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Purpose: Leptospirosis is an endemic disease in India and uveitis is its late complication. Several Indian reports showed diversity of serovars, changing patterns and existence of new serovars. Failure to add new serovars in testing panel result in increased false-negativity in serology. Aim: To analyse seroprevalence, changing patterns and to discuss the resulting challenges in diagnosis. Methods: In this retrospective study covering the period from 1994 to 2020, we analysed data from laboratory records of patients diagnosed with leptospiral uveitis in South India. Microscopic agglutination Test (MAT) and/or Enzyme-Linked Immunosorbent Assay (ELISA) were performed on clinically diagnosed leptospiral uveitis cases from our hospital, as well as on systemic leptospirosis patients from government and private hospitals. Results: Out of a total of 87 216 new uveitis cases with varying causes over 27 years, 3,658 (4.1%) were clinically diagnosed as leptospiral uveitis. Among them, 1,268 (34.7%) patients were seropositive. In 1994, 92% of clinically diagnosed leptospirosis patients were seropositive in the MAT performed at the Centers for Disease Control and Prevention in Atlanta. However, the positivity rate gradually declined to 35% over the years. The predominant serovars identified were L. autumnalis, L. icterohaemorrhagiae, and L. australis. There were notable variations in the distribution of serovars over the years. Conclusions: The data suggest a declining sensitivity of MAT and ELISA, possibly due to the emergence of new serovars. Customizing the panel based on local isolates could enhance the performance of MAT. Critical need is the addition of advanced molecular techniques to improve the diagnosis. [ABSTRACT FROM AUTHOR]

The management of glaucoma in uveitis is challenging. A meticulous combination of anti-glaucoma and anti-inflammatory agents is often needed to control the intraocular pressure (IOP) and preserve the visual status in an otherwise blinding disease. To study the clinical course and management of glaucoma in uveitic eyes. A retrospective study analyzing the case records of patients over 12 years, referred for the management of uveitic glaucoma in the last two decades. The analysis of 582 uveitic glaucoma eyes of 389 patients was done, and the mean IOP at baseline was 25.89 (±13.1) mmHg. Non-granulomatous uveitis (102 eyes) was the most common diagnosis. Granulomatous uveitis was the most common diagnosis among the treatment failure eyes and in eyes requiring more than one surgical intervention for glaucoma. An appropriate and adequate combination of anti-inflammatory and IOP-lowering therapy will lead to better clinical outcomes. [ABSTRACT FROM AUTHOR]

Some patients taking methotrexate (MTX) or mycophenolate mofetil (MMF) experience intolerable side effects at full doses. We evaluated whether dose reduction affected treatment outcomes in uveitis patients. Subanalysis of the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial. Patients were randomized to receive MTX (25 mg weekly) or MMF (3 g daily). A pre-specified dose reduction protocol could be employed for intolerable side effects. Primary analysis was performed at 6 months. 43/194 patients (22%) required dose reduction. 88/151 patients (58%) on maximum doses and 32/43 patients (74%) on reduced doses were deemed treatment successes at 6 months. The odds ratio point estimate (1.60, 95% CI 0.72–3.74) favored dose-reduction but this was not significant. Following reduction, adverse events improved at the subsequent study visit (79 events reduced to 63 events). Dose reduction of antimetabolites was not associated with worse outcomes in this subanalysis of a uveitis trial. [ABSTRACT FROM AUTHOR]

Purpose: Leptospirosis is a waterborne zoonotic disease prevalent in tropical regions, causing significant morbidity and mortality. It can involve any organ in its primary stage, and uveitis is its late complication. While advanced laboratory diagnosis is available only in tertiary care centers globally, a cost‑effective bedside assessment of clinical signs and their scoring could offer a provisional diagnosis. Aim: To analyze the diagnostic potential of demographic and clinical signs in a large cohort of serologically confirmed leptospiral uveitis patients. Methods: In this retrospective study, demographic and clinical parameters of 876 seropositive leptospiral uveitis patients and 1042 nonleptospiral uveitis controls were studied. Multivariable logistic regression analysis with bootstrap confidence interval (CI) characterized the diagnostic predictors. The performance of the model was evaluated using the area under the receiver operating curve (AUROC). Results: Presence of nongranulomatous uveitis (odds ratio [OR] = 6.9), hypopyon (OR = 4.6), vitreous infiltration with membranous opacities (OR = 4.3), bilateral involvement (OR = 4), panuveitis (OR = 3.3), vasculitis (OR = 1.9), disc hyperemia (OR = 1.6), absence of retinochoroiditis (OR = 15), and absence of cystoid macular edema (OR = 8.9) emerged as predictive parameters. The AUROC value was 0.86 with 95% CI of 0.846–0.874. At a cut‑off score of 40, the sensitivity and specificity were 79.5 and 78.4, respectively. Conclusion: The study demonstrates that ocular signs can serve as diagnostic predictors for leptospiral uveitis, enabling primary care ophthalmologists to make bedside diagnosis. This can be further confirmed by laboratory methods available at tertiary care centers. [ABSTRACT FROM AUTHOR]

Purpose: Leptospirosis is a waterborne zoonotic disease that primarily causes systemic illness, followed by uveitis. After heavy flooding in Madurai district, an epidemic outbreak of systemic and ocular leptospirosis occurred in 1994. Our data shows a transition to endemicity after each epidemic. Aim: The aim of this study is to report the clinical signs, epidemic outbreaks, and persistent endemicity of leptospiral uveitis, as well as the diagnostic dilemmas associated with it. Methods: A retrospective analysis of clinical signs was conducted using medical records of leptospiral uveitis patients over a period of 27 years (1994-2020) in a tertiary care eye hospital. The clinical workup of uveitis included a detailed clinical history, systemic, and ophthalmic examination. Microagglutination tests (MATs) was done at the Centers for Disease Control and Prevention (CDC) in Atlanta and later in our regional laboratory. Serum samples were collected from human systemic leptospirosis cases and a small group of animals in and around Madurai. Results: The first epidemic outbreak resulted in 200 seropositive patients. Subsequent epidemic outbreaks occurred in 1997, 1998, 2001, 2005, and 2012, with Madurai experiencing multiple outbreaks. However, the disease remained endemic, with 25-50 patients being observed per year in between the peaks. Ocular examination revealed acute non-granulomatous uveitis (94.9%), pan uveitis (59.8%), vitreous inflammatory reaction (55.4%), retinal vasculitis (29.5%), disc hyperemia (20.9%), and hypopyon. (16.2%). New serovars emerged every year, resulting in decreased sensitivity of the MAT. Over time, the MAT started to miss diagnoses. Conclusion: The persistent endemicity of leptospiral uveitis emphasizes the need for accessible diagnostic tests. The low performance of the MAT can be attributable to the use of an older panel. The incorporation of new isolates in the MAT by a national laboratory will improve the accuracy of diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: Patient safety errors can arise due to similarity in packaging of medications. We aimed to describe the clinical features of patients presenting with accidental application of joint pain liniments and gum lotion in the eye due to confusion arising from similarity in packaging.Methods: This was a retrospective case series with eight consecutive patients presenting from December 2020 to August 2021 with history of accidental application of joint pain liniments or gum lotion in the eye instead of eye drops. All patients underwent visual acuity assessment and slit-lamp examination with fluorescein staining of the cornea to look for corneal involvement and was reassessed till complete resolution.Results: Of the eight patients, three were males and five were females. Seven had accidentally applied joint pain liniment, while one had applied gum lotion into the eye. Five of them had corneal involvement ranging from punctate erosions to near-total epithelial defects. Two patients needed referral to a tertiary center and hospital admission. Treatment duration ranged from 2 days to 1 month. Two patients were lost to follow-up.Conclusion: This study highlights patient safety errors arising from confusion of medication due to similar labeling and packaging of different drugs. While there was no permanent morbidity, such confusions lead to needless discomfort and waste of time, money, and effort for the patient as well as the health-care system. [ABSTRACT FROM AUTHOR]

Uveitis is a complex disorder including both infectious and non-infectious etiologies. Clinical diagnosis is a challenge because many diseases share common clinical signs. Laboratory support is crucial for confirming the clinical diagnosis. Laboratory diagnosis includes direct tests and indirect tests. For example smear, culture, and molecular diagnostics demonstrate the pathogens, hence they are direct tests. Immunologic tests employ an antigen to detect presence of antibodies to a pathogen, or an antibody to detect the presence of an antigen, of the pathogen in the specimens. The immunological tests used in laboratories are made by producing artificial antibodies that exactly "match" the pathogen in question. When these antibodies come into contact with a sample they bind to the matching pathogen if found in the sample. Hence they are grouped under indirect evidence. There are several investigations in uveitis to reach the confirmed diagnosis including microbiological, immunological, imaging and molecular diagnostic testing. In this section we will discuss immunological investigations of infectious and non-infectious uveitis. [ABSTRACT FROM AUTHOR]

Importance: Methotrexate and mycophenolate mofetil are commonly used immunomodulatory therapies for achieving corticosteroid-sparing control of noninfectious uveitis, but there is uncertainty about which drug is more effective.Objective: To compare the effect of methotrexate and mycophenolate for achieving corticosteroid-sparing control of noninfectious intermediate uveitis, posterior uveitis, and panuveitis.Design, Setting, and Participants: The First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial screened 265 adults with noninfectious uveitis requiring corticosteroid-sparing immunosuppressive therapy from 9 referral eye centers in India, the United States, Australia, Saudi Arabia, and Mexico between August 22, 2013, and August 16, 2017. Follow-up ended on August 20, 2018.Interventions: Patients were randomized to receive oral methotrexate, 25 mg weekly (n = 107), or oral mycophenolate mofetil, 3 g daily (n = 109).Main Outcomes and Measures: The primary outcome was treatment success at 6 months, which was defined as having control of inflammation in both eyes, no more than 7.5 mg prednisone daily and less than or equal to 2 drops of prednisolone acetate 1%, and no treatment failure due to safety or intolerability. Patients underwent follow-up to 12 months while receiving the same treatment or switched to the other antimetabolite, depending on their 6-month outcome.Results: Among 216 patients who were randomized (median age, 38 years; 135 (62.5%) women), 194 (89.8%) completed follow-up through 6 months. Treatment success occurred in 64 (66.7%) patients in the methotrexate group vs 56 (57.1%) in the mycophenolate group (difference, 9.5% [95% CI, -5.3% to 21.8%]; odds ratio [OR], 1.50 [95% CI, 0.81 to 2.81]; P = .20). Among patients with posterior uveitis or panuveitis, treatment success was achieved in 58 (74.4%) in the methotrexate group vs 42 (55.3%) in the mycophenolate group (difference, 19.1% [95% CI, 3.6% to 30.6%]; OR, 2.35 [95% CI, 1.16 to 4.90]; P = .02); whereas among patients with intermediate uveitis treatment success occurred in 6 (33.3%) in the methotrexate group vs 14 (63.6%) in the mycophenolate group (difference, -30.3% [95% CI, -51.6% to 1.1%]; OR, 0.29 [95% CI, 0.08 to 1.05]; P = .07; P for interaction = .004). Elevated liver enzymes were the most common nonserious laboratory adverse event, occurring in 14 patients (13.0%) in the methotrexate group and 8 patients (7.4%) in the mycophenolate group.Conclusions and Relevance: Among adults with noninfectious uveitis, the use of mycophenolate mofetil compared with methotrexate as first-line corticosteroid-sparing treatment did not result in superior control of inflammation. Further research is needed to determine if either drug is more effective based on the anatomical subtype of uveitis.Trial Registration: ClinicalTrials.gov Identifier: NCT01829295. [ABSTRACT FROM AUTHOR]

Episcleritis, scleritis, and anterior uveitis are common clinical manifestations of ocular leprosy. Erythema nodosum leprosum (ENL) is an acute, exaggerated systemic immunological reaction that complicates the course of this chronic indolent disease. We present an ocular immunohistochemical study of severe form of ENL involving even the ciliary body and choroid resulting in the perforation of the globe on the initiation of anti leprosy therapy. We used CD-3, CD-68, S-100, and CD-20 for immunohistochemistry. It revealed plenty of CD-3-positive T-cells and CD-68-positive macrophages and a few S-100 and CD-20-positive cells. The inflammatory exudates stained positive for IgG and IgM. The diagnosis was ocular ENL. [ABSTRACT FROM AUTHOR]

Leptospirosis is a bacterial cause for nongranulomatous uveitis in tropical countries. It is known to cause rapid maturation of cataract in young adults. Here we present six patients who had presenting sign as fully matured pearly white unilateral cataract without history of any trauma in their first visit. All except one patient were positive for leptospirosis by ELISA testing. Histopathological analyses of those lenses showed globular degeneration. [ABSTRACT FROM AUTHOR]

To report a rare case of Muller cell sheen dystrophy and to describe its clinical and diagnostic aspects. A 42-year-old woman presented with unilateral defective vision. Fundus evaluation revealed bilateral glistening retinal reflexes throughout the posterior pole with a wrinkled appearance in the right. Spectral Domain-OCT in the right showed abnormal internal limiting membrane, intraretinal schisis with serous detachment at macula. Angiography revealed staining along vessels. Electroretinogram in the affected eye was negative. At 4 months of follow up, vision dropped and intraretinal schisis increased. Family screening was negative. [ABSTRACT FROM AUTHOR]

All other cited papers address etiological diagnosis.[[3]],[[4]],[[5]] If an EMR is not updated immediately, as soon as new information is gathered - such as test results - anyone viewing that EMR could be receiving incorrect or incomplete information. Electronic medical records (EMRs) have a great impact in clinical practice. However, in materials and in results they have reviewed only the medical records of secondary-center and the tertiary-center patients, probably because they assumed that all uveitis patients of the 176 vision centers were referred to tertiary centers. [Extracted from the article]

Purpose: To evaluate how changes in visual acuity are associated with changes in quality of life (QoL) among patients with non-infectious uveitis taking antimetabolites., Methods: This secondary analysis of the multicenter First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial involves 216 participants randomized to methotrexate or mycophenolate mofetil. Vision-related (NEI-VFQ and IND-VFQ) and health-related (PCS and MCS SF-36v2) QoL and visual acuity were measured at baseline and 6-month primary endpoint., Results: Visual acuity was significantly associated and correlated with all QoL measures (Spearman correlation coefficients = 0.5, 0.5, 0.3, and 0.4 for NEI-VFQ, IND-VFQ, SF-36v2 MCS and PCS, respectively). All observed changes in QoL met or exceeded the minimal clinically important difference definition on each scale. Treatment group was not significantly associated with any QoL measure., Conclusion: By adding insight beyond visual acuity, QoL provides a more comprehensive picture of the patient experience during uveitis treatment. Abbreviations and Acronyms: QoL = quality of life; VR-QoL = vision-related quality of life; HR-QoL = health-related quality of life; FAST = First-line Antimetabolites as Corticosteroid Sparing Treatment; NEI-VFQ = National Eye Institute Visual Functioning Questionnaire; IND-VFQ = Indian Visual Functioning Questionnaire; SF-36v2 = Medical Outcomes Study 36-Item Short Form Survey; PCS = physical component score; MCS = mental component score; 95% CI = 95% confidence interval; MCID = minimal clinically important difference.

Background: MicroRNA (miRNA) expression analysis has been shown to provide them as biomarkers in several eye diseases and has a regulatory role in pathogenesis. However, miRNA expression analysis in the vitreous humor (VH) of intraocular tuberculosis (IOTB) is not studied. Thus, we aim to find miRNA expression signatures in the VH of IOTB patients to identify their regulatory role in disease pathogenesis and to find them as potential biomarkers for IOTB., Methods and Results: First, we profiled miRNAs in VH of three IOTB and three Macular hole (MH) samples as controls through small-RNA deep sequencing using Illumina Platform. In-house bioinformatics analysis identified 81 dysregulated miRNAs in IOTB. Further validation in VH of IOTB (n = 15) compared to MH (n = 15) using Real-Time quantitative PCR (RT-qPCR) identified three significantly upregulated miRNAs, hsa-miR-150-5p, hsa-miR-26b-5p, and hsa-miR-21-5p. Based on the miRNA target prediction, functional network analysis, and RT-qPCR analysis of target genes, the three miRNAs downregulating WNT5A, PRKCA, MAP3K7, IL7, TGFB2, IL1A, PRKCB, TNFA, and TP53 genes involving MAPK signaling pathway, PI3K-AKT signaling pathway, WNT signaling pathway, Cell cycle, TGF-beta signaling pathway, Long-term potentiation, and Sphingolipid signaling pathways, have a potential role in disease pathogenesis. The ROC analysis of RT-qPCR data showed that hsa-miR-150-5p with AUC = 0.715, hsa-miR-21-5p with AUC = 0.789, and hsa-miR-26b-5p with AUC = 0.738; however, the combination of hsa-miR-21-5p and hsa-miR-26b-5p with AUC = 0.796 could serve as a potential biomarker for IOTB., Conclusions: This study provides the first report on miRNA expression signatures detected in VH for IOTB pathogenesis and also provides a potential biomarker for IOTB., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The antimetabolites methotrexate (MTX) and mycophenolate mofetil (MMF) are commonly used as initial corticosteroid-sparing treatment for uveitis. There is little data examining risk factors for failing both MTX and MMF. The objective of this study is to determine risk factors for failing both MTX and MMF in patients with non-infectious uveitis., Main Body: This is a sub-analysis of the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial, which was an international, multicenter, block-randomized, observer-masked, comparative effectiveness trial comparing MTX and MMF as initial treatments for non-infectious uveitis. This study was undertaken at multiple referral centers in India, the United States, Australia, Saudi Arabia and Mexico between 2013 and 2017. A total of 137 patients who completed all 12 months of follow-up from the FAST trial, were included in this study. The primary outcome was failing both antimetabolites over the 12 months of the trial. Potential predictors included: age, sex, bilateral involvement, anatomic location of the uveitis, presence of cystoid macular edema (CME) and retinal vasculitis at baseline visit, uveitis duration, and country/study sites as risk factors for failing both MTX and MMF. The presence of retinal vasculitis posterior to the equator on fluorescein angiogram was associated with failing both MTX and MMF., Conclusion: Retinal vasculitis may be a risk factor for failing multiple antimetabolites. Clinicians could consider more quickly advancing these patients to other medication classes, such as biologics., (© 2023. The Author(s).)

Purpose: Sub-analysis of the FAST Trial comparing change in CD4 (∆CD4) from baseline through 12 months in uveitis patients treated with mycophenolate mofetil (MMF) and methotrexate (MTX)., Methods: Patients were randomly allocated to 1.5 g twice daily MMF or 25 mg weekly MTX. Individuals with CD4 counts at baseline, 6 months (or treatment failure prior), and 12 months (or treatment failure between 6 and 12 months) were included. The association between treatment and ∆CD4 (cells/μL) was analyzed using multivariable linear regression., Results: There was no significant difference in ∆CD4 between MMF and MTX at 6 months (-31.7 cells/μL for MMF compared to MTX; 95% CI: -358.2 to 294.8, P = .85) and 12 months (-78.3 cells/μL for MMF compared to MTX; 95% CI: -468.0 to 311.3; P = .69)., Conclusion: There was no significant difference in ∆CD4 between MMF and MTX from baseline to 12 months, suggesting that MMF does not confer additional risk of CD4 lymphopenia in uveitic patients.ClinicalTrials.gov Identifier: NCT01829295.

Aim: To look at markers to differentiate ocular sarcoidosis from ocular tuberculosis in a high TB endemic population., Materials & Methods: Retrospective multicenter study involving seven tertiary eyecare centers in India between July 2016 to December 2016. Demographic, clinical and laboratory data were retrieved from respective hospital databases. Group A included biopsy-proven ocular sarcoidosis while group B included ocular tuberculosis., Results: Data from 2726 consecutive patients with uveitis were retrieved from the databases. Group A had 61 cases while group B included 307 cases. The mean age in group A was 43 ± 16.55 years while in group B was 38 ± 13.13 years. Females were more common in group A. Uveitis with low Schirmer test (OR-30, CI-95%), candlewax retinal vasculitis (OR-8.69, CI-95%), hilar lymphadenopathy (OR-15.23, CI-95%), fissural nodules (OR-39.11, CI-95%) had higher odds of having ocular sarcoidosis., Conclusion: Presence of dry eye, candlewax retinal vasculitis, hilar lymphadenopathy, and fissural nodules if present in a patient with uveitis, could help differentiate ocular sarcoidosis from ocular tuberculosis in a high TB endemic population.

Purpose: To evaluate changes in health-related and vision-related quality of life (VRQoL) among patients with noninfectious uveitis who were treated with antimetabolites., Design: Secondary analysis of a randomized controlled trial., Participants: Patients with noninfectious uveitis from India, the United States, Australia, Saudi Arabia, and Mexico., Methods: From 2013 through 2017, 216 participants were randomized to receive 25 mg weekly oral methotrexate or 1.5 g twice daily oral mycophenolate mofetil. Median changes in quality of life (QoL) were measured using Wilcoxon signed-rank tests, and differences between treatment groups were measured using linear mixed models, adjusting for baseline QoL score, age, gender, and site. Among Indian patients, VRQoL scores from a general scale (the National Eye Institute Visual Function Questionnaire [NEI-VFQ]) and a culturally specific scale (the Indian Visual Function Questionnaire [IND-VFQ]) were compared using Pearson correlation tests., Main Outcome Measures: Vision-related QoL (NEI-VFQ and IND-VFQ) and health-related QoL (HRQoL; physical component score [PCS] and mental component score [MCS] of the Medical Outcomes Study 36-Item Short Form Survey [SF-36v2]) were measured at baseline, the primary end point (6 months or treatment failure before 6 months), and the secondary end point (12 months or treatment failure between 6 and 12 months)., Results: Among 193 participants who reached the primary end point, VRQoL increased from baseline by a median of 12.0 points (interquartile range [IQR], 1.0-26.1, NEI-VFQ scale), physical HRQoL increased by a median of 3.6 points (IQR, -1.4 to 14.9, PCS SF-36v2), and mental HRQoL increased by a median of 3.0 points (IQR, -3.7 to 11.9, MCS SF-36v2). These improvements in NEI-VFQ, SF-36v2 PCS, and SF-36v2 MCS scores all were significant (P < 0.01). The linear mixed models showed that QoL did not differ between treatment groups for each QoL assessment (NEI-VFQ, IND-VFQ, PCS SF-36v2, and MCS SF-36v2; P > 0.05 for all). The NEI-VFQ and IND-VFQ scores for Indian participants were correlated highly at baseline and the primary and secondary end points (correlation coefficients, 0.87, 0.80, and 0.90, respectively)., Conclusions: Among patients treated with methotrexate or mycophenolate mofetil for uveitis, VRQoL and HRQoL improved significantly over the course of 1 year and did not differ by treatment allocation. These findings suggest that antimetabolites could improve overall patient well-being and daily functioning., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

An international, expert led consensus initiative was set up by the Collaborative Ocular Tuberculosis Study (COTS) group to develop systematic, evidence, and experience-based recommendations for the treatment of ocular TB using a modified Delphi technique process. In the first round of Delphi, the group identified clinical scenarios pertinent to ocular TB based on five clinical phenotypes (anterior uveitis, intermediate uveitis, choroiditis, retinal vasculitis, and panuveitis). Using an interactive online questionnaires, guided by background knowledge from published literature, 486 consensus statements for initiating ATT were generated and deliberated amongst 81 global uveitis experts. The median score of five was considered reaching consensus for initiating ATT. The median score of four was tabled for deliberation through Delphi round 2 in a face-to-face meeting. This report describes the methodology adopted and followed through the consensus process, which help elucidate the guidelines for initiating ATT in patients with choroidal TB.