Asymptomatic Ophthalmomyiasis Interna Posterior with Central Pigment Accumulation in the Inner Retina.

PURPOSE: To report a case of ophthalmomyiasis interna posterior which was asymptomatic and had pigment clumps in the inner retina at the macula. METHODS: Single-centre, observational, retrospective case report. RESULTS: A routine refractive error check-up for an asymptomatic 52-year-old Asian Indian woman, who had relied on glasses for 8 years, unfolded a captivating narrative within her retina. This coloured fundus photo unveils mid-peripheral retinal disease with multiple outer retinal atrophic tracts, circumlinear patterns, and intricately intertwined RPE atrophic tracts. These were hyper-autofluorescent on blue autofluorescence. The inferonasal periphery had two-disc diameters of pigmented retinal-choroidal atrophic scar. The macula revealed a collection of black intraretinal pigments in parafoveal areas. The distinct clinical presentation, marked by multiple tracts and unilateral manifestation without disc pallor, hinted at the intriguing possibility of self-resolved "Ophthalmomyiasis interna posterior." CONCLUSION: The course of disease in ophthalmomyiasis interna posterior can be self-limiting and asymptomatic. The presence of inner retinal pigments at foveal and parafoveal areas, possibly due to pigment migration from the peripheral outer retinal tracts, is a rare presentation.

Systemic and ocular outcomes in TB-immunoreactive patients receiving immunomodulatory therapy for non-infectious uveitis: a case-control study.

BACKGROUND: Tuberculosis (TB)-immunoreactivity, measured in vivo (tuberculin skin test (TST)) or in vitro (interferon gamma release assay (IGRA)), can be found in latent, active or even following clearance of TB infection. In this case-control study, we compared the systemic and ocular outcomes between patients with or without TB-immunoreactivity, who received immunomodulatory therapy (IMT) for non-infectious uveitis. METHODS: We retrospectively reviewed charts of patients with (cases) or without (controls) TB-immunoreactivity (TST±IGRA), who received conventional IMT for ≥6 months, for the treatment of non-infectious uveitis. Patients who received prior or concomitant anti-TB therapy were excluded. Systemic and ocular outcomes were compared between both groups. RESULTS: 36 cases and 70 controls (gender-matched and age-matched) were included. New-onset pulmonary or extrapulmonary TB developed in one case and none of the controls. Based on this outcome, the absolute risk increase for systemic TB reactivation was noted to be 0.028 (95% CI 0.005 to 0.051) and the number needed to harm was 36. The incidence of persistent or recurrent (worsening ≥2 grades) intraocular inflammation during IMT was comparable between both groups (cases 18/36, controls 35/70, p=1.0). A change in anatomical site of presentation at recurrence was not seen in any case, but in six controls (p=0.15). No new focal chorio-retinal lesions were noted in either group. CONCLUSIONS: Conventional IMT has a very low risk of systemic TB reactivation, and no additional detrimental effect on ocular outcomes, in TB-immunoreactive patients with non-infectious uveitis.

Anterior Non-Necrotizing Scleritis with Active Uveitis in Cases of Ocular Syphilis.

PURPOSE: To study clinical characteristics and management outcomes of cases of ocular syphilis co-presenting with scleritis and active uveitis. METHODS: A retrospective analysis of cases diagnosed with ocular syphilis between January 2020 and December 2023 was conducted at a tertiary eye care centre. Clinical records, investigations, and outcomes were reviewed to identify cases with scleritis with active uveitis. Demographic data, clinical features, treatment modalities, and resolution patterns were analyzed. RESULTS: Among the 135 eyes of 95 cases of ocular syphilis studied, scleritis with uveitis was observed in 3.70% of eyes (five eyes). All cases with scleritis and uveitis were unilateral and male, with ages ranging from 32 to 61 years. Concurrent features included placoid chorioretinitis, retinal vasculitis, and anterior uveitis. Misdiagnosis with subsequent oral steroid therapy precipitated scleritis as an exacerbation in two cases. Three cases, which were previously undiagnosed, were found to be HIV-positive. Scleritis manifested as anterior, non-necrotizing inflammation, often accompanied by chemosis, and responded rapidly to antibiotic and non-steroidal anti-inflammatory therapy. Scleritis resolution preceded that of chorioretinitis and retinal vasculitis. CONCLUSIONS: Non-necrotizing anterior scleritis with chemosis can be a rare presentation of active syphilitic uveitis. Large placoid chorioretinitis lesions, preceding inadvertent oral steroid and/or undiagnosed HIV status were the possible risk factors for the development of concurrent scleritis.

Intraocular Immune Response in Human Uveitis: Time to Look Beyond Animal Models.

PURPOSE: To review the current and future approaches to investigating the intraocular immune response in human uveitis. DESIGN: Perspective. METHODS: Review of currently available methods for investigating the immune response in ocular tissues and fluids in patients with intraocular inflammation/ uveitis. The advantages and disadvantages of human studies have been compared to those of animal models of uveitis. RESULTS: Animal models, while being excellent tools for mechanistic studies, do not replicate the clinical and immunologic heterogeneity of human uveitis. Opportunities for immunological studies in human uveitis are mostly limited to histological studies, or sampling of intraocular fluids and peripheral blood. Histopathological studies can be enhanced by revisiting published historical data, tissue repositories, or autopsy specimens. Intraocular fluids can be investigated by a variety of techniques. Among these, flow cytometry and single-cell RNA sequencing (scRNAseq) provide single-cell resolution. While the current technology is costly and labor-intensive, scRNAseq is less limited by the low cellular yield from intraocular fluids and allows unbiased immune profiling enabling discovery of new cellular subsets. Immunological phenotypes uncovered from human data can be further investigated in animal studies. CONCLUSION: The diversity of the intraocular immune response in uveitis patients remains challenging but can be studied by multiple techniques including histopathology, flow cytometry, and scRNAseq. Human data can be combined with animal studies for translating uveitis research into novel therapies.

Macular Punctate Lesions Presenting as a Primary Manifestation of Ocular Toxoplasmosis.

PURPOSE: To study clinical features and outcomes of primary ocular Toxoplasmosis (OT) cases presenting as macular punctate lesions. METHODS: Retrospective review of three cases of OT with positive Toxoplasma serology. RESULTS: We describe three cases presenting as primary OT with no evidence of old retinochoroidal scar in either eye. All the cases had multiple foveal or extrafoveal, punctate, inner/outer, or combined lesions at macula with minimal vitreous reaction. During the first/primary episode, all the lesions resolved with 1. retinal atrophy, thinning (n = 1) or 2. Progressed to limited full-thickness retinitis lesions (n = 2). Recurrence as typical retinochoroiditis was seen in one eye. More than four-fold IgG positivity was seen in all cases while IgM positivity was seen in two cases. CONCLUSIONS: Macular punctate lesions (inner/outer/combination) can be the primary manifestation of ocular toxoplasmosis in the absence of old retinochoroiditis scars in either eye.

Role of IgG avidity in eyes with active Toxoplasma retinochoroiditis.

PURPOSE: To study the role of Toxoplasma IgG avidity in evaluating the stage of systemic infection during manifestation as toxoplasma retinochoroiditis and its clinical implications in eastern India. METHODS: Retrospective chart review of Toxoplasma retinochoroiditis cases with Toxoplasma serology for IgG, IgM, and IgG avidity. RESULTS: Included in this study were 17 eyes of 17 patients who had active retinitis located in the macula (14), mid-periphery (2), or periphery (1). They were either primary lesions (12) or reactivations (5). All the cases had Toxoplasma IgG positive; one case had IgM positivity, while all the cases had high IgG avidity values. IgG avidity had a positive correlation with the duration of symptoms. CONCLUSION: We observed high IgG avidity values in active retinochoroiditis in both primary ocular Toxoplasmosis and reactivation subgroups. These results indicate a late ocular manifestation after initial systemic infection with a possible incubation period ranging from 5 weeks to 5 months.

Clinico-Microbiological Correlation in Salmonella Endophthalmitis: Case Series and Review of Literature.

PURPOSE: To report two rare cases of Salmonella endogenous endophthalmitis in an immunocompromised premature baby and an immunocompetent adult and do a brief literature review of related cases. Diagnosis in both cases was confirmed only after the pathogen grew from ocular samples, in the absence of clear signs of enteric fever. METHODS: Retrospective analysis of medical and microbiology records. RESULTS: Both of our cases of Salmonella endophthalmitis had poor visual outcome, despite timely and aggressive management and irrespective of immune status of the patient. Salmonella infection being a rare cause of endophthalmitis was not initially suspected as the adult had minimal systemic symptoms 2 weeks before presentation, while the preterm baby was still on milk feeds. These were just two microbiologically confirmed cases of Salmonella endophthalmitis at our institute over the past 10 years, though enteric fever due to Salmonella species is endemic in Asian countries. CONCLUSIONS: Salmonella endophthalmitis, though rare, leads to poor visual outcomes despite early recognition and aggressive management and may be confused with other infections or non-infectious entities such as necrotizing retinoblastoma in babies, in the absence of clear systemic signs of the disease.

VKH disease in the elderly: Variations in clinical course as compared to VKH disease in adults.

PURPOSE: To describe disease characteristics and outcomes of Vogt-Koyanagi-Harada (VKH) disease in elderly patients. METHODS: Retrospective analysis of patients older than 50 years with VKH disease at two referral centers in India. Demographics, extraocular and ocular involvement, treatment, complications, and visual acuity outcomes were noted. RESULTS: In total, 69 patients (mean age at presentation: 56.4 ± 4.7 years) were analyzed; 6/69 patients had diabetes mellitus at presentation, and 10/69 had hypertension. Clinical signs included anterior chamber cells >2+ (29%), granulomatous keratic precipitates (23%), disc hyperemia (26%), neurosensory retinal detachment (34.7%), and "sunset-glow" fundus (52.1%). Patients were classified as probable (n = 50, 72.4%), incomplete (n = 18, 26%), and complete VKH (n = 1, 1.4%). The mean follow-up period was 20.2 ± 19.4 months. Improvement in mean BCVA of (0.63 LogMAR, 6 Snellen lines) was noted on the last follow-up. Patients receiving systemic steroids with immunosuppressants ( P < 0.0001) had better visual outcomes at final follow-up compared to steroids alone ( P = 0.103). Eight patients (11.6%) had complications due to systemic immunosuppressants, and 17 patients (24.6%) developed diabetes mellitus or had worsening of diabetes while on systemic corticosteroids. CONCLUSION: Few patients presented with systemic manifestations in our cohort. Those treated with steroids and concurrent immunosuppressants had better outcomes. However, therapy with immunosuppressants was encountered with major dose-limiting complications in a significant number of elderly patients with VKH syndrome.

Tubercular Serpiginous-Like Choroiditis in Patients with Negative TB-Immunoreactivity Tests.

BACKGROUND: Serpiginous-like choroiditis (SLC) denotes ocular tuberculosis (TB), in the presence of positive tuberculin skin test (TST) or interferon gamma release assay (IGRA). METHODS: Retrospective review of SLC patients from a TB-endemic country, with negative TST and IGRA tests, but responsive to anti-TB therapy. RESULTS: Fifteen patients (13 bilateral) with active SLC were included. Eleven (73.3%) patients had received corticosteroids ± immunosuppressive therapy prior to presentation. Chest radiographic abnormalities were found in four (26.7%) patients. We treated all patients with a combination of anti-TB therapy (ATT) and corticosteroids. Paradoxical worsening was noted in nine (60%) patients, complete resolution of lesions in 12 (80%), persistent inflammation (post-ATT) in one, while two were yet to complete ATT. None had recurrence after complete resolution of lesions (median follow-up of 71 weeks [range 15-676 weeks]). CONCLUSIONS: TB-SLC may present with negative TST and IGRA tests but may still have clinical appearance, and treatment response, like test-positive disease.

Case Report: Ocular Tissue Diagnosis of Previously Undiagnosed, Extensively Drug-Resistant Pulmonary Tuberculosis.

We describe a patient with concurrent ocular and pulmonary tuberculosis (TB) in whom the diagnosis of extensively drug-resistant TB was made through phenotypic drug-sensitivity testing of an ocular fluid sample after sputum testing yielded incomplete results. Our results are remarkable, because culture-based diagnosis of TB in ocular fluid is unusual. We not only overcame this limitation, but also were able to create a complete drug-sensitivity testing profile from ocular samples, which led to effecting appropriate therapy for the patient.

Diabetes, Diabetic Retinopathy, and Inflammatory Disorders.

This review summarizes the impact of systemic and ocular inflammatory disorders on diabetes mellitus (DM) and diabetic retinopathy (DR). Local inflammation is a key pathology in diabetic retinopathy (DR) and is also an evolving target for clinical therapy. The legacy effects of local inflammation at the intracellular level make DR a persistent self-driven vicious process. Ocular inflammation is accompanied as well as incited by systemic inflammation due to diabetes mellitus (DM) itself. Over the years, a multitude of studies have evaluated the impact of systemic inflammatory disorders (SIDs, like rheumatoid arthritis, lupus, psoriasis, etc.) and anti-inflammatory drugs prescribed for managing them on manifestations of DM. Recent studies have indicated increased insulin resistance to be a result of chronic inflammation, and the anti-inflammatory drugs to have a protective effect towards DM. Very few studies have evaluated the impact of SIDs on DR. Furthermore, the evidence from these studies is conflicting, and while local anti-inflammatory therapy has shown a lot of clinical potential for use in DR, the results of systemic anti-inflammatory therapies have been inconsistent. The impact of local ocular inflammation due to uveitis on DR is a crucial aspect that has not been evaluated well at present. Initial pre-clinical studies and small-sized clinical reports have shown a strong and positive relationship between the presence of uveitis and the severity of DR as well as its progression, while larger cross-sectional patient surveys have refuted the same. The long term impact of ocular inflammation due to uveitis on DR needs to be studied while adjusting for confounders.

Beaded Pearls Appearance in Syphilitic Chorioretinitis.

PURPOSE: To report an atypical case of bilateral syphilitic chorioretinitis. METHODS: A case report. RESULTS: A young male presented with bilateral pigmentary retinal changes along with multifocal chorioretinal lesions along the blood vessels giving a "beaded pearl" appearance. He was a hitherto undiagnosed case of human immunodeficiency virus infection and was diagnosed to have syphilis. He had a favourable visual and anatomical outcome following treatment. CONCLUSION: Multifocal chorioretinal lesions along blood vessels forming a "beaded pearls" appearance can be a rare and unique presentation of syphilis.

Pathogenesis of Bacterial Uveitis.

PURPOSE: To describe the pathogenesis and the general immune mechanisms of the most frequent causes of bacterial uveitis. METHODOLOGY: Narrative review. RESULTS: Both extra- and intracellular bacteria can induce uveitis, whereas intracellular bacteria are generally transported into the inner eye via cells of the innate immune system, mainly macrophages. Systemic adaptive immunity is usually induced before the bacteria are localized to the inner eye, and once T and B cells have detected the pathogens behind the blood-eye barriers they elicit an acute and/or chronic inflammatory response deteriorating visual acuity that can severely affect the non-regenerating, intraocular tissues. CONCLUSIONS: An understanding of pathogenic mechanisms, and its correlation with clinical and imaging features, can facilitate early recognition of microbial factors and institution of appropriate therapy.

Mixed B- and T-lymphocyte Vitreous Infiltrate in Multiple Sclerosis Associated Uveitis.

A 23-year-old man, under treatment for relapsing remitting multiple sclerosis, presented with sudden drop in vision in the left eye for the past 1 week. We noted optic atrophy with sclerosed vessels in multiple quadrants in both eyes, moderate vitreous haze, and active retinal vasculitis in left eye. The patient received therapeutic pars plana vitrectomy in the left eye, and the vitreous sample was analyzed for immunophenotypes by flow cytometry (T-cells) and immunohistochemistry (B-cells). 65.1% of total vitreous cells were CD3+ T-cells. These included 42.4% CD4+, and 20.6% CD8+ T-cells. Immunohistochemistry detected CD20+ B-cells (not quantifiable). Our analysis demonstrated a mixed B- and T-lymphocyte vitreous infiltrate in multiple sclerosis-associated uveitis.

Antigen-Specific Intraocular Cytokine Responses Distinguish Ocular Tuberculosis From Undifferentiated Uveitis in Tuberculosis-Immunoreactive Patients.

PURPOSE: To compare antigen-specific intraocular immune responses between different clinical phenotypes of tuberculin skin test (TST)-positive and TST-negative uveitis. DESIGN: Single center, retrospective cross-sectional study. METHODS: Patients requiring diagnostic or therapeutic vitrectomy for the management of intraocular inflammation were divided into 3 groups based on Standardization of Uveitis Nomenclature (SUN) classification criteria for tubercular uveitis. Group 1 included patients with ocular tuberculosis (OTB; n = 23) who were TST-positive patients, met the SUN criteria, and/or had a polymerase chain reaction (PCR)-positive test for TB. Group 2 included patients with uveitis of unknown origin (UNK; n = 24) who were undifferentiated TST-positive patients who had not met SUN criteria. Group 3 included non-TB uveitis patients (n = 24) who were TST-negative either with or without a well-defined non-TB diagnosis. Total vitreous cells were activated with Mycobacterium tuberculosis-specific Early Secreted Antigenic Target-6 (ESAT-6) or the retinal autoantigen, interphotoreceptor retinoid-binding protein peptide (pIRBP 1-20), stained for intracellular interferon gamma (IFNγ), tumor necrosis factor-alfa (TNFα), and interleukin 17 (IL-17), and analyzed by flow cytometry. Antigen-specific single and dual (polyfunctional) cytokine responses to ESAT-6 and IRBP were compared between the 3 groups. RESULTS: All cytokine responses to ESAT-6 were higher in the UNK group compared with the non-TB control subjects, while all except IL-17 were comparable between the OTB and non-TB groups. Polyfunctional responses-IFNγ/IL-17 (P = .002), TNFα/IL-17 (P = .02), and TNFα/IFNγ (P = .01)-were significantly greater for UNK than the OTB group. Polyfunctional cells also produced more cytokine per cell than respective monofunctional cells. IRBP cytokine responses were comparable between different groups and were not affected by the clinical phenotype or duration of disease. CONCLUSION: The intraocular polyfunctional cytokine response is stronger in undifferentiated TST-positive uveitis than in OTB patients, likely representing an exaggerated anti-TB immune response rather than active infection.

Absence of Evidence as The Evidence Of Absence: The Curious Case of Latent Infection Causing Ocular Tuberculosis.

Ocular tuberculosis (TB) is frequently considered as intraocular inflammation in the setting of latent TB, owing mainly to the absence of microbiological evidence of Mycobacterium tuberculosis in ocular fluid samples. Even though such lack of microbiological evidence, and of systemic signs of active TB disease, are suggestive of latent TB infection, molecular and rare histopathologic evidence of mycobacteria in the eye, and favourable response of ocular inflammation to anti-TB therapy point to the presence of active infection in ocular TB. Here, we discuss how intraocular inflammation in ocular TB is not merely an immunologic response to bacilli, but an active tuberculosis infection. We will discuss the reason for the frequent absence of microbiological evidence of TB in the eye in ocular TB and the diagnostic hierarchy to arrive at the diagnosis of this infectious uveitis entity.

Clinical and imaging characteristics of outer retinal folds in eyes with retinitis.

Purpose: To describe clinical and imaging characteristics of the outer retinal folds (ORF) in cases of retinitis, retinochoroiditis, and chorioretinitis. Methods: Retrospective review of retinitis cases with presence of ORFs either at presentation or during follow up. Results: ORFs were seen adjacent to retinitis lesions in 16 eyes of 14 cases (retinitis post-febrile illness n = 10, toxoplasma retinochoroiditis n = 2, fungal chorioretinitis n = 2) either at presentation (n = 2) or during follow up (n = 14). Optical coherence tomography (OCT) appearance was outer retinal vertical stout lesions involving ellipsoid, external limiting membrane, and outer nuclear layer. All the cases had a presence of past or concurrent subretinal fluid and/or subretinal hyperreflective material when ORF was seen. ORF resolved with variable outer retinal atrophy over a mean period of 2.86 months. Conclusion: ORF is observed in cases of retinitis with subretinal fluid either at presentation or during resolution. It is not specific to any etiological disease. Differentiation of this sign from vertical outer retinal stripes in viral retinitis on OCT is important to avoid misinterpretation.

Therapeutic Vitrectomy in the Management of Uveitis: Opportunities and Challenges.

PURPOSE: Pars plana vitrectomy (PPV) has been traditionally used for diagnostic tapping or for management of posterior segment complications, in uveitis. The anti-inflammatory potential of therapeutic PPV, independent of its role in managing uveitis complications, is yet to be realised completely. In this narrative review, we have described the indications, surgical technique, and outcomes of therapeutic PPV in the management of uveitis. METHODS: Literature review of PubMed database for articles relating directly or indirectly, to the anti-inflammatory effect of therapeutic PPV in the management of uveitis. Of the 876 articles retrieved on initial review, only 37 articles were found to be relevant for the purpose of this review. RESULTS: Therapeutic PPV is effective in controlling vitreous inflammation, improving visual outcomes and reducing the need for immunosuppressive medications in a wide range of infectious and non-infectious uveitis. Careful patient selection and meticulous surgical handling are mandatory. Post-operative complications include cataract progression, raised intraocular pressure, hypotony, retinal breaks, and worsening of cystoid macular edema. Despite being introduced more than 40 years ago, most data on therapeutic PPV remain retrospective. The possibility of therapeutic PPV replacing conventional medical therapy remains unknown. CONCLUSIONS: Therapeutic PPV can control intraocular inflammation, independent of its role in managing posterior segment complications of uveitis. However, its exact place in the anti-inflammatory armamentarium against uveitis remains uncertain.

LV Prasad Eye Institute EyeSmart electronic medical record-based analytics of big data: LEAD-Uveitis Report 1: Demographics and clinical features of uveitis in a multi-tier hospital based network in Southern India.

Purpose: To describe the demographics and epidemiology of uveitis presenting to a multi-tier ophthalmology hospital network in Southern India. Methods: Cross-sectional hospital-based study of 19,352 patients with uveitis presenting between March 2012 and August 2018. Results: In total, 1,734,272 new patients were seen across the secondary and tertiary centers of our multi-tier ophthalmology hospital network during the study period. Among them, 25,353 eyes of 19,352 patients were diagnosed with uveitis and were included in the study. Uveitis constituted 1.11% of all cases. The majority of patients were male (60.33%) and had unilateral (68.09%) affliction. The most common age group was 21-50 years with 12,204 (63.06%) patients. The most common type of uveitis was anterior uveitis, which was seen in 7380 (38.14%) patients, followed by posterior uveitis in 5397 (23.89%) patients. Among the infectious causes, tuberculosis was the most common etiology (2551 patients, 13%) followed by toxoplasmosis (1147 patients, 6%). Conclusion: Uveitis constituted 1.11% of all cases presenting to our clinics. It was more common in the age group of 21-50 and was predominantly unilateral. Anterior uveitis was the most common subtype seen in 38%.

Vogt Koyanagi Harada Disease In Paediatric Age Group: Clinical Characteristics, Remission, Recurrences and Complications in Asian Indian Population.

PURPOSE: To describe disease characteristics and outcomes of Vogt-Koyanagi-Harada (VKH) syndrome in paediatric patients. STUDY DESIGN: Retrospective chart analysis. METHODS: A RETROSPECTIVE: Analysis of all patients ≤16 years with VKH syndrome was done. Clinical presentations, complications, recurrences and outcomes in cases of paediatric VKH were reviewed. RESULTS: 72 eyes of 36 patients with a mean age at presentation of 13.7 ± 2.34 years were assessed. Mean duration of symptoms and follow up were 9.88 ± 17.3 weeks and 55 months respectively. Clinical signs at presentation included anterior chamber cells >2+(34/72eyes, 47.2%), granulomatous keratic precipitates (6 eyes, 8.3%), posterior synechiae (35 eyes,48.6%), disc edema (46 eyes, 63.8%), neurosensory retinal detachments (44 eyes, 61.1%) and 'sunset-glow' fundus (9 eyes, 12.5%). Best corrected visual acuity (BCVA) at the time of presentation was 1.3logMAR or a Snellens equivalent of 20/400 which improved to 0.51logMAR (Snellens equivalent of 20/63) at last follow up. Remission was achieved in 61.1% cases. More than half of our patients developed one or more complications. CONCLUSION: VKH in paediatric patients poses a challenge due to a delayed presentation and paediatric VKH patients have a worse visual acuity at the time of presentation as compared to adult age groups. Rates of remission may be low along with high risk of complications and hence there is a need for prolonged immunosuppression.