Neelam Kumari

Singapore Indian Eye Study 2: methodology and impact of migration on systemic and eye outcomes†

Asian Indians are the fastest growing migration groups in the world. Studies evaluating the impact of migration on disease outcomes in this population are rare.

Direct medical cost associated with diabetic retinopathy severity in type 2 diabetes in Singapore

Diabetic retinopathy (DR) is a leading cause of vision-loss globally among type 2 diabetes (T2DM) patients. Information on the economic burden of DR in Singapore is limited. We aim to identify the total annual direct medical costs of DR at different stages, and to examine factors influencing the costs. Four hundreds and seventy T2DM patients who attended the Diabetes Centre in a secondary hospital in Singapore in 2011–2014 were included. Digital color fundus photographs were assessed for DR in a masked fashion. Retinopathy severity was further categorized into non-proliferative DR (NPDR), including mild, moderate and severe NPDR, and proliferative DR (PDR). Medical costs were assessed using hospital administrative data. DR was diagnosed in 172 (39.5%) patients, including 51 mild, 62 moderate and 18 severe NPDR, and 41 PDR. The median cost in DR [2012.0 (1111.2–4192.3)] was significantly higher than that in non-DR patients [1158.1 (724.1–1838.9)] (p<0.001). The corresponding costs for mild, moderate, severe NPDR and PDR were [1167.1 (895.4–2012.0)], [2212.0 (1215.5–3825.5)], [2717.5 (1444.0–6310.7)], and [3594.8.1 (1978.4–8427.7)], respectively. After adjustment, the corresponding cost ratios for mild, moderate, severe NPDR, and PDR relative to non-DR were 1.1 (p = 0.827), 1.8 (p = 0.003), 2.0 (p = 0.031) and 2.3 (p<0.001), respectively. The other factors affecting the total cost include smoking (ratio = 1.7, p = 0.019), neuropathy (ratio = 1.9, p = 0.001) and chronic kidney disease (CKD) (ratio = 1.4, p = 0.019). The presence and severity of DR was associated with increased direct medical costs in T2DM. Our results suggest that preventing progression of DR may reduce the economic burden of DR.

Urinary Isoprostane Levels and Age-Related Macular Degeneration

Purpose Oxidative stress, characterized by an excessive production of reactive oxygen intermediates has been suggested to play a role in the pathogenesis of age-related macular degeneration (AMD). We examined the association of urinary F2-isoprostanes (F2-IsoPs), a marker of lipid peroxidation and the most reliable marker of oxidative damage with AMD. Methods We included 238 adults with AMD and 390 age- and sex-matched controls without AMD who participated in a population-based cross-sectional study in Singapore (Singapore Chinese Eye Study, 2009-2011). AMD was graded from retinal photographs using the Wisconsin Age-Related Maculopathy Grading System. Urinary-free F2-IsoPs (pmol/mmol of creatinine) were measured by gas chromatography mass spectrometry (GC-MS). The association between F2-IsoPs and AMD was examined using unconditional logistic regression models adjusted for potential confounders including smoking, body mass index (BMI), blood pressure, total and high-density lipoprotein cholesterol, and history of cardiovascular disease. Results Higher levels of F2-IsoPs were associated with AMD independent of potential confounders. Compared to quartile 1 (Q1) of F2-IsoPs, the multivariable odds ratio (95% confidence interval) of AMD in quartiles 2, 3, and 4 were 2.05 (1.26-3.32), 1.80 (1.10-2.94), and 1.76 (1.06-2.94), respectively. In subgroup analyses comparing Q4 to Q1, this association was stronger in women, those with BMI less than 25 kg/m2 and those with hypertension, but no significant interaction was found (P interaction > 0.1 for each strata). Conclusions Higher levels of urinary F2-IsoPs levels were associated with AMD independent of potential confounders in Chinese adults.

Association of serum lutein and zeaxanthin with quantitative measures of retinal vascular parameters

To evaluate the association between serum carotenoids and quantitative measures of retinal vasculature in elderly Singapore Chinese subjects. The following details were collected in 128 healthy subjects: sociodemographics, lifestyle information, medical and drug history, and anthropometric measurements. Serum concentrations of carotenoids were estimated in fasting venous blood using high performance liquid chromatography. Retinal vascular parameters were quantitatively measured from retinal photographs using a computer-assisted program (Singapore I Vessel Assessment). The mean age of the population was 54.1 years (range 40 to 81 years). In multiple linear regression analysis, per SD decrease in retinal arteriolar caliber [β = 0.045 (0.003 to 0.086), p = 0.036], per SD increase in retinal venular caliber [β = -0.045 (-0.086 to -0.003), p = 0.036] and per SD increase in arteriolar branching angle [β = -0.039 (-0.072 to -0.006), p = 0.021] were associated with decreased serum lutein. Per SD increase in retinal venular tortuosity [β = -0.0075 (-0.0145 to -0.0004), p = 0.039] and per SD increase in arteriolar branching angle (β = -0.0073 [-0.0142 to -0.0059], p = 0.041) were associated with decreased serum zeaxanthin. None of the other carotenoids demonstrated meaningful relationship with quantitative measures of retinal vasculature. Lower levels of lutein and zeaxanthin demonstrated significant relationship with adverse quantitative measures of retinal vasculature in elderly healthy subjects.

The association of serum creatinine and estimated glomerular filtration rate variability with diabetic retinopathy in Asians with type 2 diabetes: A nested case–control study

Background: Fluctuation of kidney function may signify intra-glomerular microvascular hemodynamic instability. We aim to examine the association of long-term serum creatinine and estimated glomerular filtration rate variability with diabetic retinopathy. Methods: We included type 2 diabetes mellitus patients who attended the Diabetes Centre in 2011–2014 and were followed up (median = 3.2 years). Digital colour fundus photographs were assessed for diabetic retinopathy at follow-up. Diabetic retinopathy severity was categorized into non-proliferative diabetic retinopathy and proliferative diabetic retinopathy. We conducted a nested case–control study involving 177 diabetic retinopathy (118 non-proliferative diabetic retinopathy, 50 proliferative diabetic retinopathy) and 327 age- and gender-matched non-diabetic retinopathy. Serum creatinine measured before follow-up visit was obtained (⩾3 readings/patient). Variability was calculated as intra-individual standard deviation/√n/(n – 1). Results: Diabetic retinopathy have higher adjusted-serum creatinine-standard deviation than non-diabetic retinopathy [9.1 (4.9–21.6) vs 5.4 (3.4–10.1) µM, p < 0.001]. After multivariable adjustment, adjusted-serum creatinine-standard deviation was associated with diabetic retinopathy [odds ratio = 1.47, 95% confidence interval (1.02–2.10), p = 0.04]. The area under the curve increased significantly after adding adjusted-serum creatinine-standard deviation [0.70 (0.65–0.75) vs 0.72 (0.68–0.77), p < 0.03]. Proliferative diabetic retinopathy have higher adjusted-serum creatinine-standard deviation than non-proliferative diabetic retinopathy [15.5 (6.6–39.7) vs 7.47 (4.52–17.8) µM, p < 0.001]. After adjustment, adjusted-serum creatinine-standard deviation remained associated with non-proliferative diabetic retinopathy [1.48 (1.04–2.12), p = 0.03] and proliferative diabetic retinopathy [2.43 (1.34–4.39), p = 0.003; p-trend = 0.002]. Similar findings were observed for estimated glomerular filtration rate variability. Conclusion: Serum creatinine and estimated glomerular filtration rate variability is associated with the presence and severity of diabetic retinopathy independent of intra-individual means. This may inform novel therapeutic strategies aiming to achieve stable renal function in type 2 diabetes mellitus.

Beyond vision loss: the independent impact of diabetic retinopathy on vision-related quality of life in a Chinese Singaporean population

Background/aims To assess the independent impact of diabetic retinopathy (DR) on three domains of vision-related quality of life (VRQoL) in a Chinese Singapore population. Methods The Singapore Chinese Eye Study (n=3353; 2009–2011) was a population-based, prospective, cross-sectional study conducted at the Singapore Eye Research Institute. The study population included 292 adults with diabetes, with and without DR. DR (better eye) was categorised as presence and absence of any DR; severity of DR (no vision-threatening DR (VTDR); severe non-proliferative DR (NPDR); PDR and/or clinically significant macular oedema and VTDR). Our main outcome was VRQoL which was measured using Rasch-calibrated scores from the ‘Reading’, ‘Mobility’ and ‘Emotional’ domains of the Impact of Vision Impairment questionnaire. The relationship between DR and VRQoL was assessed using multiple linear regression models. Results Of the 292 individuals (mean age 61.35 ± 9.66 years; 55.8% male), 201 (68.8%), 49 (16.8%), 20 (6.8%), 22 (7.5%) and 27 (9.2%) had no DR, minimal-mild NPDR, moderate-severe NPDR, PDR and VTDR, respectively. Any DR and VTDR were independently associated with 6% and 12% worse Reading scores and 7% and 18% poorer Emotional well-being, respectively, compared with those without DR. These associations persisted after separate adjustment for visual impairment and presenting visual acuity. No significant difference was found in the Mobility domain between persons with and without DR. Conclusions We documented that DR, particularly VTDR, was independently associated with restrictions in Reading and Emotional well-being. Understanding factors underlying the detrimental DR-VRQoL relationship may optimise rehabilitation outcomes for individuals with DR.

High prevalence of undiagnosed eye diseases in individuals with dementia.

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