Systemic Hypertension:

Systemic hypertension, defined as systolic blood pressure of 140 mmHg or greater or diastolic blood pressure greater than 90 mmHg, affects more than 50 million adults in the United States today (17). Persistent elevation of the arterial pressure can result in lesions of the brain, heart, kidneys and eye. Narrowing of the retinal arterioles is the hallmark sign of hypertension and is almost always bilateral (1). Retinal hemorrhages, cotton-wool spots, and lipid exudates may also develop when hypertension is severe.

Prolonged systemic hypertension causes arteriosclerotic changes of the retinal vessels, which result in focal narrowing and constriction. As the sclerotic process advances, the arterioles undergo a color change from bright red to copper. Further progression can result in a silver appearance indicating sclerosis from prolonged increase in diastolic blood pressure. Thickening of the arteriole wall will affect the appearance of the arteriovenous crossing. At the site of crossing, the arteriole and venule share a common adventitial sheath. Vascular sclerosis causes compression of the underlying lumen of the venule resulting in "A/V nicking" (Fig. 1), or a tapering of a venule on either side of the crossing junction. Compression of the venule (Gunn's sign) can vary from mild to more severe. Although extremely rare, such compression has been reported to result in complete interruption in the blood column (20). In more common cases, the degree of vascular compression may impede blood flow and induce some degree of ischemia. Circulatory compromise seen in the later stages of hypertensive retinopathy may induce formation of microaneurysms, nerve fiber layer hemorrhages, cotton-wool spots, capillary nonperfusion, optic nerve head edema, macular edema, and the development of a collateral vascular system.

Fig. 1: A/V NICKING ALONG THE SUPEROTEMPORAL ARCADE IN A HYPERTENSIVE INDIVIDUAL

Vascular Occlusive Disease:

Branch retinal vein occlusion (BRVO) affects men and women equally and is seen most frequently between the ages of 60 to 70. The development of a branch retinal vein occlusion is typically of sudden onset. Patients may therefore present with blurred vision or a visual field defect with the visual symptoms directly related to the location of the retina that has been affected; A branch retinal vein occlusion can also present asymptomatically on a routine fundus evaluation.

The location of the venous blockage determines the pattern of retinal hemorrhage that develops. A blockage that occurs near the optic nerve may present with retinal hemorrhage involving two quadrants of the fundus, whereas a blockage occurring distal to the optic nerve will be seen as a sector of retinal hemorrhage. Fortunately, a branch retinal vein occlusion is most commonly unilateral, although up to 10 percent of patients may develop a branch retinal vein occlusion in the fellow eye. Vision limiting complications of a branch vein occlusion include macular edema, macular nonperfusion or fundus ischemia elsewhere and retinal hemorrhage (12). Vitreous cavity hemorrhage may also be seen secondary to retinal neovascularization.

The classic clinical appearance of a branch vein occlusion is a sectoral area of retinal hemorrhage extending distally from the point of the venous obstruction. The most common quadrant affected is the superotemporal quadrant of the retinal vasculature (Fig. 2). Visual acuity depends on the extent of the vascular occlusion and whether it involves the central macular area.

Fig. 2: SECTOR OF HEMORRHAGE CONSISTENT WITH A BRANCH RETINAL VEIN OCCLUSION
 

The management of a branch retinal vein occlusion is two-fold. The first area to address is to try to determine why the occlusion has occurred. As systemic hypertension is the most common background factor for venous occlusions, the blood pressure should be measured. If the blood pressure is elevated, further care should be coordinated with the primary care physician for control.

Care of the eye itself is the second principal area to manage with a venous occlusion. Guidelines for laser treatment have been published by the Branch Vein Occlusion Study Group. Formal study results have proven the value of laser photocoagulation for macular edema (Fig. 3) and/or retinal ischemia to control neovascularization. The criteria for laser treatment include visual acuity of 20/40 or worse secondary to macular edema of greater than three months' duration. In this circumstance, macular grid laser photocoagulation is recommended (3). Furthermore, laser therapy is advised to control potential neovascularization in patients who have greater than 5 disk diameter of capillary nonperfusion as seen clinically or angiographically (4).

Fig. 3: FLUORESCEIN ANGIOGRAM ILLUSTRATING POOLING OF FLUORESCEIN DYE IN THE CENTRAL MACULA
 

Central Retinal Vein Occlusion:

A central retinal vein occlusion (CRVO) is a condition with potentially blinding complications. Up to 80 percent of central retinal vein occlusions are thought to be associated with systemic hypertension (10). In contrast to a branch retinal vein occlusion, the retinal hemorrhages in a central retinal vein occlusion will involve all four retinal quadrants because the causal mechanism is secondary to a thrombosis at the level of lamina cribrosa (21). The clinical appearance does vary from a few scattered retinal hemorrhages and cotton-wool patches to a marked hemorrhagic appearance with or without optic nerve head edema. The onset of vision loss is most always sudden in nature.

There are two principal categories of a central retinal vein occlusion. The first type is nonischemic, and the second is ischemic (10). The differentiating factors that are used for this classification involve clinical appearance, visual acuity, pupillary testing, and intravenous fluorescein angiography. The two types of a central retinal vein occlusion have differing clinical characteristics, visual prognoses, management, and follow-up recommendations.

A nonischemic central retinal vein occlusion is characterized by modest intraretinal dot-and-blot hemorrhages in all four retinal quadrants, with intraretinal edema and varying degrees of macular edema (Fig. 4). The entering visual acuity may vary depending on the degree of macular edema.

Fig. 4: A NONISCHEMIC CENTRAL RETINAL VEIN OCCLUSION

An ischemic central retinal vein occlusion will have a significant amount of intraretinal dot-and-blot hemorrhages. The hemorrhages are typically larger and are usually accompanied by a marked degree of intraretinal edema. Numerous cotton-wool spots and striking macular edema are typically present (Fig. 5). Retinal neovascularization may also be evident on the surface of the optic nerve or elsewhere. Vitreous cavity hemorrhage may in turn be present, secondary to retinal neovascularization.
 

Fig. 5: AN ISCHEMIC CENTRAL RETINAL VEIN OCCLUSION WITH MARKED RETINAL HEMORRHAGE AND OPTIC NERVE SWELLING

The visual prognosis of CRVO is variable. One can expect a better visual acuity and prognosis in a nonischemic CRVO compared to that of an ischemic CRVO. Severe vision loss secondary to neovascular glaucoma has been reported to occur in up to 20 percent of all CRVO cases (15). Neovascularization of the iris occurs as a result of retinal hypoxia with progression of the iris neovascularization resulting in a blockage of the trabecular meshwork and subsequent development of increased intraocular pressure. Baseline fluorescein angiography can be quite helpful in determining if a CRVO is ischemic, as well as predicting the development of iris neovascularization and secondary neovascular glaucoma.

Arteriole Obstruction:

Retinal artery obstruction is caused typically by an embolus derived from a proximal source which lodges in the lumen of a retinal vessel. The underlying systemic etiology for an arteriole obstruction is most commonly systemic hypertension, but diabetes, carotid occlusive disease and cardiac valvular disease may result in emboli as well. It has been noted that systemic hypertension is present in about two thirds of patients with an arteriole obstruction (5). Diabetes is seen in approximately 25 percent of cases (5,1) and carotid occlusive disease in up to 45 percent (19). Cardiac valvular disease is noted in approximately 25 percent (5,1). Not only is an arteriole obstruction sight threatening, the underlying systemic condition can be life threatening as well.

Branch Retinal Artery Occlusion:

A branch retinal artery occlusion (BRAO) most commonly affects the superior temporal branch of the central retinal artery (18). It appears ophthalmoscopically as an area of superficial retinal whitening along the distribution of the occluded arteriole (Fig. 6). The visual prognosis with a branch retinal artery occlusion is typically better than that of a central arteriole occlusion. Approximately 80 percent of eyes with a branch retinal artery occlusion seem to stabilize with central visual acuity of 20/40 or better; however, residual visual field defects remain (7).

Fig.6:BRANCH RETINAL ARTERY OCCLUSION

A person who develops a branch retinal artery occlusion may present with visual symptoms of a sudden onset. The area of circulation compromise and retinal involvement will determined the character of the scotoma and vision loss. If the fovea and papillomacular bundle is intact, the central visual acuity may remain normal.

The systemic workup for a branch retinal artery occlusion should include testing such as fluorescein angiography and carotid Doppler evaluation to attempt to identify the underlying source of the emobli.

Central Retinal Artery Occlusion:

The incidence of central retinal artery occlusion (CRAO) is approximately 1 in 10,000 adults with an average age between 60 and 65 (5). A person who develops a central retinal artery occlusion typically presents with a history of sudden painless vision loss of the eye. Often patients may describe episodes of amaurosis fugax prior to their sudden vision loss.

The clinical features of a central retinal artery occlusion depend on the elapsed time of the occlusive event. Early changes include narrowing of retinal arterioles and retinal edema which appears as a whitish haze. The white color of the retina contrasts with the underlying choroidal perfusion in the central macular area resulting in the "cherry red spot" (Fig. 7) which is pathognomonic for a central retinal artery occlusion. The retinal veins may appear segmented - termed "venous beading" - which indicates the reduction of retinal blood flow overall.

Fig. 7: CLASSIC CHERRY-RED SPOT IN A CENTRAL RETINAL ARTERY OCCLUSION
 

As the duration of the central retinal artery occlusion lengthens, re-canalization of the artery occurs and the retinal whitening resolves. The fundus may subsequently appear normal, although optic atrophy and retinal vascular attenuation may exist.

Chronic ischemia from a CRAO may persist in some patients. Although the incidence of neovascular glaucoma secondary to rubeosis iridis has been reported as rare, more recent studies show that the development of rubeosis iridis may be as high as 18.2 percent (2). Although Rubeosis iridis may develop at any time the most common time frame is two weeks to three months after the central retinal artery occlusion.

The visual prognosis for central retinal artery occlusion is poor and depends on immediate initiation of therapy. The standard protocol for a central retinal artery obstruction is to rapidly lower the intraocular pressure by means of topical and systemic agents. An anterior chamber paracentesis is recommended for arteriole obstructions less than 24 hours old (11). In this procedure a 30-gauge needle is inserted into the anterior chamber and 0.1 to 0.4 ml of aqueous is removed to immediately lower intraocular pressure in hopes that the systemic perfusion pressure will dislodge the obstructing embolus. Unfortunately, irreversible retinal damage has been shown to occur after 90 minutes of a complete central retinal artery occlusion (11). Other therapeutic measures include ocular massage with a Goldmann contact lens or digital pressure; and the inhalation of oxygen-carbon dioxide gas mixtures in an effort to stimulate vasodilation. Having the patient breath into a paper bag to cause inhalation of carbon dioxide has also been advocated in the past in an effort to promote retinal vasodilation and increased blood flow (8).

Systemic workup for patients who suffer an embolic occlusion of a retinal arteriole should include testing to rule out undiagnosed hypertension, a carotid duplex scan (Doppler) search for carotid stenosis, and an echocardiogram for possible cardiac valvular disease. Laboratory testing should include evaluation for diabetes. Although an arteriole obstruction is typically embolic, local obstruction from vessel inflammatory disease can also occur. Conditions such as temporal arteritis may be present, so a Westergren sedimentation rate should also be performed. A systemic abnormality can be found in up to 90 percent of patients (5,7). Aspirin therapy should be considered in patients of the atherosclerotic cardiovascular age group when the systemic workup is negative.

Carotid Occlusive Disease/Ocular Ischemic Syndrome:

The most common manifestation of carotid occlusive disease is that of retinal emboli or an arteriole occlusion. Significant carotid stenosis can result in the development of "the ocular ischemic syndrome." Kearns and Hollenhorst initially reported this occurring secondary to an obstruction of the carotid artery in 1963 (13).

The ocular ischemic syndrome rarely develops in young patients, with 65 being the mean age of affected. Males tend to be at a 2:1 greater risk than females, and bilateral involvement occurs up to 20 percent of the time (6).

Vision loss is the most common symptom of the ocular ischemic syndrome. The onset of vision loss is typically gradual and may appear over weeks to months, but it is severe in up to 90 percent of patients at the time of presentation (6). In addition, up to 40 percent of patients may present with ocular pain described as a dull ache over the eyebrow which radiates to the temple. This is thought to develop secondary to ischemia of the globe and/or neovascular glaucoma. About two thirds of the eyes with the ocular ischemic syndrome will present with rubeosis iridis and flare in the anterior chamber at the time of initial examination (6).

Retinal findings of the ocular ischemic syndrome include arteriole constriction, venous dilation, large blot retinal hemorrhages, retinal neovascularization and cotton-wool spots. Retinal hemorrhages are seen in up to 80 percent of eyes with the ocular ischemic syndrome and are typically more numerous in the temporal fundus as opposed to the nasal fundus (6). They tend to be less numerous than those found in a central retinal vein occlusion and are almost never confluent. Large, blotchy peripheral retinal hemorrhages should also cause suspicion of underlying retinal ischemia (Fig. 8). These hemorrhages develop secondary to chronically low retinal perfusion as a result of carotid artery stenosis. Slowing of the circulation time causes congestion of the retinal vessels and breakdown of their respective capillary walls. Neovascularization of the optic disc is seen in greater than one third of eyes with the ocular ischemic syndrome (6). The finding of retinal neovascularization or rubeosis iridis in a non-diabetic elderlyindividual should make the clinician suspicious of an underlying ocular ischemic syndrome.

Fig.8: PERIPHERAL RETINAL HEMORRHAGES IN A PATIENT FOUND TO HAVE SIGNIFICANT CAROTID STENOSIS
 

Fluorescein angiography can be a very beneficial diagnostic test to assess carotid occlusive disease. Angiographically, there is a delay in the arm to choroid time of the sodium fluorescein. With normal retinal perfusion, the fluorescein dye is seen to enter the choroidal vasculature in approximately 10 seconds. A patient with carotid stenosis will show a delay in the filling time of the choroidal and retinal vasculature. Normally, the choroidal vasculature is completely filled within five seconds after the initial appearance of the dye but, in a patient with the ocular ischemic syndrome, there can still be large patches of choroidal nonperfusion after 5 seconds. In the later phases of the angiogram, up to 85 percent of patients with the ocular ischemic syndrome will illustrate staining and/or leakage of the retinal vasculature (6)(Fig. 9).

Fig. 9: STAINING OF RETINAL VESSELS INDICATING SEVERE RETINAL ISCHEMIA
 

A patient who is thought to have findings consistent with the ocular ischemic syndrome should undergo ultrasonic carotid imaging. Patients with this syndrome will typically have 90 percent or greater obstruction of the internal carotid artery.

Treatment for the ocular ischemic syndrome varies depending on the presentation. If severe retinal ischemia is present and neovascularization is seen, prompt referral to a specialist is recommended for scattered laser photocoagulation to prevent neovascular glaucoma. Carotid endarterectomy may be the most beneficial treatment in stabilizing vision for a patient with the ocular ischemic syndrome. It is also useful in reducing the risk of stroke (14).

References

1. Appen, RE, Wray, SH, and Cogan, DG: Central retinal artery occlusion, Am J. Ophthalmol 79:374-381, 1975

2. Ausburger, JJ, and Magargal, LE: Visual prognosis following treatment of acute central retinal artery obstruction, Br J Ophthalmol 64:913-917, 1980

3. Branch Vein Occlusion Study Group: Argon laser photocoagulation for macular edema in branch vein occlusion, Am J Ophthalmol 98:271-282, 1984

4. Branch Vein Occlusion Study Group: Argon laser scatter photocoagulation for prevention of neovascularization and vitreous hemorrhage in branch vein occlusion, Arch Ophthalmol 104:34-41, 1986

5. Brown, GC, and Margargal, LE: Central retinal artery obstruction and visual acuity, Ophthalmology 89:14-19, 1982

6. Brown, GC, and Margargal, LE: The ocular ischemic syndrome: Clinical, fluorescein and angiographic and carotid angiographic features, Int Ophthalmol (in press)

7. Brown, GC, Magargal, LE, Shields, JA, Goldberg, RE, and Walsh, PN: Retinal arterial obstruction in children and young adults, Ophthalmology 88:18-25, 1981

8. Frayser, R, and Hickam, JB: Retinal vascular response to breathing increased carbon dioxide and oxygen concentrations, Invest Ophthalmol 3:427-431, 1964

9. Gutman, FA: Evaluation of a patient with central retinal vein occlusion, Ophthalmology 90:481-483, 1983

10. Hayreh, SS: Classification of central retinal vein occlusion, Ophthalmology 90:458-474, 1983

11. Hayreh, SS, Kolder, HE, and Weingeist, TA: Central retinal artery occlusion and retinal tolerance time, Ophthalmology 87:75-78, 1980

12. Joffe, L, Goldberg, RE, Margargal, LE, and Annesley, WH: Macular branch vein occlusion, Ophthalmology 87:91-98, 1980

13. Kearns, TP, and Hollenhorst, RW: Venous-stasis retinopathy of occlusive disease of the carotid artery, Mayo Clin Proc 38:304-312, 1963

14. Kearns, TP, Younge, BR, and Peipgras, DG: Resolution of venous stasis retinopathy after carotid artery bypass surgery, Mayo Clin Proc 55:342-346, 1980

15. Margaral, LE, Brown, CG, Augsburger, JJ, et al: Efficacy of panretinal photocoagulation in preventing neovascular glaucoma following ischemic central retinal vein obstruction, Ophthalmology 89:780-784, 1982

16. Murphy, RP, and Clew, EY: Retina Vol II, Mosby, Chp. 78:449-455

17. National High Blood Pressure Education Program. The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Bethesda (MD): US Department of Health and Human Services. Public Health Service, National Institutes of Health, National Health, Lung and Blood Institute, 1997; NIH Publication No. 98-4080.

18. Sanborn, GE, Margaral LE: Arterial obstructive disease of the eye, in Tasman W (ed): Duane's Clinical Ophthalmology, Vol 3, Philadelphia: JB Lippincott, 14:1-29, 1992.

19. Shah, HG, Brown, GC, and Goldberg, RE: Digital subtraction carotid angiography and retinal arterial obstruction, Ophthalmology 92:68-72, 1985.

20. Tso, MOM, and Jampol, LM: Pathophysiology of hypertensive retinopathy, Ophthalmologica 89:1132, 1982.

21. Zegarra H, Gutman FA, Conforto J: The natural course of central retinal vein occlusion, Ophthalmology 86:1931-1939, 1979.

Questions or concerns about courses should be directed to the individual authors and/or the Continuing Education Department at the College of Optometry at kundart@pacificu.edu.