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Review of optometry
Retinal Atlas, Part 2
What the Eye Reveals About Vascular Disease
How to diagnose and manage common retinal vasculopathies.
Joseph W. Sowka, O.D.
Alan G. Kabat, O.D.
Ft. Lauderdale, Fla.

The eye is a singularly revealing window to the human vascular system. Nowhere else in the body can clinicians so readily view the local effects of systemic vascular disease. You can use that ability not only to diagnose retinal vascular disease, but also to detect signs of underlying pathology. This article, the second in a series of retinal “Atlases”, describes the retinal vasculopathies you will see most commonly.

Diabetic Retinopathy
This is the most common retinal vascular disease, accounting for 10 percent of new cases of blindness each year, and is the leading cause of blindness for those age 20–74. 1, 2 Yet, half of all patients with high–risk retinopathy go undiagnosed. 2.

Patients may have either juvenile–onset (type–1) diabetes, or adult–onset (type–2) diabetes. The former causes a higher incidence and greater severity of retinopathy. The retinopathy begins when the llary basement membrane thickens, leading to vessel closure. There’s a dropout of pericytes, the cells that keep normal capillaries tight. The capillary walls weaken, causing microaneurysms that then rupture, with leakage of serum proteins, lipids and blood.

Blood accumulates as dot and blot hemorrhages in the retina’s inner nuclear and outer plexiform layers, and flame–shaped hemorrhages form in the nerve fiber layer. Serum lipids aggregate as exudates, and a build–up of serous fluid causes retinal edema. This can lead to clinically significant macular edema (CSME).

Venous beading results, and further capillary closure leads to focal hypoxia and cotton wool spots. More widespread hypoxia causes a release of a vascular endothelial growth factor, stimulating neovascularization either from the disc or the capillaries of the retina or iris.

Neovascularization of the disc or elsewhere on the retina poses risk for vitreal hemorrhage and subsequent tractional retinal detachment. Iris neovascularization may cause neovascular glaucoma with secondary angle closure.

Intraretinal microvascular abnormalities may be a precursor to retinal neovascularization. Diabetic retinopathy is either proliferative (with neovascularization) or non–proliferative (without ovascularization). 3, 4 Diabetic maculopathy is considered a separate entity, consisting of dot and blot hemorrhages, hard exudates and CSME. 5.

Diabetic maculopathy calls for laser treatment only in cases involving CSME. The surgeon applies argon laser photocoagulation to all leaking microaneurysms more than 500µm from the center of the foveal avascular zone. If fluorescein angiography reveals that microaneurysms are the cause of CSME, they receive focal photocoagulation. If diffuse leakage causes CSME, the surgeon applies photocoagulative burns in a grid pattern. 6–8. The aim is to preserve the remaining vision.

Cases of high–risk proliferative retinopathy when vision may drop to 5/200 or worse as well as iris neovascularization warrant panretinal photocoagulation. Argon laser burns destroy areas of hypoxic retina from just beyond the vascular arcades of the posterior pole to the far periphery. 4, 9 The eye’s oxygen demand decreases, and the neovascularization regresses. Prompt treatment of high–risk proliferative retinopathy or iris neovascularization reduces the risk of severe vision loss by 50 percent. 4.

Hypertensive Retinopathy
Systemic hypertensive vascular changes can affect the retinal vessels. 10 Hypertensive retinopathy initially involves narrowing of the retinal arterioles. In prolonged systemic hypertension, the retinal vessels become arteriolosclerotic. Fibrosis in the vessel wall and perivascular tissue causes further narrowing.

As the sclerotic process advances, the arterioles change color, first exhibiting increased luster, then changing to copper, then silver. Ultimately the arterioles take on a cord like appearance with no apparent bloodstream. They’ll also show focal constriction representing sclerosis from prolonged diastolic pressures of 110mm Hg or higher. 11.

You’ll also see arteriovenous crossing constrictions. As the sclerotic arteriole crosses a weak–walled venule, it compresses that venule. This impedes drainage and can contribute to a branch vein occlusion.

Later stages of hypertensive retinopathy will reveal flame–shaped hemorrhages in the nerve fiber layer. Arteriolar occlusion with subsequent cotton wool spots will also occur within the nerve fiber layer.

Macular edema may develop in hypertensive retinopathy, but tends to be self–limiting, and is amenable to photocoagulation. Edematous residue in the form of a macular exudative star signals advanced, long–standing hypertension. Disc edema often accompanies malignant hypertension. We don’t fully understand its cause. In some cases it may be due to increased intracranial pressure. Edema of the disc and surrounding retina, often with an accompanying macular star, is a medical emergency.

Managing hypertensive retinopathy involves little direct intervention. If there’s persistent macular edema, refer the patient for photocoagulation. Also refer to a primary care physician to manage the hypertension.

Retinal Vein Occlusion
Retinal vein occlusions manifest in four forms: central retinal vein occlusion (CRVO), hemi–central retinal vein occlusion (HRVO), branch retinal vein occlusion (BRVO) and papillophlebitis.
CRVO and HRVO develop in similar ways: The central retinal vein compresses while passing through the lamina cribrosa, blocking drainage from the retina. The cause of this blockage is thought to be thrombosis due to compression from a sclerotic central retinal artery, altered blood flow or a combination of these factors. BRVO develops when a sclerotic retinal arteriole compresses a thin–walled venule, blocking drainage. 12 Papillophlebitis is essentially a CRVO in a young, healthy adult, the difference is that papillophlebitis is thought to develop from an inflammatory process. 13, 14.

CRVO appears as dilated, tortuous veins in all four retinal quadrants, deep retinal dot and blot hemorrhages, superficial NFL hemorrhages, and macular and disc edema. There may be neovascularization of the disc, retina or iris. Retinal exudates and collateral vessels on the optic disc are also common. 15, 16 Papillophlebitis and HRVO share this appearance, though the latter involves only half the retina. 13–17 BRVO affects only one quadrant, 15, 16 and the hemorrhaging tends to be triangular with its apex at an A–V crossing.

In these vein occlusions the major vessels themselves do not leak. Rather, the leakage comes from the thin–walled retinal capillaries draining into the major vessels. A profound occlusion can destroy the integrity of the retinal capillaries. The subsequent ischemia puts the patient at risk for neovascularization. In ischemic CRVO, patients are likely to develop iris neovascularization and neovascular glaucoma. 18 In ischemic HRVO and BRVO, patients tend to manifest neovascularization on the optic disc and retina, this raises the risk of vitreal hemorrhage and tractional retinal detachment. 19, 20 Papillophlebitis rarely develops any noticeable ischemia. In rare case where there is marked ischemia, the condition behaves much like ischemic CRVO. 13, 14.

Macular edema is the most common cause of vision reduction in retinal vein occlusions. In BRVO or HRVO, macular edema is amenable to argon laser photocoagulation, but in many cases it resolves without treatment. Clinicians usually wait at least three months before taking this step. If the edema persists beyond 18 months, however, it will permanently disrupt the RPE with irreversible vision loss, and photocoagulation will bring no benefit. 21, 22.

As for macular edema in CRVO, doctors used to treat it with argon laser photocoagulation. Research shows this treatment doesn’t improve vision in these patients. 23

Ischemic vein occlusions with neovascularization require panretinal photocoagulation to prevent severe vision loss. Clinicians once used prophylactic laser treatment to prevent neovascularization. Recent research, however, indicates you should monitor for neovascularization, and only then refer for treatment. 24.

The best way to assess ischemia in retinal vein occlusions is fluorescein angiography. However, wait several weeks after the occlusion appears to allow the hemorrhages to clear. Visual acuity and pupil testing can lend insight. If there’s an APD and vision worse than 20/200, the occlusion is likely ischemic. 25.

Visual acuity reduction of 20/200 or worse may be due to macular edema and hemorrhage. Otherwise, the most likely cause is macular infarction and destruction of the perifoveal capillary network. Angiography will show an enlarged foveal avascular zone and hypofluorescence beyond the macular region. Visual loss in these cases is irreversible.

Patients with retinal vein occlusions have a higher incidence of systemic disease, particularly vascular conditions. Refer to a primary care physician for evaluation. 26–28.

Retinal Artery Occlusion
Retinal artery occlusions manifest in two forms: central (CRAO) and branch (BRAO). In both, an embolism dislodges from an ulcerated, thrombosed carotid artery or from the heart. The embolus may then migrate to the eye and lodge in either the central or a branch retinal artery. Profound ischemia results. 29 Up to 10 percent of CRAO cases occur because inflammatory cells in giant cell arteritis infiltrate the vessel wall. Two–thirds of these cases progress to bilateral involvement within hours to days. 30, 31 Patients over 60 require a sed rate.

CRAO causes a sudden, painless loss of vision, typically finger counting or barely light perception. You’ll also note an APD. The inner retina will appear edematous and milky–white, as the underlying choroidal blood flow is obscured. You’ll see a “Cherry–red spot” in the macula as some choroidal blood does show through. The retinal edema and opaque appearance disappear over time, leaving a normal looking retina, attenuated retinal arterioles and an atrophic and pale optic nerve. 15, 16.

In BRAO you may see an embolus on ophthalmoscopy. Patients remain asymptomatic if the macula is not affected. Usually, though, they experience a severe reduction of visual acuity and/or field.

There’s little we can do to improve visual outcomes in CRAO or BRAO. In CRAO some doctors have had success dislodging the embolus by anterior chamber paracentisis, compressing the globe or increasing blood CO2 levels–thereby restoring blood flow and function to the retina. Yet, research shows that these measures have no greater effect than no treatment at all.

Retinal artery occlusion carries profound systemic implications, most commonly arteriosclerosis. Others include myocardial infarction, hypertension, carotid artery disease, diabetes, cardiac valve abnormalities and giant cell arteritis. 32, 33 Refer these patients to a cardiologist.

Ocular Ischemic Syndrome
Ocular ischemic syndrome (OIS) involves a constellation of posterior and anterior segment findings, and is commonly mistaken for diabetic retinopathy or CRVO. OIS typically affects the elderly, and is more common in men than women. 34.

OIS involves atheromatous ulceration and stenosis of the carotid artery. Most patients have an underlying disease such as hypertension, diabetes, hyperlipidemia, cardiac disease or clotting abnormalities. Besides carotid artery occlusion, OIS may result from collagen–vascular disease, endarteritis or giant cell arteritis. For patients over 60, order a sedimentation rate for giant cell arteritis.

As perfusion pressure to the eye decreases, several things happen. Blood flow shunts through the external carotid system, leading to a unilateral red eye. Anterior segment ischemia leads to cataract, a breakdown of the blood–aqueous barrier and an anterior chamber reaction. Rubeosis may lead to neovascular glaucoma, but usually won’t because ciliary body ischemia halts aqueous production. Hypotony, due to poor perfusion pressure, is more common.

Retinal findings include mid–peripheral dot and blot hemorrhages, microaneurysms, narrow arterioles and dilated veins. You may see spontaneous arterial pulsation and neovascularization of the disc and retina. 34–36.

The signs mimic non–ischemic CRVO. The biggest difference is that in CRVO the retinal veins are dilated and tortuous, in OIS the veins are dilated but not tortuous (owing to decreased blood flow). OIS is also frequently confused with diabetic retinopathy, especially since these patients are often diabetic. The main difference is asymmetry of disease. Diabetic retinopathy typically develops symmetrically in both eyes, OIS is unilateral in 80 percent of cases, and in the others will show profound retinopathy only in one eye.

OIS may cause anterior segment changes: conjunctival and episcleral injection, anterior chamber reaction, cataract, rubeosis irides (and possibly neovascular glaucoma), corneal edema and keratic precipitates. IOP may either be elevated due to neovascular glaucoma or, more likely, reduced. The eye may be painful due to neovascular glaucoma, ocular angina or dural ischemia.

If you see asymmetric retinopathy, ocular hypotony, asymmetric cataract and/or anterior uveitis in an elderly patient, check for OIS. Ophthalmodynomometry can help by showing reduced perfusion pressure to the eye. Carotid Doppler ultrasound can confirm your diagnosis.

The prognosis for OIS is poor. About 90 percent of patients who develop iris neovascularization from OIS will have finger–counting vision within a year. These patients usually receive panretinal photocoagulation, but the results are poor. 37, 38 OIS patients have about a 40 percent chance of dying within five years, most often from myocardial infarction.

Refer these patients to a cardiologist. Blood thinning therapy with aspirin or warfarin (Coumadin) may have modest success. Carotid endarterectomy is the surgery of choice, but the risks are significant.

Sickle Cell Retinopathy
Seen mostly in blacks, this disease is an inherited disorder involving abnormal hemoglobin, the principal protein of erythrocytes. Normal erythrocytes appear as pliable, biconcave discs, in sickle cell disease they lose their biconcave shape. The sickled cells become rigid and restrict blood flow, causing hypoxia. Tissues deprived of oxygen then undergo pathologic changes.

Sickle cell retinopathy, like diabetic retinopathy, may be proliferative or non–proliferative. Non–proliferative sickle cell retinopathy represents necrosis of retinal vessel walls. Findings include dark–without–pressure, intraretinal (Salmon–patch) hemorrhages, hemosiderin deposits combined with RPE hyperplasia (Black sunburst), venous tortuosity and angioid streaks (with possible choroidal neovascularization).

Proliferative sickle retinopathy results from peripheral arteriolar occlusion. Hypoxia leads to neovascularization with a “Sea fan” appearance. Fibrotic proliferation and scaffolding associated with the neovascularization can lead to vitreal hemorrhage and tractional retinal detachment. 39 Often, the neovascularization will spontaneously regress, leaving a characteristic whitish tuft. 40.

The Sickledex test as well as hemoglobin electrophoresis can be helpful. Non–proliferative retinopathy requires only observation. Refer those with proliferative retinopathy for possible laser treatment.

Retinal Macroaneurysm
Patients with retinal macroaneurysms are typically in the 50–80 age range, female and hypertensive. 41, 42 The condition involves a focal dilatation of a major retinal arterial (or, rarely, venous) branch.

Weakening of the vessel wall leads to the aneurysm. There’s no associated microvasculopathy as seen in diabetic retinopathy, but there is a strong association with hypertension. The condition is less commonly associated with retinal embolization, arteriosclerosis and cardiovascular disease.

Patients are frequently asymptomatic, but if the macula is involved they will present with reduced visual acuity and field. 41, 42 Often there is significant leakage, with exudates and extensive intraretinal or subretinal hemorrhage around it. The vascular dilatation may be obscured by hemorrhage. Fluorescein angiography can aid in this diagnosis. The aneurysm will hyperfluoresce early with a balloon–like appearance.

Asymptomatic, non–leaking macroaneurysms simply require monitoring every 4–6 months. If hemorrhage or exudation occurs but does not threaten the macula, monitor every 1–3 months. If hemorrhage does involve or threatens the macula, or if macular edema persists, photocoagulation may be indicated. The laser treatment scleroses the macroaneurysm but leaves the vessel patent. If a non–hemorrhaging macroaneurysm spontaneously pulsates, photocoagulation may prevent rupture. Since these patients have a predilection for systemic vascular disease, refer for evaluation.

Retinal Telangiectasia
Three conditions involve retinal telangiectasia: Leber’s miliary aneurysm, Coats’ disease and idiopathic juxtafoveal telangiectasia. Each occurs due to abnormal retinal capillaries. Coats’ disease and Leber’s miliary aneurysm share a similar appearance and origin, they may be different forms of the same disease.

Leber’s miliary aneurysm involves an aneurysm and telangiectasia in the retinal periphery. It’s more common in males, and is typically discovered in the first decade of life. In Leber’s, the vessels remain patent with minimal leakage.

When the telangiectatic vessels lead to extensive leakage and exudation, the condition is diagnosed as Coats’ disease. A growth hormone may stimulate these changes, which may explain why most Coats’ disease cases are diagnosed in the first two decades of life. 43.

In Coats’ disease cystic cavities develop in response to a breakdown in the blood–retinal barrier due to the telangiectasis. These cystic cavities fill with proteins and lipids on and below the retina. There’s also a macrophage response, with lipids migrating deep within the retina. This brings subretinal accumulation of exudates and a retinal detachment.

Retinal edema may also be persistent, causing decreased acuity when it reaches the macula. Ischemia may develop as well, with neovascularization and subsequent vitreal hemorrhage and retinal detachment.

Leber’s miliary aneurysm calls for periodic monitoring. Coats’ disease, if left unchecked, will lead to total retinal detachment. Treatment consists of laser photocoagulation or cryoretinopexy to destroy the abnormal vessels, as well as scleral buckling to repair any retinal detachment.

Idiopathic juxtafoveal retinal telangiectasia (IJRT) is not associated with Leber’s miliary aneurysm or Coats’ disease, but may be a variation of the same disease process. IJRT, which is more benign than Coats’ disease, involves a capillary malformation at the edge of the foveal avascular zone. 44.

IJRT may be unilateral or bilateral. The unilateral form only affects men, and typically is not discovered until after age 40–44 Patients with unilateral IJRT are usually asymptomatic. However, leakage may cause macular edema and reduced visual acuity. Fundus assessment often reveals parafoveal dot and blot hemorrhages and, rarely, exudates.

Bilateral IJRT affects women as well as men, typically between ages 40 and 60. The presentation is often symmetrical, and involves retinal edema, parafoveal hemorrhaging, RPE hyperplasia and possibly choroidal neovascularization. Despite these changes, vision tends to be 20/30 or better.

Clinicians frequently overlook IJRT as a cause of retinal edema, parafoveal hemorrhages and exudates. For diabetic or hypertensive patients, doctors often wrongly attribute the parafoveal findings to these diseases. Suspect IJRT when you note parafoveal hemorrhaging, particularly when there is no peripheral hemorrhaging in diabetics, or no systemic ischemic vascular disease.

Occasionally, you may observe the juxtafoveal telangiectasia on ophthalmoscopy. The parafoveal vessels may take an irregular course, like they’re being dragged toward the foveal avascular zone. Angiography will readily reveal the details.

The prognosis of IJRT is excellent. Most cases present only with several isolated, unexplained parafoveal dot and blot hemorrhages. Once you’ve ruled out diabetes, anemia and hypertension as possible causes, you can simply monitor the condition, particularly if vision is unaffected. In cases of unremitting macular edema, focal photocoagulation may help. Since no systemic conditions are associated with IJRT, you don’t need to refer to a primary care physician.

Many systemic diseases manifest in readily observable retinal vascular changes. By understanding the complexities of retinal vascular disease, you can take steps to reduce morbidity not only to the eye, but to the patient as a whole.

Dr. Sowka is an associate professor at the Nova Southeastern University College of Optometry. Dr. Kabat is an assistant professor there.