Case of the Month

Edited by Robert N. Johnson, MD

Figure 1: Color fundus photo montages of the right (1A) and left eye (1B), respectively.  Note in the right eye the venous dilation, without tortuoisity and scattered dot blot hemorrhages mostly in the midperiphery. In the left eye, moderate vascular attenuation and large patches of geographic atrophy in the macula involving the fovea is evident.

Case History

An 86 year-old man presents with intermittent episodes of blurred vision in the right eye for the past few months.  The patient describes the episodes as sudden, lasting 5-10 minutes, occurring a few times a day, and appearing as darkening of the vision.  His past medical history is significant for hypertension, TIA, colon cancer and arthritis.  His medications include aspirin, losartan, hydrochlorothiazide/triamterene, atorvastatin, and levothyroxine.  His past ocular history is significant for a central retinal vein occlusion in the left eye.  Family and social history were noncontributory.

On examination, best-corrected visual acuity was 20/25 in the right eye and 4/200 in the left eye.  Intraocular pressure (IOP) was normal in both eyes.  The anterior segment examination was unremarkable.  The posterior segment examination of the right eye revealed venous dilation without tortuosity and many scattered dot blot hemorrhages in the midperiphery surrounding the posterior pole (Figure 1A).  The central retinal artery in the right eye closed easily to light digital pressure. The fundus exam of the left eye showed moderate vascular attenuation and large patches of geographic atrophy in the macula (Figure 1B) without notable hemorrhage.

Fluorescein angiography of the right eye (Figure 2A) highlighted many microaneurysms scattered throughout the posterior pole as well as blockage from the hemorrhage.  Initial dye appearance in the right eye was delayed somewhat at 19 seconds (Figure 2C). Complete venous filling was prolonged as well and was 36 seconds (Fig 2D). The left eye displayed window defects in the areas of atrophy in the macula (Figure 2B).  Spectral domain OCT (SD-OCT) of the right eye (Figure 3A) exhibited mild vitreomacular adhesion while the SD-OCT of the left eye (Figure 3B) had significant cystoid macular edema.

Figure 2: Fluorescein angiogram montage of the right eye (2A) and left (2B) eye. There is blockage from the hemorrhages as well as hyperfluorescence consistent with many microaneurysms scattered throughout the posterior pole in the right eye. The left eye displayed window defects in the areas of atrophy in the macula. The early phases of the angiogram show delay in dye appearance in the eye (Fig 2C) as well as some delay in complete venous filling (Fig 2D).

Figure 3: SD-OCT of right (A) and left (B) eye.  The right eye has mild vitreomacular adhesion while the left eye has mild macular edema.

Differential Diagnosis

Ocular ischemic syndrome (OIS), diabetic retinopathy, central retinal vein occlusion, hyperviscosity syndromes (Multiple myeloma, leukemia, etc), autoimmune uveitis.

Additional Case History

 Further workup revealed an 80% stenosis of the carotid artery on the right side.  The patient underwent successful carotid endarterectomy (CEA).  Following CEA, the patient noted resolution of his daily episodes of vision loss. Examination showed that the midperipheral hemorrhages in the right fundus quickly resolved (Figure 4).

Discussion

Our case of OIS did not show all of the florid findings of more severe cases, such as rubeosis, anterior segment inflammation, or retinal neovascularization.  While it could be argued that this is a case of a mild central retinal vein occlusion for these reasons, we feel that OIS is a more likely diagnosis due to the distribution of the hemorrhages as well as the type of hemorrhages (dot-blot rather than flame-shaped), the lack of venous tortuosity, no disc edema, and that the central retinal artery closed easily with light digital pressure.  Furthermore, the temporal rapid improvement symptomatically and ophthalmoscopically following CEA also supports our diagnosis.

Ocular ischemic syndrome is an assortment of ocular signs and symptoms that result from severe, chronic arterial hypoperfusion to the eye.  Athlerosclerosis, resulting in carotid stenosis, is the most common cause of OIS, but other published causes include dissecting aneurysm of the carotid, giant cell arteritis, Takayasu arteritis, Behcet’s disease, and trauma.¹ The mortality rate in patients with OIS can be as high as 40% within 5 years, with cardiovascular disease and stroke being the most common causes of death. Referral to internal medicine, cardiology, and neurology is extremely important.¹

 Over 90% of patients with OIS will report vision loss, with 67% reporting gradual loss over weeks to months, 12% over days, and 12% sudden loss over minutes.² However, the classic presentation of amaurosis fugax, where patients experience a darkening or slow black out of vision that returns to normal after a few minutes, only occurs in 10% of affected individuals. Other symptoms include loss of visual acuity, delayed recovery of visual function after exposure to bright light, visual field deficits, and dull eye pain relieved by lying down.¹

 Patients may present with both anterior and posterior segment signs.  Anterior ischemia signs include dilated conjunctival and episcleral vessels, corneal edema, iris atrophy, and iris neovascularization.³ Rubeosis iridis is a poor prognostic sign, with 82% of patients in one study found to have count fingers vision or worse at 1 year.² Despite fibrovascular tissue obscuring the angle, patients with OIS may have normal or low IOP due to ciliary body ischemia and reduced aqueous humor production.  The IOP may then rise acutely following surgical reperfusion, so patients should be monitored closely for neovascular glaucoma following carotid endarterectomy.³ Posterior segment signs include narrowed retinal arteries with venous dilation, hemorrhage, macular edema, central retinal artery occlusion, ischemic optic neuropathy, and retinal neovascularization.

 Ancillary testing, particularly fluorescein angiography, can be helpful in diagnosis.  Patchy or delayed choroidal filling, which is found in 60% of eyes with OIS, or prolonged choroidal filling time, the most specific angiographic sign, are especially supportive but prolonged retinal arteriovenous time, staining of retinal vessels, and macular edema are also often seen.³ Workup for OIS should include blood pressure monitoring, HgA1c, complete blood cell count with differential, serum protein electrophoresis, immunoelectrophoresis, ESR/CRP, carotid Doppler study, echocardiogram and stress test, with or without CTA/MRA of the head and neck to evaluate for treatable causes.

 Carotid endarterectomy is recommended in patients with symptomatic stenosis of 50-99% if the perioperative risk of stroke or death is less than 6% or in asymptomatic stenosis of 60-99% if the perioperative risk of stroke or death is less than 3%.⁴ CEA is clearly most beneficial when performed early before the onset of neovascular glaucoma,⁵ although the overall visual improvement after CEA is minimal.  Carotid artery stenting and extracranial-intracranial arterial bypass surgery have been explored as alternatives to CEA but are poorly studied in OIS.

 Medical therapy for neovascular glaucoma includes intraocular pressure management with topical or surgical therapy, intravitreal injections of anti-VEGF agents, and panretinal photocoagulation or cryotherapy.  While PRP only induces regression of rubeosis in 36% of treated eyes with OIS,³ it appears to reduce the incidence of neovascular glaucoma and improve patient comfort.²

References

1. Terelak-Borys B, Skonleczna K, Grabska-Liberek I. Ocular ischemic syndrome – a systematic review. Med Sci Monit. 2012;18(8):RA138-144.
2. Sivalingam A, Brown GC, Magargal LE. The ocular ischemic syndrome. III. Visual prognosis and the effect of treatment. Int Ophthal. 1990;15(1): 15-20.
3. Mendrinos E, Machinis TG, Pournaras CJ. Ocular Ischemic Syndrome. Surv Ophthal. 2010;55:2-34.
4. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. NEJM. 1991;325:445-53.
5. Mizener JB, Podhajsky P, Hayreh SS. Ocular Ischemic Syndrome. Ophthalmology. 1997;104:859-864.