A plethora of articles aiming to enhance care of patients with uveitis was published in the past year. This year-in-review article will summarize several high-impact uveitis articles published between the end of 2022 and 2023. This review is only able to highlight a small number of the many excellent papers written during this time frame.

The MERIT Trial Results¹

The MERIT trial explored intravitreal therapies for uveitic macular edema. This was a single-masked, randomized, controlled clinical trial evaluating 3 separate intravitreal treatments (dexamethasone implant, methotrexate, ranibizumab) for persistent or resistant macular edema in patients with minimally active or inactive uveitis. One hundred ninety-four participants were included (225 eyes) in any of the 3 groups, and received at least 1 injection of their assigned treatment. At 12 weeks, the primary endpoint, which was reduction in the central subfield thickness (CST) compared to baseline, was assessed. The group that showed the most improvement was dexamethasone (35%), followed by ranibizumab (22%) and methotrexate (11%). The reduction in the dexamethasone group was significantly greater compared to either the methotrexate or ranibizumab group. Improvement in the best-corrected visual acuity was also significantly higher in the dexamethasone group. Intraocular pressure spikes were also more common in the dexamethasone group, but elevations to over 30 mmHg were uncommon and not significantly different between the 3 groups. This study showed that intravitreal dexamethasone had the best visual and anatomic outcomes of the 3 intravitreal medications without many IOP spikes over 30 mmHg.

Tocilizumab in Juvenile Idiopathic Arthritis‒Associated Uveitis²

Tocilizumab is an interleukin-6 receptor inhibitor. Interleukin-6 is a known proinflammatory cytokine involved in the inflammatory pathway of multiple uveitic conditions. This was a retrospective observational study of patients with juvenile idiopathic arthritis with refractory uveitis. Thirteen patients were enrolled; the uveitis flare rate per year per patient was 1.6 while on immunosuppression before the initiation of tocilizumab, which decreased to 0.4 after tocilizumab initiation. Five of these patients achieved complete quiescence. The authors concluded that the drug was safe and well tolerated, and no side effects were noted during the treatment period.

Tumor Necrosis Factor³

There is concern that the formation of antibodies against tumor necrosis factor inhibitors may impede their efficacy in noninfectious uveitis and other rheumatologic disorders. This study was a retrospective cross-sectional study that included 54 patients, 42 of whom received adalimumab and 12 whom received infliximab. It involved assessing drug levels, clinical response, concurrent use of antimetabolites, and antidrug antibody levels. In the adalimumab group, the average drug level was 9.72 μg/mL, antidrug antibody level was 84.2 arbitrary units/mL, and antidrug antibody frequency occurred in 15 of 42 patients (35.7%). In those with antidrug antibodies, the mean drug level was statistically significant and lower. The use of an antimetabolite increased the average mean drug levels. In the adalimumab group, the presence of higher antidrug antibody levels was associated with an increased risk of treatment failure. There were no antidrug antibodies noted in the infliximab group. The findings of this study suggest that therapeutic drug and antidrug antibody monitoring may be helpful in assessing patients who do not respond to tumor necrosis factor inhibitors.

Tubulointerstitial Nephritis and Uveitis During the COVID-2019 Pandemic⁴

There has been speculation that inflammatory patterns have changed after the COVID-19 pandemic, specifically regarding anecdotal reports of an increased incidence of tubulointerstitial nephritis and uveitis (TINU). This was a single-center retrospective chart review of new patient diagnoses. Prior to the pandemic, 1 of 561 new patient visits (0.18%) were diagnosed with TINU, whereas after, 15 of 581 patients (2.58%) were diagnosed with TINU. Additionally, posterior involvement was noted at higher frequency after the pandemic. This study points to a possible association between the COVID-19 pandemic and the increased development of TINU.

Uveitis and COVID Vaccination^5,6

Various reports have assessed the risk of noninfectious uveitis after COVID-19 vaccination. One study⁵ was a retrospective matched cohort study and self-controlled case series using a longitudinal data set of 4,611,378 patients in years prior to and after COVID-19 vaccination. The matched cohort analysis did not detect an increased risk of noninfectious uveitis after vaccination in patients without a history of uveitis. However, there was an increased risk found in a subgroup aged between 5 to 44 years (incidence rate ratio 1.40), which may speak to their heightened immune response.

Another study showed an increased incidence of COVID-19 vaccine–related uveitis.⁶ This was a retrospective study using the Centers for Disease Control and Prevention Vaccine Adverse Event Reporting System. There were 1,094 reported cases of vaccine-associated uveitis, with a crude reporting rate of 0.57, 0.44, and 0.35 (per million doses) per BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and Ad26.COV2.S (Janssen), respectively. The majority of cases were reported after the first dose and within the first week, and the observed vs expected ratio of vaccine-associated uveitis was comparable between the 3 groups.

Cystoid Macular Edema After Cataract Surgery⁷

This was a retrospective, longitudinal, case-controlled study of 3.1 million patients aged 18 years or older through the American Academy of Ophthalmology IRIS registry. Patients who developed cystoid macular edema (CME) 90 days after cataract surgery were compared to those who did not develop CME within that time period. Cystoid macular edema developed on average 6 weeks after cataract surgery and occurred in 25,595 eyes (0.8%). Risk factors for CME included being Black, being male, having history of smoking, and having cataract surgery before the age of 65, and in those with diabetic retinopathy. Patients who developed CME had a significantly higher chance of a poorer visual outcome (20/30 or worse). The authors concluded that although the incidence of CME remains low, there are certain risk factors that predispose patients to its development and worse outcomes.

Complications After Steroids in Vitrectomized Eyes⁸

The effects of intravitreal triamcinolone and dexamethasone implants are less well known for vitrectomized vs nonvitrectomized eyes. This was a retrospective, comparative case series of 148 eyes, 75 of which received in the dexamethasone implant and 72 of which received intravitreal triamcinolone. The mean follow-up period was 2.5 years, without significant difference between the 2. There was a significantly higher rate of ocular hypotony in eyes receiving the intravitreal dexamethasone injection than in eyes receiving intravitreal triamcinolone (13% vs 3%). Although the visual acuity did decrease with the transient hypotony, it returned to prehypotony levels on follow-up. Ocular hypertension also occurred more frequently in the intravitreal dexamethasone group compared to the intravitreal triamcinolone group (31% vs 22%), but this did not obtain statistical significance. This paper raises awareness of the potential for transient hypotony and visual decline following injection with intravitreal dexamethasone in vitrectomized eyes.

Retinal Vasculitis and/or Retinal Vascular Occlusion Following Brolucizumab Treatment⁹

This study is the largest descriptive analysis of inflammatory changes and imaging findings following the administration of brolucizumab (Beovu; Novartis). This was a retrospective analysis of optical coherence tomography, fundus photography, and fluorescein angiography of patients treated with the medication who were reported to Novartis after developing retinal vasculitis or a retinal vascular occlusion. The analysis included 222 eyes, of which 72 had retinal vasculitis only, 9 had retinal occlusion, 63 had a combined presentation of retinal vasculitis and retinal occlusion, and 31 had posterior-segment inflammation. In eyes with a combined retinal vasculitis and occlusion picture, the most common imaging findings included leakage on fluorescein angiography, perivascular sheathing, and hyperreflective dots on OCT. Retinal vascular occlusions were most commonly multiple and arterial. The authors showed that while there is no phenotype specific to brolucizumab-associated inflammation, there was an enlarged spectrum of inflammatory consequences following treatment, and widefield imaging is important in these cases. RP

Sruthi Arepalli, MD, is an assistant professor in the vitreoretinal and uveitis service at Emory University in Atlanta, Georgia. Dr. Arepalli reports consultancy to Eyepoint Pharmaceuticals. Reach her at sruthiarepalli@gmail.com.

REFERENCES

1. Multicenter Uveitis Steroid Treatment Trial (MUST) Research Group Writing Committee, Acharya NR, Vitale AT, et al. Intravitreal therapy for uveitic macular edema-ranibizumab versus methotrexate versus the dexamethasone implant: the MERIT trial results. Ophthalmology. 2023;130(9):914-923. doi:10.1016/j.ophtha.2023.04.011
2. Marino A, Marelli L, Nucci P, Caporali R, Miserocchi E. Subcutaneous tocilizumab in juvenile idiopathic arthritis associated uveitis. Ocul Immunol Inflamm. 2023;1-4. doi:10.1080/09273948.2022.2161916
3. Bellur S, McHarg M, Kongwattananon W, Vitale S, Sen HN, Kodati S. Antidrug antibodies to tumor necrosis factor α inhibitors in patients with noninfectious uveitis. JAMA Ophthalmol. 2023;141(2):150-156. doi:10.1001/jamaophthalmol.2022.5584
4. Huang L, Ta Kim D, Rosenberg CR, Lin P, Suhler E. Diagnosis and characteristics of presentation of tubulointerstitial nephritis and uveitis syndrome during the COVID-2019 pandemic [published online ahead of print, 2023 Sep 12]. Ocul Immunol Inflamm. 2023;1-8. doi:10.1080/09273948.2023.2244077
5. Kumar A, Miller DC, Sun Y, Arnold BF, Acharya NR. Risk of noninfectious uveitis after coronavirus disease 2019 vaccination in a United States claims database. Ophthalmology. 2023;S0161-6420(23)00502-X. doi:10.1016/j.ophtha.2023.07.017
6. Singh RB, Parmar UPS, Kahale F, Agarwal A, Tsui E. Vaccine-associated uveitis after COVID-19 vaccination: Vaccine Adverse Event Reporting System database analysis. Ophthalmology. 2023;130(2):179-186. doi:10.1016/j.ophtha.2022.08.027
7. Iftikhar M, Dun C, Schein OD, Lum F, Woreta F. Cystoid macular edema after cataract surgery in the United States: IRIS registry (Intelligent Research in Sight) analysis. Ophthalmology. 2023;130(10):1005-1014. doi:10.1016/j.ophtha.2023.06.001
8. Wakabayashi T, Liu CK, Anderson HE, et al. A comparison of ocular complications after 0.7 mg dexamethasone implant versus 2 mg of intravitreal triamcinolone in vitrectomized eyes. Ophthalmol Retina. 2023;7(6):480-488. doi:10.1016/j.oret.2022.12.009
9. Grewal DS, Wykoff CC, Dsouza D, Jhl V, Alecu I, Jaffe GJ. Imaging features of retinal vasculitis and/or retinal vascular occlusion following brolucizumab treatment in the post-marketing setting. Ophthalmol Sci. Forthcoming 2023. doi:10.1016/j.xops.2023.100361