Retinopathies

Definition

The retinopathies are a group of retinal diseases that cause vascular and neurological changes in the retina of the eye. They are reflective of ongoing systemic diseases, such as diabetes, arteriosclerosis, hypertension, and sickle cell anemia.

Description

The retina is an outward extension of the central nervous system that lines the inside of the eye. It has 10 layers and is comprised of the photoreceptor rods and cones and support cells, such as Mueller cells. The retinal pigment epithelium (RPE) is a single cell layer located behind the retina, which services the photoreceptors. Bruch's membrane is a basement membrane found between the RPE and the choriod, a highly vascular layer that includes the choriocapillaris, which supplies nutrients to the RPE and to the photoreceptors. The central retinal artery and its branches supply blood to the rest of the retina. The cilio-retinal artery that emerges from the optic nerve supplies the macula. The macula is located temporal to the optic nerve and is the part of the retina that contains the highest concentration of photoreceptors, especially cones. The part of the macula with the highest concentration of cones is the fovea. The vitreous humor is a gelatinous body that is located between the retina and the lens of the eye. The optic nerve is a large nerve in the posterior part of the eye through which the central artery and vein pass. It is actually formed from the axons of cells in the retina. It is through the optic nerve that visual stimuli leave the eye for the occipital lobe of the brain, where vision is processed. Hemoglobin is a molecule in red blood cells responsible for the transport of oxygen.

The presentation and pathogenesis of each of these retinal diseases are unique; and the signs can be seen by an ophthalmologist or an optometrist on dilation of the eye. All of these retinopathies can lead to blindness.

Causes and symptoms

Diabetic retinopathy

Diabetic retinopathy is the leading cause of blindness in the United States for people between 20 and 74 years of age. Risk factors for diabetic retinopathy include hypertension, elevated HgA1C (a hemoglobin test ), a history of smoking, and number of years as a diabetic. Within 10 years of diagnosis, over 70% of type I diabetics will have some retinopathy, and within 16 years of diagnosis, 60% of type II diabetics will have retinopathy. A diabetic may have normal vision, yet still have severe retinopathy.

The underlying pathogenesis of diabetic retinopathy is hypoxia, a decreased oxygen supply that is caused by elevated blood sugar or hyperglycemia. Glucose is needed in the cells of the body for energy, and oxygen and insulin are required for entry of the glucose molecules. The diabetic, because of insufficient insulin or because of cellular resistance to insulin, cannot absorb glucose into the cell effectively. The pathologic response of the retina to a decreased oxygen supply is first a thickening of, and then a break-down of the retinal capillary basement membrane. Pericytes, cells that surround the capillaries and produce an inhibitor for angiogenesis, also degenerate. In the absence of this inhibitor, retinal neovascularization, or new vessel formation, is stimulated by vascular endothelial growth factor (VEGF). The new vessels that form are very fragile and can easily rupture, causing bleeding in the vitreous and subsequently leading to vitreous traction. Degeneration of retinal neural cells precedes the vascular changes of diabetic retinopathy.

Diabetic retinopathy is a condition that initially affects only the posterior pole of the retina. The peripheral retina is affected only in the extreme cases. Diabetic retinopathy is divided into two phases: nonproliferative and proliferative. In the nonproliferative phase the retina has microaneurysms, dot and blot hemorrhages, hard lipid exudates, a beading pattern of some of the venules, areas of local ischemia where there is little or no oxygen perfusion (called cotton-wool spots), or macular edema. The macular edema is called clinically significant macula (CSME) when there are hard exudates and macular thickening or edema, close to the fovea. In the proliferative phase of diabetic retinopathy, neovascularization of the retina and of the optic nerve can be observed. A fibrous substance that materializes when the new retinal vessels form adheres to the vitreous, causing retinal traction and retinal detachments. The newly formed blood vessels can invade the anterior part of the eye, causing neovascular glaucoma. Vitreous hemorrhaging occurs when the blood vessels attach to the vitreous. Venous and arterial occlusions are also seen in diabetic retinopathy.

Arteriosclerotic retinopathy

Arteriosclerotic retinopathy is the ocular manifestation of arteriosclerosis, a systemic condition in which the arterial walls thicken and harden. The risk factors for arteriosclerotic retinopathy include heart disease and elevated serum cholesterol. Arteriosclerotic retinopathy can be involved in hypertensive retinopathy. One of the first ophthalmoscopic signs of arterio-sclerotic retinopathy is an increased arterial reflex due to thickening of the retinal arterial walls. As the arteriosclerosis progresses, the vessels undergo color changes to a copper-wire and then to a silver-wire appearance. Arteriovenous or A-V crossing defects are also synonymous with arteriosclerotic retinopathy. In advanced arteriosclerosis, banking—a type of A-V crossing that completely cuts off distal venous circulation, forming a large dilated vein—occurs.

Arterial occlusion can occur as a result of arterio-sclerotic retinopathy. An embolus from the carotid artery or from the aortic arch of the heart can travel to the retina, occluding either the central retinal artery (CRAO) or one of its branches (BRAO). An embolus from the carotid artery usually is a cholesterol plaque; and that from the heart is usually fibrotic in appearance. Immediately after a CRAO, the retina becomes ischemic and then edematous. Due to the surrounding ischemia, the fovea takes on a characteristic cherry-red appearance. A pupil abnormality, called an afferent pupillary defect (APD), may be noted. The vision loss in a CRAO is severe, sudden, and painless, although the patient may have a history of amaurosis fugax. After resolution of the CRAO the retina takes on a normal appearance, but the retinal blood vessels are narrowed and the optic nerve shows pallor. Macular function will be intact if there is cilioretinal circulation. Patients with a BRAO may be asymptomatic if there is no macular involvement, but usually there is field loss in the affected quadrant as well as decreased visual acuity.

Hypertensive retinopathy

Hypertensive retinopathy is an ocular presentation of the effects of systemic hypertension, defined as systolic pressure over 140 mm/Hg and diastolic pressure over 90 mm/Hg. This type of retinopathy is usually bilateral. There is narrowing of retinal arterioles in systemic hypertension. Constriction of vessels in older hypertensive patients may not be observed because of involutional sclerosis of the arteries, which occurs during aging. When the integrity of the retinal vessels is compromised because of long-term hypertension, leakage of blood occurs, and flame-shaped hemorrhages that are characteristic of hypertensive retinopathy can be observed in the retina. Also, a star-shaped pattern of exudation appears in the macula. In the advanced stages of hypertensive retinopathy there will be cotton wool spots close to the optic nerve. In malignant hypertension the optic nerve will become swollen and the patient will often experience blurred vision, and, if the blood pressure is extremely elevated, encephalopathy can develop.

Retinal vein occlusions

Retinal vein occlusions block the drainage of the retina. They can be either central (CRVO) or branched (BRVO). They are usually seen in older patients who have arteriosclerosis, hypertension or diabetes. Vein occlusions can also strike patients with sickle-cell anemia. Papillophlebitis is a form of retinal vein occlusion that is inflammatory in nature and seen in younger patients. A hemi-central vein occlusion is similar to a CRVO, but affects only one-half of the retina. A CRVO occurs when the central retinal artery compresses the central vein as it leaves the lamina cribosa. A BRVO occurs when there is constriction of a venule by a sclerotic artery that affects only one quadrant, usually the superior temporal one.

A CRVO can be either ischemic (characterized by decreased blood flow) or nonischemic. Approximately 80% of CRVO events are nonischemic. In the non-ischemic CRVO, hemorrhages are evident throughout the retina, but usually there are no cotton-wool spots. The optic nerve swelling is usually mild and macular edema is not always present. The visual acuity may be only mildly reduced. Months after such an occlusion, collateral blood vessels may appear on the optic nerve. Up to 20% of individuals with a nonischemic CRVO may progress to an ischemic event. The hallmark of ischemic CRVO is extensive capillary nonperfusion. Ophthalmoscopic examination following an ischemic event reveals extensive venous tortuosity and enlargement of the retinal veins. Edema of the macula and optic nerve are always present and cotton wool spots are common. Visual acuity is usually less than 20/200. Neovascularization of the iris and neovascular glaucoma are common complications of CRVO. There can be optic nerve neovascularization, bleeding into the vitreous, and vitreal traction, which increases the risk of a retinal detachment. The signs of a BRAO are similar, but present in just one quadrant.

Sickle-cell retinopathy

The underlying cause of sickle-cell retinopathy is different from that of the other retinopathies. Sickle-cell anemia is a genetically inherited condition seen primarily in persons of African descent. Close to 10% of African Americans carry one of the sickle-cell traits. Sickle-cell anemia is caused by mutant hemoglobin molecules that form either because of an amino acid substitution of valine for glutamic acid, causing a structural defect in the hemoglobin molecule, or because of a deficiency in the synthesis of one of the hemoglobin peptide chains. A normal red blood cell has a biconcave appearance and can easily pass through the capillary bed. A "sickle" cell does not have this biconcave shape, is less pliable than a normal red blood cell, and thus does not move well through the capillaries, triggering retinal microvascular occlusions and then ischemia.

Sickle-cell retinopathy can be nonproliferative or proliferative and affects primarily the peripheral retina. In the nonproliferative stage, the retinal vessel walls begin to deteriorate. The ophthalmoscopic signs of nonproliferative sickle-cell retinopathy include: venous tortuosity; intraretinal "salmon patch" hemorrhages, found near a vessel occlusion; "black sunburst" lesions, that develop when a vascular occlusion damages the RPE; silver-wired arterioles; and breaks in Bruch's membrane, called angioid streaks. Sickle-cell retinopathy becomes proliferative when neovascularization, in the form of arteriovenous anastomoses or connections between veins and arteries, appears in a sea-shaped formation. These vessels can adhere to the vitreous, but usually regress, forming a characteristic white tuft. Vitreous traction and retinal detachments are not common in sickle-cell retinopathy.

Diagnosis

The ophthalmologist or optometrist uses fluorescein angiography to determine the extent of vessel leakage and perfusion in the retinopathies. The fluorescein dye is injected into the body through a vein in the hand. Rarely does a patient have a reaction to the dye, but a localized redness at the injection site is occasionally observed. The fluorescein molecule binds to proteins in the blood and it excited by light of 490 nanometers (blue light). A retinal camera filters the light, such that only blue light enters the eye. Photos taken in rapid succession reveal the extent of perfusion, leakage, and ischemia in the retina. The results of this angiography help the doctor to determine if laser photocoagulation can benefit the patient.

Treatment

In laser treatment of retinopathy, the light energy of the laser is absorbed by certain cells in the retina, destroying them and thus reducing the oxygen demand of the area, while leaving the surrounding tissue intact. Pan-retinal photocoagulation (PRP) treats neovascularization following a BRAO or hemi-retinal arterial occlusion and the neovascularization of the optic nerve in diabetic retinopathy. The macular edema of arterial occlusions and diabetic retinopathy is treated by focal argon photocoagulation. Laser surgery is not performed close to the fovea. Often the edema that develops during an arterial occlusion will dissipate without treatment. Laser treatment is not usually beneficial in CRAO. Peripheral scatter photocoagulation treats the neovascularization of sickle-cell retinopathy.

The vitreous hemorrhaging of diabetes and sickle-cell retinopathy may require either a vitrectomy, which is a surgical removal of part or all of the vitreous, or cryopexy, the use of low-temperature probes to kill the blood vessels. Vitrectomy has been especially beneficial in restoring vision in diabetic patients in whom retinopathy has already affected visual acuity.

There is little that can be done to treat a CRAO. Massage of the globe to dislodge the embolus, the use of carbogen to increase blood carbon dioxide levels, and anterior chamber paracentesis have all been employed with limited success. Hyperbaric oxygen therapy has been successful in treatment of CRAO in one study.

In treatment of the patient with malignant hypertension it is important to slowly lower the blood pressure in order to reduce the risk of ischemic optic neuropathy.

The intraocular pressure must be lowered in the patient with a CRAO.

Nonmedical treatments may include changes in diet and exercise regimens.

Prognosis

Except when vitrectomy is performed (when indicated), and once the retinopathies have had an effect on vision, there is little that can be done to restore it. The goal of many of the treatments is to prevent further damage. If the proliferative phases of these retinopathies are treated early enough, normal vision is possible. The prognosis for patients with nonproliferative retinopathy is better than for patients with proliferative disease.

Health care team roles

The role of the allied health professional in diagnosis and treatment of retinopathy is to assist the ophthalmologist or optometrist in diagnosis. Ophthalmic technicians or nurses may instill the drops for dilation of the eye, inject the fluorescein dye used in angiography. The ophthalmic technician or a retinal photographer takes the photos needed for analysis of retinopathy. Dieticians assist diabetics, hypertensives, and those with heart disease.

Prevention

The first line in prevention of the retinopathies is an annual dilated eye exam performed by an ophthalmologist or an optometrist. Patients with systemic disease that can cause retinopathy must understand the ocular complications of their disease and the consequences if medical therapy is not followed as recommended by a physician.

Depending on the type of retinopathy, other preventive measures need to be taken. All patients with retinal emboli need a cardiac workup, including analysis of blood lipid levels. This is the case even in the absence of an occlusion. Older patients need testing for temporal arteritis once CRAO is detected. Over 65% of patients with temporal arteritis will have a CRAO in the fellow eye within days of the initial event. Since 70% of patients with BRAO have hypertension, all patients with such occlusions need to be evaluated for hypertension. Since sickle-cell anemia can cause a BRVO, African Americans need a Sickledex test. In the event of unilateral hypertensive retinopathy, a carotid artery obstruction should be suspected and a carotid workup is imperative. Finally, the best prevention of the retinopathies is management of the underlying systemic diseases.

KEY TERMS

Exudation— Leakage of cells, proteins, and fluids through the blood vessel wall into the surrounding tissue.

Ischemia— Lack of blood supply to a tissue or organ.

Neovascularization— Formation of new blood vessels.

Proliferative retinopathy— Retinopathy with neovascularization.

Resources

BOOKS

Muchnick, Bruce G. Clinical Medicine in Optometric Practice. St. Louis: Mosby-Yearbook, 1994.

Spalton, Roger J., et al. Atlas of Clinical Ophthalmology, 2nd ed. Wolfe Publishing, 1994.

PERIODICALS

Alexander, Larry J. "The Essentials of Managing Ocular Diabetes." Review of Optometry (Sept. 15, 1998): 108-123.

Arrigg, Paul G., and Jerry Cavallerano. "The Role of Vitrectomy for Diabetic Retinopathy." Journal of the American Optometric Association (Nov. 1998): 733-40.

Beaser, Richard S. "Managing Diabetes: Current Strategies." Journal of the American Optometric Association (Nov. 1998): 711-25

Brown, Gary. "Be Ready When Vascular Occlusion Strikes." Review of Ophthalmology (March 1998): 107-109.

Dunbar, Mark T. "What's New in Retinal Disease." Review of Optometry (May 15, 2001): 77-83.

Eisenberg, Jeffery S. "Raising Hopes of Preventing Diabetic Blindness." Review of Optometry 96-104.

Gurwood, Andrew S., et al. "Understanding Angioid Streaks." Journal of the American Optometric Association (May 1997): 309-324.

Marshall, Edwin C. "Hypertension and the Eye: Applications of the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure." Journal of the American Optometric Association (May 1998): 281-291.

Sowka, Joseph W., and Allan G. Kabat. "What the Eye Reveals About Vascular Disease." Review of Optometry (Feb. 15, 1998): 90-98.

Stokkermans, Thomas J. W. "Inside Hypertension: The Causes and Consequences of High Blood Pressure." Review of Optometry (Jan. 15, 1999): 78-99.