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 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.

Vogt-Koyanagi-Harada Disease Associated with COVID-19 mRNA Vaccine.

A 54-year-old Chinese male with no previous ocular history presented to the ophthalmology department for the bilateral acute painless blurring of vision after receiving the 1st dose of COVID-19 mRNA vaccine (PFIZER-BioNTech/COMIRNATY). Clinical examination and imaging tests were consistent with Vogt-Koyanagi-Hara disease. The patient responded well with a high dose of intravenous methylprednisolone followed by a tapering dose of oral prednisolone.

Ocular Adverse Events After COVID-19 Vaccination.

PURPOSE: The COVID-19 pandemic has galvanized the development of new vaccines at an unprecedented pace. Since the widespread implementation of vaccination campaigns, reports of ocular adverse effects after COVID-19 vaccinations have emerged. This review summarizes ocular adverse effects possibly associated with COVID-19 vaccination, and discusses their clinical characteristics and management. METHODS: Narrative Literature Review. RESULTS: Ocular adverse effects of COVID-19 vaccinations include facial nerve palsy, abducens nerve palsy, acute macular neuroretinopathy, central serous retinopathy, thrombosis, uveitis, multiple evanescent white dot syndrome, Vogt-Koyanagi-Harada disease reactivation, and new-onset Graves' Disease. Studies in current literature are primarily retrospective case series or isolated case reports - these are inherently weak in establishing association or causality. Nevertheless, the described presentations resemble the reported ocular manifestations of the COVID-19 disease itself. Hence, we hypothesize that the human body's immune response to COVID-19 vaccinations may be involved in the pathogenesis of the ocular adverse effects post-COVID-19 vaccination. CONCLUSION: Ophthalmologists and generalists should be aware of the possible, albeit rare, ocular adverse effects after COVID-19 vaccination.

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 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 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.

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.

Association of LOXL1 polymorphisms with pseudoexfoliation in the Chinese.

PURPOSE: Single nucleotide polymorphisms (SNPs) within the lysyl oxidase like-1 gene (LOXL1; rs1048661 and rs3825942) were found to confer risk to pseudoexfoliation glaucoma (XFG) through the pseudoexfoliation syndrome (XFS) in Nordic, Caucasian, and two Asiatic populations (Indian and Japanese). The prevalence (0.2%-0.7%) of XFS in the Chinese is considerably lower compared to Nordic populations. The aim of this study was to determine the association of LOXL1 in Chinese subjects with XFS/XFG. METHODS: Chinese subjects with clinically diagnosed XFS/XFG and normal controls were recruited. Genomic DNA was extracted, and the two LOXL1 SNPs (rs1048661 and rs3825942) were genotyped by bidirectional sequencing. Allele and genotype frequencies were compared between cases and unrelated controls using PLINK. Linkage disequilibrium (LD) calculations and haplotype association analysis were done using the Haploview package and WHAP package, respectively. RESULTS: Sixty-two Chinese patients (17 XFG and 45 XFS) and 171 Chinese controls were studied. The G allele of LOXL1 SNP rs3825942 was moderately associated (OR=10.97, p=0.0018) with pseudoxfoliation in the Chinese. The frequency of the G allele of rs1048661 was not significantly different in cases compared to controls (p=0.142) in the allelic association test. However, the genotype test showed marginal association for rs1048661 (p=0.030). Only three haplotypes were observed (T-G, G-G, and G-A) with G-G as a risk haplotype (p=0.0034) and G-A as a protective haplotype (p=0.00039). T-G, which was a risk haplotype in the Japanese, was not associated with XFG in the Chinese (p=0.124). CONCLUSIONS: Polymorphisms in LOXL1 confer risk to XFS/XFG in the Chinese. The lower incidence of XFS compared to other populations suggests additional genetic or environmental factors to have a major influence on the phenotypic expression of XFS in the Chinese. The G allele of rs3825942 has been shown to be associated with XFS/XFG in all populations studied to date.

Epidemiology and clinical features of intraocular lymphoma in Singapore.

INTRODUCTION: Intraocular lymphoma is rare. There are very few studies on intraocular lymphoma published from Asian countries. OBJECTIVE: To report our case series of intraocular lymphoma patients from a tertiary eye centre in Singapore. SUBJECTS AND METHODS: Nine patients with intraocular lymphoma managed between January 2005 and December 2014 were identified from Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) database. Demographic characteristics, clinical presentation, investigations performed and outcomes recorded. RESULTS: There were almost equal distribution between males (four patients) and females (five patients) with mean age of presentation was 60.3 years. Five patients had bilateral involvement and vitreo-retina was the most common site of infiltration. All of our patients had central nervous system involvement although four of them had presented with ocular manifestations initially. Anterior chamber fluid cytology, as a less invasive alternative to vitreous analysis was proven to be useful. The time from ocular presentation to diagnosis of ocular lymphoma was variable; from one day to 18 months. Mortality in our study group was 55% with death occurring 1 month to 8 years from diagnosis of intraocular lymphoma. CONCLUSION: Intraocular lymphoma is a masquerade syndrome that mimics chronicuveitis and poses a diagnostic challenge. The diagnosis is often delayed and despite the eventual diagnosis, the disease prognosis is poor even with aggressive treatment.

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.

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.

Risk factors for a postoperative intraocular pressure spike after phacoemulsification.

BACKGROUND: The aim of our study was to examine several potential risk factors for intraocular pressure (IOP) spikes 2 to 3 hours after phacoemulsification. METHODS: 50 eyes of 50 consecutive patients undergoing uncomplicated phacoemulsification under topical anesthesia were included in this prospective study. The following variables were recorded: preoperative IOP, nuclear colour, cortical lens opacity, posterior subcapsular lens opacity, patient age; and presence or absence of preexisting glaucoma. RESULTS: The mean IOP at each time interval was as follows: preoperatively, 14.5 (SD 3.4) mm Hg; 2-3 hours postoperatively, 23.1 (7.0) mm Hg; and 24 hours postoperatively, 17.0 (6.0) mm Hg. The postoperative IOP was significantly higher than baseline at 2-3 hours (p<0.001) and at 24 hours (p=0.002). Overall there were 10 cases (20%) of IOP spikes 2-3 hours postoperatively. Higher mean baseline IOP was significantly associated with postoperative IOP spikes (p=0.013). Patient age, sex, operating surgeon, absolute phacoemulsification time, lens nuclear colour, cortical opacity, and posterior opacity were not significantly different between groups with or without an IOP spike (p>0.05). INTERPRETATION: Patients with high IOP at the preoperative assessment are more likely to have IOP spikes after surgery and should be scheduled at the start of the operating list. In a day-case setting with restricted opening hours, postoperative checks in those patients at risk of IOP spikes can then coincide with the time IOP reaches its peak.

Herpes Simplex Acute Retinal Necrosis Presenting as Unilateral Disc Swelling in Young Immunocompetent Patients.

PURPOSE: To report two cases of young immunocompetent males with herpes simplex acute retinal necrosis (HSV ARN) with initial diagnosis of unilateral disc swelling. METHODS: Retrospective case series. RESULTS: Two young immunocompetent males who were diagnosed to have unilateral disc swelling were treated as presumed optic neuritis and started on systemic steroids. On dilated fundal examination, unilateral retinitis and vasculitis was found after 2-3 days of systemic steroids and the diagnosis of ARN was made. Tetraplex vitreous tap subsequently returned as HSV-2 and HSV for the first and second patient, respectively. Both patients had no significant systemic medical history and tested negative for human immunodeficiency virus (HIV). Despite aggressive treatment, both patients developed profound visual morbidity. CONCLUSIONS: Close monitoring of patients with unilateral disc swelling and dilated fundus evaluation is critical, particularly upon initiation of systemic steroid therapy, even if immunocompetent, as misdiagnoses can result in potentially devastating consequences.

Optical Coherence Tomography Angiography of Choroidal Neovascularization Associated with Tuberculous Serpiginous-like Choroiditis.

Choroidal neovascularization secondary to tuberculous serpiginous-like choroiditis (Tb-SLC) is uncommon and requires further invasive imaging, such as fluorescein and indocyanine green angiography. We evaluate the optical coherence tomography angiography (OCTA) findings in a patient with a Tb-SLC and present the use of this investigation as a non-invasive diagnostic and follow-up clinical tool in this disease.

Disseminated nontuberculous mycobacterial infection with multifocal retinitis and vasculitis in an immunocompromised patient with anti-IFN-É£ autoantibodies.

BACKGROUND: Nontuberculous mycobacteria (NTM) are found ubiquitously in the environment. Since exposure to NTM is universal, infection likely represents underlying host susceptibility factors. Anti-IFN-É£ autoantibodies have been described previously in patients with NTM. Up to 88 % of patients with disseminated NTM or other opportunistic infections have high-titer anti-IFN-É£ autoantibodies, compared with 2 % of patients with TB and healthy controls. FINDINGS: We report a unique presentation of a patient with anti-IFN-É£ autoantibodies with disseminated NTM infection who presents with panuveitis with multifocal retinitis and vasculitis. Treatment with systemic anti tubercular therapy resulted in complete clinical resolution with good visual recovery. CONCLUSIONS: Patients with anti-IFN-É£ autoantibodies present with a novel syndrome that links autoimmunity and immunodeficiency. This case emphasizes the importance of testing for anti-IFN-É£ autoantibodies in patients with disseminated mycobacterial infection.

Paradoxical worsening of tuberculous chorioretinitis in a Chinese gentleman.

We report a case of paradoxical worsening of tuberculous chorioretinitis after initiation of anti-tuberculous therapy (ATT). The patient had left panuveitis with tuberculous chorioretinitis and was started on systemic ATT and oral steroids a week later. However, he developed paradoxical worsening 2 months after initiation of therapy. He was continued on ATT, oral steroids and intravitreal amikacin with resolution of the chorioretinal lesion subsequently. Ocular tuberculosis often poses a diagnostic challenge, and clinicians should be aware of the possibility of paradoxical worsening despite appropriate ATT. Clinicians should strongly consider starting oral steroids concurrently with ATT when managing ocular tuberculosis.

Pseudoexfoliation syndrome at a Singapore eye clinic.

BACKGROUND: The purpose of this study was to investigate the demographics of pseudoexfoliation syndrome (PXF) and pseudoexfoliative glaucoma (PXG) in a Singapore hospital eye outpatient clinic. METHODS: A retrospective study of 93 consecutive patients (146 eyes) with PXF was undertaken by a single ophthalmologist over a period of 37 months (July 1, 2006, to July 31, 2009). RESULTS: Ninety-three (2.8%) of 3,297 patients seen during the study period were diagnosed with PXF. Forty-three (46.2%) of the 93 PXF patients were male. Indians were 5.04 times more likely to develop PXF than Chinese (P<0.001, 95% confidence interval 3.05-8.33), while Malays were 2.22 times more likely to develop PXF as compared with Chinese (P=0.029, 95% CI 1.08-4.55). Twenty-two (23.7%) of the 93 PXF patients had PXG at the time of diagnosis. There was no statistically significant difference in mean age between PXF and PXG patients. There was a larger proportion of males with PXG than females (P<0.001). CONCLUSION: PXF is not infrequent in elderly Singapore eye clinic patients, and is more likely to occur in Indians than in Chinese. In the Singapore eye clinic setting, males may be more likely to develop PXG, although larger studies will be required to confirm this.