Possible Modifying Effect of Hemoglobin A1c on Genetic Susceptibility to Severe Diabetic Retinopathy in Patients With Type 2 Diabetes.

Purpose: Glycemic control has been recognized as an important modifiable risk factor for diabetic retinopathy (DR). Whether hemoglobin A1c (HbA1c), as an indicator of glycemic control, could modify the genetic susceptibility to severe DR remains to be investigated. This study aimed to investigate whether HbA1c could modulate the genetic susceptibility to severe DR in Chinese patients with type 2 diabetes. Methods: A total of 3,093 Chinese individuals with type 2 diabetes were included in the cross-sectional case-control study: 1,051 with sight-threatening DR (STDR) and 2,042 without STDR. Sixty-nine top-ranked single nucleotide polymorphisms (SNPs) identified from previous genome-wide association studies were examined for their associations with STDR and proliferative DR as a subgroup analysis. SNPs showing suggestive associations with DR were examined in the stratified analysis by dichotomized HbA1c (<7% vs. ≥7%). An interaction analysis was performed by including an interaction term of SNP × HbA1c in the regression model. Results: Four SNPs showed suggestive associations with STDR. In the stratified analysis, patients with adequate glycemic control (HbA1c <7%) had a 42% lower risk of STDR for carrying each additional protective C allele of COL5A1 rs59126004 (P = 1.76 × 10-4; odds ratio, 0.58; 95% confidence interval, 0.44-0.77). rs59126004 demonstrated a significant interaction with dichotomized HbA1c on the risk of STDR (Pinteraction = 1.733 × 10-3). In the subgroup analysis for proliferative DR, the protective effect of rs59126004 was even more pronouncedly demonstrated (P = 8.35 × 10-5; odds ratio, 0.37; 95% confidence interval, 0.22-0.60) and it showed similar interactions with dichotomized HbA1c (Pinteraction = 1.729 × 10-3). Conclusions: Our data provided evidence for possible interactions between HbA1c and COL5A1 rs59126004 on the risk of severe DR. These findings may provide new insight into the pathophysiologic mechanism of DR.

Awareness of diabetic retinopathy and its association with attendance for systematic screening at the public primary care setting: a cross-sectional study in Hong Kong.

OBJECTIVE: To assess the association between awareness of diabetic retinopathy (DR) and actual attendance for DR screening. DESIGN: Cross-sectional study. SETTING: Two public general outpatient clinics. PARTICIPANTS: The subjects were people with diabetes mellitus (DM) who participated in a randomised controlled trial, set up in 2008, to test the impact of a copayment on attendance for DR screening. PRIMARY AND SECONDARY OUTCOME MEASURES: The subjects' awareness of DR was evaluated using a structured questionnaire conducted via a telephone interview. The attendance for screening was from the actual attendance data. Association between awareness and attendance for screening was determined using multivariate logistic regression model and was reported as ORs. RESULTS: A total of 2593 participants completed the questionnaire. A total of 42.9% (1113/2593) said they would worry if they had any vision loss and 79.6% (2063/2593) knew that DM could cause blindness. Only 17.5% (453/2593) knew that treatment was available for DR and 11.5% (297/2593) knew that early DR could be asymptomatic. The importance of having a regular eye examination was acknowledged by 75.7% (1964/2593), but 34% (881/2593) did not know how frequently their eyes should be examined. Worry about vision loss (OR=1.72, P<0.001), awareness of the importance of regular eye examination (OR=1.83, P=0.002) and awareness of the frequency of eye examinations ('every year' (OR=2.64, P<0.001) or 'every 6 months' (OR=3.27, P<0.001)) were the most significant factors associated with attendance. CONCLUSIONS: Deficits in knowledge of DR and screening were found among subjects with DM, and three awareness factors were associated with attendance for screening. These factors could be targeted for future interventions.

Impact of Genetic Loci Identified in Genome-Wide Association Studies on Diabetic Retinopathy in Chinese Patients With Type 2 Diabetes.

PURPOSE: Diabetic retinopathy (DR) is a common microvascular complication of type 2 diabetes (T2DM). Genome-wide association studies (GWAS) had identified novel DR-susceptibility genetic variants in various populations. We examined the associations of these DR-associated single nucleotide polymorphisms (SNPs) with severe DR in a Chinese T2DM cohort. METHODS: Cross-sectional case-control studies on sight-threatening DR (STDR) and proliferative DR (PDR) were performed. We genotyped 38 SNPs showing top association signals with DR in previous GWAS in 567 STDR cases, including 309 with PDR and 1490 non-DR controls. Multiple logistic regression models with adjustment for conventional risk factors, including age, sex, duration of diabetes, and presence of hypertension, were employed. RESULTS: The strongest association was found at INSR rs2115386, an intronic SNP of INSR: Padjusted = 9.13 × 10-4 (odds ratio [OR],1.28; 95% confidence interval [95%CI], 1.11-1.48) for STDR, and Padjusted= 1.12 × 10-4 (OR [95%CI],1.44 [1.20-1.74]) for PDR. rs599019 located downstream of COLEC12 (Padjusted = 0.019; OR [95%CI],1.19 [1.03-1.38]) and rs4462262 located at an intergenic region between ZWINT and MRPS35P3 (Padjusted = 0.041; OR [95%CI],1.38[1.01-1.89]) also were significantly associated with STDR, but not with PDR alone. On the other hand, MYT1L-LOC729897 rs10199521 (Padjusted = 0.022; OR [95%CI],1.25 [1.03-1.51]) and API5 rs899036 (Padjusted = 0.049; OR [95%CI],1.36 [1.00-1.85]) showed significant independent associations only with PDR. Similar results were obtained when hemoglobin A1c also was included in the adjustment models. CONCLUSIONS: We demonstrated the significant and independent associations of several GWAS-identified SNPs with DR in Chinese T2DM patients with severe DR. The findings on INSR rs2115386 are supportive of the role of insulin resistance, or the compensatory hyperinsulinemia, in the pathogenesis of DR.

Systematic screening for diabetic retinopathy (DR) in Hong Kong: prevalence of DR and visual impairment among diabetic population.

PURPOSE: To determine the prevalence of diabetic retinopathy (DR), sight threatening DR (STDR), visual impairment and other eye diseases in a systematic DR screening programme among primary care Chinese patients with diabetes mellitus (DM) in Hong Kong. METHODS: Screening for DR was provided to all subjects with DM in public primary care using digital fundus photography according to the English national screening programme. STDR was defined as preproliferative DR (R2), proliferative DR (R3) and/or maculopathy (M1). The presence of other eye diseases was noted. Visual impairment was classified as none (visual acuity in the better eye of 6/18 or better), mild (6/18 to >6/60) and severe (6/60 or worse). RESULTS: Of 174 532 subjects screened, most had never been screened before. The prevalence of DR was 39.0% (95% CI 38.8% to 39.2%) and STDR 9.8% (95% CI 9.7% to 9.9%). The most common DR status was R1 (35.7%), followed by M1 (8.6%), R2 (3.0%) and R3 (0.3%). The prevalence of mild and severe visual impairment was 4.2% and 1.3%, respectively. Subjects with STDR had a higher prevalence (9.8%) of visual impairment than those without (3.5%). CONCLUSIONS: DR was prevalent in this population and one in 10 had STDR. This suggests the need for systematic screening to ensure timely referral to an ophthalmologist for monitoring and/or treatment.

Detection of Glaucoma and Its Association With Diabetic Retinopathy in a Diabetic Retinopathy Screening Program.

PURPOSE: To determine the type of glaucoma in subjects with diabetes mellitus detected during a diabetic retinopathy screening program and to determine any association between diabetic retinopathy (DR) and glaucoma. MATERIALS AND METHODS: This is a population-based prospective cross-sectional study, in which subjects with diabetes mellitus underwent screening for DR in a primary care outpatient clinic. Digital fundus photographs were taken and graded for presence/absence and severity of DR. During this grading, those fundus photographs showing increased cup-to-disc ratio (CDR) (≥0.6) were identified and these patients were referred to the specialist ophthalmology clinic for detailed examination. The presence of glaucoma was established based on CDR and abnormal visual field (VF) defects according to Hodapp-Parrish-Anderson's criteria. An elevation of intraocular pressure was not required for the diagnosis of glaucoma. The patients said to have definite glaucoma were those with vertical CDR>/=0.6, glaucomatous defects on VF examination, or retinal nerve fiber thinning if VF was unreliable. RESULTS: Of the 2182 subjects who underwent screening, 81 subjects (3.7%) had increased CDR and 40 subjects (1.8%) had confirmed glaucoma. Normal-tension variant of primary open-angle glaucoma was the most prevalent type (1.2%) We did not find any evidence that DR is a risk factor for glaucoma [odds ratio for DR vs. no DR=1.22 (95% confidence interval, 0.59-2.51)]. CONCLUSION: The overall prevalence of glaucoma in this diabetic population, based on finding increased cupping of optic disc in a teleretinal screening program was 1.8% (95% confidence interval, 1.0-3.0).

Cost-Effectiveness of Screening for Intermediate Age-Related Macular Degeneration during Diabetic Retinopathy Screening.

PURPOSE: To determine whether screening for age-related macular degeneration (AMD) during a diabetic retinopathy (DR) screening program would be cost effective in Hong Kong. DESIGN: We compared and evaluated the impacts of screening, grading, and vitamin treatment for intermediate AMD compared with no screening using a Markov model. It was based on the natural history of AMD in a cohort with a mean age of 62 years, followed up until 100 years of age or death. PARTICIPANTS: Subjects attending a DR screening program were recruited. METHOD: A cost-effectiveness analysis was undertaken from a public provider perspective. It included grading for AMD using the photographs obtained for DR screening and treatment with vitamin therapy for those with intermediate AMD. The measures of effectiveness were obtained largely from a local study, but the transition probabilities and utility values were from overseas data. Costs were all from local sources. The main assumptions and estimates were tested in sensitivity analyses. MAIN OUTCOME MEASURES: The outcome was cost per quality-adjusted life year (QALY) gained. Both costs and benefits were discounted at 3%. All costs are reported in United States dollars ($). RESULTS: The cost per QALY gained through screening for AMD and vitamin treatment for appropriate cases was $12,712 after discounting. This would be considered highly cost effective based on the World Health Organization's threshold of willingness to pay (WTP) for a QALY, that is, less than the annual per capita gross domestic product of $29,889. Because of uncertainty regarding the utility value for those with advanced AMD, we also tested an extreme, conservative value for utility under which screening remained cost effective. One-way sensitivity analyses revealed that, besides utility values, the cost per QALY was most sensitive to the progression rate from intermediate to advanced AMD. The cost-effectiveness acceptability curve showed a WTP for a QALY of $29,000 or more has a more than 86% probability of being cost effective compared with no screening. CONCLUSIONS: Our analysis demonstrated that AMD screening carried out simultaneously with DR screening for patients with diabetes would be cost effective in a Hong Kong public healthcare setting.

The Correlation of Retinal Nerve Fiber Layer Thickness With Blood Pressure in a Chinese Hypertensive Population.

To investigate the association between retinal nerve fiber layer (RNFL) thickness and blood pressure (BP) in subjects with systemic hypertension. Subjects with systemic hypertension on anti-hypertensive medications were screened by fundus photography and referred for glaucoma work-up if there was enlarged vertical cup-to-disc (VCDR) ratio ≥0.6, VCDR asymmetry ≥0.2, or optic disc hemorrhage. Workup included a complete ophthalmological examination, Humphrey visual field test, and RNFL thickness measurement by optical coherence tomography. The intraocular pressure (IOP) and RNFL thicknesses (global and quadrant) were averaged from both eyes and the means were correlated with: the systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) using Pearson correlation. Among 4000 screened hypertensive subjects, 133 were referred for glaucoma workup and 110 completed the workup. Of the 4000 screened subjects, 1.3% had glaucoma (0.9% had normal tension glaucoma [NTG], 0.2% had primary open angle glaucoma, and 0.2% had primary angle closure glaucoma), whereas 0.3% were NTG suspects. The SBP was negatively correlated with the mean superior RNFL thickness (P = 0.01). The DBP was negatively correlated with the mean global (P = 0.03), superior (P = 0.02), and nasal (P = 0.003) RNFL thickness. The MAP was negatively correlated with the mean global (P = 0.01), superior (P = 0.002), and nasal (P = 0.004) RNFL thickness while positively correlated with the mean IOP (P = 0.02). In medically treated hypertensive subjects, glaucoma was present in 1.3%, with NTG being most prevalent. MAP control may help with IOP lowering and RNFL preservation, although future prospective studies will be needed.

Prospective study on the efficacy of treating normal tension glaucoma with a single session of selective laser trabeculoplasty.

PURPOSE: The purpose of this study was to investigate the efficacy of selective laser trabeculoplasty (SLT) in the treatment of normal tension glaucoma (NTG). METHODS: This prospective cohort study recruited consecutive cases of NTG on antiglaucoma medication. Cases were excluded for previous glaucoma surgery or laser. All patients underwent a 1-month washout of medication followed by a mean baseline intraocular pressure (IOP) measured at 9 AM, 1 PM, and 5 PM. A 30% reduction from baseline was set as the target IOP. A single session of SLT was performed to 360 degrees of the trabecular meshwork. IOP phasing was repeated at 1 month after SLT and medication was resumed to achieve the target IOP. Patients were followed up to 6 months after SLT. RESULTS: In 83 eyes of 46 subjects, the mean prestudy IOP was 14.2 ± 3.1 mm Hg when on 1.5 ± 0.9 antiglaucoma medication. The mean baseline IOP without medication was 16.1 ± 2.2 mm Hg. The mean SLT shots applied was 187.8 ± 27.5 using a mean energy of 1.0 ± 0.07 mJ. At 1-month post-SLT, the IOP was 12.7 ± 2.0 mm Hg (21.6% IOP reduction) from baseline without medication (P<0.05). The 6-month IOP was 11.4 ± 1.6 mm Hg when on 1.1± 1.0 medications, representing a 19.7% reduction from prestudy IOP, a 29.6% reduction from baseline IOP, and a 26.7% reduction in antiglaucoma medication (all P< 0.05). A higher baseline IOP was correlated with greater IOP reduction with SLT (r=0.3, P=0.009). CONCLUSIONS: A single session of SLT for NTG achieved an additional 20% reduction in IOP with 27% less medication at 6 months compared with prestudy levels while maintaining a 30% reduction from baseline IOP.

Screening for diabetic retinopathy with or without a copayment in a randomized controlled trial: influence of the inverse care law.

OBJECTIVE: To examine whether the inverse care law operates in a screening program for diabetic retinopathy (DR) based on fee for service in Hong Kong. DESIGN: Randomized controlled trial. PARTICIPANTS: All those with type 1 or 2 diabetes from 2 clinics were recruited. INTERVENTION: Diabetic retinopathy screening with a small copayment versus free access in a publicly funded family medicine service. MAIN OUTCOME MEASURES: Uptake of screening and severity of DR detected. Association between these outcome variables and independent variables were determined using multivariate logistic regression models and reported as odds ratios (ORs). RESULTS: After randomization, 1387 subjects in the free group and 1379 subjects in the pay group were eligible for screening, and 94.9% (1316/1387) and 92.6% (1277/1379), respectively, agreed to participate in the study. The offer of screening was accepted by 94.8% (1247/1316) in the free group and 91.2% (1164/1277) in the pay group, and the final uptake ratios were 88.5% (1165/1316) and 82.4% (1052/1277), respectively (Pearson chi = 19.74, P<0.001). Being in the pay group was associated with a lower uptake of screening than being in the free group (OR, 0.59; confidence interval [CI], 0.47-0.74) and a lower detection rate of DR (OR, 0.73; CI, 0.60-0.90) after adjustment for potential confounding factors. Subjects with higher socioeconomic status were more likely to attend screening and had a lower prevalence of DR detected. CONCLUSIONS: The inverse care law seems to operate in a preventive intervention when a relatively small copayment is applied. There is a case for making effective preventive services free of charge. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Detection of glaucoma in a cohort of chinese subjects with systemic hypertension.

Purpose. To determine the presence and type of glaucoma in a cohort of adult Chinese subjects with systemic hypertension. Methods. This prospective cohort study included 200 hypertensive Chinese adults aged >40 years old who underwent screening via frequency doubling technology (FDT) perimetry and intraocular pressure (IOP) measurement by noncontact tonometry (NCT) in a general outpatient clinic. Those with IOP > 21 mmHg and/or visual field (VF) defects on FDT were referred for complete ophthalmological examination. The diagnosis of glaucoma was based on an abnormal VF on Humphrey Field Analyzer (HFA) by Hodapp-Parrish-Anderson's criteria and an increased vertical cup-disc ratio (VCDR). Results. The mean age of the subjects was 64.66 ± 9.47 years, and the male:female ratio was 92 : 108. All patients were hypertensive with a mean blood pressure (BP) of 131.1 ± 15.1/76.6 ± 11.1 mmHg whilst on systemic antihypertensive medication. Of the 111 patients that had an abnormal initial screening, 14 (7.9%) were confirmed to have glaucoma with the highest prevalence of normal tension glaucoma (NTG) (6.2%), followed by primary angle closure glaucoma (PACG) (1.1%) and primary open angle glaucoma (POAG) (0.5%). The positive predictive value of FDT perimetry was 71%. Conclusion. Nearly 8% of the adults with systemic hypertension had glaucoma, and NTG was the most prevalent type.

Medication-induced acute angle closure attack.

OBJECTIVE: To review acute angle closure attacks induced by local and systemic medications. DATA SOURCES: PubMed literature searches up to August 2011. STUDY SELECTION: The following key words were used for the search: "drug", "iatrogenic", "acute angle closure glaucoma". DATA EXTRACTION: A total of 86 articles were retrieved using the key words. Only those concerning acute angle closure attack triggered by local or systemic drug administration were included. For articles on the same or related topics, those published at later or more recent dates were selected. As a result, 44 articles were included and formed the basis of this review. DATA SYNTHESIS: An acute attack of angle closure can be triggered by dilatation of the pupil, by anatomical changes in the ciliary body and iris, or by movement of the iris-lens diaphragm. Local and systemic medications that cause these changes have the potential to precipitate an attack of acute angle closure. The risk is higher in subjects who are predisposed to the development of angle closure. Many pharmaceutical agents including ophthalmic eyedrops and systemic drugs prescribed by general practitioners and various specialists (in psychiatry, otorhinolaryngology, ophthalmology, medicine, and anaesthesia) can precipitate an acute angle closure attack. The medications include: anti-histamines, anti-epileptics, antiparkinsonian agents, antispasmolytic drugs, mydriatic agents, sympathetic agents, and botulinum toxin. CONCLUSION: Since acute angle closure attack is a potentially blinding eye disease, it is extremely important to be vigilant and aware of ophthalmic and systemic medications that can lead to such attacks in predisposed subjects and to diagnose the condition when it occurs.