Adalimumab in Vogt-Koyanagi-Harada Disease Refractory to Conventional Therapy

Background: No study explores the effectiveness of adalimumab in sight-threatening Vogt-Koyanagi-Harada (VKH) patients in China.Objective: To evaluate the short-term effectiveness and safety of adalimumab (ADA) in patients with sight-threatening Vogt-Koyanagi-Harada (VKH) disease refractory to conventional therapy.Methods: Medical records of VKH patients who had been treated with systemic glucocorticoids and immunosuppressants but whose condition was poorly controlled were collected and analyzed. Primary outcomes comprised of best-corrected visual acuity (BCVA), intraocular inflammation, relapses, and glucocorticoid-sparing effects. Other outcomes included central macular thickness (CMT), intraocular manifestations and adverse events (AEs).Results: Nine refractory VKH patients with a median age of 30 (16, 43) years old were enrolled in this study and received treatment for a median of 10 (7, 11) months. Mean BCVA improved from LogMar 0.63 ± 0.50 (20/72 or 0.36 ± 0.26 in Snellen chart) at baseline to LogMar 0.50 ± 0.37 (20/82 or 0.41 ± 0.28 in Snellen chart) at final visit (P = 0.090). The anterior chamber cell grade decreased from 2 (1.75, 3)+ at baseline to 0.5 (0, 1.25)+ cell at final visit (P < 0.001). The vitritis grade decreased from 1 (1, 1) + cell at baseline to 0 (0, 1)+ cell at final visit (P < 0.001). Patients suffered a median of 1 (0, 2) relapse during treatment. CMT remained stable from 238.50 ± 144.94 μm at baseline to 219.28 ± 77.20 μm at final visit (P = 0.553). The mean prednisone dosage decreased from 21.91 ± 18.39 mg/d to 2.73 ± 4.10 mg/d (P = 0.005). No severe AEs were found during treatment.Conclusions: The outcomes indicated that ADA was an effective and safe option for VKH patients refractory to conventional therapy by controlling inflammation, preserving visual function and reducing the daily glucocorticoid dose.

Optical Coherence Tomographic Features and Prognostic Values of Macular Edema in Vogt-Koyanagi-Harada Disease

Purpose: To determine optical coherence tomographic (OCT) features of macular edema (ME) and identify potential prognostic values for ME and visual outcomes in Vogt-Koyanagi-Harada disease (VKH).Methods: In the retrospective case series, a total of 1,377 VKH patients who were seen in a tertiary uveitis center between September 2011 and January 2018 were reviewed on their demographics, visual acuity, ocular and extraocular manifestations, modes of treatment, and OCT examinations. Of these patients, 79 (5.7%) having ME were included for analysis of OCT features. Four patients were missed without ME resolution, and the remaining 75 patients who either had ME resolved or were followed up for 2 years were included for analysis of disease outcomes.Results: Of the 115 affected eyes in these 79 patients, 100 (87.0%) had cystoid ME (CME), accounting for the most common OCT feature of VKH-related ME. Disruption of the inner-segment/outer-segment junction (IS/OS) band seen in 33 (28.7%) affected eyes of 24 (30.4%) patients was found as a risk factor for the development of persistent ME [10 of 62 (16.1%) vs. 13 of 13 (100%); P < 0.001] and a poor visual outcome (1.16 ± 0.42 vs. 1.17 ± 0.46 in logMAR unit; P = 0.89). CME patients with a concurrent choroidal neovascular membrane often had a disrupted IS/OS band, thus becoming refractory cases. A 6-month well-controlled intraocular inflammation following standard treatment regimens was found to associate with complete resolution of the refractory edema [4 of 5 (80%) vs. 2 of 13 (15%); P = 0.02].Conclusions: Intraretinal cystoid changes are most commonly seen in the edematous macula of VKH patients. Disruption of the IS/OS band is a useful risk sign for poor ME and visual outcomes in VKH-related ME, and a long-term well-controlled intraocular inflammation may be critical for the resolution of refractory cases.

Manifestations of intraocular inflammation over time in patients on brolucizumab for neovascular AMD

Purpose To describe the adverse events associated with brolucizumab, in particular the sequence of intraocular inflammation (IOI), retinal vasculitis (RV), and/or retinal vascular occlusion (RO). Methods This was an unmasked post hoc analysis of the randomized HAWK/HARRIER clinical trials. Patients with neovascular AMD in the brolucizumab arms of the trials were included. IOI-related adverse events reported by study investigators were analyzed to determine early signs and the time course of IOI-related adverse events, using a subgroup of patients with definite/probable IOI cases identified in an independent unmasked post hoc review by an external safety review committee. A limited literature review on IOI following anti-VEGF therapy was also conducted. Results Among 50 patients with definite/probable IOI cases identified by the safety review committee, 12 had RV or RO adverse events reported by the investigators. For 6 of 12, IOI (other than RV) was reported before RV or RO. The duration from the first IOI adverse event to the first RV or RO adverse event ranged from 16 to 171 days for 5 patients and was 553 days for 1 patient. Four of the 6 patients received ≥ 1 brolucizumab injection on or after the date of the first IOI adverse event and before the first RV or RO adverse event. Conclusions IOI may precede RV or RO in some patients treated with brolucizumab.

Risk factors for emerging intraocular inflammation after intravitreal brolucizumab injection for age-related macular degeneration

Purpose To analyze the risk factors associated with emerging intraocular inflammation (IOI) after intravitreal brolucizumab injection (IVBr) to treat age-related macular degeneration (AMD). Methods This study included 93 eyes of 90 patients. The incidence of emerging IOI was analyzed. The patients were classified into IOI or non-IOI groups, and background clinical characteristics in each group were compared. Results IOI occurred in 14 eyes of 14 cases (16%; five women, nine men [5:9]; IOI group) after IVBr; contrastingly, no IOI occurred in 76 patients (10 women, 66 men [10:66]; non-IOI group). The mean ages in IOI and non-IOI groups were 79.4 ± 8.1 and 73.8 ± 8.9 years old, respectively, and the average age in the IOI group was significantly higher than that in the non-IOI group (P = 0.0425). In addition, the percentages of females in the IOI and non-IOI groups were 43% and 13%, respectively, and IOI occurred predominantly in females (odds ratio: 4.95, P = 0.0076). Moreover, the prevalence of diabetes in the IOI and non-IOI groups was 64% and 32%, respectively, with a significant difference (odds ratio: 3.90, P = 0.0196). In contrast, the prevalence of hypertension in the IOI and non-IOI groups was 36% and 57%, respectively, with no significant difference (P = 0.15). Conclusion The comparison of clinical profiles of IOI or non-IOI cases in IVBr treatment for AMD suggests that the risk factors for IOI are old age, female sex, and history of diabetes; however, IOI with vasculitis or vascular occlusion in this cohort does not seem to cause severe visual impairment. Further studies are required to investigate potential risk factors for IOI.

Evaluation of the prevalence of silicone oil droplets in the vitreous in patients treated with multiple intravitreal drug injections

Background. At present, intraocular drops of silicone oil, which is a lubricant for disposable syringes used for intravitreal injections, are being actively studied. Among the undesirable effects of their presence are patient’s complaints of visual discomfort associated with floating opacities, as well as a potential connection with episodes of intraocular inflammation and increased intraocular pressure.The aim: to assess the prevalence of silicone oil droplets in the vitreous in patients treated with multiple intravitreal injections.Materials and methods. A single-center retrospective cohort study was carried out. Inclusion criterion: treatment with multiple (at least 5) intravitreal injections of drug solutions performed according to registered indications. The study group consisted of 86 eyes of 85 patients (56 women, 29 men; age – from 36 to 89 y.o., average – 71.7 y.o.), who received an average of 13.2 injections of solutions of various drugs.Results. Drops of silicone oil were detected by biomicroscopy in 57 eyes (66.28 %) and by ultrasonography in 76 (88.37 %). The coincidence of the results of applying the methods was recorded in 73.26 % of observations. Seven (8.1 %) patients had characteristic complaints. Four patients (4.7 %) had a history of aseptic vitreitis. The hypothesis was confirmed that the possibility of silicone oil droplets getting into the vitreous increases with the number of intravitreal injections. A similar relationship was established in relation to the possibility of the appearance of characteristic complaints in patients due to the presence of drops and episodes of aseptic vitreitis.Conclusion. The release of drops of silicone oil from syringes during intravitreal injections is an urgent problem that requires further study. In the Russian Federation, the situation is aggravated by the lack of prefilled syringes with drugs approved for administration into the eye cavity, as well as the lack of syringe models designed for use in ophthalmology.