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Background: Optic neuritis (ON) may be the initial manifestation of neuromyelitis optica spectrum disorder (NMOSD). Aquaporin-4 antibody (AQP4 Ab) is used to diagnose NMOSD. This has implications on prognosis and is important for optimal management. We aim to evaluate if clinical features can distinguish AQP4 Ab seropositive and seronegative ON patients., Methods: We reviewed patients with first episode of isolated ON from Tan Tock Seng Hospital and Singapore National Eye Centre who tested for AQP4 Ab from 2008 to 2017. Demographic and clinical data were compared between seropositive and seronegative patients., Results: Among 106 patients (120 eyes) with first episode of isolated ON, 23 (26 eyes; 22%) were AQP4 Ab positive and 83 (94 eyes; 78%) were AQP4 Ab negative. At presentation, AQP4 Ab positive patients had older mean onset age (47.9 ± 13.6 vs 36.8 ± 12.6 years, P < 0.001), worse nadir VA (OR 1.714; 95% CI, 1.36 to 2.16; P < 0.001), less optic disc swelling (OR 5.04; 95% CI, 1.682 to 15.073; p = 0.004), and higher proportions of concomitant anti-Ro antibody (17% vs 4%, p = 0.038) and anti-La antibody (17% vs 1%, p = 0.008). More AQP4 Ab positive patients received steroid-sparing immunosuppressants (74% vs 19%, p < 0.001) and plasma exchange (13% vs 0%, p = 0.009). AQP4 Ab positive patients had worse mean logMAR VA (visual acuity) at 12 months (0.70 ± 0.3 vs 0.29 ± 0.5, p = 0.051) and 36 months (0.37±0.4 vs 0.14 ± 0.2, p = 0.048) follow-up., Conclusion: Other than older onset age and retrobulbar optic neuritis, clinical features are non-discriminatory for NMOSD. We propose a low threshold for AQP4 Ab serology testing in inflammatory ON patients, particularly in high NMOSD prevalence populations, to minimize diagnostic and treatment delays., Competing Interests: K. Tan has received travel grants and compensation from Novartis, Merck, Sanofi, Eisai, and Viela Bio for consulting services. The remaining authors report no conflicts of interest., (Copyright © 2022 by North American Neuro-Ophthalmology Society.)

Purpose: To identify ocular factors that affect signal strength in spectral-domain optical coherence tomography (SD-OCT)., Methods: Data from 1312 participants of the population-based Singapore Malay Eye Study-2 (SiMES-2) were included in the analysis. All participants underwent standardized ophthalmic examination, including measurements of best-corrected visual acuity (BCVA), refractive error, axial length, corneal curvature and presence of cataracts. Optic disc and macular cube scans were acquired using the Cirrus HD-OCT (software version 6.0, Carl Zeiss Meditec, Dublin, CA, USA). Signal strength of the optical coherence tomography (OCT) scan was recorded for each study eye. Multivariable linear regression analyses were performed to evaluate the associations between ocular factors and signal strength of the OCT scans., Results: The mean (±SD) age of our study participants was 61 ± 9 years, and 44.6% were male. Mean optic disc scan signal strength was 7.90 ± 1.25, range = 0-10, while mean macular scan signal strength was 8.80 ± 1.27, range = 0-10. In multivariable regression analyses, poorer signal strength in optic disc and macular cube scans was each associated with older age (per decade, β = -0.373, p < 0.001; β = -0.373, p < 0.001, respectively), poorer BCVA (per logMAR line; β = -0.123, p < 0.001; β = -0.156, p < 0.001, respectively), greater degree of myopia (per negative dioptre of spherical equivalent; β = -0.112, p < 0.001; β = -0.117, p < 0.001, respectively), presence of cortical cataracts (β = -0.331, p < 0.001; β = -0.314, p < 0.001, respectively) and presence of posterior subcapsular cataracts (β = -0.910, p < 0.001; β = -0.797, p < 0.001, respectively)., Conclusion: We found that older age, poorer BCVA, greater degree of myopia and presence of cortical and posterior subcapsular cataracts were associated with reduced signal strength in Cirrus SD-OCT. Our findings provide information on the barriers to obtaining good image quality when using SD-OCT, and allow clinicians to potentially identify individuals who are more likely to have unreliable OCT measurements., (© 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: The purpose of this study was to explore the interrelationships among retinal vascular caliber, retinal nerve fiber layer (RNFL), and glaucoma; in particular, whether the relationship between narrower retinal vascular caliber and glaucoma is mediated by thinning of RNFL., Methods: A total of 9407 participants, including 253 glaucoma and 195 primary open-angle glaucoma (POAG) cases from the Singapore Epidemiology of Eye Diseases Study were included in this study. All participants underwent standardized examinations. Glaucoma was defined according to International Society for Geographical and Epidemiologic Ophthalmology criteria. Logistic regression analyses were used to determine the total direct effects of retinal vascular calibers on glaucoma. Regression-based mediation analyses were used to evaluate the indirect effects of retinal vascular caliber on glaucoma through RNFL thinning., Results: After we adjusted for relevant covariates, narrower retinal arteriolar caliber (per standard deviation [SD], 15.1-μm decrease) was associated with glaucoma (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.06-1.38) and POAG (OR, 1.23; 95% CI, 1.06-1.43). Similarly, narrower retinal venular caliber (per SD, 21.6μm decrease) was associated with glaucoma (OR, 1.51; 95% CI, 1.32-1.73) and POAG (OR, 1.64; 95% CI, 1.41-1.91). In addition, there were significant indirect effects of retinal vascular narrowing on glaucoma through thinning of RNFL (all P < 0.001), with mediated proportion of 36.9% and 12.9% in retinal arteriole- and venule-related analysis, respectively., Conclusions: Mediation analyses indicated that the effect of retinal vascular narrowing on glaucoma was partially the result of thinning of RNFL. These findings provide additional mechanistic insights linking retinal vascular narrowing and glaucoma.

We examined the joint effects of intraocular pressure (IOP) and myopia on the risk of primary open angle glaucoma (POAG) in a multi-ethnic Asian population. A total of 9,422 participants (18,469 eyes) in the Singapore Epidemiology of Eye Diseases Study were included. Of them, 213 subjects (273 eyes) had POAG. All participants underwent standardised examinations. The independent and joint effects of IOP and myopia on POAG were examined using logistic regression models. Generalised estimating equation models were used to account for correlation between eyes. Higher IOP, longer axial length, and more negative spherical equivalent were independently associated with POAG, after adjusting for relevant covariates (all P ≤ 0.005). Significant interaction between IOP and myopia on POAG was observed (P interaction = 0.025). Eyes with moderate-to-high myopia (<-3.0 dioptres) with high IOP (≥20 mmHg) were 4.27 times (95% CI, 2.10-8.69) likely to have POAG, compared to eyes without myopia (>-0.5 dioptres) and with IOP <20 mmHg. Eyes with AL of ≥25.5 mm and high IOP (≥20 mmHg) were 16.22 times (95% CI, 7.73 to 34.03) likely to have POAG, compared to eyes with shorter AL (<23.5 mm) and lower IOP (<20 mmHg). These findings may provide additional insights into the pathophysiology of POAG and are particularly relevant for Asian populations.

We investigated the relationship of visual impairment (VI) and age-related eye diseases with mortality in a prospective, population-based cohort study of 3,280 Malay adults aged 40-80 years between 2004-2006. Participants underwent a full ophthalmic examination and standardized lens and fundus photographic grading. Visual acuity was measured using logMAR chart. VI was defined as presenting (PVA) and best-corrected (BCVA) visual acuity worse than 0.30 logMAR in the better-seeing eye. Participants were linked with mortality records until 2012. During follow-up (median 7.24 years), 398 (12.2%) persons died. In Cox proportional-hazards models adjusting for relevant factors, participants with VI (PVA) had higher all-cause mortality (hazard ratio[HR], 1.57; 95% confidence interval[CI], 1.25-1.96) and cardiovascular (CVD) mortality (HR 1.75; 95% CI, 1.24-2.49) than participants without. Diabetic retinopathy (DR) was associated with increased all-cause (HR 1.70; 95% CI, 1.25-2.36) and CVD mortality (HR 1.57; 95% CI, 1.05-2.43). Retinal vein occlusion (RVO) was associated with increased CVD mortality (HR 3.14; 95% CI, 1.26-7.73). No significant associations were observed between cataract, glaucoma and age-related macular degeneration with mortality. We conclude that persons with VI were more likely to die than persons without. DR and RVO are markers of CVD mortality.

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.

To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged <25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for each cohort separately using logistic regression. Meta-analysis was conducted using a fixed effects model. In the older European group the most strongly associated marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E-8). No other region reached genome-wide significance, and association signals were lower for the younger European group and Asian group. In the meta-analysis of all cohorts, no marker reached genome-wide significance: The most strongly associated regions were, NRXN1 (rs1401327, P = 2.93E-07), TOX (rs7823467, P = 3.47E-07) and LINC00340 (rs12212674, P = 1.49E-06). For 34 markers identified in prior GWAS for spherical equivalent refractive error, the beta coefficients for genotype versus spherical equivalent, and genotype versus refractive astigmatism, were highly correlated (r = -0.59, P = 2.10E-04). This work revealed no consistent or strong genetic signals for refractive astigmatism; however, the TOX gene region previously identified in GWAS for spherical equivalent refractive error was the second most strongly associated region. Analysis of additional markers provided evidence supporting widespread genetic co-susceptibility for spherical and astigmatic refractive errors.

Cataract formation may be an indicator of early siderosis and has been associated with intralenticular foreign bodies. We report a unique case of histopathologically proven lens siderosis in a young man with a preceding history of trauma but no signs of retained intraocular foreign body. He presented with a total white cataract with brownish deposits on anterior capsule and underwent cataract surgery for same followed by histopathological staining of anterior capsule for iron deposits. This case illustrates the importance of close monitoring of patients with history of trauma or previous penetrating injury to the eye, albeit no intraocular foreign body, as they might develop ocular siderosis at a later stage.