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 immune response in tubercular uveitis and its implications for treatment:From anti-tubercular treatment to host-directed therapies

Tubercular uveitis (TB-uveitis) remains a conundrum in the uveitis field, which is mainly related to the diverse clinical phenotypes of TB-uveitis. Moreover, it remains difficult to differentiate whether Mycobacterium tuberculosis (Mtb) is present in the ocular tissues, elicits a heightened immune response without Mtb invasion in ocular tissues, or even induces an anti-retinal autoimmune response. Gaps in the immuno-pathological knowledge of TB-uveitis likely delay timely diagnosis and appropriate management. In the last decade, the immunopathophysiology of TB-uveitis and its clinical management, including experts' consensus to treat or not to treat certain conditions with anti-tubercular treatment (ATT), have been extensively investigated. In the meantime, research on TB treatment, in general, is shifting more toward host-directed therapies (HDT). Given the complexities of the host-Mtb interaction, enhancement of the host immune response is expected to boost the effectiveness of ATT and help overcome the rising burden of drug-resistant Mtb strains in the population. This review will summarize the current knowledge on the immunopathophysiology of TB-uveitis and recent advances in treatment modalities and outcomes of TB-uveitis, capturing results gathered from high- and low-burden TB countries with ATT as the mainstay of treatment. Moreover, we outline the recent progress of HDT development in the pulmonary TB field and discuss the possibility of its applicability to TB-uveitis. The concept of HDT might help direct future development of efficacious therapy for TB-uveitis, although more in-depth research on the immunoregulation of this disease is still necessary.Ministry of Health (MOH)National Medical Research Council (NMRC)Published versionRLDN was supported by Riset Inovatif Produktif - Lembaga Pengelola Dana Pendidikan (RISPRO-LPDP) [RISPRO/KI/B1/KOM/5/15219/4/ 2020]. The funding source supported the creation of the figures from Biorender.com. The funding source had no involvement in the collection, analysis, interpretation, writing of the report, and decision to submit the article for publication. RA has been supported by National Medical Research Council (NMRC) grants from Ministry of Health (MOH), Singapore (The grant details: MOH-CSAINV19nov-0003 and MOH-CSAINV22jul-0004). The funding source has provided funding to RA to conduct original studies related to ocular TB and nothing to do with this particular publication

Sympathetic ophthalmia: epidemiology and cohort-based assessment of clinical outcomes

Background: The purpose of this study was to report the incidence, time after inciting event, aetiology and risk after specific intraocular procedures and the visual outcomes associated with sympathetic ophthalmia (SO) occurrence. Methods: This study reports data from multiple retrospective cohorts: retrospective population-based data were extracted from the TRICARE service network (between 2017 and 2021) and retrospective case-based data from the Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) database (cohorts from the UK, South India and North India). Results: There were 159 patients with SO identified. The length of time from sensitising event to SO occurrence was a median of 151 days (range: 6–9100 days). In the TRICARE database, 2 patients developed SO after open globe trauma and primary repair (of 615 eyes, rate 0.33%; 95% CI 1.26% to 1.30%). None developed SO after vitrectomy (total of 23 903 events; 95% CI 0% to 0.012%). The combined North Indian and UK cohorts reported 78.6% (81 patients) after trauma, 18.45% (19 patients) after elective surgery. Visual outcomes were reported in the OASIS database for 98.01% of patients (155 of 157 patients). The median presenting and final best corrected visual acuity (BCVA) for the inciting eye were no perception of light, the median presenting and final BCVA for the sympathising eye were 0.65 and 0.3 logMAR, respectively. Conclusion: This study identified 159 cases of SO. With poor visual outcomes in the inciting eye, early diagnosis and management are crucial for optimising visual outcomes in the sympathising eye

Sympathetic ophthalmia: epidemiology and cohort-based assessment of clinical outcomes

Background: The purpose of this study was to report the incidence, time after inciting event, aetiology and risk after specific intraocular procedures and the visual outcomes associated with sympathetic ophthalmia (SO) occurrence. Methods: This study reports data from multiple retrospective cohorts: retrospective population-based data were extracted from the TRICARE service network (between 2017 and 2021) and retrospective case-based data from the Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) database (cohorts from the UK, South India and North India). Results: There were 159 patients with SO identified. The length of time from sensitising event to SO occurrence was a median of 151 days (range: 6–9100 days). In the TRICARE database, 2 patients developed SO after open globe trauma and primary repair (of 615 eyes, rate 0.33%; 95% CI 1.26% to 1.30%). None developed SO after vitrectomy (total of 23 903 events; 95% CI 0% to 0.012%). The combined North Indian and UK cohorts reported 78.6% (81 patients) after trauma, 18.45% (19 patients) after elective surgery. Visual outcomes were reported in the OASIS database for 98.01% of patients (155 of 157 patients). The median presenting and final best corrected visual acuity (BCVA) for the inciting eye were no perception of light, the median presenting and final BCVA for the sympathising eye were 0.65 and 0.3 logMAR, respectively. Conclusion: This study identified 159 cases of SO. With poor visual outcomes in the inciting eye, early diagnosis and management are crucial for optimising visual outcomes in the sympathising eye

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

Exploring patient and health care provider perspectives on barriers to diabetic retinopathy screening in public health facilities in North India.

Diabetic retinopathy (DR), a prevalent microvascular complication of diabetes mellitus (DM), can be prevented with early detection and timely intervention. DR is asymptomatic in its early stages, highlighting the importance of screening for accurate referral and effective management. Multiple barriers impede access to diabetic retinopathy screening (DRS), creating significant public health challenges in regions with high DM prevalence. This study explores the perspectives of people with DM (PwDM) and healthcare providers (HCP) on these barriers. A qualitative study using in-depth interviews (IDI) was conducted between October 2022 and January 2023 in Punjab and Chandigarh. Through purposive sampling, IDIs were conducted with 7 PwDM and 19 HCPs, including retina specialists, ophthalmologists, optometrists, medical officers (MO), Community Health Officers (CHO), and ASHA workers from various public health facilities. A semi-structured topic guide facilitated the interviews, and thematic analysis was applied, utilizing the healthcare access barrier (HCAB) model as a framework. The study identified financial barriers due to insurance unawareness and employment constraints. Structural challenges included insufficient DRS infrastructure, untrained staff, the need for accompaniment, and limited access to screening sites. Limited awareness and misconceptions about DR characterized cognitive barriers, while psychological barriers involved mistrust of the health system, anxiety, and frustration from low vision. Addressing these issues is essential to improve DRS uptake and eye health outcomes. Managing diabetes and VTDR is challenging, highlighting the need for community-level DRS. Enhancing DR awareness and promoting public health insurance benefits are crucial for overcoming barriers and improving screening rates