Should Aquaporin-4 Antibody Test Be Performed in all Patients With Isolated Optic Neuritis?

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.

Profiles of Ganglion Cell-Inner Plexiform Layer Thickness in a Multi-Ethnic Asian Population: The Singapore Epidemiology of Eye Diseases Study.

PURPOSE: To examine the normative profile and determinants of macular ganglion cell-inner plexiform layer (GCIPL) thickness based on spectral-domain OCT (SD-OCT) in a nonglaucoma, multi-ethnic Asian population. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: Ethnic Chinese, Malay, and Indian adults aged ≥40 years recruited from the Singapore Epidemiology of Eye Diseases Study. METHODS: All participants underwent standardized examinations. The GCIPL thickness was measured using Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA). Participants with glaucoma or poor-quality scans were excluded. Eye-specific data were used. Associations of ocular and systemic factors with GCIPL thickness parameters were investigated using multivariable linear regression with generalized estimating equation models to account for correlation between both eyes. MAIN OUTCOME MEASURES: GCIPL thickness. RESULTS: A total of 4464 participants (7520 eyes) consisting of 1625 Chinese, 1212 Malay, and 1627 Indian adults contributed to this analysis. Average GCIPL thickness was 82.6±6.1 µm in Chinese, 81.5±6.8 µm in Malays, and 78.0±6.9 µm in Indians (P < 0.001 by analysis of variance). The 5th percentile limit of average GCIPL thickness was 72 µm in Chinese, 70 µm in Malays, and 67 µm in Indians. In multivariable analysis adjusting for age, gender, axial length, presence of cataract, OCT signal strength, disc area, hypertension, diabetes, and hyperlipidemia, eyes of Indians were observed to have 3.43 µm thinner GCIPL on average compared with Chinese (P < 0.001) and 3.36 µm thinner GCIPL compared with Malays (P < 0.001). In addition, older age (per decade; ß = -2.51), female (ß = -1.57), longer axial length (per mm; ß = -1.54), and presence of chronic kidney disease (ß = -1.49) were significantly associated with thinner average GCIPL (all P ≤ 0.008). Larger optic disc area (per mm2; ß = 0.78; P < 0.001) was associated with thicker GCIPL. These factors were consistently observed to be significant for superior and inferior hemisphere GCIPL thickness. CONCLUSIONS: GCIPL thickness profiles were significantly thinner in Indians compared with Chinese and Malays. Our findings further highlight the need of a more refined, ethnic-specific normative database for GCIPL thickness, which in turn may improve the detection and diagnosis of glaucoma in Asians.

Factors affecting signal strength in spectral-domain optical coherence tomography.

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, ß = -0.373, p < 0.001; ß = -0.373, p < 0.001, respectively), poorer BCVA (per logMAR line; ß = -0.123, p < 0.001; ß = -0.156, p < 0.001, respectively), greater degree of myopia (per negative dioptre of spherical equivalent; ß = -0.112, p < 0.001; ß = -0.117, p < 0.001, respectively), presence of cortical cataracts (ß = -0.331, p < 0.001; ß = -0.314, p < 0.001, respectively) and presence of posterior subcapsular cataracts (ß = -0.910, p < 0.001; ß = -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.

Inter-Relationships Between Retinal Vascular Caliber, Retinal Nerve Fiber Layer Thickness, and Glaucoma: A Mediation Analysis Approach.

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.

Joint Effects of Intraocular Pressure and Myopia on Risk of Primary Open-Angle Glaucoma: The Singapore Epidemiology of Eye Diseases Study.

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.

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.

Impact of Visual Impairment and Eye diseases on Mortality: the Singapore Malay Eye Study (SiMES).

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.

Reliability and determinants of retinal vessel oximetry measurements in healthy eyes.

PURPOSE: To assess the reliability and determinants of retinal vessel oximetry measurements with the Oxymap T1 Retinal Oximeter in normal Asian eyes. METHODS: Subjects older than 40 years without a history of stroke and heart disease were recruited from a community-based clinic. Subjects underwent standardized systemic and ocular examinations. Normal eyes were defined as eyes without major eye diseases such as age-related macular degeneration, glaucoma, or retinopathy. Retinal vessel oximetry levels were measured by using the Oxymap T1 Retinal Oximeter. Intra- and intergrader reliability of retinal vessel oximetry measurements were assessed by using 50 images. Intravisit repeatability of retinal vessel oximetry measurements was assessed by using 20 paired images. Univariable linear regression was performed to examine the associations between retinal vessel oximetry measurements and systemic determinants. RESULTS: A total of 118 retinal oximetry images were included in the final analysis. Intra- (intraclass correlation coefficient [ICC] values: 0.89-0.99) and intergrader (ICC values: 0.77-0.94) reliability, and intravisit (ICC values: 0.85-0.96) repeatability were both high. In the linear regression analysis, older age was associated with reduced overall retinal venular oximetry levels (ß: -2.61%; 95% confidence interval [CI]: -4.92 to -0.29) and reduced inferior-nasal retinal venular oximetry levels (ß: -3.53%; 95% CI: -6.07 to -0.99). CONCLUSIONS: The Oxymap Retinal Oximeter allows reliable and repeatable retinal vessel oximetry measurements. Age is the main factor that influences retinal venular oximetry levels and should be taken into account when retinal oximetry measurements are interpreted.

Histopathologically proven siderotic cataract with disintegrated intralenticular foreign body.

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.

Histopathologically proven siderotic cataract with disintegrated intralenticular foreign body.

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.