Chui Ming Gemmy Cheung

Age-related macular degeneration and polypoidal choroidal vasculopathy in Asians.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in elderly people globally. It is estimated that there will be more Asians with AMD than the rest of the world combined by 2050. In Asian populations, polypoidal choroidal vasculopathy (PCV) is a common subtype of exudative AMD, while choroidal neovascularization secondary to AMD (CNV-AMD) is the typical subtype in Western populations. The two subtypes share many common clinical features and risk factors, but also have different epidemiological and clinical characteristics, natural history and treatment outcomes that point to distinct pathophysiological processes. Recent research in the fields of genetics, proteomics and imaging has provided further clarification of differences between PCV and CNV-AMD. Importantly, these differences have manifested as disparity in response to intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) treatment between PCV and CNV-AMD, emphasizing the need for accurate diagnosis of PCV and in distinguishing PCV from CNV-AMD, particularly in Asian patients. Current clinical trials of intravitreal anti-VEGF therapy and photodynamic therapy will provide clearer perspectives of evidence-based management of PCV and may lead to paradigm shifts in therapeutic strategies away from those currently employed in the treatment of CNV-AMD. Further research is needed to clarify the relative contribution of specific pathways in inflammation, complement activation, extracellular matrix dysregulation, lipid metabolism and angiogenesis to the pathogenesis of PCV. Findings from this research, together with improved diagnostic technology and new therapeutics, will facilitate more optimal management of Asian AMD.

Prevalence of and Risk Factors for Age-Related Macular Degeneration in a Multiethnic Asian Cohort

OBJECTIVE To describe the prevalence of and risk factors for age-related macular degeneration (AMD) in a multiethnic Asian cohort of Chinese, Malay, and Indian persons. METHODS In this population-based study, 3172 persons of Chinese, Malay, and Indian ethnicities 40 years and older were included. Participants underwent comprehensive systemic and ocular examination, retinal photography, and laboratory investigations. Early and late AMD signs were graded from retinal photographs. Age-standardized prevalence estimates were calculated using the 2010 Singapore adult population as the standard population. Association with a range of systemic risk factors was analyzed. RESULTS Of 3172 participants, AMD was present in 211 subjects. Age-standardized prevalence of AMD was 7.0% in persons 40 years and older. The age-standardized prevalence was similar in all 3 Asian ethnic groups: Chinese, 7.3%; Malay, 7.7%; and Indian, 5.7% (P value = .44). The prevalence increased with age and was higher in men. Of the range of risk factors evaluated, only myopic refractive error (<-0.5 D) was significantly associated with a lower risk for AMD (odds ratio, 0.44; P < .001, compared with emmetropia) in Chinese men. CONCLUSIONS The prevalence of AMD was similar in the 3 major ethnic groups in Asia and comparable with white populations. Myopic refractive error was associated with reduced risk of AMD in Chinese men.

Emerging Evidence Concerning Systemic Safety of Anti-VEGF Agents – Should Ophthalmologists Be Concerned?

NTRAOCULAR INJECTIONS OF ANTI–VASCULAR ENDOTHElial growth factor (VEGF) agents have yielded dramatic improvements in the management of a wide variety of neovascular ocular diseases including age-related macular degeneration (AMD), 1 diabetic retinopathy (DR), 2 retinal vein occlusion, 3 and now even retinopathy of prematurity. 4 These agents have thus become one of the most commonly employed treatments, with 824 525 anti-VEGF intraocular injections given in 2008 in the United States. 5 There are currently 2 widely used agents: ranibizumab (Lucentis), which is FDA-approved, and bevacizumab (Avastin), 5 given offlabel. Despite its off-label status, a majority of the intravitreal anti-VEGF injections given in the United States and around the world are for bevacizumab, 5 accounting for 58% of all injections in a US review of Medicare fee-for-service Part B claims for neovascular AMD during 2008. Two new studies add to the growing debate on the relative merits and concerns on the use of ranibizumab vs bevacizumab for the treatment of AMD. The 1-year results of the Comparison of Age-Related Macular Degeneration Treatments Trial (CATT) 6 have for the first time demonstrated in a randomized controlled trial that bevacizumab and ranibizumab have somewhat equivalent efficacy, with few differences in visual outcomes using either a monthly injection schedule or treatment on an as-needed basis. In terms of safety, the frequencies of arteriothrombotic and venothrombotic events and mortality did not differ significantly between the 2 compounds. However, the proportion of patients with serious systemic adverse events was 24.1% for bevacizumab and 19.0% for ranibizumab (P .04). After adjustment for demographic features and coexisting illnesses at baseline, the risk of serious systemic adverse events for bevacizumab was higher by 29% (P .04), although no specific organ system consistently accounted for the difference in adverse events, with differences in rates greatest for infections and gastrointestinal disorders. It should be re-emphasized, however, that the CATT was not primarily designed or adequately powered to conclusively detect differences in adverse event rates between these 2 agents.

Prevalence, Racial Variations, and Risk Factors of Age-Related Macular Degeneration in Singaporean Chinese, Indians, and Malays

OBJECTIVE To describe the prevalence and risk factors for age-related macular degeneration (AMD) in a multiethnic Asian cohort of Chinese, Malay, and Indian persons. DESIGN Population-based cross-sectional study. PARTICIPANTS A total of 10 033 persons (3280 Malay, 3400 Indian, and 3353 Chinese; response rate, 75%) 40 years of age or older residing in Singapore. METHODS We performed comprehensive systemic and ocular examinations, retinal photography, and laboratory investigations for all participants. We graded early and late AMD signs from retinal photographs using the modified Wisconsin AMD grading scale. We calculated the age-standardized prevalence of AMD using the 2010 Singapore adult population and analyzed risk factors for AMD using logistic regression models. MAIN OUTCOME MEASURES Early and late AMD. RESULTS Of the 9799 participants with gradable photographs, 588 had early AMD and 60 had late AMD. The age-standardized prevalence was 5.1% (95% confidence interval [CI], 4.6-5.5) for early AMD and 0.5% (95% CI, 0.4-0.6) for late AMD. The prevalence of early AMD was similar between Chinese (5.7%) and Indian (4.5%; P = 0.27) persons and lower in Malays (3.5%; P = 0.002 compared with Chinese; P = 0.09 compared with Indians); in contrast, the prevalence for late AMD was similar across ethnic groups (Chinese, 0.6%; Indian, 0.3%; and Malay, 0.3%; P = 0.20). Risk factors for early AMD were older age (odds ratio [OR], 1.40 per 5-year increase in age; 95% CI, 1.33-1.47), male gender (OR, 1.81; 95% CI, 1.43-2.29), hypertension (OR, 1.28; 95% CI, 1.02-1.61), and hyperopic refraction (OR, 1.17 per 1-diopter increase in spherical equivalent; 95% CI, 1.11-1.24). Risk factors for late AMD include older age (OR, 1.87 per 5-year increase in age; 95% CI, 1.54-2.19), smoking more than 5 packs per week (OR, 3.63; 95% CI, 1.34-9.80), and presence of chronic kidney disease (OR, 2.17; 95% CI, 1.22-3.88). CONCLUSIONS Early AMD is more common in Chinese and Indians than in Malays, but there were no racial variations in the prevalence of late AMD.

Relationship of smoking and cardiovascular risk factors with polypoidal choroidal vasculopathy and age-related macular degeneration in Chinese persons.

PURPOSE Polypoidal choroidal vasculopathy (PCV) has been described as a distinct clinical entity from choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The present study aimed to determine risk factors for PCV and to compare associations with those for CNV secondary to AMD. DESIGN Case-control study. PARTICIPANTS Patients of Chinese ethnicity with clinically and angiographically diagnosed PCV (n = 123) or CNV secondary to AMD (n = 128) were recruited from a tertiary eye hospital in Singapore. Controls without signs of PCV, CNV secondary to AMD, or other retinal pathologic features (n = 1489) were selected from a population-based study. METHODS Patients underwent an ophthalmologic examination including digital color fundus photography, stereoscopic fluorescein angiography (FA), and indocyanine green angiography (ICGA). Classification into PCV or CNV secondary to AMD was based on FA and ICGA findings. Risk factors were determined from a standardized interview, with blood pressure recorded using a digital automatic blood pressure monitor. MAIN OUTCOME MEASURES Polypoidal choroidal vasculopathy or CNV secondary to AMD. RESULTS Persons who smoked were more likely to have PCV (39.9% vs. 13.4%) or CNV secondary to AMD (45.0% vs. 12.3%) than those who did not smoke. After controlling for age, gender, diabetes, hypercholesterolemia, and hypertension, persons who smoked were 4 times more likely to have PCV (odds ratio [OR], 4.4; 95% confidence interval [CI], 2.5-7.7; P<0.001) and CNV secondary to AMD (OR, 4.9; 95% CI, 2.7-8.8; P<0.001). A significant, negative association also was found between diastolic blood pressure and CNV secondary to AMD (OR, 0.7; 95% CI, 0.5-0.9; P = 0.017, adjusted for age, gender, smoking, diabetes, and hypercholesterolemia), but diastolic blood pressure was not associated with PCV. CONCLUSIONS Smoking but not other vascular risk factors is significantly associated with both PCV and CNV secondary to AMD in Chinese persons. The similarity of associations suggests that there may be common risk factors and pathological mechanisms.

Is age-related macular degeneration a manifestation of systemic disease? New prospects for early intervention and treatment

Age‐related macular degeneration (AMD) is a common vision‐threatening condition affecting the elderly. AMD shares common risk factors and processes, including vascular and inflammatory pathways, with many systemic disorders. Associations have been reported between AMD and hypertension, cardiovascular disease, cerebrovascular disease, dyslipidaemia, chronic kidney disease and neurodegenerative disorders. An increasing amount of evidence suggests that individuals with AMD are also at risk of systemic diseases such as stroke. In this review, we summarize the latest evidence to support the notion that AMD is an ocular manifestation of systemic disease processes, and discuss the potential systemic side effects of ocular AMD therapy of which general physicians should be aware. Recent genetic discoveries and understanding of the pathogenic pathways in AMD in relation to systemic disorders are also highlighted.

Prevalence and Risk Factors for Age-Related Macular Degeneration in Indians: A Comparative Study in Singapore and India

PURPOSE To compare the prevalence and risk factors for age-related macular degeneration (AMD) in 2 Indian populations, 1 living in urban Singapore and 1 in rural central India. DESIGN Population-based, cross-sectional studies of Indians aged 40+ years. METHODS Our analysis included 3337 Singapore-residing participants and 3422 India-residing participants. All participants underwent comprehensive systemic and ocular examinations and retinal photography. AMD was graded from retinal photographs according to the Wisconsin Age-Related Maculopathy Grading System. Systemic and ocular risk factors were assessed for association with AMD. RESULTS Singapore-residing participants were older (mean age 57.8 years vs 53.8 years) and, after adjusting for age and sex, were more likely to have previous cataract surgery, higher body mass index, hypertension, diabetes, previous myocardial infarction, higher cholesterol, and lower creatinine levels, but less likely to be current smokers, than India-residing participants. The age-standardized prevalence of early and late AMD was 4.45% and 0.34%, respectively, in Singapore and 5.80% and 0.16%, respectively, in India. Shorter axial length was associated with early AMD in both Singapore and India, whereas previous cataract surgery, higher body mass index, hypertension, and lower cholesterol were associated with early AMD in Singapore but not in India. CONCLUSION The prevalence of AMD was similar among Indian adults living in urban Singapore and rural India, despite differences in cardiovascular risk factor profile and demographics.

Choroidal vascularity index as a measure of vascular status of the choroid: Measurements in healthy eyes from a population-based study.

The vascularity of the choroid has been implicated in the pathogenesis of various eye diseases. To date, no established quantifiable parameters to estimate vascular status of the choroid exists. Choroidal vascularity index (CVI) may potentially be used to assess vascular status of the choroid. We aimed to establish normative database for CVI and identify factors associated with CVI in healthy eyes. In this population-based study on 345 healthy eyes, choroidal enhanced depth imaging optical coherence tomography scans were segmented by modified image binarization technique. Total subfoveal choroidal area (TCA) was segmented into luminal (LA) and stromal (SA) area. CVI was calculated as the proportion of LA to TCA. Linear regression was used to identify ocular and systemic factors associated with CVI and subfoveal choroidal thickness (SFCT). Subfoveal CVI ranged from 60.07 to 71.27% with a mean value of 65.61 ± 2.33%. CVI was less variable than SFCT (coefficient of variation for CVI was 3.55 vs 40.30 for SFCT). Higher CVI was associated with thicker SFCT, but not associated with most physiological variables. CVI was elucidated as a significant determinant of SFCT. While SFCT was affected by many factors, CVI remained unaffected suggesting CVI to be a more robust marker of choroidal diseases.

Comparison of Exudative Age-related Macular Degeneration Subtypes in Japanese and French Patients: Multicenter Diagnosis With Multimodal Imaging

PURPOSE To compare and analyze differences and similarities between Japanese and French patients in subtype diagnosis of exudative age-related macular degeneration (AMD) as determined by fundus photography (FP) and fluorescein angiography (FA), and a multimodal imaging involving FP, FA, indocyanine green angiography (ICGA), and optical coherence tomography (OCT). DESIGN Retrospective chart review. METHODS We determined the subtype diagnosis for 99 consecutive Japanese eyes and 94 consecutive French eyes with exudative AMD. The first-step diagnosis was made using FP and FA, while the second-step diagnosis was made using FP, FA/ICGA, and OCT. The diagnoses made by Japanese and French physicians were compared, and when the diagnoses differed, a third institute was consulted to arrive at a final consensus and diagnosis. RESULTS The first-step diagnosis showed 20%-30% disagreement against the final diagnosis, but the second-step diagnosis showed only 10% disagreement. Polypoidal choroidal vasculopathy (PCV) was observed more in Japanese patients (48%) than in French (9%), and the rate of PCV with type 1 or 2 choroidal neovascularization (CNV) was extremely low: 3% in Japanese and 0% in French. Type 1 CNV was found significantly more in French cases (53.3% vs 35.1%, P=.018), while the rate of eyes with type 2 CNV only or chorioretinal anastomosis was similar between populations. CONCLUSIONS Multimodality imaging significantly improved the sub-classification of AMD. There were significant differences between the 2 series in the proportions of type 1 CNV and PCV, while the proportions of type 2 CNV only and chorioretinal anastomosis were similar between groups.

Conversion to aflibercept for diabetic macular edema unresponsive to ranibizumab or bevacizumab

Background The purpose of this study was to determine if eyes with diabetic macular edema (DME) unresponsive to ranibizumab or bevacizumab would benefit from conversion to aflibercept. Methods This study was conducted as a retrospective chart review of subjects with DME unresponsive to ranibizumab and/or bevacizumab and subsequently converted to aflibercept. Results In total, 21 eyes from 19 subjects of mean age 62±15 years were included. The majority of subjects were male (63%). The median number of ranibizumab or bevacizumab injections before switching to aflibercept was six, and the median number of aflibercept injections after switching was three. Median follow-up was 5 months after the switch. Mean central foveal thickness (CFT) was 453.52±143.39 mm immediately prior to the switch. Morphologically, intraretinal cysts were present in all cases. Mean CFT after the first injection decreased significantly to 362.57±92.82 mm (Wilcoxon signed-rank test; P<0.001). At the end of follow-up, the mean CFT was 324.17±98.76 mm (P<0.001). Mean visual acuity was 0.42±0.23 logMAR just prior to the switch, 0.39±0.31 logMAR after one aflibercept injection, and 0.37±0.22 log-MAR at the end of follow-up. The final visual acuity was significantly better than visual acuity before the switch (P=0.04). Conclusion Eyes with DME unresponsive to multiple ranibizumab/bevacizumab injections demonstrate anatomical and visual improvement on conversion to aflibercept.