Gavin Tan

Diabetes, Metabolic Abnormalities, and Glaucoma: The Singapore Malay Eye Study

OBJECTIVE To examine the relationship of diabetes mellitus and metabolic abnormalities with intraocular pressure and glaucoma. METHODS A population-based study was conducted in 3280 (78.7% response) Malay adults aged 40 to 80 years. Diabetes was defined as a random serum glucose level of 200 mg/dL or greater or physician diagnosis of diabetes mellitus. Metabolic abnormalities including body mass index, lipid levels, and blood pressure were measured. Glaucoma was defined from a standardized examination by means of the International Society for Geographical and Epidemiological Ophthalmology criteria. RESULTS There were 764 persons (23.3%) who had diabetes. After controlling for age, sex, education, smoking, central corneal thickness, and diabetes treatment, intraocular pressure was higher in persons with than without diabetes (16.7 vs 15.0 mm Hg, P < .001) and in those with higher serum glucose levels (P < .001), glycosylated hemoglobin concentrations (P < .001), total cholesterol levels (P = .001), triglyceride levels (P = .002), and body mass index (P = .001). However, the prevalence of glaucoma was similar between persons with and without diabetes (4.7% vs 4.5%). In multivariate logistic regression models adjusting for age, sex, education, smoking, central corneal thickness, and diabetes treatment, diabetes was not associated with glaucoma (odds ratio, 1.00; 95% confidence interval, 0.63-1.61). CONCLUSION These data suggest that, although diabetes and metabolic abnormalities may be associated with a small increase in intraocular pressure, they are not significant risk factors for glaucomatous optic neuropathy.

Population Prevalence of Tilted and Torted Optic Discs Among an Adult Chinese Population in Singapore: The Tanjong Pagar Study

OBJECTIVE To determine the prevalence of tilted and torted optic discs and associated risk factors among Chinese adults in Singapore. METHODS As part of a population-based survey, optic disc stereophotographs of both eyes were obtained, and left eyes were analyzed using imaging software. A tilted optic disc was defined as an index of tilt (ratio of minimum to maximum optic disc diameter) less than 0.75. The angle of tilt was defined as the angle between the maximum and vertical optic disc diameter, and optic discs were graded as torted if the angle of tilt exceeded 15 degrees . RESULTS Twenty-six of 739 subjects (3.5%) had tilted optic discs, and 478 (64.7%) had torted optic discs. Myopia was present in 23 of 26 eyes (88.5% [95% confidence interval, 69.9%-97.6%]) with tilted optic discs and in 211 of 661 eyes (31.9% [28.4%-35.6%]) without tilted optic discs (P < .001). On multivariate analysis, myopia (spherical equivalent) was a significant risk factor for tilted optic discs (P < .001). Index of tilt was not associated with corneal astigmatism or with cylindrical refractive error. Seventeen eyes (65.4%) with tilted optic discs had an optic disc morphologic abnormality, but none were glaucomatous. CONCLUSIONS The prevalence of tilted optic discs among this Chinese population was 3.5%. Tilted optic discs were associated with myopia but not with glaucoma.

Development and Validation of a Deep Learning System for Diabetic Retinopathy and Related Eye Diseases Using Retinal Images From Multiethnic Populations With Diabetes

Importance A deep learning system (DLS) is a machine learning technology with potential for screening diabetic retinopathy and related eye diseases. Objective To evaluate the performance of a DLS in detecting referable diabetic retinopathy, vision-threatening diabetic retinopathy, possible glaucoma, and age-related macular degeneration (AMD) in community and clinic-based multiethnic populations with diabetes. Design, Setting, and Participants Diagnostic performance of a DLS for diabetic retinopathy and related eye diseases was evaluated using 494 661 retinal images. A DLS was trained for detecting diabetic retinopathy (using 76 370 images), possible glaucoma (125 189 images), and AMD (72 610 images), and performance of DLS was evaluated for detecting diabetic retinopathy (using 112 648 images), possible glaucoma (71 896 images), and AMD (35 948 images). Training of the DLS was completed in May 2016, and validation of the DLS was completed in May 2017 for detection of referable diabetic retinopathy (moderate nonproliferative diabetic retinopathy or worse) and vision-threatening diabetic retinopathy (severe nonproliferative diabetic retinopathy or worse) using a primary validation data set in the Singapore National Diabetic Retinopathy Screening Program and 10 multiethnic cohorts with diabetes. Exposures Use of a deep learning system. Main Outcomes and Measures Area under the receiver operating characteristic curve (AUC) and sensitivity and specificity of the DLS with professional graders (retinal specialists, general ophthalmologists, trained graders, or optometrists) as the reference standard. Results In the primary validation dataset (n = 14 880 patients; 71 896 images; mean [SD] age, 60.2 [2.2] years; 54.6% men), the prevalence of referable diabetic retinopathy was 3.0%; vision-threatening diabetic retinopathy, 0.6%; possible glaucoma, 0.1%; and AMD, 2.5%. The AUC of the DLS for referable diabetic retinopathy was 0.936 (95% CI, 0.925-0.943), sensitivity was 90.5% (95% CI, 87.3%-93.0%), and specificity was 91.6% (95% CI, 91.0%-92.2%). For vision-threatening diabetic retinopathy, AUC was 0.958 (95% CI, 0.956-0.961), sensitivity was 100% (95% CI, 94.1%-100.0%), and specificity was 91.1% (95% CI, 90.7%-91.4%). For possible glaucoma, AUC was 0.942 (95% CI, 0.929-0.954), sensitivity was 96.4% (95% CI, 81.7%-99.9%), and specificity was 87.2% (95% CI, 86.8%-87.5%). For AMD, AUC was 0.931 (95% CI, 0.928-0.935), sensitivity was 93.2% (95% CI, 91.1%-99.8%), and specificity was 88.7% (95% CI, 88.3%-89.0%). For referable diabetic retinopathy in the 10 additional datasets, AUC range was 0.889 to 0.983 (n = 40 752 images). Conclusions and Relevance In this evaluation of retinal images from multiethnic cohorts of patients with diabetes, the DLS had high sensitivity and specificity for identifying diabetic retinopathy and related eye diseases. Further research is necessary to evaluate the applicability of the DLS in health care settings and the utility of the DLS to improve vision outcomes.

Determinants of lens vault and association with narrow angles in patients from Singapore.

PURPOSE To describe the distribution and determinants of lens vault and to investigate the association of lens vault with narrow angles. DESIGN Prospective cross-sectional study. METHODS Phakic subjects 50 years and older were evaluated at a primary healthcare clinic with gonioscopy, partial laser interferometry, and anterior segment optical coherence tomography (AS-OCT). Narrow angles were defined as posterior trabecular meshwork not visible for ≥2 quadrants on non-indentation gonioscopy. Lens vault was defined as the perpendicular distance between the anterior pole of the crystalline lens and the horizontal line joining the 2 scleral spurs on horizontal AS-OCT scans. Analysis of covariance, multivariate logistic regression, and area under the receiver operating characteristic curves (AUC) were performed. RESULTS Of the 2047 subjects recruited, 582 were excluded because of poor image quality or inability to locate scleral spurs, leaving 1465 subjects for analysis. Eyes with narrow angles had greater lens vault compared to eyes with open angles (775.6 µm vs 386.5 µm, P < .0001). Women had significantly greater lens vault than men (497.28 µm vs 438.56 µm, P < .001), and lens vault increased significantly with age (P for trend <.001). Adjusted for age and sex, significant associations with greater lens vault were shorter axial length, shallower anterior chamber depth(ACD), higher intraocular pressure, and more hyperopic spherical equivalent (all P < .001). On multivariate analysis, subjects with lens vault >667.6 µm were more likely to have narrow angles (OR 2.201, 95% CI: 1.070-4.526) compared to those with lens vault ≤462.7 µm. The AUC for lens vault (0.816) and ACD (0.822) for detecting narrow angles were similar (P = .582). CONCLUSIONS Lens vault was independently associated with narrow angles and may be useful in screening to detect eyes with narrow angles.

Blindness and long-term progression of visual field defects in Chinese patients with primary angle-closure glaucoma.

PURPOSE To investigate the long-term rates of blindness and visual field (VF) progression in treated primary angle-closure glaucoma (PACG) patients. DESIGN Retrospective observational case series. METHODS PACG patients with ≥10 years of follow-up were analyzed. All VFs (static automated perimetry, central 24-2 threshold test) performed were reviewed and reliable VFs (fixation losses <20%, false positives and false negatives <33%) were scored using the Advanced Glaucoma Intervention Study (AGIS) system. Progression of a VF defect was defined as a change of ≥4 from baseline on 2 consecutive VF tests. RESULTS From the 137 eyes of 87 patients with PACG with ≥10 years of follow-up identified, 6% and 30.1% were blind based on initial visual acuity (VA) and VF criteria respectively and 12.0% had an initial AGIS score of 20; these were excluded. Eighty-three eyes from 57 patients (all Chinese, mean age 59.9 ± 8.2 years, 67.5% female) were analyzed. The mean AGIS score was 5.14 ± 4.37 at baseline. VF deterioration was detected in 27 eyes (32.5%) of 21 patients, with 4.8% and 7.2% of eyes progressing to blindness based on VA and VF criteria respectively. On Cox regression, eyes with VF progression had higher mean overall IOP (P < .001), and higher prevalence of previous acute angle closure (AAC, P = .008). CONCLUSIONS Over 10 years, a third of PACG patients were found to have VF progression, with 7% progressing to blindness while on treatment. Eyes with higher mean overall IOP and a history of previous AAC were more likely to have VF progression.

Diabetic macular oedema

Diabetic macular oedema, characterised by exudative fluid accumulation in the macula, is the most common form of sight-threatening retinopathy in people with diabetes. It affects one in 15 people with diabetes resulting in more than 20 million cases worldwide. Few epidemiological studies have been done to specifically investigate risk factors for diabetic macular oedema, although poor glycaemic and blood pressure control are associated with the presence and development of the disorder. The pathophysiological processes begin with chronic hyperglycaemia, and interplay between vascular endothelial growth factor (VEGF) and inflammatory mediators. Non-invasive imaging using optical coherence tomography has allowed clinicians to detect mild levels of diabetic macular oedema in order to monitor progress and guide treatment. Although focal or grid laser photocoagulation was the traditional mode of treatment, intraocular pharmacotherapy with anti-VEGF agents is now the standard of care. However, these therapies are expensive and resource intensive. Emerging therapeutic strategies include improving efficacy and duration of VEGF suppression, targeting alternative pathways such as inflammation, the kallikrein-kinin system, the angiopoietin-Tie2 system, and neurodegeneration, and using subthreshold and targeted laser therapy. Ongoing research should lead to improvements in screening, diagnosis, and management of diabetic macular oedema.

Optical Coherence Tomographic Angiography in Type 2 Diabetes and Diabetic Retinopathy

Importance Optical coherence tomographic angiography (OCT-A) is able to visualize retinal microvasculature without the need for injection of fluorescein contrast dye. Nevertheless, it is only able to capture a limited view of macula and does not show leakage. Objectives To evaluate the retinal microvasculature using OCT-A in patients with type 2 diabetes as well as the association of OCT-A characteristics with diabetic retinopathy (DR) and systemic risk factors. Design, Setting, and Participants A prospective, observational study was conducted from January 1 to June 30, 2016, at medical retina clinics at the Singapore National Eye Center among 50 patients with type 2 diabetes with and without DR (n = 100 eyes). We examined the retinal microvasculature with swept-source OCT-A and a semiautomated software to measure the capillary density index (CDI) and fractal dimension (FD) at the superficial vascular plexus (SVP) and deep retinal vascular plexus (DVP). We collected data on histories of patients’ glycated hemoglobin A1c, hypertension, hyperlipidemia, smoking, and renal impairment. Main Outcomes and Measures The CDI and FD at the SVP and DVP for each severity level of DR and the association of systemic risk factors vs the CDI and FD. Results The mean (SD) glycated hemoglobin A1c of the 50 patients (26 men and 24 women; 35 Chinese; mean [SD] age, 59.5 [8.9] years) was 7.9% (1.7%). The mean (SD) CDI at the SVP decreased from 0.358 (0.017) in patients with no DR to 0.338 (0.012) in patients with proliferative DR (P < .001) and at the DVP decreased in patients with no DR from 0.361 (0.019) to 0.345 (0.020) in patients with proliferative DR (P = .04). The mean (SD) FD at the SVP increased from 1.53 (0.05) in patients with no DR to 1.60 (0.05) in patients with proliferative DR (P < .01) and at the DVP increased from 1.55 (0.06) in patients with no DR to 1.61 (0.05) in patients with proliferative DR (P = .02). For systemic risk factors, hyperlipidemia (odds ratio [OR], 9.82; 95% CI, 6.92-11.23; P < .001), smoking (OR, 10.90; 95% CI, 8.23-12.34; P < .001), and renal impairment (OR, 3.72; 95% CI, 1.80-4.81; P = .05) were associated with reduced CDI, while increased glycated hemoglobin A1c (≥8%) (OR, 8.77; 95% CI, 5.23-10.81; P < .01) and renal impairment (OR, 10.30; 95% CI, 8.21-11.91; P < .001) were associated with increased FD. Conclusions and Relevance Optical coherence tomographic angiography is a novel imaging modality to quantify the retinal capillary microvasculature in patients with diabetes. It can be potentially used in interventional trials to study the effect of systemic risk factors on the microvasculature that was previously not accessible in a noninvasive manner. The relevance of these findings relative to visual acuity, however, remains largely unknown at this time.

Prevalence and determinants of undiagnosed diabetic retinopathy and vision-threatening retinopathy in a multiethnic Asian cohort: the Singapore Epidemiology of Eye Diseases (SEED) study

Objective To determine the prevalence and risk factors of undiagnosed diabetic retinopathy (DR), in particular vision-threatening DR (VTDR) in a multiethnic Asian cohort. Design A population-based survey of 3353 Chinese, 3280 Malays and 3400 Indians (73.6% response) aged 40–80 years residing in Singapore. Diabetes mellitus (DM) was defined as random glucose ≥11.1 mmol/L, use of diabetic medication or a previous physician diagnosis. DR severity was graded from retinal photographs following the modified Airlie House classification. VTDR was defined as the presence of severe non-proliferative DR (NPDR), proliferative DR (PDR) or clinically significant macular oedema (CSMO), using the Eye Diseases Prevalence Research Group definition. Participants were deemed ‘undiagnosed’ if they reported no prior physician diagnosis in structured interviews, in those with the condition. Results Of 10 033 participants, 2376 had DM (23.7%), of which 805 (33.9%) had DR. Among 2376 with DM, 11.1% (n=263) were undiagnosed. Among 805 with DR, 671 (83.3%) were undiagnosed. Among 212 with VTDR, 59 (27.3%) were undiagnosed. In multivariate models, factors associated with undiagnosed VTDR were higher low-density lipoprotein (LDL) cholesterol (OR=1.53, 95% CI 0.99 to 2.35, p=0.05) and absence of visual impairment or blindness in any eye in terms of best-corrected vision OR=3.00, 95% CI 1.47 to 6.11, p=0.003). Conclusions In this community, a quarter with VTDR is undiagnosed, and 8 in 10 with any DR are undiagnosed, compared with only 1 in 10 with DM undiagnosed. These findings suggest that screening for diabetes is successful, while screening for DR is currently inadequate in our population. Public health strategies to aid early diagnosis of DR in Singapore are urgently warranted to reduce blindness due to diabetes.

Visual acuity after acute primary angle closure and considerations for primary lens extraction

Background/aim: Primary lens extraction has been advocated for acute primary angle closure (APAC), but it is not known if this is warranted in all cases. The aim of this study was to investigate the visual acuity (VA) of APAC eyes shortly after resolution of the acute episode in order to assess the appropriateness of performing such surgery in this condition. Methods: This was a prospective observational case series. As part of a randomised controlled trial comparing phacoemulsification and laser iridotomy, 135 consecutive APAC subjects over a 2 year period underwent subjective refraction and measurement of Snellen VA once the acute episode had resolved with reduction of intraocular pressure (IOP) and improved corneal clarity. Results: Subjects were predominantly Chinese (95.6%) and female (79.3%), with a mean age of 63.6 (SD 9.6) years. When assessed 1.7 (2.7) days after presentation, the majority of APAC cases (50.4%) had good VA (6/12 or better), with more than a quarter of cases having VA of 6/7.5 or better. Poor VA was associated with duration of symptoms (p = 0.04, OR = 4.1, 95% CI 1.1 to 15.7) and time taken to resolution of APAC (p = 0.04, OR = 2.2, 95% CI 1.02 to 4.6), but not with sex (p = 0.31), age (p = 0.26), duration from presentation to measurement of visual acuity (p = 0.53), or presenting IOP (p = 0.73). Conclusion: Within days after APAC, more than half of APAC affected eyes had good VA (6/12 or better). The role of lens extraction in the management of APAC warrants further debate, especially for eyes with good VA.

Retinal ganglion cell neuronal damage in diabetes and diabetic retinopathy.

To examine the association of diabetes and diabetic retinopathy (DR) with retinal ganglion cell (RGC) loss.