The Collaborative Ocular Tuberculosis Study (COTS) calculator-a consensus-based decision tool for initiating antitubercular therapy in ocular tuberculosis.

OBJECTIVE: To introduce the Collaborative Ocular Tuberculosis Study (COTS) Calculator, an online clinical scoring system for initiating antitubercular therapy (ATT) in patients with ocular tuberculosis (TB). METHOD: The COTS Calculator was derived from COTS Consensus (COTS CON) data, which has previously published consensus guidelines. Using a two-step Delphi method, 81 experts evaluated 486 clinical scenario-based questions, ranking their likelihood of initiating ATT in each specific scenario. Each scenario was a permutation of the results and/or availability of five following components-clinical phenotype, endemicity, two immunological (tuberculin skin test, interferon-γ release assay) and one radiological (chest X-Ray) test results-and a sixth component further stratifying three of the clinical phenotypes. The median scores and interquartile ranges (IQR) of each scenario were tabulated, representing the expert consensus on whether to initiate ATT in that scenario. The consensus table was encoded to develop the COTS Calculator. RESULTS: The COTS Calculator can be accessed online at: https://www.oculartb.net/cots-calc . The attending physician can select the conditions present in the patient, which will generate a median score from 1 to 5. 114 out of 486 scenarios (24%) deliberated had a median score of 5 indicating expert consensus to initiate ATT. CONCLUSION: The COTS Calculator is an efficient, low-cost, evidence and experience-based clinical tool to guide ATT initiation. While it holds substantial promise in improving standard-of-care for ocular-TB patients, future validation studies can help to as certain its clinical utility and reliability.

Correlation between Subfoveal Choroidal Thickness and Anterior Segment Inflammation in Patients with Chronic Stage of Vogt-Koyanagi-Harada Disease.

PURPOSE: To correlate changes in subfoveal choroidal thickness (SCT) with the degree of anterior inflammatory activity in chronic Vogt-Koyanagi-Harada (VKH) disease. METHODS: Anterior segment inflammation was assessed using SUN anterior chamber cell grading criteria, and SCT was measured using EDI-OCT in patients with VKH at multiple visits. ANOVA was used to compare the mean SCT for each anterior chamber cell grade. Regression analysis was used to correlate the anterior segment cell grade and the SCT. RESULTS: 14 patients were included in the study. A total of 432 data points consisting of SCT and anterior segment cell values were analyzed. ANOVA demonstrated significant difference between the mean SCT for different anterior chamber cell grades (p < .0001). Regression analysis demonstrated significant correlation between SCT and grade of anterior chamber cells (R2 = 0.37, p < .001). CONCLUSIONS: Chronic VKH is characterized by a dynamic change in SCT that correlates with anterior segment inflammatory activity.

Perinatal risk factors associated with central retinal changes in former preterm children on optical coherence tomography angiography.

PURPOSE: To assess the association between perinatal risk factors for retinopathy of prematurity (ROP) and central retinal structures of former preterm children seen on optical coherence tomography angiography (OCTA). METHODS: This prospective cohort study included 40 children with a history of preterm birth and 33 healthy full-term children. We documented their birth weight, gestational age, other significant risk factors for ROP development and presence of ROP. Imaging was performed using swept-source OCTA, and quantitative evaluation was performed. Analytic parameters included the area of foveal avascular zone (FAZ), foveal depth (FD), central subfoveal retinal thickness (CSFT) and capillary density index (CDI) of the deep and superficial capillary plexus. RESULTS: Preterm children had significantly smaller FAZ, lower FD and higher CSFT compared to controls (all p < 0.001). Both groups exhibited no differences in total CDI at the superficial (p = 0.969) and deep capillary plexus (p = 0.370). The duration of mechanical ventilation correlated negatively with FAZ and FD but positively with CSFT. The duration of supplemental oxygen treatment correlated negatively with FD. The presence of intraventricular haemorrhage correlated negatively with FAZ and FD but positively with CSFT. Regression analysis found that the duration of mechanical ventilation and the presence of bronchopulmonary dysplasia were associated with lower FD (p = 0.002 and 0.01, respectively) and higher CSFT (p = 0.002 and 0.028, respectively). CONCLUSION: Central retinal anomalies were identified in former preterm children using OCTA. Macular changes were associated with several risk factors for ROP development.

Reversibility of retinochoroidal vascular alteration in patients with obstructive sleep apnea after continuous positive air pressure and surgical intervention.

Purpose: The aim of this work was to study various retinochoroidal parameters in patients with obstructive sleep apnea syndrome (OSAS) and the effect of interventions on these parameters at 6 months follow-up. Methods: A total of 36 patients were recruited prospectively from the otorhinolaryngology clinics of a large tertiary center between September 2018 to March 2020. The subjects were divided into three groups depending upon intervention chosen for OSAS: Group A (surgery, i.e., uvulopalatopharyngoplasty), group B (medical therapy, i.e., continuous positive air pressure) and group C (no intervention). Various retinochoroidal parameters which were studied included retinal thickness (RT), choroidal thickness (CT), choroidal vascularity index (CVI), arteriovenous ratio (AVR), capillary density index (CDI) in superficial and deep retina, at baseline and 6 months of follow-up after the intervention. Results: In group A, CT increased significantly at 6 months (332.76 ± 86.41 um) compared to baseline (306.28 ± 78.19) (P = 0.0004). Similarly, CDI at both superficial and deep capillary plexus increased significantly at 6 months (superficial CDI: 0.65 ± 0.04, deep CDI: 0.38 ± 0.01) compared to baseline (superficial CDI: 0.62 ± 0.03, deep CDI: 0.36 ± 0.02) (P = 0.004 and 0.002 respectively). In group B, CT increased significantly at 6 months (361.38 ± 78.63 um) compared to baseline (324.21 ± 76.97 um) (P = 0.008). Also, CVI showed a significant decrease at 6 months (65.74 ± 1.84%) compared to baseline (67.36 ± 1.57%) (P = 0.019). In group C, all except CDI in deep capillary plexus showed a significant decrease at 6 months (0.35 ± 0.01) compared to baseline (0.36 ± 0.02) (P = 0.003). Conclusion: OSAS alters various retinochoroidal parameters and timely intervention in patients with OSAS can prevent these alterations. Also, these retinochoroidal parameters could serve as one of the markers to monitor the disease progression.

Consensus Recommendations for the Diagnosis of Vitreoretinal Lymphoma.

PURPOSE: To provide recommendations for diagnosis of vitreoretinal lymphoma (VRL). METHODS: Literature was reviewed for reports supporting the diagnosis of VRL. A questionnaire (Delphi 1 round) was distributed to 28 participants. In the second round (Delphi 2), items of the questionnaire not reaching consensus (75% agreement) were discussed to finalize the recommendations. RESULTS: Presenting symptoms include floaters and painless loss of vision, vitreous cells organized into sheets or clumps. Retinal lesions are usually multifocal creamy/white in the outer retina. Other findings include retinal lesions with "leopard-skin" appearance and retinal pigment epithelium atrophy. Severe vitreous infiltration without macular edema is the most likely presentation. Diagnostic vitrectomy should be performed. Systemic corticosteroid should be discontinued at least 2 weeks before surgery. An interleukin (IL)-10:IL-6 ratio > 1, positive mutation for the myeloid differentiation primary response 88 gene and monoclonality are indicators of VRL. Multi-modal imaging (optical coherence tomography, fundus autofluorescence) are recommended. CONCLUSIONS: A consensus meeting allowed the establishment of recommendations important for the diagnosis of VRL.

Fungal Endogenous Endophthalmitis during Pregnancy as a Complication of In-Vitro Fertilization.

Purpose: To report a Candida endogenous endophthalmitis in a pregnant woman with a prior history of in-vitro fertilization (IVF).Methods: Case report.Results: 21-year-old healthy woman within the first trimester of her pregnancy of a successful IVF developed a focal retinitis and panuveitis. Ocular findings suggested fungal endophthalmitis. The patient was treated with pars plana vitrectomy and repeated intravitreal antifungal injections. No systemic therapy was given. Cultures showed Candida albicans. IVF procedure was the only identifiable risk factor for endogenous endophthalmitis.Conclusions: In-vitro fertilization appeared as a possible risk factor for endogenous endophthalmitis during pregnancy. In the absence of systemic fungal infection, local intravitreal antifungal injections seem to be effective options to treat endogenous candida endophthalmitis, especially in the first trimester.

Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis-Report 1: Guidelines for Initiating Antitubercular Therapy in Tubercular Choroiditis.

TOPIC: An international, expert-led consensus initiative organized by the Collaborative Ocular Tuberculosis Study (COTS), along with the International Ocular Inflammation Society and the International Uveitis Study Group, systematically developed evidence- and experience-based recommendations for the treatment of tubercular choroiditis. CLINICAL RELEVANCE: The diagnosis and management of tubercular uveitis (TBU) pose a significant challenge. Current guidelines and literature are insufficient to guide physicians regarding the initiation of antitubercular therapy (ATT) in patients with TBU. METHODS: An international expert steering subcommittee of the COTS group identified clinical questions and conducted a systematic review of the published literature on the use of ATT for tubercular choroiditis. Using an interactive online questionnaire, guided by background knowledge from published literature, 81 global experts (including ophthalmologists, pulmonologists, and infectious disease physicians) generated preliminary consensus statements for initiating ATT in tubercular choroiditis, using Oxford levels of medical evidence. In total, 162 statements were identified regarding when to initiate ATT in patients with tubercular serpiginous-like choroiditis, tuberculoma, and tubercular focal or multifocal choroiditis. The COTS group members met in November 2018 to refine these statements by a 2-step modified Delphi process. RESULTS: Seventy consensus statements addressed the initiation of ATT in the 3 subtypes of tubercular choroiditis, and in addition, 10 consensus statements were developed regarding the use of adjunctive therapy in tubercular choroiditis. Experts agreed on initiating ATT in tubercular choroiditis in the presence of positive results for any 1 of the positive immunologic tests along with radiologic features suggestive of tuberculosis. For tubercular serpiginous-like choroiditis and tuberculoma, positive results from even 1 positive immunologic test were considered sufficient to recommend ATT, even if there were no radiologic features suggestive of tuberculosis. DISCUSSION: Consensus guidelines were developed to guide the initiation of ATT in patients with tubercular choroiditis, based on the published literature, expert opinion, and practical experience, to bridge the gap between clinical need and available medical evidence.

Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis-Report 2: Guidelines for Initiating Antitubercular Therapy in Anterior Uveitis, Intermediate Uveitis, Panuveitis, and Retinal Vasculitis.

TOPIC: The Collaborative Ocular Tuberculosis Study (COTS), supported by the International Ocular Inflammation Society, International Uveitis Study Group, and Foster Ocular Immunological Society, set up an international, expert-led consensus project to develop evidence- and experience-based guidelines for the management of tubercular uveitis (TBU). CLINICAL RELEVANCE: The absence of international agreement on the use of antitubercular therapy (ATT) in patients with TBU contributes to a significant heterogeneity in the approach to the management of this condition. METHODS: Consensus statements for the initiation of ATT in TBU were generated using a 2-step modified Delphi technique. In Delphi step 1, a smart web-based survey based on background evidence from published literature was prepared to collect the opinion of 81 international experts on the use of ATT in different clinical scenarios. The survey included 324 questions related to tubercular anterior uveitis (TAU), tubercular intermediate uveitis (TIU), tubercular panuveitis (TPU), and tubercular retinal vasculitis (TRV) administered by the experts, after which the COTS group met in November 2019 for a systematic and critical discussion of the statements in accordance with the second round of the modified Delphi process. RESULTS: Forty-four consensus statements on the initiation of ATT in TAU, TIU, TPU, and TRV were obtained, based on ocular phenotypes suggestive of TBU and corroborative evidence of tuberculosis, provided by several combinations of immunologic and radiologic test results. Experts agreed on initiating ATT in recurrent TAU, TIU, TPU, and active TRV depending on the TB endemicity. In the presence of positive results for any 1 of the immunologic tests along with radiologic features suggestive of past evidence of tuberculosis infection. In patients with a first episode of TAU, consensus to initiate ATT was reached only if both immunologic and radiologic test results were positive. DISCUSSION: The COTS consensus guidelines were generated based on the evidence from published literature, specialists' opinions, and logic construction to address the initiation of ATT in TBU. The guidelines also should inform public policy by adding specific types of TBU to the list of conditions that should be treated as tuberculosis.

The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Review of 447 Patients with Tubercular Intermediate Uveitis and Panuveitis.

Purpose: Tubercular intermediate uveitis (TIU) and panuveitis (TBP) are difficult to manage because of limitations in diagnostic tools and lack of evidence-based treatment guidelines. The Collaborative Ocular Tuberculosis Study (COTS) analyzed treatment regimens and therapeutic outcomes in patients with TIU and TBP.Methods: Multicentre retrospective analysis.Results A total of 138 TIU and 309 TBP patients were included. A total of 382 subjects received antitubercular therapy (ATT) (n = 382/447; 85.4%) and 382 received corticosteroids (n = 382/447; 85.4%). Treatment failure was observed in 78 individuals (n = 78/447; 17.4%), occurring less frequently in patients receiving ATT (n = 66/382; 17.2%) compared to those who did not (n = 12/65; 18.5%). The study did not show any statistically significant therapeutic effect of ATT in patients with TIU and TBP.Conclusion Taking into account the limitations of the retrospective, non-randomized study design, resultant reliance on reported data records, and unequal size of the samples, the current study cannot provide conclusive evidence on the therapeutic benefit of ATT in TIU and TBP.

Ocular surface manifestations of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis.

PURPOSE: This study was performed to determine the occurrence of ocular surface manifestations in patients diagnosed with coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: A systematic search of electronic databases i.e. PubMed, Web of Science, CINAHL, OVID and Google scholar was performed using a comprehensive search strategy. The searches were current through 31st May 2020. Pooled data from cross-sectional studies was used for meta-analysis and a narrative synthesis was conducted for studies where a meta-analysis was not feasible. RESULTS: A total of 16 studies reporting 2347 confirmed COVID-19 cases were included. Pooled data showed that 11.64% of COVID-19 patients had ocular surface manifestations. Ocular pain (31.2%), discharge (19.2%), redness (10.8%), and follicular conjunctivitis (7.7%) were the main features. 6.9% patients with ocular manifestations had severe pneumonia. Viral RNA was detected from the ocular specimens in 3.5% patients. CONCLUSION: The most common reported ocular presentations of COVID-19 included ocular pain, redness, discharge, and follicular conjunctivitis. A small proportion of patients had viral RNA in their conjunctival/tear samples. The available studies show significant publication bias and heterogeneity. Prospective studies with methodical collection and data reporting are needed for evaluation of ocular involvement in COVID-19.

The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Descriptive Review of Tubercular Uveitis in Paediatric Population.

Purpose: To examine disease profile of tubercular uveitis (TBU) in Paediatric population.Methods: Among 945 patients of the retrospective multinational study by the Collaborative Ocular Tuberculosis Study (COTS)-1, 29 Paediatric patients diagnosed with TBU were analyzed.Results: Mean age of disease presentation was 12.8 (range 4-18 years), with predominance of males (n = 14/20; 70.0%) and Asian ethnicity (n = 25/29; 86.2%). Posterior uveitis (n = 14/28; 50%) was the most frequent uveitis phenotype, with choroidal involvement occurring in 64.7% (n = 11/17). Incidence of optic disc edema and macular edema was higher in children (n = 8/18; 44.4% and n = 5/18; 27.8%, respectively) than in adults (n = 160/942; 16.9% and n = 135/942; 14.3%, respectively). Comparison of optic disc edema between subgroups showed a significant difference (P =.006). All patients received oral corticosteroids, most of them with antitubercular therapy. Treatment failure developed in 4.8% (n = 1/21).Conclusions: Children have a more severe inflammatory response to the disease, and an intensive anti-inflammatory therapeutic regimen is required to achieve a positive treatment outcome.

Effect of weight loss on the retinochoroidal structural alterations among patients with exogenous obesity.

PURPOSE: To evaluate the changes in the retinochoroidal vasculature in patients with exogenous obesity using swept-source optical coherence tomography (SS-OCT) and OCT angiography (OCTA). METHODS: In this prospective study, 60 patients diagnosed with obesity (47 males) (mean age: 46.47±10.9 years) were included, of which 30 patients underwent bariatric surgery (Group A), and 30 patients underwent conservative management (exercise/diet) (Group B). Parameters including choroidal thickness (CT), choroidal vascularity index (CVI) and retinal capillary density index (CDI) and arteriovenous ratio (AVR) were measured at the baseline and three months follow up. 30 eyes (30 age and gender-matched) of normal participants were included for comparison. RESULTS: Baseline CT was lower in 60 participants with obesity compared to controls. Compared with normal subjects, subjects with obesity had higher mean CVI (0.66±0.02 versus 0.63±0.04; p<0.01), smaller FAZ area (0.26±0.07 versus 0.45±0.32; p<0.01), higher CDI (superficial plexus: 0.7±0.04 versus 0.68±0.06; p = 0.04, deep plexus: 0.38±0.02 versus 0.35±0.06; p = 0.01), and lower AVR (0.68±0.05 versus 0.70±0.03 versus; p<0.01). At 3-month after intervention, CT showed a significant increase in participants from Group A (329.27±79µm; p<0.01) but not in Group B from baseline. No significant change was noted in CVI or CDI at 3-month in either group compared to baseline. AVR significantly increased in Group B (p = 0.03). CONCLUSION: Subclinical changes in retinochoroidal vasculature occurs in participants with exogenous obesity compared to healthy subjects. Surgical intervention (bariatric surgery) may have a favorable outcome on the choroidal thickness in these patients.

The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Review of 165 Patients with Tubercular Anterior Uveitis.

Purpose: The Collaborative Ocular Tuberculosis Study (COTS) Group sought to address the diagnostic uncertainty through retrospective cohort analysis of treatment regimens and therapeutic outcomes for patients with tubercular Anterior Uveitis (TAU) across international centers.Methods: Multicentre retrospective analysis of patients diagnosed with TAU between January 2004 to December 2014 that had a minimum follow-up of 1 year.Results: One hundred and sixty-five patients were included. One hundred and seven subjects received antitubercular therapy (ATT) (n = 107/165; 64.9%) with all the patients receiving topical steroid therapy. Treatment failure was noted in 17 patients (n = 17/165; 10.3%), more frequently described in patients that received ATT (n = 13/107, 12.2%), than those that did not receive ATT (n = 4/58, 6.9%).Conclusion: In this retrospective study, addition of ATT did not have any statistically significant impact on outcome in patients with TAU.

Visual Morbidity in Ocular Tuberculosis - Collaborative Ocular Tuberculosis Study (COTS)-1: Report #6.

Objective: Aim of the study was to examine extent, natural history, and clinical features associated with visual impairment (VI) in patients diagnosed with ocular tuberculosis (OTB) by the Collaborative Ocular Tuberculosis Study (COTS)-1.Methods: Multi-center retrospective cohort study. Main outcomes were VI.Results: A total of 302 patients were included in the study, including 175 patients whose data related to BCVA were available throughout the 2 years of follow up. Mean BCVA grossly improved at 12, 18, and 24 months of follow-up (p < .001). Mean BCVA was worse at 12-18th month follow-up for patients treated with ATT versus patients who were not treated with ATT, but patients treated with ATT had a statistically significant improvement in BCVA at the 24-month endpoint.Conclusions: OTB is associated with significant visual morbidity, future well-designed prospective studies are warranted to establish the causal association between OTB and visual loss.

Twenty-four Month Outcomes in the Collaborative Ocular Tuberculosis Study (COTS)-1: Defining the "Cure" in Ocular Tuberculosis.

Purpose: To report the clinical findings, anatomical features, and treatment outcomes in subjects with ocular tuberculosis (OTB) at 24 months in the Collaborative Ocular Tuberculosis Study (COTS)-1.Methods: Of the 945 subjects included in COTS-1, those who completed a 24-month follow-up after completion of treatment were included. The main outcome measure was a number of patients with treatment failure (TF).Results: 228 subjects (120 males; mean age of 42.82 ± 14.73 years) were included. Most common phenotype of uveitis was posterior (n = 81; 35.53%), and panuveitis (n = 76; 33.33%). Fifty-two patients (22.81%) had TF. On univariable analysis, odds of high TF was observed with bilaterality (OR: 3.46, p = .003), vitreous haze (OR: 2.14, p = .018), and use of immunosuppressive therapies (OR: 5.45, p = .003). However, only bilaterality was significant in the multiple regression model (OR: 2.84; p = .02).Conclusions: Majority of subjects (>75%) achieved cure in the COTS-1 at 24-month follow-up. The concept of "cure" may be a valuable clinical endpoint in trials for OTB.

Lessons in Digital Epidemiology from COTS-1: Coordinating Multicentre Research across 10 Countries Using Operational and Technology Innovation to Overcome Funding Deficiencies.

Purpose: There is controversy regarding the diagnosis and management of ocular tuberculosis (TB) due to lack of robust evidence. The Collaborative Ocular Tuberculosis Study (COTS) was conducted in stages to enable swift, accurate data collection across 25 participating centers.Method: Data collection was facilitated by a cloud-based data aggregation platform with programmed logic based on anecdotal evidence from uveitis experts corroborated with literature review.Results: The platform enabled standardization of interpretation and collection of data from patient medical records. The pre-programmed logic also ensured the platform only prompted the entry of relevant data based on initial data entered for each unit of analysis. This enabled collection of the vast amounts of data without compromising either of the breadth nor the depth of data collection.Conclusion: The final output from this effort was an in-depth retrospective analysis to facilitate the design of future prospective investigations on ocular TB and develop best practice guidelines.

The Collaborative Ocular Tuberculosis Study (COTS) Consensus (CON) Group Meeting Proceedings.

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.

Management of Intraocular Infections in HIV.

Purpose: Overview of treatment options for the most common intraocular opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS), including ocular syphilis, ocular tuberculosis, toxoplasmic chorioretinitis, and viral retinitis. Method: Narrative Review. Results: Despite the huge advances in the development of combined antiretroviral therapy (cART) for the management of patients with human immunodeficiency virus (HIV) infection, opportunistic infections still represent a significant diagnostic dilemma and cause of ocular morbidity in patients with HIV. Conclusion: Although the treatment of intraocular infections in patients with AIDS may be challenging, prompt assessment of the clinical features and appropriate aggressive management of the underlying etiology are critical to avoid life and vision threatening.