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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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

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., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

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., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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.

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.

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.

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.

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.

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., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

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.

Purpose: To compare the time to resolution of perivascular infiltrates in tubercular retinal vasculitis (TRV) between anti-tubercular therapy (ATT) alone, and in combination with systemic corticosteroids., Methods: Observational retrospective cohort study in a tertiary eye centre in eastern India. Patients with TRV who were treated with anti-tubercular therapy (ATT) alone (Group A), or in combination with systemic corticosteroids (Group B) were included in the study. Eyes with additional inflammatory signs (cystoid macular oedema, vitritis ≥2+, optic disc oedema) were excluded. Resolution was defined as complete disappearance of perivascular infiltrates on seven-field fundus photographs. Descriptive statistics were used for demographic data. A linear mixed effects model was applied to adjust for intereye correlations, in patients with bilateral disease. The primary outcome measure was time to resolution of perivascular infiltrates. Secondary outcome measure was need for laser or surgical intervention for management of complications of TRV., Results: Fifty eyes of 39 patients (Group A 21/18 and Group B 29/21) were included. Both groups had similar demographics and severity of vasculitis. All patients had complete resolution of TRV. On adjusting for intereye correlation, the mean difference in time to resolution between the two groups (Group A, 3.24 [95% CI 2.69-3.77] months, and Group B, 4.76 [95% CI 3.52-5.99] months) was not statistically significant (0.96 weeks [-0.52 to 2.45] p = 0.21). Vaso-occlusive complications and healing patterns were similar in both groups., Conclusions: ATT alone, may be sufficient for resolution of perivascular infiltrates, in TRV without additional inflammatory signs., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

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., Competing Interests: None

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., Competing Interests: Conflict of Interest: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The Handling editor NR declared a past co-authorship with the author SB.

Background: Choroidal tuberculoma is possibly the most unequivocal manifestation of ocular infection with Mycobacterium tuberculosis. Here, we investigate the need for adjunctive corticosteroids in the management of this infection. We have compared the efficacy of anti-tubercular therapy (ATT) with or without oral corticosteroids, in management of choroidal tuberculoma., Methods: We report a retrospective, observational study of patients treated with ATT for choroidal tuberculoma. Group A patients were treated with standard 6-month ATT alone, and Group B with ATT and oral corticosteroids, with/without intravitreal triamcinolone/ bevacizumab injections. Primary outcome measure was time to complete resolution of lesions. Secondary measures were time to first sign of resolution and change in best corrected visual acuity (BCVA) at final visit., Results: Fourteen patients were included in the study-seven in Group A and seven in Group B. Both groups had similar duration of symptoms and size of lesions but not baseline BCVA (p = 0.02). Perilesional fluid was noted in all eyes in each group. Mean time to complete resolution in group A was 1.89 ± 0.28 (range 1.25-2) months, significantly lesser than group B (5.17 ± 2.64 [range 2-9] months, p = 0.005, Mann-Whitney test). Mean time to first sign of resolution (range from 5 days to 10 weeks, p = 0.35) and mean change in BCVA between presentation and final follow up (p = 0.2) were comparable between both groups., Conclusion: Anti-TB monotherapy alone, may be sufficient for resolution of at least, select cases of choroidal tuberculoma, without the need for adjunctive corticosteroids., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: Razumab™ (world's first biosimilar ranibizumab) is approved for several macular disorders including wet age-related macular degeneration (AMD). We evaluated the safety and efficacy of biosimilar ranibizumab in wet AMD., Methods: This prospective, multicentre, rAnibizumab bioSimilar Safety Efficacy postmarkeTing (ASSET) study enrolled patients aged ≥ 50 years with wet AMD having best-corrected visual acuity (BCVA) between 20/40 and 20/320. The patients received intravitreal biosimilar ranibizumab 0.5 mg every 4 weeks for 24 weeks. Safety endpoints included the incidence of adverse events (AEs), serious AEs (SAEs), and immunoreactivity after 6 months. The efficacy endpoints were the proportion of patients who lose fewer than 15 letters, increase in BCVA, change in central retinal thickness (CRT), and change in Visual Function Questionnaire-25 (VFQ-25) score, from baseline to 24 weeks., Results: Of the 126 enrolled patients, majority (95.24%) of the patients received all 6 doses of biosimilar ranibizumab (total 3 mg). Nineteen AEs were reported (n = 16; 12.7%); majority (78.9%) were mild. There were no serious AEs reported, except one AE of death which was unrelated to the study drug. None of the patients discontinued the study due to an AE. The most common ocular AE was increase in intraocular pressure (4 events) and non-ocular AE was pyrexia (5 events). A total of 7.9% (10/126) patients prior to dosing and 7.1% (9/126) patients post-treatment were positive for anti-ranibizumab antibodies. No AEs suggestive of immunogenicity were noted. At 24-weeks, 97.60% patients in the intent-to-treat (ITT) population (N = 125) and 97.41% patients in the per-protocol (PP) population (N = 116) lost < 15 letters from baseline visual acuity. In the ITT and PP populations, 31.20% and 32.76% patients, respectively, showed improved visual acuity by ≥ 15 letters. Significant improvements in BCVA (mean difference: 8.8, 9.2, p < 0.001 for ITT, PP) and VFQ-25 (8.5, 9.2, p < 0.001 for ITT, PP) were seen; CRT reduced significantly (125 µm, 119.3 µm, p < 0.001 for ITT, PP)., Conclusion: Razumab™ (world's first biosimilar ranibizumab) was well-tolerated without new safety concerns and significantly improved visual acuity in wet AMD patients. Trial registration CTRI/2016/03/006739. Registered 18 March 2016-Prospectively registered, http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=13141&EncHid=&userName=2016/03/006739.

Purpose: To determine clinical signs suggestive of tubercular etiology in retinal vasculitis., Methods: A retrospective comparative study of patients who presented with retinal vasculitis at three tertiary care centers in India. All patients underwent detailed clinical evaluation and tailored laboratory investigations for etiological diagnosis. Tubercular etiology was diagnosed on basis on the presence of retinal periphlebitis in association with ancillary evidence of systemic tuberculosis and exclusion of nontuberculosis entities. Patients with tubercular (Group A) and nontubercular (Group B) etiology were compared for demographic characteristics, supportive diagnostic evidence, and specific ocular signs. Statistical analysis was performed at 5% confidence levels., Results: Of the 114 patients diagnosed with retinal vasculitis, Group A had 69 patients (100 eyes) and Group B had 45 patients (75 eyes). Active or healed subvascular lesions (P ≤ 0.0001), focal vascular tortuosity (P ≤ 0.0001), and occlusive vasculitis (P = 0.002) were significantly more common in Group A patients than in Group B patients. All three were independent predictors of tubercular etiology on multivariate regression analysis., Conclusion: The presence of healed or active subvascular lesions, focal vascular tortuosity, and occlusive vasculitis could be predictive of tubercular etiology in retinal vasculitis.

Abstract: The role of infections in intraocular inflammation is being increasingly recognized across the world. The Asia-Pacific region, being the single largest and most populous geographical entity on the planet, is home to a wide variety of such infections. Not surprisingly, there has been an explosion in the literature on infectious uveitis emerging from Asia-Pacific countries. In this review, we have covered recent advances in the diagnosis, treatment, and pathogenesis of common forms of infectious uveitis from the Asia-Pacific region. Much of the literature is focussed on the diagnosis of these infections by clinical criteria and laboratory investigations. There has also been an increased emphasis on the application of newer modes of ocular imaging and understanding pathomechanisms of ocular inflammation in these infections. Together this research has significantly improved our understanding of the diagnosis and management of infectious uveitis., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 Asia-Pacific Academy of Ophthalmology. Published by Wolters Kluwer Health, Inc. on behalf of the Asia-Pacific Academy of Ophthalmology.)

Purpose : To standardize a nomenclature system for defining clinical phenotypes, and outcome measures for reporting clinical and research data in patients with ocular tuberculosis (OTB). Methods : Uveitis experts initially administered and further deliberated the survey in an open meeting to determine and propose the preferred nomenclature for terms related to the OTB, terms describing the clinical phenotypes and treatment and reporting outcomes. Results : The group of experts reached a consensus on terming uveitis attributable to tuberculosis (TB) as tubercular uveitis. The working group introduced a SUN-compatible nomenclature that also defines disease "remission" and "cure", both of which are relevant for reporting treatment outcomes. Conclusion : A consensus nomenclature system has been adopted by a large group of international uveitis experts for OTB. The working group recommends the use of standardized nomenclature to prevent ambiguity in communication and to achieve the goal of spreading awareness of this blinding uveitis entity.

Competing Interests: None

Ocular tuberculosis (OTB) encompasses all forms of intra- and extra-ocular inflammation associated with Mycobacterium tuberculosis (Mtb) infection. However, the organism is rarely found in ocular fluid samples of diseased eyes, rendering the pathomechanisms of the disease unclear. This confounds clinical decision-making in diagnosis and treatment of OTB. Here, we critically review existing human and animal data related to ocular inflammation and TB pathogenesis to unravel likely pathomechanisms of OTB. Broadly there appear to be two fundamental mechanisms that may underlie the development of TB-associated ocular inflammation: a. inflammatory response to live/replicating Mtb in the eye, and b. immune mediated ocular inflammation induced by non-viable Mtb or its components in the eye. This distinction is significant as in direct Mtb-driven mechanisms, diagnosis and treatment would be aimed at detection of Mtb-infection and its elimination; while indirect mechanisms would primarily require anti-inflammatory therapy with adjunctive anti-TB therapy. Further, we discuss how that most clinical phenotypes of OTB likely represent a combination of both mechanisms, with one being predominant than the other., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: To study the prevalence, antibiotic susceptibility profile, clinical outcomes and plasmid-mediated transfer of colistin resistance (CLR) among Gram-negative bacilli (GNB) isolates from different ocular infections., Design: Prospective case-control study in eastern India., Methods: Consecutive ocular samples with GNB isolates from clinically diagnosed cases of microbial keratitis, infectious endophthalmitis and orbital infections were included. Inclusion criteria were significant GNB growth from ocular samples and > 6 weeks follow-up. Clinical outcomes were determined by disease-specific criteria for each clinical group. Antibiotic susceptibility was tested by broth microdilution for colistin and Kirby-Bauer disc diffusion method for others. Plasmid detection for CLR genes mcr-1 and mcr-2 genes was done by standard protocols., Results: Sixty GNB isolates were studied. Overall prevalence of CLR (intrinsic plus acquired) was 40% (n = 24), acquired being 37.5% of CLR isolates (n = 9). The prevalence varied from 45.5% (10/22) and 45% (9/20) in microbial keratitis and infectious endophthalmitis, respectively, to 26.3% (5/19) in orbital infections. Clinical outcomes in CLR patients were significantly worse in microbial keratitis (p = 0.018) and orbital infections (p = 0.018), and comparable to colistin-susceptible ones (p = 0.77) in infectious endophthalmitis. CLR isolates had significantly higher resistance to Amikacin, Gentamicin and Ceftazidime but were susceptible to Piperacillin, Carbapenems and fluoroquinolones. Plasmids mcr-1 and mcr-2 were detected in 6.25% (n = 1) and 25%(n = 4), respectively, of the 16 tested isolates., Conclusions: CLR is highly prevalent in ocular isolates and affects clinical outcomes. CLR isolates may still remain susceptible to Carbapenems, Piperacillin and fluoroquinolones. Plasmid mcr-1- and mcr-2-mediated CLR remains low in ocular infections.

Purpose: To report the clinical course, microbiological spectrum and visual outcomes of three cases of post-operative endophthalmitis caused by unusual combination of micro-organisms., Methods: Retrospective review of medical charts at a tertiary eye care centre over a period of 1 year, of subjects with post-operative endophthalmitis and more than one microbiological isolate., Results: We report 3 cases with unusual combination of microorganisms. In case 1, two organisms (Burkholderia cepacia and Aeromonas veronii, from the vitreous cavity and capsular bag, respectively) with an identical antibiotic sensitivity pattern were found, while in case 2, the organisms (Streptococcus pneumoniae and Sphingomonas paucimobilis, from cornea and vitreous cavity, respectively) isolated had different sensitivity patterns. In case 3, two different strains of the same organism (Enterococcus faecalis) were found. Cases 1 and 2 achieved good anatomical and visual outcomes, while in case 3, vision remained poor despite a good anatomical outcome., Conclusion: Unusual combinations of organisms in post-operative endophthalmitis can introduce unique clinical characteristics and should specifically be considered in atypical clinical presentations, poor response to standard therapy and unusual recurrence patterns.

Introduction: To report a case of retinal vasculitis associated with cutaneous leukocytoclastic vasculitis., Methods: Retrospective chart review., Results: A 28-year-old man, who initially presented with occlusive retinal vasculitis and vitreous hemorrhage in right eye that resolved with sectoral photocoagulation. Laboratory investigations for tuberculosis, sarcoidosis, syphilis and sickle cell disease were negative. Past history included recent diagnosis of Enterobacter epididymo-orchitis and multiple red nodules on skin of forearm. Fourteen months later, he developed active retinal vasculitis in right eye and recurrent nodules on forearm. Skin biopsy revealed neutrophilic infiltrates in and around dermal vessels with destruction of vessel walls leading to scattered neutrophils, lymphocytes and histiocytes between collagen bundles, suggestive of leukocytoclastic vasculitis. Both skin and ocular lesions resolved with oral corticosteroid and methotrexate therapy and did not recur over a six-year period., Conclusion: We have reported the first case of clinically manifest retinal vasculitis, associated with a common form of cutaneous vasculitis.

Purpose: Pars plana vitrectomy (PPV) is commonly performed for managing complications of uveitis but the anti-inflammatory potential of PPV has not been extensively investigated beyond aqueous/vitreous inflammation. We studied the effect of PPV on resolution of focal posterior segment lesions in tuberculosis-associated uveitis (TBU)., Design: Case control study., Participants: Patients with bilateral TBU and active retinal/choroidal lesions in both eyes, and who received PPV in one eye were included. Fellow eyes of same patients, matched for patient characteristics and systemic therapy, were designated as controls., Methods: Study eyes received 3-port 23-guage PPV, involving removal of nearly the entire vitreous. Part of vitreous sample was used for quantitative polymerase chain reaction (qPCR) for Mycobacterium tuberculosis. Post-operatively, anti-TB and/or systemic corticosteroid therapy was initiated depending on level of clinical suspicion of tubercular etiology, degree of intraocular inflammation and qPCR results. Focal lesions were documented in preoperative and postoperative fundus diagrams. Clinical photographs were taken whenever adequate media clarity was present., Main Outcome Measures: Primary outcome measures were rate of clinical resolution of focal posterior segment lesions and improvement in best-corrected visual acuity (BCVA), at 1 month post-surgery., Results: Thirty-six patients with bilateral posterior segment lesions consistent with TBU were included. Possible and probable TBU (depending on radiographic evidence of TB) were diagnosed in 28 (77.7%) and 4 (11.1%) patients respectively, whereas remaining 4 patients were diagnosed only on basis of qPCR results. Focal posterior segment lesions included retinal vasculitis (n = 27), multifocal-serpigenoid choroiditis (n = 5), multifocal choroiditis (n = 3) and focal choroiditis (n = 1). At one month postvitrectomy, 28 eyes (73.7%) showed complete resolution of focal posterior segment lesions compared to 7 non-vitrectomised eyes (19.4%), while improvement in BCVA was significantly more in study eyes (0.38 logarithm of the minimum angle of resolution [logMAR], P = 0.04), compared to controls (0.12 logMAR, P = 0.17). Time to resolution following vitrectomy was unaffected by duration of disease, pre-operative systemic steroids or grade of vitritis. At 3 months, complete resolution was noted in 29 of 30 study eyes (96.7%) and 25 of 30 control eyes (83.3%)., Conclusions: PPV facilitates faster resolution of focal posterior segment inflammation and BCVA improvement in TBU., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To study whether immediate pars plana vitrectomy at the time of sampling vitreous for culture alter the visual and structural outcomes in fungal endophthalmitis., Methods: Surgical results of 66 consecutive patients with culture-positive fungal endophthalmitis attending a tertiary eye care hospital in eastern India were analyzed. Based on the timing of vitrectomy, they were divided into 2 groups: Group 1-immediate vitrectomy (n = 31) and Group 2-diagnostic vitrectomy alone (n = 35) as the first-line intervention. The demographics, clinical features, and visual and structural outcomes were compared between the groups., Results: The proportion of postoperative (54.83 vs. 51.42%), traumatic (29.03 vs. 34.28%), and endogenous (16.12 vs. 14.28%) endophthalmitis and clinical signs such as pain (54.83 vs. 60%), lid edema (48.38 vs. 48.57%), conjunctival congestion (87.09 vs. 94.28%), and corneal involvement (87.09 vs. 80%) in Groups 1 and 2, respectively, were comparable. Logarithm of the minimum angle of resolution vision improvement in Group 1 was significant (P = 0.0278) though there was no statistically significant difference in posttreatment vision between the groups (P = 0.322). Phthisis was seen in 25.8% in Group 1 and 25.7% in Group 2 (P = 0.993). Aspergillus species was the most common fungal pathogen isolated. Early vitrectomy plus intravitreal antifungals in a subset of clinically suspected fungal endophthalmitis resulted in statistically significant visual improvement over diagnostic vitrectomy plus intravitreal antifungals (P = 0.013)., Conclusion: A strong clinical suspicion that translates into early vitrectomy plus intravitreal antifungal antibiotics leads to favorable visual and structural outcomes. A long wait till microbiological confirmation to institute antifungal therapy may result in poorer outcome.

Polymerase chain reaction (PCR)-based diagnosis of tuberculosis-associated uveitis (TBU) in TB-endemic countries is challenging due to likelihood of latent mycobacterial infection in both immune and non-immune cells. In this study, we investigated normalised quantitative PCR (nqPCR) in ocular fluids (aqueous/vitreous) for diagnosis of TBU in a TB-endemic population. Mycobacterial copy numbers (mpb64 gene) were normalised to host genome copy numbers (RNAse P RNA component H1 [RPPH1] gene) in TBU (n = 16) and control (n = 13) samples (discovery cohort). The mpb64:RPPH1 ratios (normalised value) from each TBU and control sample were tested against the current reference standard i.e. clinically-diagnosed TBU, to generate Receiver Operating Characteristic (ROC) curves. The optimum cut-off value of mpb64:RPPH1 ratio (0.011) for diagnosing TBU was identified from the highest Youden index. This cut-off value was then tested in a different cohort of TBU and controls (validation cohort, 20 cases and 18 controls), where it yielded specificity, sensitivity and diagnostic accuracy of 94.4%, 85.0%, and 89.4% respectively. The above values for conventional quantitative PCR (≥1 copy of mpb64 per reaction) were 61.1%, 90.0%, and 74.3% respectively. Normalisation markedly improved the specificity and diagnostic accuracy of quantitative PCR for diagnosis of TBU., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The molecular basis of intraocular tuberculosis (TB) is not well understood. In this study, we investigated the role of two constituents of viable Mycobacterium tuberculosis - Early Secreted Antigenic Target-6 (ESAT-6), and mycobacterial RNA- in inflammasome activation in the retinal pigment epithelium (RPE), a key site of inflammation in intraocular TB. We found that ESAT-6 induced caspase-1 activation and inflammasome priming in mouse RPE cells, substantially more in wild-type than in Tlr2/3/4/7/9 -/- , Myd88 -/- or Nlrp3 -/- RPE cells. Sub-retinal ESAT-6 injection resulted in greater RPE degeneration in wild-type than in Nlrp3 -/- mice. In human ocular TB tissue sections, NLRP3 staining was noted in retina as well as RPE. Mycobacterial RNA, specifically its double stranded component, also induced caspase-1 activation, and the double stranded RNA was immunolocalized to human ocular TB sections. Our observations suggest that inflammasome activation in RPE by viable M. tuberculosis could potentially contribute to human intraocular TB., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

An 11-month-old boy presented with bilateral vision loss following upper respiratory tract infection. Extensive perivascular sheathing resembling frosted branch angiitis and severe macular edema was noted in both eyes. All tests for etiological diagnosis were negative. Treatment with systemic corticosteroids and antibiotics caused resolution of perivascular infiltrates. Macular edema resolved with improvement in visual acuity following consecutive bilateral intravitreal triamcinolone acetonide injections. To our knowledge, this is the youngest reported case of frosted branch angiitis., (Copyright © 2012 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.)