Highlights from the 2019 International Myopia Summit on 'controversies in myopia'.

Myopia is an emerging public health issue with potentially significant economic and social impact, especially in East Asia. However, many uncertainties about myopia and its clinical management remain. The International Myopia Summit workgroup was convened by the Singapore Eye Research Institute, the WHO Regional Office for the Western Pacific and the International Agency for the Prevention of Blindness in 2019. The aim of this workgroup was to summarise available evidence, identify gaps or unmet needs and provide consensus on future directions for clinical research in myopia. In this review, among the many 'controversies in myopia' discussed, we highlight three main areas of consensus. First, development of interventions for the prevention of axial elongation and pathologic myopia is needed, which may require a multifaceted approach targeting the Bruch's membrane, choroid and/or sclera. Second, clinical myopia management requires co-operation between optometrists and ophthalmologists to provide patients with holistic care and a tailored approach that balances risks and benefits of treatment by using optical and pharmacological interventions. Third, current diagnostic technologies to detect myopic complications may be improved through collaboration between clinicians, researchers and industry. There is an unmet need to develop new imaging modalities for both structural and functional analyses and to establish normative databases for myopic eyes. In conclusion, the workgroup's call to action advocated for a paradigm shift towards a collaborative approach in the holistic clinical management of myopia.

25-years Trends and Risk factors related to Surgical Outcomes of Giant Retinal Tear-Rhegmatogenous Retinal Detachments.

To describe the 25-year surgical trends, long-term outcomes and risk factors affecting the outcomes of giant retinal tear-related rhegmatogenous retinal detachments (GRT-RRD). Patients' demographics, pre-operative characteristics, risk factors, operative procedures and post-operative outcomes were collected and divided into three groups - Group A: 1991 to 2015 (overall); Group B: 1991 to 2005, and Group C: 2006 to 2015. Functional and anatomical successes were monitored over a 5-year period. Multivariate logistic regression analysis was performed to identify the risk factors related to functional and anatomical success.127 eyes of 127 patients were included in the study. At 5th year, 69.4% patients had visual acuity (VA) < logMAR 1.0 with 87.5% primary anatomical success rate. While the functional outcome remained the same between group B and C, there was an increase in the anatomical success from 89.7% to 100%, albeit not statistically significant. Patients with worse presenting VA, 150 degrees or more of giant retina tear, macula-detached status and presence of PVR were associated with VA of> logMAR 1.0 (all p < 0.05). The types of surgery (TPPV vs combined SB/TPPV), number of breaks, lens extraction and additional cryotherapy were not associated with the functional or anatomical success. In conclusion, the GRT-RRD functional and structural outcomes were comparable between 1991-2005 and 2006-2015, albeit a statistically insignificant improvement of anatomical outcome over the past 25 years. Worse presenting VA, 150 degrees or more of giant retinal tear, detached macula and presence of PVR were associated with poorer visual outcome.

Quantitative Microvascular Analysis With Wide-Field Optical Coherence Tomography Angiography in Eyes With Diabetic Retinopathy.

Importance: Wide-field optical coherence tomographic angiography (OCTA) may provide insights to peripheral capillary dropout in eyes with diabetic retinopathy (DR). Objective: To describe the diagnostic performance of wide-field OCTA with and without large vessel removal for assessment of DR in persons with diabetes. Design, Setting, and Participants: This case-control study was performed from April 26, 2018, to April 8, 2019, at a single tertiary eye center in Singapore. Case patients were those with type 2 diabetes for more than 5 years and bilateral DR diagnosed by fundus imaging; control participants included those with no self-reported history of diabetes, a fasting glucose level within the normal range in the past year, and no ocular pathologic findings. A wide-field (12 × 12-mm2) fovea-centered scan was performed using a prototype swept source OCTA system. Retinal microvasculature was examined by separating the angiograms into large vessels, capillaries, and capillary dropout regions. Main Outcomes and Measures: Area under the receiver operating characteristic curve (AUC) for DR severity discrimination using wide-field vascular metrics. Retinal perfusion density (RPD), capillary perfusion density (CPD), large vessel density (LVD), and capillary dropout density (CDD) were calculated. Low-contrast regions were excluded from the calculation. Results: A total of 49 eyes in 27 control participants (17 male [63.0%]; mean [SD] age, 59.96 [7.63] years; age range, 44-79 years) and 76 eyes in 47 patients with diabetes (29 male [61.7%]; mean [SD] age, 64.36 [8.08] years; range, 41-79 years) were included. Among eyes in patients with diabetes, 23 were in those with diabetes but no DR, 25 in those with mild nonproliferative DR, and 28 in those with moderate to severe nonproliferative DR. There was no difference in RPD, CPD, LVD, and CDD between the control group and the group with diabetes and no DR. There was a stepwise decrease in RPD, CPD, and CDD in the diabetes with no DR, mild nonproliferative DR, and moderate to severe nonproliferative DR groups, whereas LVD was not associated with DR staging. The nonproliferative DR group had decreased RPD, CPD, and CDD compared with the control group. The CPD had higher AUCs than RPD for discriminating diabetes with nonproliferative DR (combined mild and moderate to severe nonproliferative DR) vs no DM (AUC, 0.92 [95% CI, 0.87-0.98] vs 0.89 [95% CI, 0.83-0.95], P = .01), diabetes with no DR vs mild nonproliferative DR (AUC, 0.81 [95% CI, 0.68-0.94] vs 0.77 [95% CI, 0.64-0.91], P = .18), and mild nonproliferative DR vs moderate to severe nonproliferative DR (AUC, 0.82 [95% CI, 0.71-0.94] vs 0.78 [95% CI, 0.65-0.91], P = .01) but similar AUCs for no DM vs diabetes with no DR. The total perfusion density and CPD in wide-field OCTA had better discriminative power than the central 6 × 6-mm2 field (CPD, 0.89 [95% CI, 0.83-0.95] vs 0.84 [95% CI, 0.77-0.92], P = .06; total perfusion density, 0.93 [95% CI, 0.87-0.98] vs 0.90 [95% CI, 0.83-0.96], P = .06). Conclusions and Relevance: The findings suggest that wide-field OCTA provides information on microvascular perfusion and may be useful for detecting predominant peripheral capillary dropout in eyes with nonproliferative DR. A vascular selectivity approach excluding the large vessels may improve the discriminative power for different stages of DR.

PEDIATRIC RETINAL DETACHMENT IN AN ASIAN POPULATION WITH HIGH PREVALENCE OF MYOPIA: Clinical Characteristics, Surgical Outcomes, and Prognostic Factors.

PURPOSE: To evaluate the clinical characteristics and surgical outcomes of pediatric retinal detachments (RDs) in an Asian population. METHODS: Retrospective review of 171 eyes of 152 pediatric patients with rhegmatogenous RD over a 20-year period. RESULTS: Myopia was the most common risk factor in our population. At 6 months, primary anatomical success was 60.7%, and overall anatomical success was 86.7%. A total of 46.8% had best-corrected visual acuity of 20/40 or better, and 81.6% had best-corrected visual acuity of 20/200 or better. In primary RDs, high myopia (≤-6D) patients had a lower primary anatomical success compared to patients with moderate myopia (≤-2D) (59.3 vs. 100% P = 0.03). Increasing age and absence of proliferative vitreoretinopathy were associated with anatomical and visual success. Pars plana vitrectomy as the primary procedure was associated with decreased odds of anatomical success. A longer duration of symptoms, cataract, and a larger RD extent were associated with poorer functional outcome. CONCLUSION: Myopia was the commonest risk factor for pediatric RD in our population. Good anatomical and functional outcome can be achieved with surgery. Increasing age at presentation and absence of proliferative vitreoretinopathy was associated with anatomical and functional success. High myopia was associated with poorer anatomical and functional outcome.

Human pharyngeal microbiota in age-related macular degeneration.

BACKGROUND: While the aetiology of age-related macular degeneration (AMD)-a major blinding disease-remains unknown, the disease is strongly associated with variants in the complement factor H (CFH) gene. CFH variants also confer susceptibility to invasive infection with several bacterial colonizers of the nasopharyngeal mucosa. This shared susceptibility locus implicates complement deregulation as a common disease mechanism, and suggests the possibility that microbial interactions with host complement may trigger AMD. In this study, we address this possibility by testing the hypothesis that AMD is associated with specific microbial colonization of the human nasopharynx. RESULTS: High-throughput Illumina sequencing of the V3-V6 region of the microbial 16S ribosomal RNA gene was used to comprehensively and accurately describe the human pharyngeal microbiome, at genus level, in 245 AMD patients and 386 controls. Based on mean and differential microbial abundance analyses, we determined an overview of the pharyngeal microbiota, as well as candidate genera (Prevotella and Gemella) suggesting an association towards AMD health and disease conditions. CONCLUSIONS: Utilizing an extensive study population from Singapore, our results provided an accurate description of the pharyngeal microbiota profiles in AMD health and disease conditions. Through identification of candidate genera that are different between conditions, we provide preliminary evidence for the existence of microbial triggers for AMD. Ethical approval for this study was obtained through the Singapore Health Clinical Institutional Review Board, reference numbers R799/63/2010 and 2010/585/A.

Change in vision-related quality of life and influencing factors in Asians receiving treatment for neovascular age-related macular degeneration.

AIM: To assess the change in vision-related quality of life (VRQoL) after treatment for neovascular age-related macular degeneration (nAMD) and factors influencing this change in an Asian population. METHODS: In this longitudinal study, 116 patients (mean age±SD=66.5±9.9 years; 59.5% male) who underwent treatment for nAMD were recruited from a tertiary eye centre in Singapore. Best-corrected visual acuity (BCVA) and the Impact of Vision Impairment (IVI) questionnaire were evaluated at baseline and month 12. We defined three categories of BCVA change in the treated eye: BCVA gain ≥2 lines; no change in BCVA; BCVA loss ≥2 lines. The main outcome measures were the Rasch-derived IVI Reading, Mobility, and Emotional Scores. Multivariable linear regression analyses assessed the influence of sociodemographic, clinical and treatment-related factors on change in VRQoL. RESULTS: Following treatment, mean treated-eye BCVA improved by almost 2 lines (-0.22±0.40 logMAR, p<0.001) and 43% (n=50) patients reported a gain in BCVA of ≥2 lines. Mean±SD scores for Reading, Mobility and Emotional demonstrated positive changes of 0.43±1.73, 0.45±1.54 and 0.66±1.6, respectively (p<0.001 for all). In multivariable models, a ≥2 line improvement in BCVA was independently associated with a 47% (ß=0.20; CI 0.01 to 0.39) increase in Reading Scores, but was not independently associated with Mobility or Emotional Scores. CONCLUSION: Nearly half of patients undergoing treatment for nAMD reported a 2-line improvement in vision which was, in turn, associated with substantial positive increases in Reading Scores. Improvements in Mobility and Emotional Scores appear to be driven by factors other than visual acuity.

Choroidal Remodeling in Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy: A 12-month Prospective Study.

Choroid thinning occurs in age-related macular degeneration (AMD). However, it remains unclear whether the reduction is due to reduction in choroidal vessels or shrinkage of choroidal stroma, or both. The purpose of this study was to evaluate the changes of the choroidal vascular and stromal area in 118 patients with typical AMD (t-AMD) and polypoidal choroidal vasculopathy (PCV) over a 12-month period. We used spectral-domain optical coherence tomography (SD-OCT) with enhanced depth imaging (EDI) mode to measure the subfoveal choroidal thickness (CT), central retinal thickness (CRT) and choroidal vascularity index (CVI - ratio of luminal area to total choroidal area). At baseline, PCV eyes had higher CRT (471.6 µm vs 439.1 µm, p = 0.02), but comparable subfoveal CT and CVI, compared to t-AMD. Eyes with high CVI at baseline showed marked reduction in stromal area compared with eyes with average or low CVI. Over 12 months, CRT and subfoveal CT significantly decreased (p < 0.001) in both subtypes. Eyes with high baseline CVI showed significant CVI reduction from baseline to month 12 (p < 0.001), whereas eyes with average to low baseline CVI showed increase in CVI. These differences in choroidal vascularity may reflect different predominant pathogenic processes and remodeling in AMD eyes with varying spectrum.

DETAILED CHARACTERIZATION OF CHOROIDAL MORPHOLOGIC AND VASCULAR FEATURES IN AGE-RELATED MACULAR DEGENERATION AND POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: To characterize and compare morphologic and vascular features of the choroid in patients with typical age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) and to determine if PCV subtypes can be identified based on these choroidal features. METHODS: Choroidal features of patients with AMD and PCV recruited from the prospectively planned Asian AMD Phenotyping Study were analyzed. Patients underwent choroidal imaging using spectral-domain optical coherence tomography with enhanced depth imaging. Raw optical coherence tomographic images were loaded on a custom-written application on MATLAB that enabled delineation for detailed morphologic and vascular analyses, including the curvature of the choroid-sclera interface, number of inflection points, choroidal thickness and choroidal vascular area within the macular (6 mm centered on fovea) and foveal (1.5 mm centered on fovea) regions. An inflection point represents the contour of the choroid-sclera interface, with >1 point signaling irregular shape. RESULTS: A total of 156 eyes of 156 patients (78 affected eyes of 78 patients with typical AMD and 78 affected eyes of 78 patients with PCV) were analyzed. Eyes with PCV had thicker baseline choroidal thickness and greater choroidal vascular area compared with those with typical AMD (P < 0.05); these differences were no longer significant after adjusting for age and hypertension (P > 0.05). Typical PCV subtype with choroidal thickness of ≥257 µm had significantly greater choroidal vascular area at macular (mean difference = 0.054 mm; P < 0.001) and foveal (mean difference = 0.199 mm; P < 0.001) regions compared with eyes with typical AMD. However, eyes with PCV without thick choroid had similar choroidal vascular area as eyes with typical AMD. CONCLUSION: Based on the choroidal vascular features, two subtypes of PCV can be classified: typical PCV with increased choroid vascularity and polypoidal choroidal neovascularization with low choroidal vascularity. These data provide further understanding of different AMD and PCV subtypes.

Prevalence and clinical correlates of focal choroidal excavation in eyes with age-related macular degeneration, polypoidal choroidal vasculopathy and central serous chorioretinopathy.

PURPOSE: To describe the prevalence and clinical characteristics of focal choroidal excavation (FCE) in patients with exudative maculopathy due to age-related macular degeneration with choroidal neovascularisation (AMD-CNV), polypoidal choroidal vasculopathy (PCV) and central serous chorioretinopathy (CSC). METHODS: Three hundred and forty-three patients (343 presenting eyes and 255 fellow unaffected eyes) from consecutive patients presenting with untreated AMD-CNV, PCV or CSC are prospectively recruited. Two independent retinal specialists masked to the clinical diagnosis graded the presence of FCE by examining the findings from spectral-domain optical coherence tomography (SD-OCT). The frequency and clinical characteristics of FCE in each of the three clinical diagnosis groups were compared. RESULTS: The diagnosis in the presenting eye was AMD-CNV in 92 patients, PCV in 149 patients, retinal angiomatous proliferation (RAP) in 3 patients and CSC in 99 patients; 255 fellow eyes free of clinical diseases were also graded. The prevalence of FCE was 2.3% (total 14 eyes; 10 presenting eyes, 4 fellow eyes) out of 598 eyes examined. In presenting eyes, FCE was most prevalent in PCV (6.0%), followed by AMD-CNV (1.0%) and CSC (0%), p=0.02. In fellow eyes, the prevalence of FCE was 2.9%, 0% and 1.2% in patients with PCV, AMD-CNV and CSC, respectively. Eyes with FCE had a significantly longer axial length (24.93±1.65 mm vs 23.49±1.10 mm, p<0.001), but otherwise, all other characteristics were similar. CONCLUSIONS: FCE is more common in PCV than AMD-CNV and CSC. Disturbance in the choroid/retinal pigment epithelium/Bruch membrane interface affected by FCE may be linked to the pathogenesis of PCV and AMD-CNV.

MYOPIC RETINOSCHISIS IN ASIANS: Structural Features and Determinants of Visual Acuity and Prognostic Factors for Progression.

PURPOSE: To describe microstructural changes and schisis extent in eyes with myopic retinoschisis and to determine their influence on visual acuity at baseline and follow-up. METHODS: In this prospective observational study, 50 eyes of 38 patients with myopic retinoschisis were evaluated using spectral domain optical coherence tomography, and the patients were followed for at least 12 months. The presence of microstructural changes and the extent of retinoschisis at baseline on spectral domain optical coherence tomography, and the association between these parameters and the risk of visual acuity deterioration were analyzed. RESULTS: Median presenting visual acuity and central retinal thickness were 0.31 logMAR (≈20/40) and 395 µm, respectively. Twenty-six eyes (52%) had entire macular area retinoschisis. Common microstructural changes included photoreceptor detachment (24%), foveal ellipsoid zone (EZ) disruption (34%), partial-thickness macular hole (26%), and full-thickness macular hole (16%). Visual acuity was poorer in eyes with photoreceptor detachment, EZ disruption, full-thickness macular hole, and central retinal thickness >300 µm. Eyes with entire macular area retinoschisis had the poorest visual acuity and thickest central retinal thickness, and they were more likely to have photoreceptor detachment, EZ disruption, and retinal detachment. Over a mean follow-up of 31.7 ± 7.7 months, 14 eyes (28%) had worsening visual acuity of ≥2 lines. Ten of these 14 eyes had entire macular retinoschisis at baseline. CONCLUSION: Most eyes with myopic retinoschisis remain stable. However, eyes with extensive retinoschisis involving the entire macular area are more likely to progress and have microstructural abnormalities and poorer vision. Early surgery should be considered for these eyes.

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.

Prognostic factor analysis of vitrectomy for myopic foveoschisis.

PURPOSE: To describe the anatomical and functional outcomes in a cohort of subjects undergoing vitrectomy for myopic foveoschisis, and to analyse the factors predicting foveal reattachment and visual improvement. METHODS: This retrospective case series evaluated case records and optical coherence tomography images 6 months after surgery. Multivariate linear and logistic regressions were performed to assess the factors predicting anatomical and visual improvement. RESULTS: In total, 55 eyes of 54 patients were analysed. The mean spherical equivalent refraction was -11.83±4.94D. Foveal detachment was present in 63.5% of eyes preoperatively and subjects with foveal detachment had 0.70 logMAR units (95% CI 0.02 to 1.39) poorer visual acuity than subjects without (p=0.046). The mean preoperative visual acuity was 0.84±0.59 logMAR units and the mean postoperative visual acuity was 0.64±0.64 logMAR units (mean difference 0.20±0.68 logMAR units (p=0.04)). The proportion of eyes with foveal detachment was significantly lower after surgery (12.5%; p<0.001). However, the proportion of eyes with ellipsoid zone disruption was significantly higher after surgery (59.6% vs 34.0%; p<0.001). In multivariate analyses, the preoperative central foveal thickness significantly predicted postoperative visual improvement by two or more lines (OR 1.004 (95% CI 1.000 to 1.007), per µm increase; p=0.049). The presence of ellipsoid zone disruption preoperatively was associated with 0.96 logMAR (95% CI 0.2 to 1.72) poorer final acuity (p=0.02). CONCLUSIONS: Eyes with myopic foveoschisis with preoperative ellipsoid disruption and thinner central foveal thickness tend to have poorer visual outcomes. While current surgical manoeuvres are effective in reattaching the fovea, they may also cause iatrogenic injury to the photoreceptors.

SCLERAL BUCKLING VERSUS VITRECTOMY IN THE MANAGEMENT OF MACULA-OFF PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT: A COMPARISON OF VISUAL OUTCOMES.

PURPOSE: To compare visual outcomes between pars plana vitrectomy (PPV) with or without scleral buckling (SB) and SB alone in the management of uncomplicated macula-off primary rhegmatogenous retinal detachment. METHODS: Case-control study of 723 patients with uncomplicated macula-off primary rhegmatogenous retinal detachment seen at the Singapore National Eye Centre from 2005 to 2011. The primary outcome measure was the proportion of eyes achieving functional success, defined as logMAR best-corrected visual acuity of ≤0.3 logMAR at 6 months postoperatively. Multivariable logistic regression analysis was performed adjusting for the following preoperative covariates: age, gender, race, lens status, number of tears found, presence of proliferative vitreoretinopathy, operative procedure, logMAR best-corrected visual acuity, and duration of symptoms. RESULTS: Three hundred and eight eyes underwent SB alone, and 415 eyes underwent PPV ± SB. In the SB group, 133 eyes (43.2%) achieved functional success compared with 116 eyes (28.0%) in the PPV ± SB group. This difference was statistically significant on both univariate (P < 0.001) and multivariable analyses (OR: 1.51, 95% CI: 1.03-2.21, P = 0.03). CONCLUSION: Scleral buckling alone may achieve visual outcomes that are at least comparable with PPV ± SB in the management of macula-off primary rhegmatogenous retinal detachment.

IMPROVED SPECIFICITY OF POLYPOIDAL CHOROIDAL VASCULOPATHY DIAGNOSIS USING A MODIFIED EVEREST CRITERIA.

PURPOSE: To evaluate the performance of polypoidal choroidal vasculopathy (PCV) diagnosis using fundus camera-based indocyanine green angiography, comparing a single sign of "subretinal focal hyperfluorescence" on indocyanine green angiography with a modification of the EVEREST criteria. METHODS: Color fundus photograph, flash fundus camera-based fluorescein angiography, and indocyanine green angiography of 241 eyes of 230 consecutive patients with exudative maculopathy due to PCV or typical age-related macular degeneration were graded independently by 2 retinal specialists using a modified EVEREST criteria, which requires the presence of subretinal focal hyperfluorescence plus any 1 of 5 additional criteria. Discordant cases were adjudicated by a senior retinal specialist to arrive at the final diagnosis. Sensitivity, specificity, and area under the receiver operating curve of subretinal focal hyperfluorescence versus the EVEREST criteria and combinations of individual EVEREST criteria were compared. RESULTS: Among the 241 eyes with exudative maculopathy, 131 eyes had PCV and 110 eyes had typical age-related macular degeneration. Using a single sign of subretinal focal hyperfluorescence alone for the diagnosis of PCV, sensitivity was 85.3% and specificity was 80.9%, with an area under the receiver operating curve of 83.1%. When applying the EVEREST definition, sensitivity was reduced to 78.4% but specificity improved to 87.1% with a similar area under the receiver operating curve of 82.8%. The frequency of individual criteria was highly variable, with stereo nodular appearance (73.7%) and orange nodule (55.0%) being the most common and branching vascular network, massive hemorrhage, and hypofluorescent halo in the presence of subretinal focal hyperfluorescence being less common (21.5%-28.1%). CONCLUSION: The EVEREST criteria have a higher specificity for the diagnosis of PCV than subretinal focal hyperfluorescence alone and may be applied to flash fundus camera-based indocyanine green angiography in a clinical setting. Stereo nodular appearance is the most important additional criterion.

THREE-YEAR RESULTS OF POLYPOIDAL CHOROIDAL VASCULOPATHY TREATED WITH PHOTODYNAMIC THERAPY: Retrospective Study and Systematic Review.

PURPOSE: To evaluate the 3-year outcome in eyes with polypoidal choroidal vasculopathy (PCV) treated with photodynamic therapy with verteporfin. METHODS: Retrospective study and review of the literature. We performed a retrospective study of patients with PCV who were treated with photodynamic therapy between January 2007 and December 2008. Patients were excluded if they had received photodynamic therapy before the study period, but those who received previous treatment with other modalities (thermal laser or intravitreal therapies) were allowed. The main outcome measures were best-corrected visual acuity, repeat photodynamic therapy, and recurrence of PCV at the end of Years 1, 2, and 3. We further conducted a systematic review of the literature using the terms "polypoidal choroidal vasculopathy" and "photodynamic therapy" and compared the visual outcome of studies over 3 years using meta-analytical methods. RESULTS: The retrospective study included 68 eyes. The mean best-corrected visual acuity was 0.73 ± 0.56 logMAR (20/107, Snellen equivalent) at baseline, 0.73 ± 0.70 logMAR (20/107, Snellen equivalent) at 1 year, 0.96 ± 0.76 logMAR (20/182, Snellen equivalent) at 2 years, and 1.07 ± 0.81 logMAR (20/235, Snellen equivalent) at 3 years. The cumulative recurrence rates of PCV were 16.1% (1 year), 34.9% (2 years), and 52.7% (3 years) and eyes with recurrence were more likely to suffer ≥3 lines loss compared with eyes without recurrence (63.2 vs. 17.6%, P = 0.006). The systematic review summarized results from 48 published studies and our retrospective study. The pooled analysis from 29 studies (316 eyes reporting the 3-year visual outcome) reported mean best-corrected visual acuity improvement of 0.115 logMAR at 1 year (n = 1,669), 0.066 logMAR at 2 years (n = 701), and 0.027 logMAR at 3 years (n = 316). Reported recurrence rates were 5.9% to 50.0% after 1 year, 9.1% to 83.3% after 2 years, and 40.0% to 78.6% after 3 years or longer of follow-up. CONCLUSION: The visual outcome in eyes with PCV was stable until 2 years, but the outcome at 3 years worsened, particularly in eyes that experienced recurrence.

The natural history of polypoidal choroidal vasculopathy: a multi-center series of untreated Asian patients.

PURPOSE: We aimed to evaluate the long-term natural history of polypoidal choroidal vasculopathy (PCV) in untreated patients. METHODS: This is a retrospective observational case series. Patients with symptomatic PCV who did not receive any treatment for at least 12 months were included from the records of three ophthalmic clinics in Asia. The medical records and imaging data were reviewed. Visual outcomes at month 12 and at last follow-up were analyzed. The influence of demographics and presenting features on visual outcome was analyzed. RESULTS: A total of 32 eyes (32 patients) were included in this analysis. The mean follow-up was 59.9 months (range, 18-119 months), the mean age was 65.7 years and 21 (65.6 %) patients were male. The mean presenting logMAR visual acuity was 0.79 (Standard deviation [SD] 0.49). The center of the fovea was involved by the PCV complex in 25 eyes (78.1 %). The mean greatest linear dimension (GLD) of the PCV complex was 2584 µm (SD 880). Twenty-three eyes (71.9 %) had a cluster-of-grapes configuration on indocyanine green angiography. Leakage of fluorescein angiography was present in 29 eyes (90.6 %). The mean logMAR vision deteriorated from 0.79 at baseline to 0.88 at month 12 (p = 0.11), and further to 1.14 (p = 0.003) at the last follow-up. The proportion of eyes that improved, remained unchanged and worsened was 21.9 %, 31.3 % and 46.9 %, respectively, at month 12; and 28.1 %, 9.4 % and 62.5 %, respectively, at last follow-up. The proportion of eyes with logMAR vision worse than 1.0 was 28.1 % at presentation, and increased to 31.3 % at month 12 and further to 53.1 % at last follow-up. Reasons for poor vision were due to retinal, subretinal or vitreous hemorrhage, and retinal pigment epithelium (RPE) atrophy and scarring. None of the presenting features were found to significantly influence visual outcome. CONCLUSIONS: Half of eyes presenting with symptomatic PCV had a relatively benign course without treatment and some even had vision improvement. However, in the remaining eyes, vision deteriorated significantly, mainly due to hemorrhage and scarring. There may be subtypes of PCV with divergent natural history.

New loci and coding variants confer risk for age-related macular degeneration in East Asians.

Age-related macular degeneration (AMD) is a major cause of blindness, but presents differently in Europeans and Asians. Here, we perform a genome-wide and exome-wide association study on 2,119 patients with exudative AMD and 5,691 controls, with independent replication in 4,226 patients and 10,289 controls, all of East Asian descent, as part of The Genetics of AMD in Asians (GAMA) Consortium. We find a strong association between CETP Asp442Gly (rs2303790), an East Asian-specific mutation, and increased risk of AMD (odds ratio (OR)=1.70, P=5.60 × 10(-22)). The AMD risk allele (442Gly), known to protect from coronary heart disease, increases HDL cholesterol levels by 0.17 mmol l(-1) (P=5.82 × 10(-21)) in East Asians (n=7,102). We also identify three novel AMD loci: C6orf223 Ala231Ala (OR=0.78, P=6.19 × 10(-18)), SLC44A4 Asp47Val (OR=1.27, P=1.08 × 10(-11)) and FGD6 Gln257Arg (OR=0.87, P=2.85 × 10(-8)). Our findings suggest that some of the genetic loci conferring AMD susceptibility in East Asians are shared with Europeans, yet AMD in East Asians may also have a distinct genetic signature.

Relationship of systemic endothelial function and peripheral arterial stiffness with diabetic retinopathy.

BACKGROUND: To investigate possible associations between diabetic retinopathy (DR) and systemic vascular endothelial function and arterial stiffness measured using reactive hyperaemia peripheral arterial tonometry. METHODS: This was a cross-sectional observational clinical study. Subjects with diabetes were recruited and DR was graded from retinal photographs. Systemic endothelial function was measured using reactive hyperaemia peripheral arterial tonometry (EndoPAT) and expressed as the reactive hyperaemia index (RHI). Peripheral arterial stiffness was measured using the same device and expressed as the augmentation index (AI). RESULTS: In total, 164 eyes of 95 Chinese patients were evaluated. The mean age of the subject eyes was 60.1±8.2 years and 76.8% were men. The mean duration of diabetes was 15.5±9.8 years, and the mean HbA1c was 8.1±1.4%. In age-gender-adjusted models, increasing severity of DR was associated with increasing mean RHI (p=0.001) and increasing mean AI (p<0.001). In multivariate models, adjusting additionally for smoking, mean duration of diabetes, HbA1c and hypertension, the associations with RHI and AI persisted (p=0.011 and 0.001, respectively). In analyses of the dichotomous outcomes clinically significant macular oedema (CSME), moderate DR and vision-threatening DR, AI was a significant predictor of CSME and vision-threatening DR. In multivariate-adjusted models, for every SD increase in AI, the odds of having CSME was 1.78 times higher (95% CI 1.05 to 2.99; p=0.029). For every SD increase in AI, the odds of having vision-threatening DR was 1.73 times higher (95% CI 1.17 to 2.56; p=0.003). CONCLUSIONS: Subjects with more severe DR have larger peripheral reactive hyperaemic responses and greater peripheral vascular stiffness. These findings support the link between the microvascular changes of diabetes and macrovascular disease.

Incidence of myocardial infarction, stroke, and death in patients with age-related macular degeneration treated with intravitreal anti-vascular endothelial growth factor therapy.

PURPOSE: To describe the rates of myocardial infarction (MI), stroke, and mortality in patients who have treatment with intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections for age-related macular degeneration (AMD). DESIGN: A retrospective population linkage study. METHOD: We identified patients aged 40 years and above who received treatment with intravitreal anti-VEGF injections for AMD from January 1, 2008 to December 31, 2011 at the Singapore National Eye Centre. We used a national record linkage database to identify patients who developed MI, stroke, and all-cause mortality after the first injection, excluding those with previous MI or stroke at baseline from the respective analysis. We compared rates of MI, stroke, and mortality to that of the total Singapore population. RESULTS: A total of 1182 individuals had an intravitreal anti-VEGF injection included in this analysis, with the majority receiving bevacizumab (n = 1011). Overall, 19 patients developed MI, 16 developed stroke, and there were 43 mortalities, giving an age-adjusted incidence rate of 350.2 per 100 000 person-years for MI, 299.3 per 100 000 person-years for stroke, and 778.9 per 100 000 person-years for mortality. This is comparable to the weighted incidence rates of the Singapore population (427.1 per 100 000 person-years for MI, 340.4 per 100 000 person-years for stroke, and 921.3 per 100 000 person-years for mortality). CONCLUSION: The incidence rate of MI, stroke, and death in this cohort of AMD patients treated with anti-VEGF was low, and was not significantly higher than the age-adjusted incidence rate of these events in the Singapore population.