Retina Society 2021: COVID/Uveitis Session

Jordan D Deaner, MD
Vitreoretinal Surgery Fellow
Duke University Eye Center

The final day of Retina Society 2021 started off with Thomas Albini and Steven Yeh moderating a dozen presentations covering inflammation, many with a focus on the effects of the ongoing COVID-19 pandemic.

Steven Yeh was first up to the podium, to discuss the relationship between retinopathy and systemic disease morbidity in severe COVID-19. Dr. Yeh and his team retrospectively reviewed the charts of patients with severe COVID-19 who were admitted and had an ophthalmic examination. They found that about a third of patients had retinopathy (retinal hemorrhage, cotton wool spots, or branch retinal artery occlusion) in the setting of severe COVID-19. The findings of retinopathy in severe COVID-19 were significantly associated with multi-organ failure and serum inflammatory markers.

Aleksandra Rachitskaya spoke to the effects of delay in care during the COVID-19 pandemic on visual acuity outcomes in patients requiring intravitreal injections. Her team performed a retrospective review of all patients who received intravitreal injections for age-related macular degeneration, diabetic retinopathy, and vein occlusions and missed at least 1 scheduled visit during the pandemic. Nearly 40% of patients missed at least 1 visit. Being older, female, and having lower baseline vision were risk factors for missing a visit during the pandemic. Those who missed a visit were more likely to lose vision (-2.48 vs +0.82 logMAR visual acuity) and this was especially pronounced in patients with diabetes and vein occlusions. Thankfully, the vision loss did not persist at 1 year follow-up.

COVID-19 changed many of our practice patterns in ophthalmology and Jesse Jung described how the pandemic lockdown changed the practice patterns and outcomes for primary retinal detachments. This multicenter study reviewed the outcomes of primary retinal detachments during and after the shelter in place order was in effect. During the shelter in place order, patients presented on average 22 days later than those after the shelter in place order, leading to more cases of proliferative vitreoretinopathy and a significantly lower single anatomic success rate (85% vs 75%).

Avni Finn continued the COVID-19 theme detailing a series of retinal vein occlusions that were associated with COVID-19 infections. This multi-centered retrospective review detailed 12 cases of retinal vein occlusions that occurred in 12 patients with confirmed COVID-19 infection. These patients did not have any risk factors for retinal vein occlusion, had negative thrombophilia screening, were less than 50 years old, and did not require positive pressure ventilation. There were 8 eyes with a central retinal vein occlusion and 4 eyes with a hemiretinal vein occlusion. Dr. Finn highlights a possible relationship between COVID-19 associated coagulopathy and retinal vein occlusions, recognizing that COVID-19 prevalence is high, and a causal relationship cannot be definitively established at this point.

Ajay Kuriyan and his coauthors prospectively simulated intravitreal injection scenarios with various masking scenarios. They found that those patients who wore tight fitting masks with tape over the nose and did not talk 2 minutes prior to the injection had significantly fewer colony forming units (CFUs) on a blood agar plate taped to their forehead compared to those doing the same without tape. Similarly, in scenarios where they allowed patients to talk, those patients who wore tight fitting masks with tape over the nose has less CFUs compared to those without tape, a loose facemask, and those without a mask altogether. There was no difference in CFU’s between those with a tight-fitting surgical face mask and tape compared to an N95 mask, regardless of the presence of talking.

Rounding out the COVID-19 talks, Samir Patel went on to detail the influence of universal face mask use on endophthalmitis risk after intravitreal anti-VEGF injections. In his multicentered, retrospective study of over half a million intravitreal injections, he found that there was an observed increase in the rate of post-injection presumed endophthalmitis in the cohort which did not use masks (0.0289%) compared to the cohort in which there was universal mask use (0.0213%), but it did not reach statistical significance. The difference became statistically significant between the two groups when culture positive endophthalmitis cases were analyzed (0.0092% no-mask vs 0.004% universal mask use).

Intraocular inflammation, infection, and drug toxicity were the focus of the final 6 talks, beginning with Mrinali Gupta. Dr. Gupta reported on outcomes using adoptive immunotherapy with CMV-specific cytotoxic T-cells (CMV-CTLs) to treat CMV retinitis. Dr. Gupta began by detailing the limitations of our current CMV retinitis therapy, specifically noting that the ultimate treatment is restoration of the patient’s immune system, but that immune recovery is not always possible. She detailed how CMV-CTLs can be pooled from donors, HLA matched, and infused into patients who have resistant CMV, intolerance to standard therapy, or progression of disease while on standard therapy. Dr. Gupta presented the results of 7 patients (10 eyes) with CMV retinitis who were treated with CMV-CTLs. Resolution of CMV retinitis was seen in 90% of eyes treated with CMV-CTLs.

Timothy Boyce went on to discuss the long-term outcomes and risk factors for severe vision loss in autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV). Dr. Boyce reviewed the patient records of the four families with well-established ADNIV including 130 eyes from 65 patients. He highlighted the early slow visual decline that sharply worsened around the 5th decade of life that was significantly associated with tractional retinal detachments. Dr. Boyce highlighted that the presence of hyaloidal fibrosis tended to precede the tractional retinal detachment and is a new feature to monitor in this phenotypically variable disease.

Thomas Albini reported on OCT anatomic and temporal biomarkers of uveitic macular edema. Dr. Albini et al performed a post-hoc analysis of the two phase 3 clinical trials assessing suprachoroidal triamcinolone acetonide (CLS-TA) for the treatment of non-infectious uveitis (PEACHTREE and AZALEA). His team analyzed the OCT images for ellipsoid zone (EZ) integrity, subretinal fluid, and presence and location of cystoid spaces. Eyes with normal subfoveal EZ, subfoveal cystoid spaces, and subfoveal subretinal fluid at baseline showed greater visual acuity recovery compared to those who did not have these features at baseline. Notably, he found that in all eyes treated with CLS-TA anatomic improvement preceded visual improvement by nearly 4 weeks.

Pouya Dayani reviewed the safety and visual outcomes of suprachoroidal triamcinolone compared to rescue therapies for uveitic macular edema. This was again a post-hoc analysis of the PEACHTREE clinical trial. Dr. Dayani compared the patients who received CLS-TA that did not require any rescue treatments to the sham group who were given rescue therapy per protocol, but the type of rescue therapy was at the discretion of the treating physician. Intravitreal or periocular steroids were used as rescue therapy in the majority of the control patients. There was a trend towards greater visual acuity gain and there was a significant reduction in OCT central subfield thickness in the CLS-TA group compared to the sham rescued group. Patients who received CLS-TA had less incidence of cataract and intraocular pressure rise compared to the sham rescued patients.

The diagnosis of autoimmune retinopathy (AIR) remains a challenge. Nieraj Jain presented on his efforts to establish an imaging-based diagnosis of non-paraneoplastic AIR largely based upon widefield fundus autofluorescence (FAF). Dr. Jain highlighted that FAF in non-paraneoplastic AIR reveals speckled hypoautofluorescence with a predilection for the perimacular (71%) and perivenular (62%) regions. 57% of eyes had a ring of hyperautofluorescence in the macula. Notably, this disease is asymmetric in 92% of cases.

Finally, Jasmine Francis took the podium and described the clinical and morphologic characteristics of 20 patients (40 eyes) with extracellular signal-regulared kinase (ERK)-inhibitor associated retinopathy. Dr. Francis noted that ERK-inhibitor retinopathy is always bilateral with pockets of subretinal fluid that oftentimes involve the fovea (95%) and are frequently multifocal (75%). OCT reveals thickening of the EZ and interdigitation zone in 70% of eyes and sometimes a novel subretinal fluid formation called “multifoil” which can help differentiate it from its sister retinopathy that occurs with MEK-inhibitors. 31% of patients treated with an ERK-inhibitor will develop retinopathy with 80% of cases occurring after the first dose. Thankfully, the retinopathy is self-limited and although patients may be symptomatic, all cases self-resolved with recovery of baseline vision and resolution of all symptoms. ERK-inhibitor therapy does not need to be decreased or discontinued if retinopathy develops.