Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) - Report 6: Dengue Uveitis at a Tertiary Eye Institution in Singapore.

OBJECTIVES: To identify the characteristics, treatment, and visual outcomes of dengue uveitis at a tertiary eye care centre in Singapore. METHODS: Retrospective case record review of all consecutive dengue uveitis patients (2004 to 2015) from the Ocular Autoimmune Systemic Inflammatory and Infectious Study (OASIS) database. RESULTS: Fifty-four patients were identified from the OASIS database. The most common ocular symptom was blurring of vision (n = 41, 75.9%), followed by floaters (n = 9, 17.0%), scotoma (n = 5, 9.3%), and metamorphopsia (n = 3, 5.7%). Scotoma based on history, Amsler grid, and perimetry accounted for 27 (50%) patients. Majority presented with either a posterior uveitis or retinal vasculitis (n = 51, 94.4%). Treatments ranged from close observation for spontaneous improvement, to the use of high-dose corticosteroids. CONCLUSIONS: Dengue uveitis may present with a spectrum of disease manifestations including posterior uveitis, vasculitis, and macula edema. Scotoma is significant and may be found on history taking, Amsler charting, and perimetry.

Brief Report: Retinal Microvasculature and Immune Restoration Among South Eastern Asian Patients With HIV/AIDS Over a 9-Month Antiretroviral Therapy.

BACKGROUND: Longitudinal evidence on retinal microvasculature and subsequent systemic inflammatory alteration is lacking. We investigated the association between retinal microvasculature and immune response among patients with HIV/AIDS over a 9-month antiretroviral therapy. METHODS: We conducted a prospective cohort study on patients with HIV/AIDS at Singapore Communicable Disease Centre since June 2011. We recruited all eligible patients and then reviewed them every 3 months over a 9-month follow-up, including performing blood tests (CD4+/CD8+ T-cell counts and HIV viral load), blood pressure, anthropometry measurements, and retinal photography at each visit. We assessed retinal vascular indexes using a semiautomated computer-based program. Finally, we applied a linear mixed model to analyze associations between baseline retinal vascular indexes and 9-month changes of CD4+/CD8+ T-cell counts and HIV viral load throughout study observation, after adjusting for major confounders. RESULTS: We found that narrower arteriolar caliber (per 10 µm decrease), wider venular caliber (per 10 µm increase), and larger arteriolar branching angle (per 10° increase) in the retina assessed at baseline were significantly associated with 9-month reductions in CD4+ T-cell count by 52.97 cells/µL (P = 0.006), 33.55 cells/µL (P = 0.01), and 39.09 cells/µL (P = 0.008), accordingly. CONCLUSION: Patients with HIV/AIDS with a suboptimal retinal microvascular morphology tended to fail immune restoration undertaking a 9-month antiretroviral therapy.

UNUSUAL CAUSE OF BRANCH RETINAL ARTERY OCCLUSION: POLYCYTHEMIA IN A TRANSGENDER MAN FROM UNREGULATED TESTOSTERONE USE.

PURPOSE: We report a transgender patient with branch retinal artery occlusion who had secondary polycythemia from unregulated testosterone injections and review the literature on the mechanisms of supraphysiologic and standard doses of testosterone causing a hypercoagulable state. METHODS: Case report. RESULTS: A 45-year-old Chinese transgender man with no medical history presented with a 1-week history of a scotoma in his left eye vision. Ophthalmologic examination revealed retinal pallor and edema along the superotemporal arteriole in the left eye. Optical coherence tomography showed increased thickness of the inner retinal layers of the superotemporal retina. Fluorescein angiography demonstrated an arm-retina time of 1 minute and 43 seconds, with no vascular sheathing and capillary fallout. A diagnosis of left superotemporal branch retinal artery occlusion was made. Initial blood tests revealed a hemoglobin level of 19.3 g/dL (11.8-14.6 g/dL), hematocrit of 62% (34.3-43.0%), and erythrocytes of 6.56 × 1012/L (3.7-4.8 × 1012/L). He revealed later that he had been on weekly testosterone injections (testosterone enanthate 250-mg depot injection) since 2011. He was also exposed to a moderately high altitude, when his symptoms occurred, raising the possibility of worsening hypercoagulability resulting in his thrombotic event. CONCLUSION: To the best of our knowledge, this is the first documented case of a trans man who developed branch retinal artery occlusion after self-administering supraphysiological doses of testosterone. In a young patient with no history of cardiovascular risk factors who develops retinal arterial occlusion, other causes such as hypercoagulable syndromes must be excluded. This case warns of the dangers of unregulated testosterone use, especially at supraphysiologic doses, and the risks of thrombotic events from secondary polycythemia.

Clinical Features and CD4+ T Cells Count in AIDS Patients with CMV Retinitis: Correlation with Mortality.

PURPOSE: To explore the all-cause mortality in patients with acquired immune deficiency syndrome (AIDS) and Cytomegalovirus (CMV) retinitis. METHODS: A retrospective cohort study of patients with CMV retinitis (CMVR) presented to a tertiary referral center in Singapore from January 1, 2004, through December 31, 2015. RESULTS: A total of 144 patients were studied (87 survived, 11 lost to follow up, 46 died). Patients with bilateral CMVR and six-month follow up CD4 + T cell count < 50 cells/mm3 have shorter time to mortality, compared to patients with CD4 + T cell count > 50 cells/mm3 (p < .001) and unilateral disease (p = .043). Baseline CD4 + T cell count, size and zone of initial primary retinitis lesions, recurrences of retinitis, and timing of combined antiretroviral therapy (cART) are not significantly associated with mortality. CONCLUSION: Bilateral ocular involvement and lack of immune recovery in patients with AIDS and CMVR are associated with shorter survival time.

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.

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.

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.

The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Description of the Spectrum of Choroidal Involvement in 245 Patients with Tubercular Uveitis.

Purpose: To contribute a global description of the spectrum of choroidal involvement in tubercular uveitis (TBU).Methods: Retrospective cohort study of TBU patients with choroidal involvement from 25 centers between January 2004 and December 2014. Medical records of patients with a minimum follow-up of 1 year were reviewed.Results: 245 patients were included. The phenotypic variations included serpiginous-like choroiditis (SLC) (46%), tuberculoma (13.5%), multifocal choroiditis (MFC) (9.4%), ampiginous choroiditis (9%), among others. 219 patients were treated with anti-tubercular therapy (ATT) (n = 219/245, 89.38%), 229 patients with steroids (n = 229/245, 93.47%) and 28 patients with immunosuppressive agents (n = 28/245, 11.42%). Treatment failure was noted in 38 patients (n = 38/245, 15.5%). Patients with SLC and ampiginous choroiditis appeared to have superior outcomes on survival analysis (p = 0.06).Conclusion: This study provides a comprehensive description of choroidal involvement in TBU. Patients with SLC and ampiginous choroiditis may have better clinical outcomes.

Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) - Report 2: Pattern of Uveitis Investigations in Singapore.

Purpose: To analyze the pattern of laboratory investigations of uveitis at a tertiary referral eye care center in Singapore.Methods: Retrospective analysis of 2040 uveitis cases from the Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) database over a 12-year period (2004 - 2015).Results: Patients with retinal vasculitis (RV) had the most tests utilized per patient (6.79), followed by intermediate uveitis (IU) (5.25), panuveitis (Pan) (5.12), posterior uveitis (PU) (4.17), anterior uveitis (AU) (2.75), and keratouveitis (KU) (1.10). The most frequently utilized test for infective etiology were the VDRL (41.3%), Syphilis IgG (29.5%), and T-SPOT.TB (24.6%). For autoimmune tests, ANA was most utilized (18.2%), followed by anti-dsDNA (14.8%), and HLA-B27 (12.4%).Conclusion: There was high utilization of autoimmune tests such as ANA, anti-dsDNA, RF, and ANCA, despite its limited yield. Rationalization of investigations in patients with ocular inflammation via a stepladder approach may help optimize the use of limited resources.

Tubercular Uveitis: Nuggets from Collaborative Ocular Tuberculosis Study (COTS)-1.

Background: Tuberculosis (TB) is a major infection that can affect the eye as first and sole presentation without features of systemic disease. Controversy exists regarding diagnosis and management of tubercular uveitis (TBU), further compounded by regional variations in disease expression. Purpose: Collaborative Ocular Tuberculosis Study (COTS)-1 aims to address knowledge deficits through collaboration amongst uveitis specialists across the globe by sharing the data of patients with TBU presented at participating centers from January 2004 to December 2014. Methods: Data collection was facilitated by a novel method of real-time encrypted web-based data entry allowing regular updates as new data and recommendations become available. Results: Information on clinical features, investigation findings, management, and treatment outcomes were reviewed to get an idea about real world scenario. Conclusion: The current review aims to focus on methodology and briefing of published reports from COTS group in COTS-1 study to highlight key messages from this large data.

Ocular Autoimmune Systemic Inflammatory Infectious Study - Report 3: Posterior and Panuveitis.

PURPOSE: To report the pattern of posterior and panuveitis at a tertiary referral center in Singapore. METHODS: Subgroup retrospective analysis of 334 new posterior and panuveitis cases, from the Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) database. Descriptive analysis was performed and visual outcome and complications were reported. RESULTS: The etiology for posterior uveitis and panuveitis was infectious in 162 patients (48.5%), non-infectious in 144 patients (43.1%), and idiopathic in 28 patients (8.4%). More patients with bilateral disease had a non-infectious etiology (n = 82, 50.9%) (p = 0.012). The most common complication was epiretinal membrane (n = 20, 12.3%) for the infectious group and cystoid macular edema (n = 12, 8.3%) for the non-infectious group. CONCLUSIONS: The proportion of etiologies in our cohort varies from other studies. Understanding the variations and demographic associations allows the diagnosis and management of posterior and panuveitis to be further improved.

The Collaborative Ocular Tuberculosis Study (COTS)-1 Report 3: Polymerase Chain Reaction in the Diagnosis and Management of Tubercular Uveitis: Global Trends.

Purpose: To analyze the role of polymerase chain reaction (PCR) of ocular fluids in management of tubercular (TB) anterior, intermediate, posterior, and panuveitis. Methods: In Collaborative Ocular Tuberculosis Study (COTS)-1 (25 centers, n = 962), patients with TB-related uveitis were included. 59 patients undergoing PCR of intraocular fluids (18 females; 53 Asian Indians) were included. Results: 59 (6.13%) of COTS-1 underwent PCR analysis. PCR was positive for Mycobacterium TB in 33 patients (23 males; all Asian Indians). 26 patients were PCR negative (18 males). Eight patients with negative PCR had systemic TB. Anti-TB therapy was given in 18 negative and 31 PCR cases. At 1-year follow-up, five patients with positive PCR (15.15%) and three with negative PCR (11.54%) had persistence/worsening of inflammation. Conclusions: Data from COTS-1 suggest that PCR is not commonly done for diagnosing intraocular TB and positive/negative results may not influence management or treatment outcomes in the real world scenario.

Clinical Features of Scleritis Across the Asia-Pacific Region.

Purpose: To examine the spectrum of scleritis in four tertiary institutions across the Asia-Pacific. Methods: Clinical records from 354 patients were reviewed from centers in Australia, Singapore, and India, excluding those with insufficient data (n = 24). Results: Indian patients presented younger (41.5 ± 13.4 years) than Australians (50.8 ± 17.5) and Singaporeans (48.6 ± 15.9), with fewer women (49% vs 62%/57%). Diffuse disease was universally most common. Autoimmune and infectious disease proportions were similar in Australia (31%/10.3%) and Singapore (27.5%/8.3%) but reversed in India (8.3%/30%). Necrotizing scleritis was most frequently associated with infection (27.3%). Presumed ocular tuberculosis accounted for 75% of infectious cases in India. Posterior scleritis had the highest complication rate (82.4%) and immunosuppressants used per patient (0.98 ± 0.31 95% CI). Conclusions: Clinical presentations of scleritis vary across the Asia-Pacific, particularly in endemic regions for tuberculosis such as India, where it affects younger men with a predominance of nodular and infectious disease.

Analysis of 130 Cases of Sympathetic Ophthalmia - A Retrospective Multicenter Case Series.

Objective: To analyze the demographic profile, treatment, and visual outcome of the patients with sympathetic ophthalmia (SO) in a multicenter collaborative retrospective cohort study.Methods: Medical records of the patients with SO from UK, Singapore, India were reviewed for history of ocular trauma or surgery and subsequent development of uveitis consistent with SO, presenting symptoms, treatment, and visual outcomes.Results: A total of 130 patients were diagnosed with SO during the study period. Eighty-one (62.3%) patients were men. The mean age was 48.4 ± 15.5 years. The most common presenting symptom was blurring of vision (89.2%), followed by pain (29.2%) and floaters (23.8%). Ninety-two (70.7%) required additional immunosuppressive therapy. Thirty-six (27.9%) patients underwent enucleation of the inciting eye.Conclusions: SO is a potentially sight-threatening disease with high rates of visual loss. It warrants prompt evaluation and treatment. With the advances and availability in immunotherapy, the visual prognosis is relatively good.

Treatment outcome in patients with presumed tubercular uveitis at a tertiary referral eye care centre in Singapore.

AIM: To report the clinical features and outcome of patients with presumed tubercular uveitis (TBU). METHODS: Retrospective analysis of patients with presumed TBU at a tertiary referral eye care centre in Singapore between 2007 and 2012 was done. Main outcome measures were failure of complete resolution of uveitis or recurrence of inflammation. RESULTS: Fifty three patients with mean age of 44.18 ± 15.26 years with 54.72% being males were included. 19 (35.85%) had bilateral involvement, with panuveitis and anterior uveitis being the most common presentations. 36 (67.92%) patients received antitubercular therapy (ATT), and 28 received concurrent systemic steroids. 15 (28.30%) eyes of 11 (30.55%) patients in the ATT group and 4 (21.05%) eyes of 3 (17.64%) patients in the non-ATT group had treatment failure (p value = 0.51). CONCLUSION: The use of ATT, with or without concurrent corticosteroid, may not have a statistically significant impact in improving treatment success in patients with presumed TBU.

Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) - Report 1: Epidemiology and Classification.

PURPOSE: To report the epidemiology and classification of ocular inflammation at a tertiary eye care center in Singapore. METHODS: Retrospective cohort study of the clinical records of consecutive new cases from the Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) database from 2004-2015. RESULTS: A total of 2200 patients were studied from the OASIS database. The most common anatomic diagnosis was anterior uveitis (55.9%), posterior uveitis (17.5%), panuveitis (9.6%), and intermediate uveitis (4.7%). In addition, scleritis (6.1%), keratouveitis (2.8%), retinal vasculitis (2.2%), and episcleritis (1.2%) were observed. Etiology was established in 65.1%, with 35.2% of patients associated with non-infectious etiologies. The most common etiologies found were presumed tuberculosis (7.2%), followed by cytomegalovirus infection (6.9%), herpetic infection (6.3%), HLA-B27-associated anterior uveitis (4.2%), and ankylosing spondylitis (3.8%). CONCLUSIONS: The pattern of ocular inflammation in Singapore has similarities with both Western and Asian populations. Anterior uveitis was the most common, with non-infectious etiologies being slightly more common than infectious etiologies.

Ocular Toxoplasmosis in Tropical Areas: Analysis and Outcome of 190 Patients from a Multicenter Collaborative Study.

PURPOSE: To describe clinical findings and outcomes for ocular toxoplasmosis in an international multicenter collaborative study. METHODS: Retrospective analysis of 190 patients diagnosed with ocular toxoplasmosis from three study sites (Brazil, India, and Singapore). RESULTS: There were 93 (48.9%) females with a mean age of 32.8 years. The most common symptoms were isolated blurring of vision (36.8%), followed by blurring of vision with floaters (21.1%). Treatment regimens varied largely from monotherapy to multiple combination therapies. Final visual acuity of ≥20/40 was achieved in 106 (74.2%) patients. In a median follow-up period of 31 weeks (range 12-749 weeks), 83/190 (43.7%) patients suffered a relapse. CONCLUSIONS: There appears to be geographical variation in the presentation of ocular toxoplasmosis. Compared to previous studies, we did not observe the '"dual peak" phenomenon of chronic and active disease based on age at presentation, and there was less bilateral and macular involvement (but more peripheral involvement).

Dataset of longitudinal analysis of tear cytokine levels, CD4, CD8 counts and HIV viral load in dry eye patients with HIV infection.

The data presented in this article shows the longitudinal analysis of tear fluid cytokine profiles, blood CD4 and CD8 counts and HIV viral load in 34 dry eye patients with HIV infection during the HAART therapy. Clinical samples were collected from HIV patients with dry eye disease at the time of presentation to the clinic (visit 1), three months (visit 2) and 6 months (visit 3) after the presentation. At each time point tear samples were evaluated for 41 cytokines using Luminex bead based multiplex assay and blood samples were tested for HIV viral load and CD4 and CD8 counts.