Case of the Month

Edited by Robert N. Johnson, MD

Case History

83 year-old Caucasian man with history of pseudophakia (performed 2.5 years prior), primary open angle glaucoma OU managed with timolol and latanoprost, chronic kidney disease stage III, hyperlipidemia, idiopathic thrombocytopenia, rheumatic heart disease with severe aortic stenosis s/p transcatheter aortic valve replacement (TAVR) with Edwards Sapien 3 valve 3 months prior, presents to primary ophthalmologist 3 days after awakening with sudden onset, painless, superior visual field loss. He was found to have retinal changes on fundus exam and referred to our clinic for consultation.

On examination, visual acuity was 20/20 and 20/32 in right and left eyes, respectively. Intraocular pressure was 17 and 29. He was confirmed to have superior visual field deficit on confrontational testing. Anterior segment exam was only remarkable for mild bilateral posterior capsular opacity. Posterior segment exam revealed soft drusen in the right eye. The left eye revealed clear media, few peripapillary and inferior disc hemorrhages with blurred inferior disc margin, nasal macular edema, and hemorrhages along the inferotemporal arcade associated with retinal whitening and edema, and boxcar segmentation of the arterioles and venules (Figures 1 and 2).

Figure 2: SD-OCT horizontal scan through the left macula. Note the marked retinal swelling as well as hyperreflectivity of the inner retina on the nasal side of the macula.

Differential Diagnosis: Branch retinal artery occlusion, Branch retinal vein occlusion, Combined Branch retinal artery and vein occlusion, giant cell arteritis.

Additional History and Diagnosis

Patient denied any of the cardinal symptoms of giant cell arteritis, such as temporal headache, scalp tenderness, jaw claudication, proximal muscle tenderness, unexplained weight loss. Given his clinical presentation and exam findings, patient was diagnosed with BRAO associated with retinal vein occlusion. An anterior chamber paracentesis was performed and the patient was counseled regarding his diagnosis. Urgent cardiac and carotid evaluation for a source for possible embolus was recommended and follow up scheduled for 1 week. He was urged to return immediately should he have recurrence of similar symptoms

Five days later, our patient presented to the local ophthalmologist with further vision loss in the left eye and new symptoms in the right eye for 1 day. He now had keratic precipitates in his left cornea and retinal hemorrhages in his right eye per phone call from the referring ophthalmologist. A diagnosis of acute retinal necrosis was made over the phone and a recommendation for the patient to be started on 2 gram of Valtrex TID and to return to our office urgently for re-evaluation. He began the oral Valtrex that evening and elected to return to our office the next morning. His visual acuity was measured to be 20/32-2 and HM, in the right and left eyes, respectively. Intraocular pressure was normal. However, he now showed mild anterior chamber inflammation with inferior pigmented keratic precipitates in the left eye. Fundus exam of right eye now revealed intraretinal hemorrhages at the macula and peripheral vascular sclerosis. The left eye showed mild vitreous haze, severe optic nerve swelling with peripapillary hemorrhages, severe macular edema, and diffuse vascular sheathing with scattered peripheral intraretinal hemorrhages. (Figures 3-5)

Figures 3A and B: Fundus photos of the right and left eye. Note the diffuse retinal opacification, particularly in the left eye, with areas of retinal hemorrhage, sheathing, vascular segmentation and in the left eye, significant optic nerve swelling and media haze.

Figures 4A and B: Wide-field fluorescein angiography of the right and left eyes. Note the extensive areas of vascular nonperfusion, and vasculitis.

Figures 5A and B: SD-OCT of the right and left macula. Note the areas of inner retinal hyperreflectivity in the right eye. The left macula shows extensive edema and progression of the inner retinal hyperreflective changes.

Modified Differential Diagnosis

• Bilateral Acute retinal necrosis
• Giant cell arteritis
• Syphilitic retinitis
• Acute multifocal hemorrhagic retinal vasculitis
• Cytomegalovirus retinopathy
• Progressive outer retinal necrosis syndrome

Additional History and Diagnosis:

Patient denied prior exposure to sexually transmitted infections, a recent herpes zoster vaccination, history of depressed immunity, and again any symptoms of giant cell arteritis. We performed bilateral diagnostic anterior chamber paracentesis to screen for viral PCR in clinic, and admission for intravenous acyclovir and intravitreal injections of ganciclovir. The admitting team ordered MRI/MRA brain that found no evidence of cerebral vasculitis, but revealed numerous incidental chronic microhemorrhages concerning for chronic hypertension or chronic emboli, as well as 3 foci of enhancement concerning for subacute embolic ischemia. Subsequent transthoracic echocardiogram found normal left and right ventricular function and functional replacement aortic valve. Carotid ultrasonography found mild atherosclerosis and stenosis. Inpatient serum workup was negative for HIV-1 and 2, ANCA vasculitides, RPR, FTA-ABS, quantiferon gold. Patient had mildly elevated ESR and normal CRP. Several days later, aqueous samples returned positive for HSV-1. Despite systemic and local antiviral treatment, the patient’s vision rapidly declined to HM bilaterally over the course of the next 24 hours. He was continued on IV acyclovir for 1 week and oral prednisone 40 mg added after 36 hours. On sequential follow-up exams, the fundus appearance was most consistent with bilateral posterior outer retinal necrosis.

Discussion:

Urayama  et al first reported in 1971 of 6 patients with acute panuveitis and retinal arteritis progressing to diffuse necrotizing retinitis and late-onset rhegmatogenous retinal detachment.¹ In 1994, the Executive Committee of the American Uveitis Society defined the acute retinal necrosis (ARN) as  (1) one or more discrete foci of retinal necrosis in the periphery, (2) rapid disease progression in the absence of therapy, (3) circumferential spread, (4) occlusive arteriolar vasculopathy, and (5) a prominent vitreous or anterior chamber inflammatory reaction.²

Progressive outer retinal necrosis was first described in 1990 as a rapidly progresive retinitis noted in two patients with HIV/AIDS and concurrent systemic herpes zoster infection.⁶ Both entities are most commonly caused by herpes zoster, but can also be caused by herpes simplex virus 1 and 2, and rarely cytomegalovirus and Epstein Barr virus. Previously, ARN and PORN were considered distinct entities, with ARN classically associated in immunocompetent patients, and PORN in immunocompromised individuals. However, more recent literature suggests these entities belong in a spectrum of necrotizing herpetic retinopathies, with mild or classic ARN on one end in patients with undetectable or slight immune dysfunction to PORN in severely immunosuppressed patients, and with intermediary forms between these extremes.⁷

Necrotizing herpetic retinopathy classically manifests as multifocal areas of retinal whitening in the periphery that later become confluent and spread posteriorly. ARN tends to spare the macula, but PORN frequently involves the macula. Perivascular infiltration, vascular occlusion, and hemorrhage is typically seen in conjunction with the retinal whitening. Anterior uveitis, vitreous inflammation, pain, ocular hypertension, and optic neuritis is commonly observed in ARN. Occasionally, the occlusive vasculitis may affect the major retinal and posterior ciliary arteries first prior to observed necrotizing retinitis. These patients may present with vision loss initially due to branch or central retinal artery occlusion.

References:

1. Urayama A, Uamada N, Sasaki T, et al. Unilateral acute uveitis with periarteritis and detachment. Jpn J Clin Ophthalmol. 1971;25:607-619
2. Holland GN. Executive committee of the American uveitis society. Am J Ophthalmol. 1994;117:663-667
3. Agarwal, A. Gass’ Atlas of Macular Diseases pg 900-908
4. Chang S, Young LH. Acute retinal necrosis: an overview. International ophthalmology clinics. 2007 Apr 1;47(2):145-54.
5. Ryan, S. Retina. Pg 1523-1529
6. Forster DJ, Dugel PU, Frangieh GT, Liggett PE, Rao NA. Rapidly progressive outer retinal necrosis in the acquired immunodeficiency syndrome. American journal of ophthalmology. 1990 Oct 1;110(4):341-8.
7. Guex-Crosier Y, Rochat C, Herbort CP. Necrotizing herpetic retinopathies A spectrum of herpes virus-induced diseases determined by the immune state of the host. Ocular immunology and inflammation. 1997 Jan 1;5(4):259-66.