (subretinal neovascularization secondary to angioid streaks) and proliferative retinal disease, refer the patient to the retinologist when you see these retinal findings. Treat proliferative disease with fluorescein angiography and panretinal photocoagulation. Cryotherapy has not been proven to be efficacious and is associated with high complication rates.
CLINICAL PEARLS
Proliferative sickle cell retinopathy breaks down into five stages:
Stage 1: peripheral retinal arteriolar occlusions
Stage 2: peripheral arterio-venous anastamoses
Stage 3: neovascular fronds known as sea fans
Stage 4: vitreous hemorrhage as tractional forces and vitreous collapse tear fragile neovascular membranes
Stage 5: advanced disease, identified by severe vitreous traction and retinal detachment
Other causes of peripheral neovascularization include sarcoidosis, diabetes, retinal venous occlusion, Eales' disease, leukemia and ocular ischemic syndrome. However, the characteristic sea fan frond is diagnostic of sickle retinopathy.
For patients with suspicious findings, laboratory tests for sickle cell disease include the Sickledex, Sickle Prep and plasma hemoglobin electrophoresis.
Oral carbonic anhydrase inhibitors should be avoided. They may exacerbate the sickling of blood cells.
SARCOIDOSIS
SIGNS AND SYMPTOMS
Sarcoidosis is a systemic granulomatous disease of unknown etiology. Clinical findings may include a debilitating, febrile illness with cough and dyspnea, fatigue, bilateral hilar lymphadenopathy (visible upon plain film radiograph), erythema nodosum, alveolitis, acute polymyositis, arthritis, musculoskeletal anomalies, lacrimal or salivary gland infiltration or sarcoid nodules of the skin. It occurs most frequently in young adults (20 to 40 years), has a predilection for women and for races of color.
Patients diagnosed with systemic sarcoidosis have nearly 20 percent incidence of ocular involvement. The most prevalent ocular sign is unilateral, anterior, granulomatous uveitis. Less common presentations include unilateral nongranulomatous uveitis, bilateral intermediate uveitis, and bilateral chronically smoldering low-grade granulomatous ocular inflammation (Lofgren's syndrome).
The common clinical ocular findings associated with sarcoid uveitis include decreased or hazy vision, pain, photophobia, lacrimation, conjunctival injection, cells and flare in the anterior chamber, granulomatous iritis with large "mutton fat" keratic precipitates scattered over the back surface of the corneal endothelium, iritis spill over leading to anterior vitritis, true vitritis with white exudative debris in the region of the ora serrata (snowball or snowbank retinopathy) with retinal vasculitis (candle wax drippings) and phlebitis (venous sheathing).
Nodules of the iris stroma (Busacca nodules), nodules of the pupillary border (Koeppe nodules), conjunctival granulomas, band keratopathy, posterior synechiae, cataract formation, secondary glaucoma, retinal hemorrhage, retinal neovascularization, cystoid macular edema, venous occlusion, optic disc swelling, optic nerve infiltration, compressive optic neuropathy, proptosis and extra ocular muscle palsy are all documented findings.
PATHOPHYSIOLOGY
Studies underscore that lymphocytes interact with macrophages. Some postulate that CD4+ T-helper 1 cells, in concert with macrophages, produce a cascade of cytokines and chemotactic factors which result in tissue changes and granulomatous lesions that affect many tissues and allow for the multi-system, multi-symptom nature of this disease. The clinical features of sarcoidosis mimic those of rheumatologic diseases, with increasing reports of coexistent autoimmune disease; however, no one has decisively determined an association.
MANAGEMENT
Manage the ocular signs and symptoms of sarcoidosis by the findings. Manage uveitis aggressively with topical cycloplegics (e.g. homatropine 5%, scopolamine 0.25%, or atropine 1%, BID), topical steroids such as Vexol (rimexolone 1%) and Pred Forte (prednisolone acetate 1%), Q1H to QID if necessary, oral steroidal or nonsteroidal anti-inflammatories. In recalcitrant cases, you may attempt periocular subtenon steroid injections of Kenalog 40 (triamcinolone) every three to four weeks. Antimetabolites such as methotrexate and cyclosporin-A have been used effectively in patients intolerant to steroids. Add topical aqueous suppressants if intraocular pressure control is required. Topical nonsteroidal anti-inflammatory agents such as Acular (Ketorolac tromethamine) and Voltaren (diclofenac sodium), QID, may be attempted if you detect cystoid macular edema. Allow the retinologist to manage peripheral retinal neovascularization and pars planitis with panretinal photocoagulation and oral or injected steroids respectively.
The primary care physician can lead systemic management. Referral for laboratory testing across the autoimmunologic, rheumatologic, infectious and inflammatory spectrum is essential, especially for atypical uveitis or optic neuropathy. Obtain or suggest to the PCP testing for anemia, leukemia, syphilis, HIV, lupus, Lyme disease, tuberculosis, arthritis, ankylosing spondylitis and hypertension. The initial battery could include complete blood count (CBC with differential), fluorescent treponemal antibody absorption test (FTA-Abs), reactive plasma reagin (RPR), purified protein derivative with anergy panel (PPD with anergy panel), anti-nuclear antibody (ANA), angiotensin converting enzyme (ACE), Lyme titre, rheumatoid factor (RF), sickle prep, chest x-ray (CXR) and sacroiliac joint films. Tests that indicate sarcoidosis most specifically are the chest x-ray, ACE and gallium scan.
CLINICAL PEARLS
Diagnose sarcoidosis through clinical (laboratory tests and biopsy) and radiologic evidence. Up to 90 percent of patients with ocular sarcoid have abnormal chest radiographs. Lung biopsy by tracheobronchial fiber optic techniques is 90 percent accurate. Biopsy of an enlarged, potentially infiltrated lacrimal gland or conjunctival granuloma is an acceptable alternative and can be handled by most general ophthalmologists.
A simple but effective practice management tool: a dictated letter to the primary care physician explaining the ocular problem, the management, the request for lab studies and the progress reports.
Vitritis without retinitis, vasculitis or phlebitis should be considered large reticulum cell sarcoma until proven otherwise. The minimum initial work up for this form of intermediate uveitis includes, but is not limited to, CBC with differential, FTA-Abs, RPR, PPD, ANA, ACE, Lyme titre, RF and CXR.
Sarcoidosis is a systemic granulomatous disease of unknown etiology. Clinical findings may include a debilitating, febrile illness with cough and dyspnea, fatigue, bilateral hilar lymphadenopathy (visible upon plain film radiograph), erythema nodosum, alveolitis, acute polymyositis, arthritis, musculoskeletal anomalies, lacrimal or salivary gland infiltration or sarcoid nodules of the skin. It occurs most frequently in young adults (20 to 40 years), has a predilection for women and for races of color.
Patients diagnosed with systemic sarcoidosis have nearly 20 percent incidence of ocular involvement. The most prevalent ocular sign is unilateral, anterior, granulomatous uveitis. Less common presentations include unilateral nongranulomatous uveitis, bilateral intermediate uveitis, and bilateral chronically smoldering low-grade granulomatous ocular inflammation (Lofgren's syndrome).
The common clinical ocular findings associated with sarcoid uveitis include decreased or hazy vision, pain, photophobia, lacrimation, conjunctival injection, cells and flare in the anterior chamber, granulomatous iritis with large "mutton fat" keratic precipitates scattered over the back surface of the corneal endothelium, iritis spill over leading to anterior vitritis, true vitritis with white exudative debris in the region of the ora serrata (snowball or snowbank retinopathy) with retinal vasculitis (candle wax drippings) and phlebitis (venous sheathing).
Nodules of the iris stroma (Busacca nodules), nodules of the pupillary border (Koeppe nodules), conjunctival granulomas, band keratopathy, posterior synechiae, cataract formation, secondary glaucoma, retinal hemorrhage, retinal neovascularization, cystoid macular edema, venous occlusion, optic disc swelling, optic nerve infiltration, compressive optic neuropathy, proptosis and extra ocular muscle palsy are all documented findings.
PATHOPHYSIOLOGY
Studies underscore that lymphocytes interact with macrophages. Some postulate that CD4+ T-helper 1 cells, in concert with macrophages, produce a cascade of cytokines and chemotactic factors which result in tissue changes and granulomatous lesions that affect many tissues and allow for the multi-system, multi-symptom nature of this disease. The clinical features of sarcoidosis mimic those of rheumatologic diseases, with increasing reports of coexistent autoimmune disease; however, no one has decisively determined an association.
MANAGEMENT
Manage the ocular signs and symptoms of sarcoidosis by the findings. Manage uveitis aggressively with topical cycloplegics (e.g. homatropine 5%, scopolamine 0.25%, or atropine 1%, BID), topical steroids such as Vexol (rimexolone 1%) and Pred Forte (prednisolone acetate 1%), Q1H to QID if necessary, oral steroidal or nonsteroidal anti-inflammatories. In recalcitrant cases, you may attempt periocular subtenon steroid injections of Kenalog 40 (triamcinolone) every three to four weeks. Antimetabolites such as methotrexate and cyclosporin-A have been used effectively in patients intolerant to steroids. Add topical aqueous suppressants if intraocular pressure control is required. Topical nonsteroidal anti-inflammatory agents such as Acular (Ketorolac tromethamine) and Voltaren (diclofenac sodium), QID, may be attempted if you detect cystoid macular edema. Allow the retinologist to manage peripheral retinal neovascularization and pars planitis with panretinal photocoagulation and oral or injected steroids respectively.
The primary care physician can lead systemic management. Referral for laboratory testing across the autoimmunologic, rheumatologic, infectious and inflammatory spectrum is essential, especially for atypical uveitis or optic neuropathy. Obtain or suggest to the PCP testing for anemia, leukemia, syphilis, HIV, lupus, Lyme disease, tuberculosis, arthritis, ankylosing spondylitis and hypertension. The initial battery could include complete blood count (CBC with differential), fluorescent treponemal antibody absorption test (FTA-Abs), reactive plasma reagin (RPR), purified protein derivative with anergy panel (PPD with anergy panel), anti-nuclear antibody (ANA), angiotensin converting enzyme (ACE), Lyme titre, rheumatoid factor (RF), sickle prep, chest x-ray (CXR) and sacroiliac joint films. Tests that indicate sarcoidosis most specifically are the chest x-ray, ACE and gallium scan.
CLINICAL PEARLS
Diagnose sarcoidosis through clinical (laboratory tests and biopsy) and radiologic evidence. Up to 90 percent of patients with ocular sarcoid have abnormal chest radiographs. Lung biopsy by tracheobronchial fiber optic techniques is 90 percent accurate. Biopsy of an enlarged, potentially infiltrated lacrimal gland or conjunctival granuloma is an acceptable alternative and can be handled by most general ophthalmologists.
A simple but effective practice management tool: a dictated letter to the primary care physician explaining the ocular problem, the management, the request for lab studies and the progress reports.
Vitritis without retinitis, vasculitis or phlebitis should be considered large reticulum cell sarcoma until proven otherwise. The minimum initial work up for this form of intermediate uveitis includes, but is not limited to, CBC with differential, FTA-Abs, RPR, PPD, ANA, ACE, Lyme titre, RF and CXR.
MYASTHENIA GRAVIS
SIGNS AND SYMPTOMS
Patients with myasthenia gravis typically present with symptoms of variable ocular fatigue and weakness. The common ocular findings include ptosis, droopy eyelids that appear worse at the end of the day, orbicularis weakness, limitation of ocular motility, paradoxical lid retraction, Cogan's lid twitch (transient eyelid retraction following an extended period of down gaze), exposure keratitis and intermittent diplopia.
A small percentage of patients possess a form of the disease known as ocular myasthenia. Here, the signs and symptoms remain strictly confined to the extraocular muscles. The pupil is never involved in MG.
Systemic symptoms include intermittent fatigue of the limbs, weakness of the facial muscles and difficulty breathing, chewing, talking and swallowing. In a small percentage of patients, dysthyroidism may also be present, resulting in the mixture of ptosis and exophthalmos. Thymic neoplasia (thymoma) is an associated finding in patients over 65. Associated disorders such as diabetes mellitus, lupus erythematosus and rheumatoid arthritis occur in 20 percent of MG patients.
PATHOPHYSIOLOGY
Myasthenia gravis (MG) is an autoimmune disease that destroys key components of the neuromuscular system responsible for governing muscular activity. It has a prevalence of approximately 1 in 20,000 persons. Females are more likely to experience early onset disease (under age 50) by a ratio of 7:3. Females reach their peak incidence by the third decade while males reach their peak incidence in the fifth decade.
Up to 75 percent of patients with myasthenia present with some type of ocular symptom. Ninety percent of patients with myasthenia gravis will develop ocular signs or symptoms, and 80 percent of patients who present with ocular involvement progress to have involvement of additional muscle groups within two years of the initial presentation.
Signs and symptoms may be initiated, exacerbated or mimicked by medications such as D-penicillamine, antibiotics (polymyxn B, neomycin, gentamicin, streptomycin), beta blockers and anticonvulsants.
MANAGEMENT
Patients who report neurological signs or symptoms require a through review of family history, illnesses, systems, medications and behaviors. Inspect and measure the palpebral apertures of patients with positional lid anomalies.
In office tests for the optometrist include:
1. asking the pertinent history
2. testing the pupils
3. assessing the orbicularis function by asking the patient to squeeze their eyelids shut while you attempt to open them forcibly
4. attempt to elicit diplopia by eliminating the occlusive effects of ptosis
5. attempt to elicit superior rectus or levator fatigue by asking the patient to sustain upgaze while you observe for unexpected eyelid droop
6. attempt to elicit the Cogan's lid twitch sign by asking the patient to look into downgaze for an extended period, then to gaze up
7. apply an ice pack to the eyelid for five to 15 minutes, reevaluating the ptosis and/or ocular motility for improved position following the ice packs removal
8. ask the patient to close their eyes for 30 minutes (sleep test), reevaluating the ocular motility and/or ptosis for improved position upon awakening. Diagnosis may also be assisted by evaluating old photographs for appearance.
The quintessential method of diagnosing MG is the endrophonium hydrochloride (Tensilon) injection test. An additional laboratory test used for diagnosing MG is the acetylcholine antibody receptor test. Medical management of MG should be handled by the neurologist or neuro-ophthalmologist.
CLINICAL PEARLS
MG should always be a consideration in cases of non-restrictive, pupil sparing CN III, IV and VI nerve palsy as well as unilateral and bilateral internuclear ophthalmoplegia.
Laboratory testing is an important consideration for patients diagnosed with MG because of its association with other systemic autoimmune diseases. Pertinent studies include fasting blood sugar (FBS: diabetes), thyroid function tests (ASH, T3, T4), antinuclear antibody (ANA: lupus), rheumatoid factor (RF: arthritis) and in suspicious cases, radiological testing of the thymus gland. A purified protein derivative (PPD: tuberculosis) should be completed because steroid regimens, used to treat MG have the potential to activate or worsen dormant disease.
Patients should always be educated to report difficulties with breathing or swallowing.
Patients with myasthenia gravis typically present with symptoms of variable ocular fatigue and weakness. The common ocular findings include ptosis, droopy eyelids that appear worse at the end of the day, orbicularis weakness, limitation of ocular motility, paradoxical lid retraction, Cogan's lid twitch (transient eyelid retraction following an extended period of down gaze), exposure keratitis and intermittent diplopia.
A small percentage of patients possess a form of the disease known as ocular myasthenia. Here, the signs and symptoms remain strictly confined to the extraocular muscles. The pupil is never involved in MG.
Systemic symptoms include intermittent fatigue of the limbs, weakness of the facial muscles and difficulty breathing, chewing, talking and swallowing. In a small percentage of patients, dysthyroidism may also be present, resulting in the mixture of ptosis and exophthalmos. Thymic neoplasia (thymoma) is an associated finding in patients over 65. Associated disorders such as diabetes mellitus, lupus erythematosus and rheumatoid arthritis occur in 20 percent of MG patients.
PATHOPHYSIOLOGY
Myasthenia gravis (MG) is an autoimmune disease that destroys key components of the neuromuscular system responsible for governing muscular activity. It has a prevalence of approximately 1 in 20,000 persons. Females are more likely to experience early onset disease (under age 50) by a ratio of 7:3. Females reach their peak incidence by the third decade while males reach their peak incidence in the fifth decade.
Up to 75 percent of patients with myasthenia present with some type of ocular symptom. Ninety percent of patients with myasthenia gravis will develop ocular signs or symptoms, and 80 percent of patients who present with ocular involvement progress to have involvement of additional muscle groups within two years of the initial presentation.
Signs and symptoms may be initiated, exacerbated or mimicked by medications such as D-penicillamine, antibiotics (polymyxn B, neomycin, gentamicin, streptomycin), beta blockers and anticonvulsants.
MANAGEMENT
Patients who report neurological signs or symptoms require a through review of family history, illnesses, systems, medications and behaviors. Inspect and measure the palpebral apertures of patients with positional lid anomalies.
In office tests for the optometrist include:
1. asking the pertinent history
2. testing the pupils
3. assessing the orbicularis function by asking the patient to squeeze their eyelids shut while you attempt to open them forcibly
4. attempt to elicit diplopia by eliminating the occlusive effects of ptosis
5. attempt to elicit superior rectus or levator fatigue by asking the patient to sustain upgaze while you observe for unexpected eyelid droop
6. attempt to elicit the Cogan's lid twitch sign by asking the patient to look into downgaze for an extended period, then to gaze up
7. apply an ice pack to the eyelid for five to 15 minutes, reevaluating the ptosis and/or ocular motility for improved position following the ice packs removal
8. ask the patient to close their eyes for 30 minutes (sleep test), reevaluating the ocular motility and/or ptosis for improved position upon awakening. Diagnosis may also be assisted by evaluating old photographs for appearance.
The quintessential method of diagnosing MG is the endrophonium hydrochloride (Tensilon) injection test. An additional laboratory test used for diagnosing MG is the acetylcholine antibody receptor test. Medical management of MG should be handled by the neurologist or neuro-ophthalmologist.
CLINICAL PEARLS
MG should always be a consideration in cases of non-restrictive, pupil sparing CN III, IV and VI nerve palsy as well as unilateral and bilateral internuclear ophthalmoplegia.
Laboratory testing is an important consideration for patients diagnosed with MG because of its association with other systemic autoimmune diseases. Pertinent studies include fasting blood sugar (FBS: diabetes), thyroid function tests (ASH, T3, T4), antinuclear antibody (ANA: lupus), rheumatoid factor (RF: arthritis) and in suspicious cases, radiological testing of the thymus gland. A purified protein derivative (PPD: tuberculosis) should be completed because steroid regimens, used to treat MG have the potential to activate or worsen dormant disease.
Patients should always be educated to report difficulties with breathing or swallowing.
GIANT CELL ARTERITIS
SIGNS AND SYMPTOMS
The patient is invariably elderly, with the mean age of 75 years. Incidence increases with advancing age. An associated condition, known as polymyalgia rheumatica (PMR), involves pain and stiffness of the muscles of the proximal limbs, particularly upon waking. In fact, PMR is likely within the same spectrum as giant cell arteritis (GCA). There is a 2:1 female to male ratio, and a higher incidence in whites.
Systemic manifestations may include malaise, weight loss and anorexia, headache in the temporal or occipital region, pulseless and indurated temporal artery, night sweats, tongue necrosis and oral ulceration, dental abscess, scalp pain, scalp necrosis and jaw claudication when eating. Other systemic manifestations include depression, mental disturbance, breast masses, gynecological disorders, persistent flu-like illness, chronic pharyngitis, vertigo, muscle aches, cardiac arrhythmia, congestive heart failure, and myocardial infarction.
Ocular manifestations include anterior ischemic optic neuropathy (AION), posterior ischemic optic neuropathy (PION), central retinal artery occlusion (CRAO), cilioretinal artery occlusion, ophthalmic artery occlusion, amaurosis fugax, diplopia and opthalmoplegia. Further ocular manifestations are tonic pupil, Horner's syndrome, ocular hypotony, chronic uveitis, episcleritis and scleritis, conjunctivitis, ocular ischemic syndrome, visual hallucinations, posterior chiasmal field loss, cortical blindness, and ocular ischemic syndrome.
PATHOPHYSIOLOGY
GCA is an idiopathic inflammation of medium and large arteries where the muscular wall of these vessels is infiltrated by monocytes, histiocytes, plasma cells, and multinucleate giant cells. Significant infiltration can lead to vessel occlusion with resultant ischemia and dysfunction of the organ system fed by the vessel. GCA is a multi-system, multi-symptom disorder-virtually any vessel within the body may be involved.
The degree of ischemia tolerated varies by system, and symptoms often appear for a period of months before diagnosis. In the eye, ischemia often manifests by amaurosis fugax, intermittent diplopia and ophthalmoplegia prior to complete occlusion of the posterior ciliary, retinal or ophthalmic arteries. When ocular symptoms occur, there is a much shorter time interval to severe permanent vision loss.
MANAGEMENT
Optimal management of giant cell arteritis means recognizing GCA as a potential cause of the above mentioned findings in an elderly patient. Once recognized, order a Westegren erythrocyte sedimentation rate (ESR) to confirm suspicions. The ESR is a non-specific index of illness, but is frequently elevated in cases of GCA. If the ESR is elevated, then refer for a temporal artery biopsy in order to conclusively diagnose GCA. Remember, however, that a small number of GCA cases do not manifest an elevated ESR. In these cases, the findings and systemic history become more diagnostically important.
GCA requires systemic steroids to preserve vision and reduce morbidity. However, do not withhold steroids pending biopsy results. If exam findings and ESR indicate GCA, then start steroids immediately. Biopsy results, though, will not be affected for several weeks after you initiate steroid therapy.
The dosage of steroids is controversial. Rheumatologists recommend low doses of prednisone, typically 10-20mg per day. However, it is argued that rheumatologists see patients with milder forms of the disease. When vision loss ensues, the patient should receive 1-2mg IV methylprednisolone for several days, with high dose (80-120mg) daily oral prednisone tapered over several weeks. Afterwards, these patients must be maintained on low dose oral prednisone for two to four years.
CLINICAL PEARLS
Vision loss from GCA is an emergency. Untreated, progression to the fellow eye occurs in a high number of cases within hours to days. Frequently, vision loss in GCA is devastating and irreversible. Don't wait until the second eye is involved to take action. You must have an emergency plan in your office in order to handle this disease.
You must consider GCA in elderly patients with AION, PION, amaurosis fugax, intermittent diplopia, CRAO, and cilioretinal occlusion and manage accordingly.
In cases of retrobulbar optic neuropathy in an elderly patient, don't be fooled into diagnosing retrobulbar optic neuritis (as seen in multiple sclerosis) as this is a disease of younger patients. Consider PION, which is typically caused by GCA and tends to involve the fellow eye.
In cases where there are multiple clinical presentations, such as combined cilioretinal artery occlusion and AION, bilateral AION, bilateral CRAO, or CRAO and contralateral tonic pupil (among others), then aggressively investigate GCA in the elderly patient.
Giant cell arteritis and its visual manifestations should not be handled by a primary care optometrist, or even a general ophthalmologist. As the prognosis is grim and morbidity high, these patients should be managed by a neurologist (or neuro-ophthalmologist) specifically skilled in the treatment of GCA. Identify such an individual well in advance, since time is crucial once the GCA patient enters your office.
The patient is invariably elderly, with the mean age of 75 years. Incidence increases with advancing age. An associated condition, known as polymyalgia rheumatica (PMR), involves pain and stiffness of the muscles of the proximal limbs, particularly upon waking. In fact, PMR is likely within the same spectrum as giant cell arteritis (GCA). There is a 2:1 female to male ratio, and a higher incidence in whites.
Systemic manifestations may include malaise, weight loss and anorexia, headache in the temporal or occipital region, pulseless and indurated temporal artery, night sweats, tongue necrosis and oral ulceration, dental abscess, scalp pain, scalp necrosis and jaw claudication when eating. Other systemic manifestations include depression, mental disturbance, breast masses, gynecological disorders, persistent flu-like illness, chronic pharyngitis, vertigo, muscle aches, cardiac arrhythmia, congestive heart failure, and myocardial infarction.
Ocular manifestations include anterior ischemic optic neuropathy (AION), posterior ischemic optic neuropathy (PION), central retinal artery occlusion (CRAO), cilioretinal artery occlusion, ophthalmic artery occlusion, amaurosis fugax, diplopia and opthalmoplegia. Further ocular manifestations are tonic pupil, Horner's syndrome, ocular hypotony, chronic uveitis, episcleritis and scleritis, conjunctivitis, ocular ischemic syndrome, visual hallucinations, posterior chiasmal field loss, cortical blindness, and ocular ischemic syndrome.
PATHOPHYSIOLOGY
GCA is an idiopathic inflammation of medium and large arteries where the muscular wall of these vessels is infiltrated by monocytes, histiocytes, plasma cells, and multinucleate giant cells. Significant infiltration can lead to vessel occlusion with resultant ischemia and dysfunction of the organ system fed by the vessel. GCA is a multi-system, multi-symptom disorder-virtually any vessel within the body may be involved.
The degree of ischemia tolerated varies by system, and symptoms often appear for a period of months before diagnosis. In the eye, ischemia often manifests by amaurosis fugax, intermittent diplopia and ophthalmoplegia prior to complete occlusion of the posterior ciliary, retinal or ophthalmic arteries. When ocular symptoms occur, there is a much shorter time interval to severe permanent vision loss.
MANAGEMENT
Optimal management of giant cell arteritis means recognizing GCA as a potential cause of the above mentioned findings in an elderly patient. Once recognized, order a Westegren erythrocyte sedimentation rate (ESR) to confirm suspicions. The ESR is a non-specific index of illness, but is frequently elevated in cases of GCA. If the ESR is elevated, then refer for a temporal artery biopsy in order to conclusively diagnose GCA. Remember, however, that a small number of GCA cases do not manifest an elevated ESR. In these cases, the findings and systemic history become more diagnostically important.
GCA requires systemic steroids to preserve vision and reduce morbidity. However, do not withhold steroids pending biopsy results. If exam findings and ESR indicate GCA, then start steroids immediately. Biopsy results, though, will not be affected for several weeks after you initiate steroid therapy.
The dosage of steroids is controversial. Rheumatologists recommend low doses of prednisone, typically 10-20mg per day. However, it is argued that rheumatologists see patients with milder forms of the disease. When vision loss ensues, the patient should receive 1-2mg IV methylprednisolone for several days, with high dose (80-120mg) daily oral prednisone tapered over several weeks. Afterwards, these patients must be maintained on low dose oral prednisone for two to four years.
CLINICAL PEARLS
Vision loss from GCA is an emergency. Untreated, progression to the fellow eye occurs in a high number of cases within hours to days. Frequently, vision loss in GCA is devastating and irreversible. Don't wait until the second eye is involved to take action. You must have an emergency plan in your office in order to handle this disease.
You must consider GCA in elderly patients with AION, PION, amaurosis fugax, intermittent diplopia, CRAO, and cilioretinal occlusion and manage accordingly.
In cases of retrobulbar optic neuropathy in an elderly patient, don't be fooled into diagnosing retrobulbar optic neuritis (as seen in multiple sclerosis) as this is a disease of younger patients. Consider PION, which is typically caused by GCA and tends to involve the fellow eye.
In cases where there are multiple clinical presentations, such as combined cilioretinal artery occlusion and AION, bilateral AION, bilateral CRAO, or CRAO and contralateral tonic pupil (among others), then aggressively investigate GCA in the elderly patient.
Giant cell arteritis and its visual manifestations should not be handled by a primary care optometrist, or even a general ophthalmologist. As the prognosis is grim and morbidity high, these patients should be managed by a neurologist (or neuro-ophthalmologist) specifically skilled in the treatment of GCA. Identify such an individual well in advance, since time is crucial once the GCA patient enters your office.
Pituitary Adenoma
Signs and Symptoms
Pituitary adenomas typically present during early adulthood, equally affecting males and females. There are no outstanding reported risk factors. The clinical presentation of pituitary adenoma varies depending on the location and severity of the tumor.
Prolactinomas, the most common form of pituitary tumor, cause amenorrhea (the loss of menstruation), galactorrhea (the spontaneous flow of milk from the breast), and infertility in females. They cause hypogonadism, decreased libido and impotence in males. Tumors that secrete excess growth hormone cause gigantism in children and acromegaly in adults. Adrenocorticotropic hormone (ACTH) secreting adenomas produce Cushing’s disease (hyperadrenalism). Symptomatic pituitary adenomas comprise 12 to 15 percent of all intracranial tumors, and must be differentiated from non-neoplastic mass lesions.
Visual symptoms vary and include bitemporal visual field loss more dense from the superior to inferior, color desaturation, diplopia as well as ophthalmoplegia tumors expand into the cavernous sinus. The funduscopic sign of long-standing chiasmal compression is primary optic atrophy (secondary to retrograde axonal degeneration). Severe optic atrophy indicates a poor prognosis for visual recovery following surgical decompression. (For visual field printout, see "Understanding Visual Fields and the Visual Pathways" page 56.)
Pathophysiology
The pituitary gland is situated within the sella turcica of the sphenoid bone, at the base of the skull. The anterior lobe of the pituitary gland secretes six hormones: thyroid stimulating hormone (TSH), ACTH, follicle stimulating hormone (FSH), leutenizing hormone, growth hormone (GH), and prolactin. The posterior pituitary gland secretes vasopressin and oxytocin.
Pituitary adenomas typically are slow growing, benign neoplasms of epithelial origin. In most circumstances they arise from the adenohypophysis (the anterior lobe of the pituitary gland) and are capable of producing both systemic and visual signs. Approximately 8 mm to 13 mm above the pituitary gland is the optic chiasm. The nasal retinal fibers of each eye (temporal visual field) cross at this point, proceeding into the contralateral optic tract.
Upwardly growing pituitary tumors, which reach appropriate sizes, impinge on the anterior notch of the chiasm at its lowest lying aspect. This produces the bitemporal hemianopsia with increased density superiorly. Since tumor growth is usually asymmetrical, the field loss between two eyes is also typically asymmetrical.
Diseases affecting the pituitary gland produce two types of disturbances: mechanical and hormonal. Mechanical disturbances occur whenever a tumor compresses adjacent structures. Hormonal manifestations result when hyper-or hyposecretions occur. Pituitary adenomas are further differentiated by size. Microadenomas have little impact on the visual system or gland function and are defined as intrasellar adenomas that measure up to one centimeter in diameter without sellar enlargement. Macroadenomas present with mass effect symptoms such as headaches and measure larger than one centimeter with generalized sellar enlargement. Macroadenomas include (in order of most common to least common): non-secreting adenomas, prolactin secreting (chromaphobe) adenomas, growth hormone secreting (acidophil) adenomas, ACTH secreting (basophil) adenomas and FSH or TSH secreting adenomas.
Secreting tumors are usually diagnosed by general physicians and endocrinologists. Non-secreting tumors are often diagnosed by eye care practitioners because they produce visual symptoms in the absence of systemic signs.
Management
Surgical therapy, medicinal therapy or radiotherapy are the three treatment options for pituitary adenomas. Since the late 1970s, the transphenoidal surgical approach has been the preferred procedure for removal of tumors. Surgery is indicated if there is evidence of tumor enlargement, especially when growth is accompanied by compression of the optic chiasm, cavernous sinus invasion, or the development of pituitary hormone deficiencies. Visual improvement following treatment is often dramatic, with the greatest degree of improvement occurring within the first few months. Perimetry and MRI occupy an important role in the post treatment monitoring of patients. Medicinal treatment is limited to prolactinomas. Bromocriptine, a dopamine agonist, is useful in shrinking the sizes of these tumors. Low dose therapy of Bromocriptine is maintained for life. If the drug therapy is discontinued, there is often regrowth and enlargement of the adenoma. Conventional radiotherapy is usually added adjunctively to prevent tumor regrowth.
Clinical Pearls
In pregnant women, bitemporal visual field loss and headache may signal pituitary apoplexy (rapid degeneration with hemorrhagic necrosis of the pituitary gland). Pituitary apoplexy is a potentially life-threatening condition. Any woman with sudden onset of headache and suspicious visual symptoms (confirmed by perimetry) should be referred for a MRI with or without lumbar puncture to rule out subarachnoid hemorrhage from the this type of tumor. Women with pituitary adenomas and MRI evidence of subarachnoid bleeding should deliver by cesarean section to avoid risk of apoplexy during delivery. Postpartum hemorrhage can cause infarction of the pituitary gland leading to hypopituitarism (Sheehan’s syndrome).
Pituitary adenomas typically present during early adulthood, equally affecting males and females. There are no outstanding reported risk factors. The clinical presentation of pituitary adenoma varies depending on the location and severity of the tumor.
Prolactinomas, the most common form of pituitary tumor, cause amenorrhea (the loss of menstruation), galactorrhea (the spontaneous flow of milk from the breast), and infertility in females. They cause hypogonadism, decreased libido and impotence in males. Tumors that secrete excess growth hormone cause gigantism in children and acromegaly in adults. Adrenocorticotropic hormone (ACTH) secreting adenomas produce Cushing’s disease (hyperadrenalism). Symptomatic pituitary adenomas comprise 12 to 15 percent of all intracranial tumors, and must be differentiated from non-neoplastic mass lesions.
Visual symptoms vary and include bitemporal visual field loss more dense from the superior to inferior, color desaturation, diplopia as well as ophthalmoplegia tumors expand into the cavernous sinus. The funduscopic sign of long-standing chiasmal compression is primary optic atrophy (secondary to retrograde axonal degeneration). Severe optic atrophy indicates a poor prognosis for visual recovery following surgical decompression. (For visual field printout, see "Understanding Visual Fields and the Visual Pathways" page 56.)
Pathophysiology
The pituitary gland is situated within the sella turcica of the sphenoid bone, at the base of the skull. The anterior lobe of the pituitary gland secretes six hormones: thyroid stimulating hormone (TSH), ACTH, follicle stimulating hormone (FSH), leutenizing hormone, growth hormone (GH), and prolactin. The posterior pituitary gland secretes vasopressin and oxytocin.
Pituitary adenomas typically are slow growing, benign neoplasms of epithelial origin. In most circumstances they arise from the adenohypophysis (the anterior lobe of the pituitary gland) and are capable of producing both systemic and visual signs. Approximately 8 mm to 13 mm above the pituitary gland is the optic chiasm. The nasal retinal fibers of each eye (temporal visual field) cross at this point, proceeding into the contralateral optic tract.
Upwardly growing pituitary tumors, which reach appropriate sizes, impinge on the anterior notch of the chiasm at its lowest lying aspect. This produces the bitemporal hemianopsia with increased density superiorly. Since tumor growth is usually asymmetrical, the field loss between two eyes is also typically asymmetrical.
Diseases affecting the pituitary gland produce two types of disturbances: mechanical and hormonal. Mechanical disturbances occur whenever a tumor compresses adjacent structures. Hormonal manifestations result when hyper-or hyposecretions occur. Pituitary adenomas are further differentiated by size. Microadenomas have little impact on the visual system or gland function and are defined as intrasellar adenomas that measure up to one centimeter in diameter without sellar enlargement. Macroadenomas present with mass effect symptoms such as headaches and measure larger than one centimeter with generalized sellar enlargement. Macroadenomas include (in order of most common to least common): non-secreting adenomas, prolactin secreting (chromaphobe) adenomas, growth hormone secreting (acidophil) adenomas, ACTH secreting (basophil) adenomas and FSH or TSH secreting adenomas.
Secreting tumors are usually diagnosed by general physicians and endocrinologists. Non-secreting tumors are often diagnosed by eye care practitioners because they produce visual symptoms in the absence of systemic signs.
Management
Surgical therapy, medicinal therapy or radiotherapy are the three treatment options for pituitary adenomas. Since the late 1970s, the transphenoidal surgical approach has been the preferred procedure for removal of tumors. Surgery is indicated if there is evidence of tumor enlargement, especially when growth is accompanied by compression of the optic chiasm, cavernous sinus invasion, or the development of pituitary hormone deficiencies. Visual improvement following treatment is often dramatic, with the greatest degree of improvement occurring within the first few months. Perimetry and MRI occupy an important role in the post treatment monitoring of patients. Medicinal treatment is limited to prolactinomas. Bromocriptine, a dopamine agonist, is useful in shrinking the sizes of these tumors. Low dose therapy of Bromocriptine is maintained for life. If the drug therapy is discontinued, there is often regrowth and enlargement of the adenoma. Conventional radiotherapy is usually added adjunctively to prevent tumor regrowth.
Clinical Pearls
In pregnant women, bitemporal visual field loss and headache may signal pituitary apoplexy (rapid degeneration with hemorrhagic necrosis of the pituitary gland). Pituitary apoplexy is a potentially life-threatening condition. Any woman with sudden onset of headache and suspicious visual symptoms (confirmed by perimetry) should be referred for a MRI with or without lumbar puncture to rule out subarachnoid hemorrhage from the this type of tumor. Women with pituitary adenomas and MRI evidence of subarachnoid bleeding should deliver by cesarean section to avoid risk of apoplexy during delivery. Postpartum hemorrhage can cause infarction of the pituitary gland leading to hypopituitarism (Sheehan’s syndrome).
Pseudotumor Cerebri
Signs and Symptoms
Pseudotumor cerebri (PTC) is encountered most frequently in young, overweight women between the ages of 20 and 45. Headache is the most common presenting complaint, occurring in more than 90 percent of cases. Dizziness, nausea, and vomiting may also be encountered, but typically there are no alterations of consciousness or higher cognitive function. Tinnitus, or a "rushing" sound in the ears, is another frequent complaint. Visual symptoms are present in up to 70 percent of all patients with PTC, and include transient visual obscurations, general blurriness, and intermittent horizontal diplopia. These symptoms tend to worsen in association with Valsalva maneuvers and changes in posture. Reports of ocular pain, particularly with extreme eye movements, have also been noted.
Funduscopic evaluation of patients with PTC demonstrates bilaterally swollen, edematous optic nerves consistent with true papilledema. Ophthalmoscopy may reveal striations within the nerve fiber layer, blurring of the superior and inferior margins of the neural rim, disc hyperemia, and capillary dilatation. More severe presentations involve engorged and tortuous retinal venules, peripapillary hemorrhages and/or cotton wool spots, and circumferential retinal microfolds (Paton’s lines). Chronic papilledema mayresult in atrophy of the nerve head, with associated pallor and gliosis. Most cases of true papilledema will not present with a relative afferent pupillary defect, although visual field deficits may be present. The most common visual field defect associated with PTC is an enlarged blind spot, followed by a nasal deficit, typically affecting the inferior quadrants. Other field losses seen in PTC include arcuate defects, nasal step, generalized constriction, and least commonly, cecocentral scotoma.
Pathophysiology
Pseudotumor cerebri is a syndrome disorder defined clinically by four criteria: (1) elevated intracranial pressure as demonstrated by lumbar puncture; (2) normal cerebral anatomy, as demonstrated by neuroradiographic evaluation; (3) normal cerebrospinal fluid composition; and (4) signs and symptoms of increased intracranial pressure, including papilledema.
While the mechanism of PTC is not fully understood, most experts agree that the disorder results from poor absorption of cerebrospinal fluid by the meninges surrounding the brain and spinal cord. The subsequent increase in extracerebral fluid volume leads to elevated intracranial pressure. However, because the process is slow and insidious, there is ample time for the ventricular system to compensate and this explains why there is no dilation of the cerebral ventricles in PTC. Increased intracranial pressure induces stress on the peripheral aspects of the brain, including the cranial nerves. Stagnation of axoplasmic flow in the optic nerve (CN II) results in papilledema and transient visual obscurations; when the abducens nerve (CN VI) is involved, the result is intermittent nerve palsy and diplopia.
Many conditions and factors have been proposed as causative agents of PTC, including excessive dosages of some exogenously administered medications (e.g., vitamin A, tetracycline, minocycline, naladixic acid, corticosteroids), endocrinologic abnormalities, anemias, blood dyscrasias, and chronic respiratory insufficiency. However the majority of cases remain idiopathic in nature.
Management
All patients presenting with suspected papilledema or other manifestations of intracranial hypertension warrant prompt medical evaluation and neurologic testing. Current protocol dictates that patients presumptively diagnosed with papilledema must undergo neuroimaging via computed tomography or, preferably, magnetic resonance imaging within 24 hours. These tests are meant to rule out space-occupying intracranial mass lesions, and therefore should be ordered with contrast media unless otherwise contraindicated. In cases of PTC, neuroimaging typically displays small to normal-sized cerebral ventricles with otherwise normal brain structure. Patients with unremarkable radiographic studies should be subsequently referred for neurosurgical consultation and lumbar puncture. (Lumbar puncture should not be ordered until neuroimaging is found negative for space-occupying mass due to risk for herniation of brainstem through foramen magnum secondary to mass during lumbar puncture.) Additional medical testing includes serologic and hematologic studies.
Therapy for patients with PTC varies, but in most instances initiate systemic medications as a first line treatment. Typically, the drug of choice for the initial management of PTC is oral acetazolamide (Diamox), although other diuretics including chlorthalidone (Hygroton) and furosemide (Lasix) may also be used effectively. Corticosteroid therapy is considered controversial in the management of PTC. While a short-term course of oral or intravenous dexamethasone may be helpful in initially lowering intracranial pressure, it is not considered to be an effective long-term therapy because of the potential for systemic and ocular complications.
For patients in whom conventional medical therapy fails to alleviate the symptoms and prevent pathologic decline, surgical intervention is the only definitive treatment. Cerebrospinal fluid shunting procedures are commonly employed in recalcitrant cases of PTC, but are successful in only 70 to 80 percent of cases. Optic nerve sheath decompression has also been advocated as a method
Pseudotumor cerebri (PTC) is encountered most frequently in young, overweight women between the ages of 20 and 45. Headache is the most common presenting complaint, occurring in more than 90 percent of cases. Dizziness, nausea, and vomiting may also be encountered, but typically there are no alterations of consciousness or higher cognitive function. Tinnitus, or a "rushing" sound in the ears, is another frequent complaint. Visual symptoms are present in up to 70 percent of all patients with PTC, and include transient visual obscurations, general blurriness, and intermittent horizontal diplopia. These symptoms tend to worsen in association with Valsalva maneuvers and changes in posture. Reports of ocular pain, particularly with extreme eye movements, have also been noted.
Funduscopic evaluation of patients with PTC demonstrates bilaterally swollen, edematous optic nerves consistent with true papilledema. Ophthalmoscopy may reveal striations within the nerve fiber layer, blurring of the superior and inferior margins of the neural rim, disc hyperemia, and capillary dilatation. More severe presentations involve engorged and tortuous retinal venules, peripapillary hemorrhages and/or cotton wool spots, and circumferential retinal microfolds (Paton’s lines). Chronic papilledema mayresult in atrophy of the nerve head, with associated pallor and gliosis. Most cases of true papilledema will not present with a relative afferent pupillary defect, although visual field deficits may be present. The most common visual field defect associated with PTC is an enlarged blind spot, followed by a nasal deficit, typically affecting the inferior quadrants. Other field losses seen in PTC include arcuate defects, nasal step, generalized constriction, and least commonly, cecocentral scotoma.
Pathophysiology
Pseudotumor cerebri is a syndrome disorder defined clinically by four criteria: (1) elevated intracranial pressure as demonstrated by lumbar puncture; (2) normal cerebral anatomy, as demonstrated by neuroradiographic evaluation; (3) normal cerebrospinal fluid composition; and (4) signs and symptoms of increased intracranial pressure, including papilledema.
While the mechanism of PTC is not fully understood, most experts agree that the disorder results from poor absorption of cerebrospinal fluid by the meninges surrounding the brain and spinal cord. The subsequent increase in extracerebral fluid volume leads to elevated intracranial pressure. However, because the process is slow and insidious, there is ample time for the ventricular system to compensate and this explains why there is no dilation of the cerebral ventricles in PTC. Increased intracranial pressure induces stress on the peripheral aspects of the brain, including the cranial nerves. Stagnation of axoplasmic flow in the optic nerve (CN II) results in papilledema and transient visual obscurations; when the abducens nerve (CN VI) is involved, the result is intermittent nerve palsy and diplopia.
Many conditions and factors have been proposed as causative agents of PTC, including excessive dosages of some exogenously administered medications (e.g., vitamin A, tetracycline, minocycline, naladixic acid, corticosteroids), endocrinologic abnormalities, anemias, blood dyscrasias, and chronic respiratory insufficiency. However the majority of cases remain idiopathic in nature.
Management
All patients presenting with suspected papilledema or other manifestations of intracranial hypertension warrant prompt medical evaluation and neurologic testing. Current protocol dictates that patients presumptively diagnosed with papilledema must undergo neuroimaging via computed tomography or, preferably, magnetic resonance imaging within 24 hours. These tests are meant to rule out space-occupying intracranial mass lesions, and therefore should be ordered with contrast media unless otherwise contraindicated. In cases of PTC, neuroimaging typically displays small to normal-sized cerebral ventricles with otherwise normal brain structure. Patients with unremarkable radiographic studies should be subsequently referred for neurosurgical consultation and lumbar puncture. (Lumbar puncture should not be ordered until neuroimaging is found negative for space-occupying mass due to risk for herniation of brainstem through foramen magnum secondary to mass during lumbar puncture.) Additional medical testing includes serologic and hematologic studies.
Therapy for patients with PTC varies, but in most instances initiate systemic medications as a first line treatment. Typically, the drug of choice for the initial management of PTC is oral acetazolamide (Diamox), although other diuretics including chlorthalidone (Hygroton) and furosemide (Lasix) may also be used effectively. Corticosteroid therapy is considered controversial in the management of PTC. While a short-term course of oral or intravenous dexamethasone may be helpful in initially lowering intracranial pressure, it is not considered to be an effective long-term therapy because of the potential for systemic and ocular complications.
For patients in whom conventional medical therapy fails to alleviate the symptoms and prevent pathologic decline, surgical intervention is the only definitive treatment. Cerebrospinal fluid shunting procedures are commonly employed in recalcitrant cases of PTC, but are successful in only 70 to 80 percent of cases. Optic nerve sheath decompression has also been advocated as a method
Sunday, November 13, 2011
Amaurosis Fugax and Transient Ischemic Attack
Signs and Symptoms
Both amaurosis fugax (AF) and transient ischemic attack (TIA) are diagnosed almost exclusively by history alone. Patients with both AF and TIA are typically elderly with a history of diabetes, hypertension, or generalized atherosclerosis. Younger patients with these conditions may have a history of cardiac valve disease, blood constituent or coagulation abnormalities, or drug use.
Amaurosis fugax is a painless, monocular loss of vision, which may be total or sectorial. This is a traditional blackout of the patient’s vision. Amaurosis fugax can occur in isolation, antecedent, or crescendo and is unprovoked and unpredictable. Vision loss typically lasts only seconds, but may last for hours and will resolve completely. There are no other neurological symptoms or findings in association with AF.
Transient ischemic attacks can result in a total painless loss of monocular vision; however, TIA may occur with no ocular involvement whatsoever. Other significant neurological signs and symptoms associated with TIA include dysphasia, contralateral hemiparesis, and paresthesia. Temporary paresis most commonly involves the contralateral arm, leg, or both face and arm, or both arm and leg. Numbness typically involves the contralateral hand, foot, face, and contralateral half of the tongue. A TIA will typically last for 15 minutes, but may go for hours.
Pathophysiology
TIA and AF result from either an embolic, thrombotic, vasospastic, or hematological phenomenon. Thrombus development occurs via cholesterol deposition and atheroma formation within vessel lumens. From this process forms a thrombus, which may cause transient blood flow cessation and symptoms of TIA or AF. Also, inflammatory cell infiltration of the muscular walls of arteries in giant cell arteritis will lead to lumen narrowing and occlusion with resultant TIA or AF. More commonly, however, the thrombus ulcerates and releases particles which lodge within vessels and result in distal ischemia. This produces the signs and symptoms of TIA or AF. Occasionally, cholesterol emboli is seen lodged at a retinal arteriole bifurcation in patients experiencing AF. However, visible retinal emboli are often not observed as their very nature allows for the emboli to break up and move distally. This explains why cholesterol emboli typically result in transient neurologic deficits. Calcific emboli may dislodge from the heart and indicate valve disturbance. This type of emboli is not malleable and more likely to cause a permanent occlusion of the retinal arteriole.
Vasospastic causes of TIA and AF may be due to non-embolic idiopathic arterial narrowing or the possible release of an as-yet-unidentified vasospastic substance. Occasionally, use of exogenous sources such as cocaine may lead to localized vasospasm and TIA and AF.
Hematological causes of TIA and AF result when there are abnormalities in the normal blood constituents. Hematological causes include polycythemia, sickle cell disease, anemia, and hypercoagulable states.
Management
There is significant morbidity and mortality associated with TIA and AF. Patients experiencing uncomplicated AF have an 85 percent likelihood of full recovery while 10 to 15 percent will eventually develop a central retinal artery occlusion. The average untreated annual stroke rate of patients with untreated AF is 2 percent. Refer these patients to a neurologist or internist for carotid artery studies, such as Doppler imaging or magnetic resonance angiography. If there is significant stenosis of the carotid artery, consult a vascular surgeon for possible endarterectomy. However, these patients are typically medicatedwith blood thinners such as aspirin and they do quite well.
Patients experiencing hemispheric TIA are at more risk. The average annual untreated stroke rate in this group is 8 percent. Refer this patient to a neurologist since other neurological areas are involved in the attack. Typically, this patient requires carotid endarterectomy. The patient with hemispheric TIA has a 25 percent mortality rate within one month, 33 percent within six months, and 60 percent within seven years.
Patients who experience either TIA or AF and have retinal emboli visible at ophthalmic exam also have a high rate of mortality. In this group, the mortality rate is 15 percent within one year, 29 percent within three years, and 54 percent within seven years. In this group, cardiac death is more prevalent than stroke and thus these patients must be referred to a cardiologist.
Clinical Pearls
Amaurosis fugax in elderly patients may be the initial sign of giant cell arteritis. In these cases, devastating vision loss from anterior ischemic optic neuropathy likely ensues within several weeks of an episode of AF. These patients need an immediate Westgren ESR, and possible temporal artery biopsy, along with the requisite carotid studies.
Most cases of TIA and AF show no visible evidence at examination. These diagnoses can be made by history. Optimal management involves referral to the appropriate medical specialist.
The number one hematological cause of AF is sickle cell disease.
Both amaurosis fugax (AF) and transient ischemic attack (TIA) are diagnosed almost exclusively by history alone. Patients with both AF and TIA are typically elderly with a history of diabetes, hypertension, or generalized atherosclerosis. Younger patients with these conditions may have a history of cardiac valve disease, blood constituent or coagulation abnormalities, or drug use.
Amaurosis fugax is a painless, monocular loss of vision, which may be total or sectorial. This is a traditional blackout of the patient’s vision. Amaurosis fugax can occur in isolation, antecedent, or crescendo and is unprovoked and unpredictable. Vision loss typically lasts only seconds, but may last for hours and will resolve completely. There are no other neurological symptoms or findings in association with AF.
Transient ischemic attacks can result in a total painless loss of monocular vision; however, TIA may occur with no ocular involvement whatsoever. Other significant neurological signs and symptoms associated with TIA include dysphasia, contralateral hemiparesis, and paresthesia. Temporary paresis most commonly involves the contralateral arm, leg, or both face and arm, or both arm and leg. Numbness typically involves the contralateral hand, foot, face, and contralateral half of the tongue. A TIA will typically last for 15 minutes, but may go for hours.
Pathophysiology
TIA and AF result from either an embolic, thrombotic, vasospastic, or hematological phenomenon. Thrombus development occurs via cholesterol deposition and atheroma formation within vessel lumens. From this process forms a thrombus, which may cause transient blood flow cessation and symptoms of TIA or AF. Also, inflammatory cell infiltration of the muscular walls of arteries in giant cell arteritis will lead to lumen narrowing and occlusion with resultant TIA or AF. More commonly, however, the thrombus ulcerates and releases particles which lodge within vessels and result in distal ischemia. This produces the signs and symptoms of TIA or AF. Occasionally, cholesterol emboli is seen lodged at a retinal arteriole bifurcation in patients experiencing AF. However, visible retinal emboli are often not observed as their very nature allows for the emboli to break up and move distally. This explains why cholesterol emboli typically result in transient neurologic deficits. Calcific emboli may dislodge from the heart and indicate valve disturbance. This type of emboli is not malleable and more likely to cause a permanent occlusion of the retinal arteriole.
Vasospastic causes of TIA and AF may be due to non-embolic idiopathic arterial narrowing or the possible release of an as-yet-unidentified vasospastic substance. Occasionally, use of exogenous sources such as cocaine may lead to localized vasospasm and TIA and AF.
Hematological causes of TIA and AF result when there are abnormalities in the normal blood constituents. Hematological causes include polycythemia, sickle cell disease, anemia, and hypercoagulable states.
Management
There is significant morbidity and mortality associated with TIA and AF. Patients experiencing uncomplicated AF have an 85 percent likelihood of full recovery while 10 to 15 percent will eventually develop a central retinal artery occlusion. The average untreated annual stroke rate of patients with untreated AF is 2 percent. Refer these patients to a neurologist or internist for carotid artery studies, such as Doppler imaging or magnetic resonance angiography. If there is significant stenosis of the carotid artery, consult a vascular surgeon for possible endarterectomy. However, these patients are typically medicatedwith blood thinners such as aspirin and they do quite well.
Patients experiencing hemispheric TIA are at more risk. The average annual untreated stroke rate in this group is 8 percent. Refer this patient to a neurologist since other neurological areas are involved in the attack. Typically, this patient requires carotid endarterectomy. The patient with hemispheric TIA has a 25 percent mortality rate within one month, 33 percent within six months, and 60 percent within seven years.
Patients who experience either TIA or AF and have retinal emboli visible at ophthalmic exam also have a high rate of mortality. In this group, the mortality rate is 15 percent within one year, 29 percent within three years, and 54 percent within seven years. In this group, cardiac death is more prevalent than stroke and thus these patients must be referred to a cardiologist.
Clinical Pearls
Amaurosis fugax in elderly patients may be the initial sign of giant cell arteritis. In these cases, devastating vision loss from anterior ischemic optic neuropathy likely ensues within several weeks of an episode of AF. These patients need an immediate Westgren ESR, and possible temporal artery biopsy, along with the requisite carotid studies.
Most cases of TIA and AF show no visible evidence at examination. These diagnoses can be made by history. Optimal management involves referral to the appropriate medical specialist.
The number one hematological cause of AF is sickle cell disease.
Demyelinating Optic Neuropathy (Optic Neuritis, Retrobulbar Optic Neuritis)
Signs and Symptoms
Optic neuritis (ON) is defined as acute inflammation of the optic nerve. While etiologies include infection (syphilis, mumps, measles), infiltrative/ inflammatory disease (sarcoidosis, lupus), ischemic vascular disease (diabetes), the most common etiology is the demyelinating disease multiple sclerosis (MS). ON is the initial presenting sign in 20 to 25 percent of MS patients. Anywhere from 35 percent to 75 percent of patients who present with ON develop clinical MS. The risk of developing MS increases steadily during the first 10 years after the initial presentation of ON. The usual age range for the diagnosis of MS is 15 to 45 years. While some sources cite a predilection for females, the topic of sexual distribution remains controversial.
The clinical presentation of demyelinating optic neuropathy varies. Patients frequently present to the office with an acute loss of vision. The natural history of MS-related vision loss is rapidly progressive acuity loss for a period of 10 days, which then stabilizes and improves. Additional ocular signs include eye pain, tenderness of the globe, dyschromatopsia, decreased brightness sense, decreased color perception, a relative afferent pupillary defect, assorted visual field defects (altitudinal and central/cecocentral), phosphenes upon eye movement and optic disc swelling with or without vitreous cells. Often, the optic nerve is normal in appearance and the dysfunction is considered retrobulbar.
Systemic signs and symptoms may include headache, nausea, Uhtoff’s sign (decreased vision with or without limb weakness following exposure to increased temperatures i.e., a bath or exercise), Romberg’s sign (patient falls when they close their eyes), Pulfrich’s stereo phenomenon (beer barrel appearance to the environment) and fever.
Pathophysiology
Multiple sclerosis is an acquired, multifactorial, inflammatory demyelinating disease, which affects the white matter located in the central nervous system. Myelin is responsible for speeding electrical impulses along nervous tissues. Loss of myelin greatly slows nervous conduction and leads to the neurologic deficits seen in MS.
Although the exact cause of MS is presently unknown, many theories regarding its etiology exist. The most common theories involve the immune system. The immune system attacks and destroys antigens by two different mechanisms. One mechanism, known as cellular immunity, involves a response by macrophages and T-cells. The other mechanism, governed by B-cells and antibodies is known as humoral immunity. Evidence suggests that the cellular immune response contributes to the loss of myelin. This patchy demyelination is thought to be caused by a deposition of mononuclear cells such as macrophages and B-cells in perivascular regions. Demyelinating optic neuropathy can damage the fibers in both the visual and pupillary pathways. This damage interrupts nerve impulses within the pathways, producing decreased vision as well as an afferent pupillary defect.
Management
In the past, controversy existed as to whether or not to treat patients with ON with corticosteroids. The Optic Neuritis Treatment Trial (ONTT) supports the administration of intravenous methylprednisolone sodium succinate (Solumedrol, 250 mg. every 6 hours) for three days followed by oral prednisone (1 mg/kg per day) for 11 days for the purposes of accelerating visual recovery. This therapy did not improve visual outcome after one year but was found to increase the rate at which patients recover. The ONTT also determined that the use of oral prednisone (1 mg/kg per day) alone for 14 days is contraindicated. Patients receiving this therapy had a higher rate of new attacks of ON in both the initially affected and fellow eyes than did the intravenous/oral group and placebo group.
As recorded in the three-year follow-up of patients in the ONTT, treatment with intravenous methylprednisolone followed by oral corticosteroid regimens reduced the two-year rate of development of clinical MS, particularly in patients with signal abnormalities consistent with demyelination on MRI of the brain at the time of study entry. Serious side effects of glucocorticoid therapy are infrequent. Therefore, outpatient administration of high-dose intravenous glucocorticoids may be recommended.
Clinical Pearls
A number of other types of demyelinating disorders have been associated with ON. They are: acute transverse myelitis, Guillain-Barré syndrome, Devic’s neuromyelitis optica, Charcot-Marie-Tooth syndrome, multifocal demyelinating neuropathy, and acute disseminated encephalomyelitis.
Diseases such as syphilis, toxoplasmosis, histoplasmosis, tuberculosis, hepatitis, rubella, human immunodeficiency virus (HIV), Lyme borreliosis, familial Mediterranean fever, Epstein-Barr virus, herpes zoster ophthalmicus, paranasal sinus disorder, sarcoidosis, systemic lupus erythematosus, Bechet’s disease, and diabetes may cause optic neuropathy and should be considered before prematurely diagnosing demyelinating optic neuropathy.
In cases of optic neuropathy presumably secondary to demyelinating disease, MRI can assist in systemic diagnosis by identifying both old and acute demyelinating plaques within periventricular white matter.
Significant pain with eye movement is present in nearly every case of demyelinating optic neuropathy.
As the visual dysfunction is due to autoimmune destruction of myelin
Optic neuritis (ON) is defined as acute inflammation of the optic nerve. While etiologies include infection (syphilis, mumps, measles), infiltrative/ inflammatory disease (sarcoidosis, lupus), ischemic vascular disease (diabetes), the most common etiology is the demyelinating disease multiple sclerosis (MS). ON is the initial presenting sign in 20 to 25 percent of MS patients. Anywhere from 35 percent to 75 percent of patients who present with ON develop clinical MS. The risk of developing MS increases steadily during the first 10 years after the initial presentation of ON. The usual age range for the diagnosis of MS is 15 to 45 years. While some sources cite a predilection for females, the topic of sexual distribution remains controversial.
The clinical presentation of demyelinating optic neuropathy varies. Patients frequently present to the office with an acute loss of vision. The natural history of MS-related vision loss is rapidly progressive acuity loss for a period of 10 days, which then stabilizes and improves. Additional ocular signs include eye pain, tenderness of the globe, dyschromatopsia, decreased brightness sense, decreased color perception, a relative afferent pupillary defect, assorted visual field defects (altitudinal and central/cecocentral), phosphenes upon eye movement and optic disc swelling with or without vitreous cells. Often, the optic nerve is normal in appearance and the dysfunction is considered retrobulbar.
Systemic signs and symptoms may include headache, nausea, Uhtoff’s sign (decreased vision with or without limb weakness following exposure to increased temperatures i.e., a bath or exercise), Romberg’s sign (patient falls when they close their eyes), Pulfrich’s stereo phenomenon (beer barrel appearance to the environment) and fever.
Pathophysiology
Multiple sclerosis is an acquired, multifactorial, inflammatory demyelinating disease, which affects the white matter located in the central nervous system. Myelin is responsible for speeding electrical impulses along nervous tissues. Loss of myelin greatly slows nervous conduction and leads to the neurologic deficits seen in MS.
Although the exact cause of MS is presently unknown, many theories regarding its etiology exist. The most common theories involve the immune system. The immune system attacks and destroys antigens by two different mechanisms. One mechanism, known as cellular immunity, involves a response by macrophages and T-cells. The other mechanism, governed by B-cells and antibodies is known as humoral immunity. Evidence suggests that the cellular immune response contributes to the loss of myelin. This patchy demyelination is thought to be caused by a deposition of mononuclear cells such as macrophages and B-cells in perivascular regions. Demyelinating optic neuropathy can damage the fibers in both the visual and pupillary pathways. This damage interrupts nerve impulses within the pathways, producing decreased vision as well as an afferent pupillary defect.
Management
In the past, controversy existed as to whether or not to treat patients with ON with corticosteroids. The Optic Neuritis Treatment Trial (ONTT) supports the administration of intravenous methylprednisolone sodium succinate (Solumedrol, 250 mg. every 6 hours) for three days followed by oral prednisone (1 mg/kg per day) for 11 days for the purposes of accelerating visual recovery. This therapy did not improve visual outcome after one year but was found to increase the rate at which patients recover. The ONTT also determined that the use of oral prednisone (1 mg/kg per day) alone for 14 days is contraindicated. Patients receiving this therapy had a higher rate of new attacks of ON in both the initially affected and fellow eyes than did the intravenous/oral group and placebo group.
As recorded in the three-year follow-up of patients in the ONTT, treatment with intravenous methylprednisolone followed by oral corticosteroid regimens reduced the two-year rate of development of clinical MS, particularly in patients with signal abnormalities consistent with demyelination on MRI of the brain at the time of study entry. Serious side effects of glucocorticoid therapy are infrequent. Therefore, outpatient administration of high-dose intravenous glucocorticoids may be recommended.
Clinical Pearls
A number of other types of demyelinating disorders have been associated with ON. They are: acute transverse myelitis, Guillain-Barré syndrome, Devic’s neuromyelitis optica, Charcot-Marie-Tooth syndrome, multifocal demyelinating neuropathy, and acute disseminated encephalomyelitis.
Diseases such as syphilis, toxoplasmosis, histoplasmosis, tuberculosis, hepatitis, rubella, human immunodeficiency virus (HIV), Lyme borreliosis, familial Mediterranean fever, Epstein-Barr virus, herpes zoster ophthalmicus, paranasal sinus disorder, sarcoidosis, systemic lupus erythematosus, Bechet’s disease, and diabetes may cause optic neuropathy and should be considered before prematurely diagnosing demyelinating optic neuropathy.
In cases of optic neuropathy presumably secondary to demyelinating disease, MRI can assist in systemic diagnosis by identifying both old and acute demyelinating plaques within periventricular white matter.
Significant pain with eye movement is present in nearly every case of demyelinating optic neuropathy.
As the visual dysfunction is due to autoimmune destruction of myelin
Optic Nerve Head Drusen
Signs and Symptoms
A condition involving retained hyaline bodies in the anterior optic nerve, optic nerve head drusen (ONHD) has been referred to in the literature by many diverse and confusing names. Among the descriptive terms are congenitally elevated or anomalous discs, pseudopapilledema, pseudoneuritis, buried disc drusen, and disc hyaline bodies. ONHD is encountered in approximately 1 percent of the general population, and is bilateral in 70 percent of cases. The condition occurs primarily in Caucasians and is believed to demonstrate an autosomal dominant inheritance pattern with incomplete penetrance. Typically, patients with ONHD remain asymptomatic, and the finding is discovered only on routine ocular evaluation. In some instances, however, the condition can present with mildly decreased visual acuity and visual field defects. An afferent pupillary defect may be noted if the condition is both significant and asymmetric. Reports of recurrent, transient visual obscurations associated with disc drusen have also been documented.
The classic appearance of ONHD involves bilaterally elevated optic discs with irregular or "scalloped" margins, a small or nonexistent cup, and unusual vascular branching patterns that arise from a central vessel core. Often there are small, refractile hyaline deposits visible on the surface of the disc and/or in the peripapillary area. ONHD most often manifests on the nasal disc margin, but can be found within any part of the nerve head. In younger patients, the disc elevation tends to be more pronounced and the drusen less calcific, making them less visible ophthalmoscopically, and hence offering a more challenging diagnostic dilemma. Unlike true disc edema, ONHD very rarely presents with juxtapapillary nerve fiber edema, exudate, or cotton-wool spots.
Pathophysiology
There is no histopathological correlation between drusen of the optic nerve head and retinal drusen; the former represent acellular laminated concretions, often partially calcified, possibly related to accumulation of axoplasmic derivatives of degenerating retinal nerve fibers. As mentioned, ONHD tend to remain "buried" in children, but slowly become visible as they enlarge toward the disc surface and as the overlying retinal nerve fiber layer progressively thins. They are usually ophthalmoscopically detectable by the early to mid-teens, although these authors have seen patients in their mid-20s who continue to display "buried drusen". Within the optic nerve, the hyaline bodies are confined anterior to the lamina cribosa and thus can compress and compromise the nerve fibers and vascular supply, leading to visual field defects and disc hemorrhages. Along with slowly developing optic atrophy in extreme cases, disruption of the juxtapapillary tissue can result in choroidal neovascular membrane formation leading to subretinal hemorrhage and disciform retinal scarring.
Management
Although ONHD is typically classified as a benign condition, it can lead to modest visual compromise. First and foremost, ONHD must be clearly differentiated from acquired disc edema, which warrants immediate neurologic evaluation and treatment. Management of ONHD includes prompt and proper diagnosis, which is aided greatly by the use of ocular ultrasonography. The high reflectivity of the calcified hyaline bodies is dramatically evident on B-scan ultrasonography, even at particularly low gain levels. Careful evaluation of optic nerve function is imperative, and should include standard Snellen acuity, contrast sensitivity, color vision testing, and threshold visual fields. Photodocumentation should be obtained for future monitoring. It is also important for patients to self-monitor their vision periodically, particularly because of the risk of choroidal neovascular membrane formation. Should these membranes be noted or suspected, intravenous fluorescein angiography is recommended, followed by laser photocoagulation as indicated. More routine cases should be monitored every six to 12 months.
Clinical Pearls
Some suggest that the vast majority of congenitally anomalous, elevated optic discs are likely associated with nerve head drusen. Recognize the clinical features associated with ONHD in comparison to those features indicative of true optic disc edema. In ONHD, expect a typically "normal" pink to pinkish-yellow color, rather than a pale waxy disc or a hyperemic disc. In addition, a spontaneous venous pulsation is present in about 80 percent of patients with ONHD, but is absent in cases of true disc edema. Most importantly, recognize that while the disc margins may be irregular in ONHD, rarely are they blurred or obscured.
Ultrasonography is probably the single most important ancillary test to perform in adults with ONHD. This procedure should be performed on all adult patients presenting with elevated optic discs that are not definitively identifiable as true optic disc edema based upon ophthalmoscopic observation or history. Keep in mind, however, that optic disc drusen are generally not calcified in children and adolescents. Hence, ultrasonography may prove to be of little help in diagnosing these cases.
While visual fields are an important method of documenting and monitoring optic nerve compromise secondary to ONHD, they are neither uniform nor diagnostic. The more common patterns encountered in ONHD include nasal step defects, enlargement of the physiologic blindspot, arcuate scotomas, sectoral field loss, and altitu
A condition involving retained hyaline bodies in the anterior optic nerve, optic nerve head drusen (ONHD) has been referred to in the literature by many diverse and confusing names. Among the descriptive terms are congenitally elevated or anomalous discs, pseudopapilledema, pseudoneuritis, buried disc drusen, and disc hyaline bodies. ONHD is encountered in approximately 1 percent of the general population, and is bilateral in 70 percent of cases. The condition occurs primarily in Caucasians and is believed to demonstrate an autosomal dominant inheritance pattern with incomplete penetrance. Typically, patients with ONHD remain asymptomatic, and the finding is discovered only on routine ocular evaluation. In some instances, however, the condition can present with mildly decreased visual acuity and visual field defects. An afferent pupillary defect may be noted if the condition is both significant and asymmetric. Reports of recurrent, transient visual obscurations associated with disc drusen have also been documented.
The classic appearance of ONHD involves bilaterally elevated optic discs with irregular or "scalloped" margins, a small or nonexistent cup, and unusual vascular branching patterns that arise from a central vessel core. Often there are small, refractile hyaline deposits visible on the surface of the disc and/or in the peripapillary area. ONHD most often manifests on the nasal disc margin, but can be found within any part of the nerve head. In younger patients, the disc elevation tends to be more pronounced and the drusen less calcific, making them less visible ophthalmoscopically, and hence offering a more challenging diagnostic dilemma. Unlike true disc edema, ONHD very rarely presents with juxtapapillary nerve fiber edema, exudate, or cotton-wool spots.
Pathophysiology
There is no histopathological correlation between drusen of the optic nerve head and retinal drusen; the former represent acellular laminated concretions, often partially calcified, possibly related to accumulation of axoplasmic derivatives of degenerating retinal nerve fibers. As mentioned, ONHD tend to remain "buried" in children, but slowly become visible as they enlarge toward the disc surface and as the overlying retinal nerve fiber layer progressively thins. They are usually ophthalmoscopically detectable by the early to mid-teens, although these authors have seen patients in their mid-20s who continue to display "buried drusen". Within the optic nerve, the hyaline bodies are confined anterior to the lamina cribosa and thus can compress and compromise the nerve fibers and vascular supply, leading to visual field defects and disc hemorrhages. Along with slowly developing optic atrophy in extreme cases, disruption of the juxtapapillary tissue can result in choroidal neovascular membrane formation leading to subretinal hemorrhage and disciform retinal scarring.
Management
Although ONHD is typically classified as a benign condition, it can lead to modest visual compromise. First and foremost, ONHD must be clearly differentiated from acquired disc edema, which warrants immediate neurologic evaluation and treatment. Management of ONHD includes prompt and proper diagnosis, which is aided greatly by the use of ocular ultrasonography. The high reflectivity of the calcified hyaline bodies is dramatically evident on B-scan ultrasonography, even at particularly low gain levels. Careful evaluation of optic nerve function is imperative, and should include standard Snellen acuity, contrast sensitivity, color vision testing, and threshold visual fields. Photodocumentation should be obtained for future monitoring. It is also important for patients to self-monitor their vision periodically, particularly because of the risk of choroidal neovascular membrane formation. Should these membranes be noted or suspected, intravenous fluorescein angiography is recommended, followed by laser photocoagulation as indicated. More routine cases should be monitored every six to 12 months.
Clinical Pearls
Some suggest that the vast majority of congenitally anomalous, elevated optic discs are likely associated with nerve head drusen. Recognize the clinical features associated with ONHD in comparison to those features indicative of true optic disc edema. In ONHD, expect a typically "normal" pink to pinkish-yellow color, rather than a pale waxy disc or a hyperemic disc. In addition, a spontaneous venous pulsation is present in about 80 percent of patients with ONHD, but is absent in cases of true disc edema. Most importantly, recognize that while the disc margins may be irregular in ONHD, rarely are they blurred or obscured.
Ultrasonography is probably the single most important ancillary test to perform in adults with ONHD. This procedure should be performed on all adult patients presenting with elevated optic discs that are not definitively identifiable as true optic disc edema based upon ophthalmoscopic observation or history. Keep in mind, however, that optic disc drusen are generally not calcified in children and adolescents. Hence, ultrasonography may prove to be of little help in diagnosing these cases.
While visual fields are an important method of documenting and monitoring optic nerve compromise secondary to ONHD, they are neither uniform nor diagnostic. The more common patterns encountered in ONHD include nasal step defects, enlargement of the physiologic blindspot, arcuate scotomas, sectoral field loss, and altitu
Acquired Glaucomatous Changes of the Optic Nerve Head (Pictorial)
Baring of a circumlinear vessel
Pronounced rim thinning and rim loss in advanced glaucoma
Notching of the inferior temporal neuroretinal rim
Beanpotting
Vertical elongation of the optic cup with peripapillary atrophy
Beanpotting
Nerve fiber layer loss
Disc Hemorrhage
Pronounced rim thinning and rim loss in advanced glaucoma
Notching of the inferior temporal neuroretinal rim
Beanpotting
Vertical elongation of the optic cup with peripapillary atrophy
Beanpotting
Nerve fiber layer loss
Disc Hemorrhage
TONIC PUPIL
SIGNS AND SYMPTOMS
The patient often complains of unequal pupil sizes, and frequently of decreased vision at near. The patient may be any age, especially if there has been history of local trauma or orbital surgery. Often when a history of trauma is not apparent, the patient will be younger and female.
A tonic pupil may occur in one or both eyes. It is typically larger than the normal fellow pupil in normal illumination. However, there is no significant change in size of the tonic pupil when going from bright to dim illumination. The tonic pupil will appear fixed and unreactive to light.
When testing near accommodation, the tonic pupil will show a slow constrictive response. Biomicroscopy often reveals segmental paralysis and flattening of the pupil border, which gives the pupil an irregular shape. There may also be a vermiform movement of the non-paralyzed sections of the iris. In cases of idiopathic tonic pupils, deep tendon reflexes often diminish, particularly in young females.
PATHOPHYSIOLOGY
A tonic pupil results from damage to the ciliary ganglion within the orbit. In the ciliary ganglion, 93 percent of the post-ganglionic fibers innervate the ciliary body for accommodation; the remaining 7 percent innervate the iris sphincter for miosis during the light reflex. When the ciliary ganglion is damaged, there is an aberrant regeneration of fibers, with post-ganglionic fibers that originally innervated the iris sphincter now innervating the ciliary body. Thus, light response is diminished, but accommodative near constriction remains. However, near constriction is often slow and segmental, and accommodation is often diminished.
Trauma is the most common cause of a tonic pupil. Other causes associated with tonic pupils include viral illness, diabetes, syphilis and giant cell arteritis. When the etiology cannot be identified, particularly in young females, the condition is termed Adie's tonic pupil.
MANAGEMENT
There is no exact management plan for tonic pupils. Address each case individually. If the patient dislikes the cosmetic asymmetry of the pupils, consider opaque contact lenses. For a patient over 60 who develops a tonic pupil, order an erythrocyte sedimentation rate (ESR) to check for giant cell arteritis. If the patient is male, and has bilateral tonic pupils, order both a specific (FTA-ABS) and non-specific treponemal (RPR) test to examine for syphilis. In most cases, try to elicit a history of trauma.
CLINICAL PEARLS
Remember that a tonic pupil in an elderly patient can be caused by giant cell arteritis, and order an ESR. This can help diagnose a vision-threatening disease before severe vision loss ensues from ischemic optic neuropathy.
Incidence of syphilis is about 45 percent in cases of bilateral tonic pupils in males. Order both a specific and non-specific treponemal test for diagnosis.
In cases of Adie's tonic pupils, testing of patellar tendon reflexes can assist in the diagnosis.
Not all tonic pupils are Adie's tonic pupils. This term is mistakenly overused. The term "Adie's tonic pupil" refers to an idiopathic tonic pupil.
The patient often complains of unequal pupil sizes, and frequently of decreased vision at near. The patient may be any age, especially if there has been history of local trauma or orbital surgery. Often when a history of trauma is not apparent, the patient will be younger and female.
A tonic pupil may occur in one or both eyes. It is typically larger than the normal fellow pupil in normal illumination. However, there is no significant change in size of the tonic pupil when going from bright to dim illumination. The tonic pupil will appear fixed and unreactive to light.
When testing near accommodation, the tonic pupil will show a slow constrictive response. Biomicroscopy often reveals segmental paralysis and flattening of the pupil border, which gives the pupil an irregular shape. There may also be a vermiform movement of the non-paralyzed sections of the iris. In cases of idiopathic tonic pupils, deep tendon reflexes often diminish, particularly in young females.
PATHOPHYSIOLOGY
A tonic pupil results from damage to the ciliary ganglion within the orbit. In the ciliary ganglion, 93 percent of the post-ganglionic fibers innervate the ciliary body for accommodation; the remaining 7 percent innervate the iris sphincter for miosis during the light reflex. When the ciliary ganglion is damaged, there is an aberrant regeneration of fibers, with post-ganglionic fibers that originally innervated the iris sphincter now innervating the ciliary body. Thus, light response is diminished, but accommodative near constriction remains. However, near constriction is often slow and segmental, and accommodation is often diminished.
Trauma is the most common cause of a tonic pupil. Other causes associated with tonic pupils include viral illness, diabetes, syphilis and giant cell arteritis. When the etiology cannot be identified, particularly in young females, the condition is termed Adie's tonic pupil.
MANAGEMENT
There is no exact management plan for tonic pupils. Address each case individually. If the patient dislikes the cosmetic asymmetry of the pupils, consider opaque contact lenses. For a patient over 60 who develops a tonic pupil, order an erythrocyte sedimentation rate (ESR) to check for giant cell arteritis. If the patient is male, and has bilateral tonic pupils, order both a specific (FTA-ABS) and non-specific treponemal (RPR) test to examine for syphilis. In most cases, try to elicit a history of trauma.
CLINICAL PEARLS
Remember that a tonic pupil in an elderly patient can be caused by giant cell arteritis, and order an ESR. This can help diagnose a vision-threatening disease before severe vision loss ensues from ischemic optic neuropathy.
Incidence of syphilis is about 45 percent in cases of bilateral tonic pupils in males. Order both a specific and non-specific treponemal test for diagnosis.
In cases of Adie's tonic pupils, testing of patellar tendon reflexes can assist in the diagnosis.
Not all tonic pupils are Adie's tonic pupils. This term is mistakenly overused. The term "Adie's tonic pupil" refers to an idiopathic tonic pupil.
OPTIC PIT
SIGNS AND SYMPTOMS
Congenital pits of the optic nerve vary in size, shape, depth and location. They often appear as small, hypopigmented, yellow or whitish, oval or round excavated defects, most often within the inferior temporal portion of the optic cup. Approximately 20 to 33 percent are found centrally, with an average size of 500µm (one-third disc diameter).
Typically, optic pits occur unilaterally (85 percent). The optic disc in these patients appears larger than normal, and 60 percent of discs with optic pits also have cilioretinal arteries. These patients have a greater propensity to develop normal-tension glaucoma.
Most patients are unaware of the presence of an optic pit. Although as many as 60 to 70 percent of patients with optic pits possess some arcuate scotoma corresponding to the loss of retinal ganglion cells, their acuity is rarely affected. Patients may notice visual distortions, metamorphopsia or blurred vision. Those with temporal pits have the greatest risk for developing serous maculopathy.
PATHOPHYSIOLOGY
The origin of optic pits remains unclear. Optic pits have been associated with colobomatous lesions, suggesting that they result from incomplete closure of the fetal fissure. Others propose that they result from abnormal differentiation of primitive epithelia papilla. Arcuate visual field defects are the result of corresponding loss of retinal ganglion cells or secondary atrophy of attenuated nerve fibers.
Some 40 to 60 percent of patients with optic pits develop non-rhegmatogenous serous macular detachments. These fluid-filled cystic maculopathies can develop into lamellar macular holes. The origin of the fluid is unknown. There is a high incidence of posterior vitreous detachment associated with these serous maculopathies.
Previous theories concerning the origin of the subretinal fluid seen in optic pit-related serous macular detachment include liquefied vitreous penetration and leaking vessels within the pit. New findings strongly suggest that serous macular detachments secondary to optic pits develop due to pre-existing schisis-like lesions which connect the macula to the optic disc. Fluid, predominantly from the outer plexiform layer, enters an already edematous retina through the optic pit via the retinal stroma, producing a macular detachment.
MANAGEMENT
Begin the management of asymptomatic optic pit with a comprehensive eye examination, including threshold visual fields. Semi-annual intraocular pressure checks and dilated evaluations with drawings or photos are appropriate. Use home acuity assessment and home Amsler grid testing to monitor for the onset of maculopathy. Educate patients about the signs and symptoms of macular complications (e.g. blurred vision, visual distortions, metamorphopsia).
Treatment for optic pit-related macular detachment varies. Periodic monitoring, prophylactic laser photocoagulation, therapeutic laser photocoagulation after maculopathy has formed, oral steroids and vitrectomy have all been tried. The current trend is laser photocoagulation following the onset of maculopathy.
CLINICAL PEARLS
Differential diagnosis includes optic disc anomalies that mimic optic pit: choroidal and scleral crescent, tilted disc syndrome, circumpapillary staphyloma, hypoplastic disc and glaucomatous optic neuropathy. Idiopathic central serous retinopathy and subretinal neovascular membrane are alternative considerations for serous macular detachment.
Any change in appearance of the optic pit over time suggests that the lesion may be an acquired notch of the neuroretinal rim secondary to glaucomatous processes.
Congenital pits of the optic nerve vary in size, shape, depth and location. They often appear as small, hypopigmented, yellow or whitish, oval or round excavated defects, most often within the inferior temporal portion of the optic cup. Approximately 20 to 33 percent are found centrally, with an average size of 500µm (one-third disc diameter).
Typically, optic pits occur unilaterally (85 percent). The optic disc in these patients appears larger than normal, and 60 percent of discs with optic pits also have cilioretinal arteries. These patients have a greater propensity to develop normal-tension glaucoma.
Most patients are unaware of the presence of an optic pit. Although as many as 60 to 70 percent of patients with optic pits possess some arcuate scotoma corresponding to the loss of retinal ganglion cells, their acuity is rarely affected. Patients may notice visual distortions, metamorphopsia or blurred vision. Those with temporal pits have the greatest risk for developing serous maculopathy.
PATHOPHYSIOLOGY
The origin of optic pits remains unclear. Optic pits have been associated with colobomatous lesions, suggesting that they result from incomplete closure of the fetal fissure. Others propose that they result from abnormal differentiation of primitive epithelia papilla. Arcuate visual field defects are the result of corresponding loss of retinal ganglion cells or secondary atrophy of attenuated nerve fibers.
Some 40 to 60 percent of patients with optic pits develop non-rhegmatogenous serous macular detachments. These fluid-filled cystic maculopathies can develop into lamellar macular holes. The origin of the fluid is unknown. There is a high incidence of posterior vitreous detachment associated with these serous maculopathies.
Previous theories concerning the origin of the subretinal fluid seen in optic pit-related serous macular detachment include liquefied vitreous penetration and leaking vessels within the pit. New findings strongly suggest that serous macular detachments secondary to optic pits develop due to pre-existing schisis-like lesions which connect the macula to the optic disc. Fluid, predominantly from the outer plexiform layer, enters an already edematous retina through the optic pit via the retinal stroma, producing a macular detachment.
MANAGEMENT
Begin the management of asymptomatic optic pit with a comprehensive eye examination, including threshold visual fields. Semi-annual intraocular pressure checks and dilated evaluations with drawings or photos are appropriate. Use home acuity assessment and home Amsler grid testing to monitor for the onset of maculopathy. Educate patients about the signs and symptoms of macular complications (e.g. blurred vision, visual distortions, metamorphopsia).
Treatment for optic pit-related macular detachment varies. Periodic monitoring, prophylactic laser photocoagulation, therapeutic laser photocoagulation after maculopathy has formed, oral steroids and vitrectomy have all been tried. The current trend is laser photocoagulation following the onset of maculopathy.
CLINICAL PEARLS
Differential diagnosis includes optic disc anomalies that mimic optic pit: choroidal and scleral crescent, tilted disc syndrome, circumpapillary staphyloma, hypoplastic disc and glaucomatous optic neuropathy. Idiopathic central serous retinopathy and subretinal neovascular membrane are alternative considerations for serous macular detachment.
Any change in appearance of the optic pit over time suggests that the lesion may be an acquired notch of the neuroretinal rim secondary to glaucomatous processes.
OPTIC NERVE HEAD HYPOPLASIA
SIGNS AND SYMPTOMS
Because optic nerve head hypoplasia is congenital, it is typically diagnosed in younger patients at their initial eye examination. Visual acuity may range from normal to no light perception.
If the condition is unilateral, a relative afferent pupillary defect may be noted. Other dysfunctions of the afferent system, such as diminished color vision, red desaturation and brightness perception will likewise be present. Visual field defects may also be elicited but vary considerably-altitudinal loss, central and cecocentral scotomas, and other field defects have been documented. In addition, up to 50 percent of patients manifest a constant strabismus, most often esotropia.
Examination reveals a smaller-than-expected optic nerve, with the vasculature appearing large relative to the disc. If unilateral, there is a notable size difference in the nerve heads. A circumpapillary ring of white or yellowish scleral tissue is typically evident ("double-ring sign"). The normally bright reflex from the nerve fiber layer is diminished. A review of the patient's history may reveal associated brain disorders (e.g., absence of the septum pellucidum, pituitary dysfunction, porencephaly) and/or gestational disease, as well as a history of maldeveloped growth.
PATHOPHYSIOLOGY
The exact mechanism of optic nerve head hypoplasia is not completely understood. But the condition is believed to represent a dysplasia of the retinal ganglion cell layer with an associated loss of the nerve fiber layer, secondary to some interruption in fetal development. Underdevelopment of the optic nerve results, and the posterior scleral foramen "fills in" with connective and scleral tissues.
Many disorders have been implicated in this disorder, including gestational diabetes, maternal infection by cytomegalovirus, syphilis, rubella, fetal alcohol syndrome and other drug use by the mother while pregnant. ONH hypoplasia may be part of larger clinical syndromes such as septo-optic dysplasia, which is marked by short stature, congenital nystagmus and a hypoplastic disc. The majority of patients, however, have no associated systemic abnormalities.
MANAGEMENT
Remember, ONH hypoplasia is a congenital condition. Appropriate management begins with proper diagnosis. Use visual field testing to confirm your suspicions.
In addition, many clinicians photograph the posterior pole of the affected eye and measure the disc-macula/disc-disc (DM/DD) ratio; this allows them to compare the horizontal diameter of the nerve head to the distance between the fovea and the center of the nerve. In a normal eye, the DM/DD measures between 2:1 and 3.2:1. Ratios greater than this suggest hypoplasia.
In uncomplicated unilateral cases, manage the condition through patient education and protective eyewear. If the history or examination indicates any associated neurological manifestations, refer the patient for studies to rule out forebrain disease. Studies may include physical and neurologic evaluation, neuroimaging and endocrinologic assessment. In more profound cases where both eyes are affected, consider visual rehabilitation services.
CLINICAL PEARLS
Make sure to clearly distinguish this condition from amblyopia. Although both amblyopia and ONH hypoplasia can present with reduced acuity, strabismus and variable refractive error, the former remains a diagnosis of exclusion. In cases of ONH hypoplasia, the associated refractive and/or binocular findings are secondary findings rather than primary causes of the problem. Furthermore, conventional amblyopia therapy will not be helpful in ONH hypoplasia. Vision therapy is a lengthy, costly, yet fruitless option for these patients.
Because optic nerve head hypoplasia is congenital, it is typically diagnosed in younger patients at their initial eye examination. Visual acuity may range from normal to no light perception.
If the condition is unilateral, a relative afferent pupillary defect may be noted. Other dysfunctions of the afferent system, such as diminished color vision, red desaturation and brightness perception will likewise be present. Visual field defects may also be elicited but vary considerably-altitudinal loss, central and cecocentral scotomas, and other field defects have been documented. In addition, up to 50 percent of patients manifest a constant strabismus, most often esotropia.
Examination reveals a smaller-than-expected optic nerve, with the vasculature appearing large relative to the disc. If unilateral, there is a notable size difference in the nerve heads. A circumpapillary ring of white or yellowish scleral tissue is typically evident ("double-ring sign"). The normally bright reflex from the nerve fiber layer is diminished. A review of the patient's history may reveal associated brain disorders (e.g., absence of the septum pellucidum, pituitary dysfunction, porencephaly) and/or gestational disease, as well as a history of maldeveloped growth.
PATHOPHYSIOLOGY
The exact mechanism of optic nerve head hypoplasia is not completely understood. But the condition is believed to represent a dysplasia of the retinal ganglion cell layer with an associated loss of the nerve fiber layer, secondary to some interruption in fetal development. Underdevelopment of the optic nerve results, and the posterior scleral foramen "fills in" with connective and scleral tissues.
Many disorders have been implicated in this disorder, including gestational diabetes, maternal infection by cytomegalovirus, syphilis, rubella, fetal alcohol syndrome and other drug use by the mother while pregnant. ONH hypoplasia may be part of larger clinical syndromes such as septo-optic dysplasia, which is marked by short stature, congenital nystagmus and a hypoplastic disc. The majority of patients, however, have no associated systemic abnormalities.
MANAGEMENT
Remember, ONH hypoplasia is a congenital condition. Appropriate management begins with proper diagnosis. Use visual field testing to confirm your suspicions.
In addition, many clinicians photograph the posterior pole of the affected eye and measure the disc-macula/disc-disc (DM/DD) ratio; this allows them to compare the horizontal diameter of the nerve head to the distance between the fovea and the center of the nerve. In a normal eye, the DM/DD measures between 2:1 and 3.2:1. Ratios greater than this suggest hypoplasia.
In uncomplicated unilateral cases, manage the condition through patient education and protective eyewear. If the history or examination indicates any associated neurological manifestations, refer the patient for studies to rule out forebrain disease. Studies may include physical and neurologic evaluation, neuroimaging and endocrinologic assessment. In more profound cases where both eyes are affected, consider visual rehabilitation services.
CLINICAL PEARLS
Make sure to clearly distinguish this condition from amblyopia. Although both amblyopia and ONH hypoplasia can present with reduced acuity, strabismus and variable refractive error, the former remains a diagnosis of exclusion. In cases of ONH hypoplasia, the associated refractive and/or binocular findings are secondary findings rather than primary causes of the problem. Furthermore, conventional amblyopia therapy will not be helpful in ONH hypoplasia. Vision therapy is a lengthy, costly, yet fruitless option for these patients.
Subscribe to:
Posts (Atom)