Young woman experiences gradual vision loss

Retinal vasculitis was observed during examination of the right eye.

Issue: August 25, 2016

ByEmily C. Wright, MD

ByCaroline R. Baumal, MD

A 21-year-old African-American woman presented to our hospital with a gradual decline in vision in both eyes over the past 2.5 years. She had been lost to all medical and ophthalmic care during this period of time. We will initially withhold her medical history for the purposes of diagnostic discussion.

On presentation, best corrected visual acuity was 20/100 in the right eye with pinhole to 20/40 and 20/50+ in the left eye with no improvement with pinhole. The patient’s current glasses prescription was –3.25, +0.75 @30 in the right eye and –3.25 sphere in the left eye. IOP was 28.5 mm Hg in the right eye and 24 mm Hg in the left eye. Pupils were symmetrically round and reactive to light with no relative afferent pupillary defect in either eye. She was able to see six out of six Ishihara color plates in the right eye and five out of six in the left eye. Confrontation to visual fields was full in the right eye, but she demonstrated generalized peripheral constriction in the left eye.

Anterior segment exam was significant for trace nuclear sclerosis and trace to 1+ posterior subcapsular cataracts in both eyes, although greater in the left. Dilated fundoscopy (Figure 1) revealed saucerized optic nerve heads in both eyes, with approximate cup-to-disc ratios of 0.6 in the right eye and 0.85 in the left eye. There was temporal pallor of the optic nerve in the left eye. The retinal vessels were sclerotic in both eyes. There were cotton wool spots in the posterior pole of the right eye and macular atrophy in the left eye. No vitritis was seen in either eye.

OCT revealed significant inner retinal atrophy of both maculas; this was slightly worse in the left eye (Figure 2). Figure 3 is an OCT through one of the cotton wool spots in the right eye posterior pole. Fluorescein angiography (FA) with transit of the right eye demonstrated blocking in the areas of the cotton wool spots as well as macular and perifoveal vasculitis with adjacent areas of non-perfusion in the late frame. FA of the left eye was unremarkable (Figure 4).

These findings were concerning for an underlying systemic etiology, prompting a thorough review of systems. Review of systems was positive for fatigue, chest pain, headaches, a rash on her foot and “joint soreness.” She denied any shortness of breath, cough, oral or genital ulcers, or hearing loss. She also denied any recent travel, risky sexual activity and illicit drugs. Blood pressure was obtained in the clinic; it was 108/70.

Figure 1. Fundus photos (right eye on left, left eye on right).

Figure 2. OCT of the macula (right eye on left, left eye on right).

Figure 3. OCT through cotton wool spot in right eye.

Figure 4. Fluorescein angiography. FA of the right eye (transit) showing macular and perifoveal vasculitis with adjacent areas of non-perfusion in the late frame (left). FA of the left eye was unremarkable (right).

What is your diagnosis?

Occlusive retinal vasculitis

The differential diagnosis of an occlusive retinal vasculitis includes inflammatory/autoimmune, infectious and hematologic causes. Highest on our differential was systemic lupus erythematosus. Other potential inflammatory causes of our patient’s clinical findings included anti-phospholipid antibody syndrome, polyarteritis nodosa, dermatomyositis, Churg-Strauss syndrome, granulomatosis with polyangiitis (Wegener’s) and inflammatory bowel disease (Crohn’s disease, ulcerative colitis). We did not include Behçet’s disease or sarcoidosis as these patients often typically have some degree of vitritis. Potential infectious etiologies of an occlusive retinal vasculitis include syphilis, tuberculosis, Lyme and HIV/CMV. Leukemia must also be considered in the hematologic category, but this was lower on the differential.

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Now, to reveal what we previously withheld, the patient’s medical history was significant for systemic lupus erythematosus (SLE) that was diagnosed at age 15 years. She had a history of lupus-related complications including carditis, nephritis and central nervous system (CNS) vasculitis. She was previously treated with Plaquenil (hydroxychloroquine), cyclophosphamide and prednisone, but she admitted to noncompliance with these medications. Her ocular history was significant for previous episodes of ischemic retinopathy secondary to SLE. She had developed ocular hypertension in the past, for which she was prescribed Alphagan ophthalmic drops (brimonidine tartrate ophthalmic solution, Allergan), with which she was also noncompliant. Given the patient’s medical and ocular histories, she was determined to have a flare of her SLE in the setting of poor compliance, with active vaso-occlusive maculopathy in the right eye.

Workup and management

The patient was admitted to the internal medicine service for further workup and management. Her laboratory workup revealed mild normocytic anemia, normal platelets, normal BUN and creatinine, normal ESR (36), ANA titer of 1:320, elevated anti-DS DNA, slightly elevated RF (22), low C3 and C4, elevated anticardiolipin IgG (IgM normal), positive silica clot time, normal beta 2 glycoprotein IgG and IgM, and negative QuantiFERON. These laboratory values placed the patient at high risk for developing antiphospholipid antibody syndrome (APAS). Based on the APAS diagnostic criteria, if she were to develop a thrombus, thrombocytopenia or recurrent miscarriages, she would meet the clinical criteria for APAS and anti-coagulation with Coumadin (warfarin, Bristol-Myers Squibb) should then be recommended.

During her admission, the patient had a normal chest X-ray without evidence of pericarditis, a normal EKG and a normal transthoracic echocardiogram. However, an MRA of her brain revealed multiple focal areas of narrowing within the anterior cerebral, middle cerebral and posterior cerebral arteries bilaterally. These findings were suggestive of a CNS vasculitis (Figure 5). MRI of her brain did not reveal any abnormal parenchymal or leptomeningeal enhancement.

Figure 5. MRA of the head showing multiple foci of narrowing of the cerebral arteries.

The patient was given a stress dose of steroids — Solu-Medrol (methylprednisolone) 1 g intravenously daily for 3 days. She was then transitioned to oral prednisone 15 mg twice daily. She was also started on CellCept (mycophenolate mofetil, Genentech), Plaquenil, a low dose of aspirin and Combigan ophthalmic drops (brimonidine tartrate 0.2%/timolol maleate 0.5% ophthalmic solution, Allergan) in both eyes. Following discharge from the hospital, she has continued to follow closely with our eye clinic as well as with her rheumatologist. Her vision has now improved to 20/30 in both eyes. She was thought to have developed a steroid response in both eyes, but her IOP has been well controlled since starting the Combigan eye drops. One of the neuro-ophthalmologists felt that the optic nerve pallor in the left eye was due to a combination of glaucomatous optic neuropathy as well as optic atrophy secondary to SLE. Her retinal exam continues to reveal atrophic and sclerotic retinal vessels consistent with prior episodes of ischemic retinopathy, but she has not developed any subsequent episodes of active vaso-occlusive vasculitis in either eye.

Discussion

SLE retinopathy is reported in the literature to occur in 3% to 29% of all patients with a diagnosis of SLE, with severe vision loss developing in 55% of those patients who develop a retinopathy. Typical clinical findings include cotton wool spots, intraretinal hemorrhages, possible optic disc edema, retinal vasculitis and oftentimes no vitritis. The main risk factors for permanent vision loss in these patients are the development of neovascularization and retinal vein occlusions. Associated risk factors for developing retinal involvement in SLE patients are a positive anticardiolipin AB, CNS involvement and elevated creatinine level. The pathogenesis of SLE retinopathy is unclear; one proposed theory is immune complex deposition in the retinal vessel walls with ensuing complement activation and fibrinoid degeneration, resulting in thrombosis and vessel leakage. The role of immunosuppressive and immunomodulatory agents in preventing further progression of retinal ischemia is not fully understood.

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There are thought to be two forms of SLE retinopathy: mild retinopathy, which is typically not vision-threatening, and severe vaso-occlusive retinopathy, which is vision-compromising. A review article by Au and colleagues included 63 cases with severe vaso-occlusive retinopathy secondary to either SLE or APAS. They found that among these patients, SLE was typically associated with positive anti-phospholipid antibodies and a possible concomitant diagnosis of APAS. Among those patients with APAS, anti-coagulation with aspirin alone was found to be ineffective in reducing the rate of recurrent thrombosis. Furthermore, among these patients, it was noted that the discontinuation of Coumadin was associated with increased risk of further thrombosis and even death. In patients with severe vaso-occlusive retinopathy, vaso-occlusion with subsequent neovascularization is generally irreversible despite initiating immunosuppression or immunomodulatory therapy. Fifty-five percent of these patients developed a best corrected visual acuity worse than 20/200, and 41.3% developed neovascularization or vitreous hemorrhage. Panretinal photocoagulation was performed in 22 of 26 eyes, of which 12 showed regression of neovascularization and stabilization of vision. Lastly, 51.1% of patients with severe vaso-occlusive retinopathy developed CNS disease, as with our patient.

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For more information:
Emily C. Wright, MD, and Caroline Baumal, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.
Edited by Jessica Moon, MD, and Emily C. Wright, MD. They can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston MA 02111; website: www.neec.com.