Hemi- and Central Retinal Vein Occlusion Associated with COVID-19 Infection in Young Patients without Known Risk Factors

Abstract

Purpose: Venous thromboembolic complications have been reported in association with coronavirus disease 2019 (COVID-19) infection. We raised awareness regarding a potential temporal association between COVID-19 infection and retinal vein occlusion (RVO).

Design: Multicenter, retrospective, nonconsecutive case series.

Subjects: Patients presenting with hemi-RVO (HRVO) or central RVO (CRVO) between March 2020 and March 2021, with confirmed COVID-19 infection, were included. The exclusion criteria were as follows: age >50 years, hypertension, diabetes, glaucoma, obesity, underlying hypercoagulable states, and those requiring intubation during hospitalization.

Methods: This was a multicenter, retrospective, nonconsecutive case series including patients presenting with hemi-RVO (HRVO) or central RVO (CRVO) between March 2020 and March 2021, with confirmed COVID-19 infection. The exclusion criteria were as follows: age >50 years, hypertension, diabetes, glaucoma, obesity, underlying hypercoagulable states, and those requiring intubation during hospitalization.

Main outcome measures: Ophthalmic findings, including presenting and final visual acuity (VA), imaging findings, and clinical course.

Results: Twelve eyes of 12 patients with CRVO (9 of 12) or HRVO (3 of 12) after COVID-19 infection were included. The median age was 32 years (range, 18-50 years). Three patients were hospitalized, but none were intubated. The median time from COVID-19 diagnosis to ophthalmic symptoms was 6.9 weeks. The presenting VA ranged from 20/20 to counting fingers, with over half (7 of 12) having a VA of ≥20/40. OCT revealed macular edema in 42% of the eyes; of these, 80% (4 of 5) were treated with anti-VEGF injections. Ninety-two percent (11 of 12) had partial or complete resolution of ocular findings at final follow-up. Four eyes (33%) had retinal thinning, as determined using OCT, by the end of the study interval. The final VA ranged from 20/20 to 20/60, with 11 of the 12 (92%) eyes achieving a VA of ≥20/40 at a median final follow-up period of 13 weeks (range, 4-52 weeks).

Conclusions: Although we acknowledge the high seroprevalence of COVID-19 and that a causal relationship cannot be established, we reported this series to raise awareness regarding the potential risk of retinal vascular events due to a heightened thromboinflammatory state associated with COVID-19 infection.

Keywords: COVID-19; Macular edema; Retinal vascular disease; Retinal vein occlusion; Venous thromboembolism.

Figure 1

Clinical response to intravitreal anti-VEGF therapy for the treatment of macular edema associated with central retinal vein occlusion after coronavirus disease 2019 infection. A, OCT (Heidelberg Spectralis) of the right eye in case 4 showed macular edema (top), which resolved (bottom) following treatment with 3-monthly intravitreal bevacizumab (Avastin, Genentech) injections. B, OCT of the left eye in case 12 lacked macular edema at presentation (top) but developed macular edema at week 6. Macular edema was persistent despite the administration of 2 intravitreal bevacizumab injections at weeks 6 (middle) and 11 (bottom).

Figure 2

Right eye in case 10 presenting with central retinal vein occlusion (CRVO) following coronavirus disease 2019 infection. A, A fundus photograph (Optos) shows intraretinal hemorrhages in all quadrants, a flame hemorrhage off the disc, and tortuous vessels, consistent with CRVO. B, Fluorescein angiography (Optos) shows delayed peripheral perfusion and diffuse small-vessel leakage. C,D, The presenting OCT (Heidelberg Spectralis) (C) showed massive cystoid macular edema, which improved (D) just 1 week after treatment with a single intravitreal bevacizumab (Avastin, Genentech) injection. There was complete resolution of macular edema and the development of residual retinal thinning, as determined using OCT (not shown), by 52 weeks of follow-up.

Figure 3

Right eye in case 2 presenting with central retinal vein occlusion following coronavirus disease 2019 infection. A, A fundus photograph (Optos) shows diffuse intraretinal hemorrhages and dilated, tortuous venules at presentation. B, Fluorescein angiography (Optos, UK) shows diffuse vascular leakage in late phases. C, Fundus abnormalities (Topcon) resolved 10 weeks later. D and E, Initial OCT (Heidelberg Spectralis) showed cystoid macular edema (D), which resolved by 10 weeks of follow-up (E) after treatment with 1 intravitreal bevacizumab (Avastin, Genentech) injection.

Figure 4

Right eye in case 8 presenting with an inferior hemiretinal vein occlusion (HRVO) after coronavirus disease 2019 infection. A, A fundus photograph (Optos) shows inferior intraretinal hemorrhages, a hemorrhage off the disc, and inferior venous dilation and tortuosity, consistent with the diagnosis of HRVO. B, OCT (Heidelberg Spectralis) showed that macular edema was lacking but revealed an area of focal hyperreflectivity, consistent with paracentral acute middle maculopathy (red asterisk). C, A fundus photograph (Optos, UK) at 10 weeks of follow-up showed normalization of the retinal anatomy. D, Final OCT at the 10-week follow-up visit demonstrated macular thinning in the area of the prior paracentral acute middle maculopathy (white asterisk).