Obstructive Sleep Apnoea, Other Sleep Parameters and Diabetic Retinopathy.

PURPOSE OF REVIEW: To summarise the association between obstructive sleep apnoea and diabetic retinopathy and diabetic macular oedema. To examine the effects of other sleep parameters on diabetic retinopathy and diabetic macular oedema. To discuss the pathophysiology of diabetic eye changes and how it is related to obstructive sleep apnoea. RECENT FINDINGS: Conflicting data exists in terms of the association of diabetic eye changes with sleep apnoea and/or other sleep parameters. Various cross-sectional studies show PDR to be associated with the prevalence of OSA. Patients who underwent continuous positive airway pressure (CPAP) treatment were significantly less likely to develop pre/proliferative DR. Secondary sleep parameters generally are not associated with DR except for long duration of sleep. Differences in reporting could be due to the different thresholds set to define OSA/ODI and severity of DR/DME, in addition to factors used in multivariate analysis. There is a need for further studies with long-term follow-up and to assess the impact of CPAP on the development and progression of diabetic eye change(s).

Meta-analysis of genome-wide association studies in multiethnic Asians identifies two loci for age-related nuclear cataract.

Age-related cataract is a leading cause of blindness worldwide, especially in developing countries where access to cataract surgery remains limited. Previous linkage and candidate gene studies suggested genetic influences on age-related nuclear cataract but few genetic markers have been identified thus far. We conducted genome-wide association studies on 4569 Asians (including 2369 Malays and 2200 Indians), and replicated our analysis in 2481 Chinese from two independent cohorts (1768 Chinese in Singapore and 803 Chinese in Beijing). We confirmed two genome-wide significant loci for nuclear cataract in the combined meta-analysis of four cohorts (n = 7140). The first locus was at chromosome 3q25.31 in KCNAB1 (rs7615568, fixed-effect Pmeta = 2.30 × 10(-8); random-effect Pmeta = 1.08 × 10(-8)). The second locus was at chromosome 21 in the proximity of CRYAA (rs11911275, fixed-effect Pmeta = 2.77 × 10(-8); random-effect Pmeta = 1.98 × 10(-9)), a major protein component of eye lens. The findings were further supported by up-regulation and down-regulation of KCNAB1 and CRYAA in human lens capsule, respectively, as the severity of nuclear cataract increases. The results offer additional insights into the pathogenesis of nuclear cataract in Asians.

Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error.

Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways.

Sleep apnea and retinal signs in cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis.

PURPOSE: The aim of the study was to examine the relationship between sleep apnea, retinal vascular caliber and retinopathy, and their impact on cardiovascular disease (CVD) risk. METHODS: A multi-ethnic cohort of 5,803 participants was examined based on standardized grading of retinal vascular caliber and retinopathy from digital fundus photographs, self-reported physician-diagnosed sleep apnea (PDSA), and incident cardiovascular events. RESULTS: In women, PDSA was associated with narrower arterioles (regression coefficient [ß] -5.76; 95 % confidence Interval [CI] -8.51, -3.02) after adjusting for cardio-metabolic risk factors. The incident rate ratio (IRR) of CVD was also associated with narrower arterioles (IRR for highest versus lowest tertile 1.91; 95 % CI 1.08, 3.38). In men, PDSA was not associated with arteriolar caliber. However, incident CVD was associated with narrower arterioles (IRR 1.67; 95 % CI 1.10, 2.52), wider venules (IRR 1.71; 95 % CI 1.13, 2.59) and PDSA (IRR 2.03, 95 % CI 1.17, 3.51). The IRR of CVD in men with PDSA increased minimally to 2.06 (95 % CI 1.18, 3.56) after adjustment for retinal arteriolar and venular caliber. Combining women and men, the IRR of CVD was 3.41 (95 % CI 1.79, 6.50) in those with both PDSA and narrower retinal arterioles. CONCLUSIONS: Sleep apnea was associated with narrower retinal arterioles in women but not in men. However, sleep apnea was also associated with incident CVD in men. These suggest potential gender differences in susceptibility to microvascular disease in association with sleep apnea.

Ethnic differences in undercorrected refractive error in Asians.

PURPOSE: To describe the ethnic variations in the prevalence and risk factors for undercorrected refractive error and its impact on vision-specific functioning (VF) in a multiethnic Asian population. METHODS: A total of 3353 Chinese, 3400 Indians, and 3280 Malays in Singapore participated in this population-based cross-sectional study. Distance presenting visual acuity (VA) was measured using a logarithm of the minimum angle of resolution number chart. Best-corrected VA was assessed using the same test protocol as presenting VA. Undercorrected refractive error was defined as an improvement of at least 0.2 logarithm of the minimum angle of resolution (two lines equivalent) in the best-corrected VA compared with the presenting VA in the better eye when presenting VA was less than 20/40 in the better eye. The VF-11 questionnaire measured participants' VF. Multivariate linear regression was performed to assess the impact of undercorrected refractive error on the overall VF score. RESULTS: Regardless of ethnicity, participants with undercorrected refractive error had a reduction in VF score compared to those with normal vision in both eyes. The overall prevalence of undercorrected refractive error was highest in Indians (25.1%), followed by Malays (22.2%) and Chinese (19.7%). Undercorrected refractive error was less common in spectacles or contact lenses wearers than in non-spectacle wearers or non-contact lenses wearers. Adults with mild to moderate refractive errors were most likely to have undercorrected refractive error (p < 0.001). In multivariate analysis, increasing age (p < 0.001), Indian race (p < 0.001), lower education level (p < 0.001) or poorer housing (p < 0.001), having refractive errors (p < 0.001), and not wearing optical corrections (p < 0.001) were significantly associated with increasing undercorrected refractive error. CONCLUSIONS: In Singapore, undercorrected refractive error is most prevalent in Indians and least prevalent in Chinese. The impact of undercorrected refractive error on VF was consistent across all three ethnicities. There may be higher barriers to visual correction among Malays or Indians compared with Chinese in Singapore.

The associations of objectively measured sleep duration and sleep disturbances with diabetic retinopathy.

AIMS: To assess the associations between objectively measured sleep duration, sleep disturbances and diabetic retinopathy (DR). METHODS: This cross-sectional study recruited 92 patients with diabetes from retinal clinics. Objective measurements of sleep duration, apnea-hypopnea index (AHI) and minimum oxygen saturations (SaO2) were obtained through polysomnography. The Epworth Sleepiness Scale and Insomnia Severity Index were administered. Retinal photographs were taken and graded according to the modified Airlie House Classification System. Regression analysis used to determine associations with outcomes including moderate DR, vision-threatening DR (VTDR) and diabetic macular edema (DME). RESULTS: Mean age of participants was 57.6 ± 8.3 years. 29 (32%) of them had moderate DR, and 17 (18.5%) had VTDR. Higher AHI (Odds Ratio [OR] 1.04; 95% confidence interval [CI] 1.00, 1.07) and short sleep duration (OR 3.22; 95%CI 1.18, 8.79) were associated with moderate DR. VTDR was associated with moderate obstructive sleep apnea (OSA) (OR 4.73; 95%CI 1.46, 15.31), higher AHI (OR 1.06; 95%CI 1.02, 1.10) and lower minimum SaO2 (OR 0.89; 95%CI 0.83, 0.96). High risk for insomnia was associated with DME (OR 4.01; 95%CI 1.09, 14.73). CONCLUSIONS: Short sleep duration was associated with moderate DR while OSA-related parameters and a high risk for insomnia were associated with moderate DR, VTDR and DME.

Associations between sleep duration, sleep quality and diabetic retinopathy.

BACKGROUND: Abnormal durations of sleep have been associated with risk of diabetes. However, it is not clear if sleep duration is associated with diabetic retinopathy (DR). METHODS: In a cross-sectional study, we included 1,231 (Malay, n = 395; Indian, n = 836) adults (mean age 64.4 ± 9.0 years, 50.4% female) with diabetes from the second visit of two independent population-based cohort studies (2011-15) in Singapore. Self-reported habitual sleep duration was categorized as short (<6 h), normal (6≤ h <8), and long (≥8 h). Questionnaires were administered to detect risk of obstructive sleep apnea (OSA), excessive daytime sleepiness, and insomnia, all of which may indicate poor quality of sleep. The associations between sleep-related characteristics with moderate DR and vision-threatening DR (VTDR) were analysed using logistic regression models adjusted for potential confounders. RESULTS: Prevalence of moderate DR and VTDR in the study population were 10.5% and 6.3% respectively. The mean duration of sleep was 6.4 ± 1.5 h. Compared to normal sleep duration, both short and long sleep durations were associated with moderate DR with multivariable odds ratio (95% confidence interval) of 1.73 (1.03-2.89) and 2.17 (1.28-3.66) respectively. Long sleep duration (2.37 [1.16-4.89]), high risk of OSA (2.24 [1.09-4.75]), and excessive daytime sleepiness (3.27 [1.02-10.30]) were separately associated with VTDR. CONCLUSION: Sleep duration had a U-shaped association with moderate DR; long sleep duration, excessive daytime sleepiness and high risk of OSA were positively associated with VTDR.

Retinal neurodegeneration on optical coherence tomography and cerebral atrophy.

Neurodegeneration in dementia is mainly evaluated by assessing cerebral atrophy, while retinal neurodegeneration can be quantified in vivo using optical coherence tomography (OCT). We examined the association of retinal nerve fibre layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thinning with global and regional cerebral atrophy on magnetic resonance imaging (MRI). Malay participants aged 60-80 years from the Epidemiology of Dementia in Singapore Study underwent comprehensive examinations, including 3-Tesla cranial MRI. RNFL and GC-IPL thicknesses were obtained from spectral domain-OCT; and cerebral grey and white matter volumes were obtained from MRI scans using a validated segmentation tool. Linear regression models were constructed with adjustment for age and sex; and additionally for vascular risk factors and MRI markers including intracranial volume. 164 participants without glaucoma with gradable quality MRI and OCT scans were included for analysis. GC-IPL thinning was associated with reduction in total brain volume in the occipital (mean change in GC-IPL per standard deviation (SD) decrease in occipital lobe volume: -1.77 µm, 95% confidence interval (CI) -6.55 to 0.01 µm) and temporal lobes (mean change in GC-IPL per SD decrease in temporal lobe volume: -3.45 µm, 95%CI -5.40 to -1.49 µm) in multivariate adjusted models. In particular, GC-IPL thinning was primarily associated with grey matter volume, whereas no association was found with white matter changes. Retinal neuronal damage, as reflected by GC-IPL thinning, was independently associated with grey matter loss in the occipital and temporal lobes, suggesting that retinal OCT may provide insights for assessing neurodegeneration in the brain.

Ethnic variation in central corneal refractive power and steep cornea in Asians.

PURPOSE: To describe ethnic differences in the distribution of central corneal refractive power and steep cornea in a multiethnic Asian population. METHODS: A total of 2968 Chinese, 2957 Indian and 2928 Malay participants aged over 40 years were included in this study. Each subject underwent standardized systematic and ocular examinations, interviewer-administered questionnaires, and blood investigations for risk factor assessment. Central corneal refractive power was measured using an autorefractor. Steep cornea was defined as central corneal refractive power exceeding 48 diopters (D) measured by keratometry. RESULTS: Mean keratometry readings were 43.9 ± 1.5 D in Malays, 44.2 ± 1.5 D in Indians and 43.9 ± 1.5 D in Chinese. The prevalence of steep cornea was 0.6% (95% confidence interval, CI, 0.3-0.9%) in Malays, 1.0% (95% CI 0.7-1.4%) in Indians and 0.5% (95% CI 0.3-0.8%) in Chinese. In multivariate analysis, increasing central corneal refractive power was associated with Indian race, shorter body height, non-smokers, absence of pterygium, shorter axial length, thinner corneas and greater anterior chamber depth, while the presence of steep cornea was significantly associated with Indian race, shorter axial length and thinner corneas. CONCLUSIONS: Indian participants had the steepest corneas among the three major ethnic groups in Singapore. Central corneal refractive power was related to several ocular parameters including anterior chamber depth, axial length and central corneal thickness. These data have important clinical implications for understanding the risk of keratoconus.

Microvascular network alterations in retina of subjects with cerebral small vessel disease.

Novel retinal imaging techniques have enabled the assessment of quantitative vascular parameters, which provide information on the microvasculature before the appearance of retinopathy signs. Advances in neuroimaging have revealed that cerebral microbleeds (CMB) - besides lacunar infarcts and white matter lesions (WML) - may be a novel marker of cerebral small vessel disease. We examine whether quantitative retinal vascular parameters are related to cerebral small vessel disease in a Chinese population. Participants from Epidemiology of Dementia in Singapore Study underwent comprehensive examinations, including 3-Tesla cranial magnetic resonance imaging and retinal-photography. Retinal vascular parameters (caliber, tortuosity, fractal dimension) were measured from photographs using a semi-automated computer-assisted program. Lacunar infarcts and CMB were visually graded. Total brain and WML volume were obtained using a validated segmentation tool. A total of 261 subjects were included, of whom 36 had lacunar infarcts, 29 had severe WML, and 83 had CMB. In age-sex-adjusted models, narrower retinal arteriolar caliber, wider venular caliber and smaller arteriolar fractal dimension were associated with presence of multiple CMB. In contrast, no association was found with lacunar infarcts and WML volume. After multivariate adjustments, associations of venular caliber, arteriolar fractal dimensions and arteriolar tortuosity with CMB remained statistically significant. In conclusion, subjects with early structural changes in retinal microvasculature were more likely to have CMBs, supporting hypothesis that CMB may be an early manifestation of cerebral small vessel disease.

Prevalence of refractive errors in a multiethnic Asian population: the Singapore epidemiology of eye disease study.

PURPOSE: To determine the prevalence of refractive errors in a multiethnic Asian population aged over 40 years and to examine secular trends and racial differences. METHODS: A total of 10,033 adults (3353 Chinese, 3400 Indians, and 3280 Malays) participated in this study. Refractive error was determined by subjective refraction. Ocular biometric parameters were determined by partial coherence interferometry. Myopia and high myopia were defined as spherical equivalent (SE) of less than -0.5 diopters (D) and -5.0 D, respectively. Hyperopia was defined as SE of more than 0.5 D. Astigmatism was defined as cylinders less than -0.5 D. RESULTS: The prevalence of myopia, high myopia, hyperopia and astigmatism in Singapore adults aged over 40 years was 38.9% (95% confidence interval [CI] 37.1, 40.6); 8.4% (95% CI 8.0, 8.9); 31.5% (95% 30.5, 32.5); and 58.8% (95% CI 57.8, 59.9), respectively. Compared with the Tanjong Pagar Survey 12 years ago, there was a significant increase in the prevalence of astigmatism and mean axial length (AL) in Chinese adults aged over 40 years in Singapore. Chinese were most likely to be affected by myopia, high myopia, astigmatism, and had the longest AL among the three racial groups. CONCLUSIONS: The prevalence of myopia in Singapore adults is lower compared with the younger "myopia" generation in Singapore. The prevalence of astigmatism and mean AL have been increasing significantly within the past 12 years in the Chinese population. Chinese adults had higher prevalence of myopia, high myopia, astigmatism, as well as the longer AL compared with non-Chinese adults in Singapore.

The impact of cataract, cataract types, and cataract grades on vision-specific functioning using Rasch analysis.

PURPOSE: To determine the impact of cataracts and their types and grades on vision-specific functioning. DESIGN: Prospective population-based cross-sectional study. METHODS: The Singapore Indian Eye Study examined 3400 of 4497 (75.6% response rate) ethnic Indians 40 years of age and older living in Singapore. Three thousand one hundred sixty-eight (93.2%) fulfilled inclusion criteria with complete information for final analysis. Cataracts were assessed on slit-lamp examination and were graded according to the Lens Opacity Classification System III. Vision-specific functioning scores were explored with the Visual Function scale, validated using Rasch analysis. RESULTS: Two hundred sixty-nine (8.5%) and 740 (23.4%) of the study participants had unilateral and bilateral cataracts, respectively, and 329 (10.4%), 800 (25.2%), and 128 (4.1%) participants had nuclear, cortical, and posterior subcapsular (PSC) cataracts, respectively. In multivariate linear regression models, the presence of bilateral rather than unilateral cataract (ß = -0.12; 95% confidence interval, -0.20 to 0.00) was associated independently with poorer vision-specific functioning, even after adjusting for undercorrected refractive error (ß = -0.11; 95% confidence interval, -0.21 to 0.00). Bilateral nuclear, cortical, and PSC cataracts also were associated with poorer vision-specific functioning (ß = -0.31, -0.15, and -1.15, respectively), with combinations of them having even greater impact. Significantly poorer vision-specific functioning occurred at Lens Opacity Classification System grades 4 (nuclear opalescence), 5 (nuclear color), 3 (cortical), and 1 (PSC) or higher. CONCLUSIONS: People with bilateral but not unilateral cataracts experience difficulty with performing vision-specific daily activities independent of refractive error, with PSC cataracts and cataract combinations having the greatest impact. Cataract types cause poorer vision-specific functioning beginning at different severity grades.