key: cord-0771814-9vgmmbjk
authors: Ashkenazy, Noy; Patel, Nimesh A.; Sridhar, Jayanth; Yannuzzi, Nicolas A.; Belin, Peter J.; Kaplan, Richard; Kothari, Nikisha; Benitez Bajandas, Gabriel A.; Kohly, Radha P.; Roizenblatt, Roberto; Pinhas, Alexander; Mundae, Rusdeep; Rosen, Richard B.; Ryan, Edwin H.; Chiang, Allen; Chang, Louis K.; Khurana, Rahul N.; Finn, Avni P.
title: Hemi- and Central Retinal Vein Occlusion associated with COVID-19 infection in Young Patients without Known Risk Factors.
date: 2022-03-10
journal: Ophthalmol Retina
DOI: 10.1016/j.oret.2022.02.004
sha: a26d5d1813c0510915b91c160763aaccb20a72ca
doc_id: 771814
cord_uid: 9vgmmbjk

PURPOSE: Venous thromboembolic complications have been reported in association with COVID-19 infection. We raise awareness of a potential temporal association between COVID-19 infection and retinal vein occlusion (RVO). DESIGN: Retrospective, non-consecutive case series. METHODS: Setting: Multicenter STUDY POPULATION: Patients presenting with hemi-RVO (HRVO) or central RVO (CRVO) between 3/2020 and 3/2021, with confirmed COVID-19 infection. Exclusion criteria: age >50 years, hypertension, diabetes, glaucoma, obesity, underlying hypercoagulable states, and those requiring intubation during hospitalization. OUTCOMES: Ophthalmic findings including presenting and final visual acuity (VA), imaging findings, and clinical course. RESULTS: Twelve eyes of 12 patients with CRVO (9/12) or HRVO (3/12) following COVID-19 infection were included. Median age was 32 (range 18-50) years. Three patients were hospitalized, but none were intubated. Median time from COVID-19 diagnosis to ophthalmic symptoms was 6.9 weeks. Presenting VA ranged from 20/20 to counting fingers (CF), with over half (7/12) having VA ≥20/40. Optical coherence tomography (OCT) revealed macular edema in 33% of eyes, 80% (4/5) treated with anti-VEGF injections. Ninety-two percent (11/12) had partial or complete resolution of ocular findings at final follow up. Four eyes (33%) had retinal thinning on OCT by the end of the study interval. Final visual acuity ranged from 20/20 to 20/60, with 11/12 (92%) eyes achieving ≥20/40 VA eyes at a median final follow-up of 13 (range 4-52) weeks. CONCLUSIONS: While we acknowledge a high seroprevalence of COVID-19 and that a causal relationship cannot be established, we report this series to raise awareness of the potential risk of retinal vascular events due to a heightened thrombo-inflammatory state associated with COVID-19 infection.

Protein S, antithrombin III, and homocysteine), were included. Patients over age 50 and 157 those with comorbidities, including hypertension, diabetes, cardiovascular disease, 158 glaucoma, obesity, and underlying hypercoagulability by laboratory evaluation, were 159 excluded. Patients with other types of pathology such as arterial occlusions, branch 160 retinal vein occlusions, and optic neuropathy, as well as patients requiring intubation or 161 positive pressure ventilation (i.e. continuous positive airway pressure or intubation) 162 during hospitalization for COVID-19 infection, were excluded. 163

After reviewing 22 collected cases, 12 eyes of 12 patients were included in the 164 series. One case that was previously published by two co-authors of the present series 165

[RNK, APF], was included. 32 We excluded 3 patients with branch retinal vein occlusions 166 (BRVO), 1 with a central retinal artery occlusion (CRAO), and 4 who were over the age 167 of 50 years with confounding comorbidities. Two others were excluded due to having a 168 laboratory evaluation positive for inherent hypercoagulability: one with a MTHFR 169

Homozygous mutation and another with a positive anti-cardiolipin and borderline 170 positive lupus anticoagulant antibodies. 171

Only CRVO and HRVO were included in this study due to the pathophysiology 172 being more strongly related to hypercoagulability and venous injury, with occlusion 173 occurring at the level of the lamina cribrosa. 38 In contrast, the authors excluded BRVO 174 because it implies a mechanical venous compression of an adjacent thick-walled artery 175 in the setting of chronic vascular risk factors. 39 Arterial occlusions and patients with 176 underlying coagulopathies were excluded due to complex mechanisms that do not 177 directly correspond with the concepts of Virchow's triad. 40 11/12 confirmed by RT-PCR, 1/12 unknown method), none were intubated, and none 188 were known to have an underlying coagulopathy. Of 12 cases, 75% (9/12) were CRVO 189 and 25% (3/12) were HRVO. The median age of presentation was 32 years (range 18-190 50 years). Twenty-five percent (3/12) were hospitalized for The median time from COVID-19 diagnosis to ocular symptoms was 6.9 (1-13) weeks, 192 with a median of 10.5 (range 1-42) days of reported symptoms prior to ophthalmic 193 diagnosis. Six (50%) of the patients had ocular symptoms within 1 month of viral 194

infection. The median follow-up duration in our cohort was 13 weeks (range 4-52 195 weeks). 196

Most eyes did not develop macular edema at any point throughout follow up. 197 Macular edema developed in 33% (5/12) of eyes; 80% (4/5) of these cases were noted 198 at presentation, and one developed at 6 weeks of follow up, and 9 weeks after the 199 diagnosis of COVID-19 infection (Figure 1) . 200

The presenting VA ranged from 20/20 to counting fingers (CF), with 58% of eyes 201 (7/12) having initial VA ≥20/40. Macular edema was associated with a poorer presenting 202 VA, as illustrated in Figure 2 . Four cases were treated with anti-endothelial growth 203 factor (anti-VEGF) injections (range 1-3 total injections) for macular edema identified on 204 optical coherence tomography (OCT), and the remaining case was observed. 205

There was partial or complete resolution of the RVO in 92% (11/12) of eyes of 206 confirmed COVID-19 infections at final follow up, as illustrated in Figure 3 . While most 207 patients did not require systemic treatment with anticoagulation, 17% (2/12) were 208 treated with antiplatelet therapy at the time of the CRVO, one of whom was also treated 209 with high dose oral prednisone (Table 1) . 210

Most eyes maintained good visual acuity (VA) throughout the follow up interval. 211 

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