Ischemic Proliferative Retinopathy as the Presenting Feature of Systemic Sarcoidosis

Abstract

Purpose:

This work reports a case of systemic sarcoidosis presenting with ischemic ocular manifestations without uveitis.

Methods:

This case report describes a 28-year-old White male who presented with pain, redness, and blurry vision of his left eye for 1 month who was found to have proliferative retinopathy and neovascular glaucoma.

Results:

Normal fasting blood glucose and glycated hemoglobin A_1c levels warranted further investigation. Abnormal findings from chest x-ray of hilar lymphadenopathy as well as an elevated angiotensin-converting enzyme level were suggestive of sarcoidosis, and they were further confirmed by histopathology derived through bronchoscopy.

Conclusions:

Systemic sarcoidosis may present with rapidly progressing ischemic retinopathy without signs of inflammation, which may obscure the diagnosis. Such presentation may be misdiagnosed, which may result in delayed treatment and poor outcome.

Introduction

Sarcoidosis is a chronic multisystem granulomatous disease that is histologically associated with noncaseating granulomas along with an elevated angiotensin-converting enzyme (ACE) and lysozyme level. ^{1 -4} Ocular involvement is found in 30% to 60% of patients with sarcoidosis, and the disease manifests most commonly as anterior uveitis. ^4,5

Per the International Workshop on Ocular Sarcoidosis in 2017, there are 7 key signs of ocular sarcoidosis. ⁶ These include mutton-fat granulomatous keratic precipitates and/or iris nodules, trabecular meshwork nodules and/or tent-shaped peripheral anterior synechiae, vitreous opacities, multiple chorioretinal peripheral lesions, nodular or segmented periphlebitis and retinal macroaneurysms, optic disc nodules or granulomas and/or solitary choroidal nodule, and bilateral ocular involvement.

Proliferative retinopathy secondary to sarcoidosis has been reported as a late consequence of ocular sarcoidosis and is usually seen in the final stage of retinal involvement. ⁷ However, it is not a common finding. Jabs and Johns reported that posterior-segment disease was seen in 28% of cases of ocular sarcoidosis. ⁸ Khalatbari published that neovascularization was found in only 5% of posterior segment disease. ⁹ We report a case of ocular sarcoidosis that manifested with proliferative retinopathy without significant active inflammation and absent systemic symptoms.

Methods

Case Report

A 28-year-old White male with no medical or ocular history presented to the emergency department with pain, redness, and blurry vision in his left eye over the prior month. He had no eye discharge, double vision, blind spots, flashes of light, or floaters. He denied any past illnesses or trauma. His family history was significant for diabetes. The right eye had a visual acuity (VA) of 20/20, and findings from anterior-segment and gonioscopy examinations were unremarkable.

The left eye had a VA of 20/200 with an intraocular pressure (IOP) of 41 mm Hg. Pupils were mildly reactive with a relative afferent pupillary defect of the left eye. Color vision was mildly decreased on red saturation test of the left eye. Anterior-segment examination results were significant for 2+ conjunctival injection, trace corneal edema, 1+ flare without cells in the anterior chamber, and diffuse neovascularization of the iris around the pupillary margin. On gonioscopy, the angle of the left eye was grade I to II and had peripheral anterior synechiae up to the trabecular meshwork.

On dilated funduscopic examination, both eyes had venous beading and scattered retinal hemorrhages in all quadrants (Figure 1). Fluorescein angiography was performed, and the right eye was found to have extensive vascular occlusions involving both arteries and veins with venous predominance, profound ischemia, and late leakages (Figure 2). The left eye notably had hazy view due to vitreous hemorrhage.

Figure 1.

Widefield fundus photograph of both eyes shows (A) scattered retinal hemorrhages in the midperipheral retina (black arrowheads) and neovascularization (white arrowhead) in the right eye; (B) the fundus view of the left eye is limited because of vitreous hemorrhage.

Figure 2.

Fluorescein angiography of the right eye (recirculation phase) shows extensive vascular occlusion predominately involving the retinal veins, peripheral nonperfusion and profound ischemia (asterisks), blockage due to hemorrhage, and late leakages from retinal neovascularization (arrowheads).

Based on this examination, the patient was suspected to have proliferative diabetic retinopathy and neovascular glaucoma. However, initial laboratory investigations demonstrated a fasting blood glucose level of 85 mg/dL and glycated hemoglobin A_1c level of 4.9%. Complete blood count and liver function test results were within normal limits. Further investigation demonstrated prominent hilar shadow on chest x-ray. Erythrocyte sedimentation rate, C-reactive protein, coagulation profile, antinuclear antibodies, anti–double-stranded DNA, and hemoglobin electrophoresis findings were within normal limits. Rapid plasma regain and fluorescent treponemal antibody absorption test results were negative. The level of angiotensin-converting enzyme was elevated at 118 units (reference range, 40-60 units).

Intravitreal bevacizumab and IOP-lowering agents were administered, which resulted in improved VA and IOP to 20/125 and 19 mm Hg, respectively. The patient then underwent pars plana vitrectomy with panretinal photocoagulation (PRP) in the left eye. In addition, oral prednisone and azathioprine were initiated for suspected sarcoidosis. One week after the surgery, IOP rose to 40 mm Hg with limited improvement after using IOP-lowering agents and another injection of intravitreal bevacizumab; thus, he underwent a tube shunt implantation in the left eye. The right eye then developed a preretinal hemorrhage and was treated with intravitreal bevacizumab and PRP.

Results

During this course, the patient was referred to the rheumatology and pulmonology departments for evaluation of sarcoidosis. Computed tomography of the chest without contrast was obtained that showed bulky bilateral hilar and mediastinal lymphadenopathy. Lymph node biopsy during bronchoscopy was performed for which pathology showed nonnecrotizing granulomas.

At the most recent ophthalmological visit, approximately 1 year after his initial presentation, the patient showed considerable improvement. His best-corrected VA was 20/20 in the right eye and 20/25 in the left eye. His IOP was 18 mm Hg in the right eye and 16 mm Hg in the left eye.

Conclusions

Proliferative retinopathy has been reported as both a late and uncommon finding of ocular sarcoidosis but is usually in conjunction with florid overt inflammation. ^{7 -9} Our patient presented with proliferative retinopathy with peripheral nonperfusion and neovascular glaucoma without signs of inflammation, which obscured diagnosis. Duker et al, in the largest series of proliferative retinopathy secondary to sarcoidosis, demonstrated the presence of some degree of inflammation in conjunction with proliferative retinopathy. Anterior uveitis and periphlebitis were present in about two-thirds of cases, with the remaining demonstrating periphlebitis only. ¹⁰ However, ocular sarcoidosis rarely presents solely with proliferative retinopathy without any sign of inflammation as in this case and in another report by Dyer et al. ¹¹ In the latter report, such presentation delayed the diagnosis for 29 months, which led to worsening of the proliferative retinopathy.

The cause of neovascularization has been proposed to be either inflammatory or ischemic. Kelly and Weiter suggested the cause to be inflammatory as they noted regression of optic nerve neovascularization with resolution of inflammation. ¹² However, Duker and colleagues suggested that the cause is rather ischemic since neovascularization arises in areas adjacent to capillary nonperfusion. ¹⁰

Corticosteroids remain the mainstay treatment of ocular sarcoidosis. Immunosuppressive agents may be required in cases of intolerance or resistance to corticosteroids. ¹³ Regarding the management of proliferative retinopathy more specifically, the most effective treatment regimen remains unclear. Kurup et al showed regression of the neovascular tissue and resolution of subretinal fluid with an intravitreal bevacizumab injection prior to addition of steroid therapy. ¹⁴ PRP has been performed in multiple cases of proliferative retinopathy due to sarcoidosis with mixed results, ^{10,11,15 -18} and it is unclear whether there is any benefit over no treatment. In our case, we treated the patient with a combination of antivascular endothelial growth factor injections, PRP, systemic steroids, and immunosuppressive therapy.

We report a case of a patient with ocular sarcoidosis presenting with rapidly progressive proliferative retinopathy without uveitis or systemic symptoms. Such presentation may be misdiagnosed, which may result in delayed treatment and poor visual outcome.