Spectral domain optical coherence tomography changes following intravitreal dexamethasone implant, Ozurdex® in patients with uveitic cystoid macular edema.

PURPOSE: To correlate the structural and functional changes following intravitreal injection of dexamethasone 0.7 mg (Ozurdex®) implant in patients with recalcitrant uveitic cystoid macular edema (CME). MATERIALS AND METHODS: In a prospective, interventional, nonrandomized study, 30 eyes (27 patients) with uveitic CME received Ozurdex® implant and were followed-up for 24 weeks at periodic intervals to monitor structural alterations seen on spectral domain optical coherence tomography (SD-OCT). The outcome measures included change in central macular thickness (CMT) and best-corrected visual acuity (BCVA) as well as structural alterations seen on OCT such as change in the height of cystoid spaces (CSs) and sub-foveal serous retinal detachment (SSRD). The integrity of external limiting membrane and inner-outer segment junction was assessed at baseline and follow-up visits. RESULTS: Mean age of the patients was 46.09 ± 15.66 years. The mean CMT decreased by 96 μm at 1-day, 231.64 μm at 1-week, 254.21 μm at 4 weeks and 249.14 μm at 12 weeks (P \u3c 0.001) compared with baseline. BCVA improved from a baseline mean of 0.62 LogMAR units to 0.49 on day 1 to 0.31 at 24 weeks (P \u3c 0.001). A decrease in the mean height of CS, that is, 133.28 μm from a baseline of 317.71 μm was noted on the 1 st day (P \u3c 0.001). 4 eyes demonstrated the presence of CS at 4 weeks, 1 eye at 6 weeks and 3 eyes at 12 weeks. At baseline, 16 eyes (53.33%) demonstrated the presence of SSRD. Among these, 11 eyes showed resolution of SSRD on day 1. SSRD resolved in all patients at 4 weeks and was maintained up to 24 weeks. CONCLUSIONS: Ozurdex® implant improves the visual outcome of patients with recalcitrant uveitic CME. Reversibility of retinal changes may be possible following treatment with dexamethasone implant. Thus final visual outcome may be independent of pretreatment CMT, the height of CS or SSRD

Vanishing retinal arterial aneurysms with anti-tubercular treatment in a patient presenting with idiopathic retinal vasculitis, aneurysms, and neuroretinitis.

BACKGROUND: Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome presents with characteristic clinical manifestations such as aneurysms at arteriolar bifurcations and optic nerve and retinal vascular inflammation. Regression of such features on treatment with anti-tubercular therapy (ATT) combined with corticosteroids has not been reported in literature. FINDINGS: A 30-year-old female with sudden painless decreased vision in the left eye was referred with a diagnosis of presumed tuberculous retinal vasculitis and a positive tuberculin skin test. Based on the clinical and angiographic features of the right eye, a diagnosis of IRVAN syndrome was made. In the left eye, the patient had vitreous hemorrhage for which pars plana vitrectomy was performed. The vitreous sample was positive for Mycobacterium tuberculosis using multiplex polymerase chain reaction, and the patient was started on standard four-drug ATT and oral corticosteroids. At 6-month follow-up, vanishing of retinal arterial aneurysms was observed. CONCLUSIONS: The pathogenesis of IRVAN syndrome is uncertain. One of the postulates is that the features of arterial aneurysms and other retinal vascular alterations occur secondary to acquired inflammatory reaction. We hypothesize that IRVAN syndrome may be a morphological diagnosis possibly associated with various entities, one of which could be ocular tuberculosis. It may be prudent to rule out intraocular tuberculosis in cases labeled as IRVAN syndrome in an endemic population

Transcriptional Profile of Mycobacterium tuberculosis in an in vitro Model of Intraocular Tuberculosis

Background: Intraocular tuberculosis (IOTB), an extrapulmonary manifestation of tuberculosis of the eye, has unique and varied clinical presentations with poorly understood pathogenesis. As it is a significant cause of inflammation and visual morbidity, particularly in TB endemic countries, it is essential to study the pathogenesis of IOTB. Clinical and histopathologic studies suggest the presence of Mycobacterium tuberculosis in retinal pigment epithelium (RPE) cells.Methods: A human retinal pigment epithelium (ARPE-19) cell line was infected with a virulent strain of M. tuberculosis (H37Rv). Electron microscopy and colony forming units (CFU) assay were performed to monitor the M. tuberculosis adherence, invasion, and intracellular replication, whereas confocal microscopy was done to study its intracellular fate in the RPE cells. To understand the pathogenesis, the transcriptional profile of M. tuberculosis in ARPE-19 cells was studied by whole genome microarray. Three upregulated M. tuberculosis transcripts were also examined in human IOTB vitreous samples.Results: Scanning electron micrographs of the infected ARPE-19 cells indicated adherence of bacilli, which were further observed to be internalized as monitored by transmission electron microscopy. The CFU assay showed that 22.7 and 8.4% of the initial inoculum of bacilli adhered and invaded the ARPE-19 cells, respectively, with an increase in fold CFU from 1 dpi (0.84) to 5dpi (6.58). The intracellular bacilli were co-localized with lysosomal-associated membrane protein-1 (LAMP-1) and LAMP-2 in ARPE-19 cells. The transcriptome study of intracellular bacilli showed that most of the upregulated transcripts correspond to the genes encoding the proteins involved in the processes such as adherence (e.g., Rv1759c and Rv1026), invasion (e.g., Rv1971 and Rv0169), virulence (e.g., Rv2844 and Rv0775), and intracellular survival (e.g., Rv1884c and Rv2450c) as well as regulators of various metabolic pathways. Two of the upregulated transcripts (Rv1971, Rv1230c) were also present in the vitreous samples of the IOTB patients.Conclusions:M. tuberculosis is phagocytosed by RPE cells and utilizes these cells for intracellular multiplication with the involvement of late endosomal/lysosomal compartments and alters its transcriptional profile plausibly for its intracellular adaptation and survival. The findings of the present study could be important to understanding the molecular pathogenesis of IOTB with a potential role in the development of diagnostics and therapeutics for IOTB

Herpetic anterior uveitis following COVID-19 vaccines: a case series.

PURPOSE To report a case series of herpetic uveitis following COVID-19 vaccinations. METHODS Demographic, clinical and treatment-related data of herpetic anterior uveitis cases was collected at five tertiary eye hospitals between January 2021 and June 2022. A retrospective database review at one of the centers comparing the number of cases of herpetic eye disease before and after the introduction of COVID-19 vaccination was performed as well. RESULTS Twenty-four patients (9 female, 15 male) with a mean age of 54 years (range 28-83 years) were diagnosed with herpetic uveitis, reporting an onset of symptoms 3-42 days after the first, second or third dose of COVID-19 vaccination. Median time between vaccination and onset of herpetic eye disease was 10 days (mean 12.7 ± 10.15 days) days. The administered vaccines were BNT162b2, mRNA-1273, BBIBP-CorV and Ad26.COV2.S. The cases included 11 HSV, 10 VZV and 1 CMV anterior uveitis, 2 were not further specified. There was an equal number of first episodes (n = 12, 50%) and recurrent episodes (n = 12, 50%). Response to established regimens was generally good. The retrospective database review revealed the exact same incidence of herpetic uveitis during the pandemic and ongoing vaccination compared to prior SARS-CoV-2. CONCLUSION This report includes 24 cases of herpetic anterior uveitis in a temporal relationship to various COVID-19 vaccines. This study supports the potential risk of herpetic eye disease following COVID-19 vaccines, but proof of a direct, causal relationship is missing

The Effects of Intravitreal Bevacizumab in Infectious and Noninfectious Uveitic Macular Edema

Background/Aims. To assess the effect of intravitreal bevacizumab injection (IVBI) for the treatment of macular edema due to infectious and noninfectious uveitides. Design. Retrospective interventional case series. Methods. A chart review was performed on all the patients who were diagnosed with uveitic macular edema (UME) and received 1.25 mg of IVBI at two referral centers in Riyadh, Saudi Arabia. All included patients had their visual acuity and macular thickness analyzed at baseline and at 1 and 3 months following IVBI and any sign of reactivation was noted. Results. The mean age of patients was 41±16 years with a mean followup of 4±1 months. Ten patients had idiopathic intermediate uveitis, 9 patients had Behcet’s disease, 10 had idiopathic panuveitis, and twelve patients had presumed ocular tuberculosis uveitis. Following IVBI, the mean LogMAR visual acuity improved from 0.8±0.8 at baseline to 0.4±0.5 at 1 month and 0.3±0.5 at 3 months (P<0.002, at 3 months). The mean macular thickness was 430±132 μm at baseline. Following IVBI macular thickness improved to 286±93 μm at 1 month and to 265±88 μm at 3 months of followup (P<0.001, at 3 months). Conclusion. Bevacizumab was effective in the management of UME associated with both infectious and noninfectious uveitides. Intravitreal bevacizumab induced remission of UME with infectious uveitis and had no immunosuppressive effect against infectious agents

KESTREL and KITE: 52-Week Results From Two Phase III Pivotal Trials of Brolucizumab for Diabetic Macular Edema.

PURPOSE To compare the efficacy and safety of brolucizumab with aflibercept in patients with diabetic macular edema (DME). DESIGN Double-masked, 100-week, multicenter, active-controlled, randomized trials. METHODS Subjects were randomized 1:1:1 to brolucizumab 3 mg/6 mg or aflibercept 2 mg in KESTREL (n = 566) or 1:1 to brolucizumab 6 mg or aflibercept 2 mg in KITE (n = 360). Brolucizumab groups received 5 loading doses every 6 weeks (q6w) followed by 12-week (q12w) dosing, with optional adjustment to every 8 weeks (q8w) if disease activity was identified at predefined assessment visits; aflibercept groups received 5 doses every 4 weeks (q4w) followed by fixed q8w dosing. The primary endpoint was best-corrected visual acuity (BCVA) change from baseline at Week 52; secondary endpoints included the proportion of subjects maintained on q12w dosing, change in Diabetic Retinopathy Severity Scale score, and anatomical and safety outcomes. RESULTS At Week 52, brolucizumab 6 mg was noninferior (NI margin 4 letters) to aflibercept in mean change in BCVA from baseline (KESTREL: +9.2 letters vs +10.5 letters; KITE: +10.6 letters vs +9.4 letters; P < .001), more subjects achieved central subfield thickness (CSFT) <280 µm, and fewer had persisting subretinal and/or intraretinal fluid vs aflibercept, with more than half of brolucizumab 6 mg subjects maintained on q12w dosing after loading. In KITE, brolucizumab 6 mg showed superior improvements in change of CSFT from baseline over Week 40 to Week 52 vs aflibercept (P = .001). The incidence of ocular serious adverse events was 3.7% (brolucizumab 3 mg), 1.1% (brolucizumab 6 mg), and 2.1% (aflibercept) in KESTREL; and 2.2% (brolucizumab 6 mg) and 1.7% (aflibercept) in KITE. CONCLUSION Brolucizumab 6 mg showed robust visual gains and anatomical improvements with an overall favorable benefit/risk profile in patients with DME

Antiviral treatment for acute retinal necrosis:A systematic review and meta-analysis

Acute retinal necrosis is a progressive intraocular inflammatory syndrome characterized by diffuse necrotizing retinitis that can lead to a poor visual outcome, mainly from retinal detachment. The antiviral treatment approach for acute retinal necrosis varies as there are no established guidelines. We summarize the outcomes of acute retinal necrosis with available antiviral treatments. Electronic searches were conducted in PubMed/MEDLINE, EMBASE, Scopus, and Google Scholar for interventional and observational studies. Meta-analysis was performed to evaluate the pooled proportion of the predefined selected outcomes. This study was registered in PROSPERO (CRD42022320987). Thirty-four studies with a total of 963 participants and 1,090 eyes were included in the final analysis. The estimated varicella-zoster virus and herpes simplex virus polymerase chain reaction-positive cases were 63% (95% CI: 55–71%) and 35% (95% CI: 28–42%), respectively. The 3 main antiviral treatment approaches identified were oral antivirals alone, intravenous antivirals alone, and a combination of systemic (oral or intravenous) and intravitreal antivirals. The overall pooled estimated proportions of visual acuity improvement, recurrence, and retinal detachment were 37% (95% CI: 27–47%), 14% (95% CI: 8–21%), and 43% (95% CI: 38–50%), respectively. Patients treated with systemic and intravitreal antivirals showed a trend towards better visual outcomes than those treated with systemic antivirals (oral or intravenous) alone, even though this analysis was not statistically significant (test for subgroup differences P = 0.83).</p