Choi Mun Chan

A Prospective Study of Treatment Patterns and 1-Year Outcome of Asian Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy

Objective To study the treatment patterns and visual outcome over one year in Asian patients with choroidal neovascular membrane secondary to age-related macular degeneration (AMD-CNV) and polypoidal choroidal vasculopathy (PCV). Design Prospective cohort, non-interventional study. Methods 132 treatment-naïve patients who received treatment for AMD-CNV and PCV were included. All patients underwent standardized examination procedures including retinal imaging at baseline and follow-up. AMD-CNV and PCV were defined on fundus fluorescein angiography and indocyanine green angiography at baseline. Patients were treated according to standard of care.We report the visual acuity (VA) and optical coherence tomography (OCT) measurements at baseline, month 3 and month 12 The factors influencing month 12 outcomes were analyzed. Main Outcome Measure Type of treatment, number of Anti-vascular endothelial growth factor (VEGF) treatments, visual outcome over one year. Results Anti-VEGF monotherapy was the initial treatment in 89.1% of AMD-CNV, but only 15.1% of PCV. The mean number of anti-VEGF injections up to month 12 was 3.97 (4.51 AMD-CNV, 3.43 PCV, p = 0.021). Baseline OCT, month 3 OCT and month 3 VA were significant in determining continuation of treatment after month 3. At month12, mean VA improved from 0.82 (∼20/132) at baseline to 0.68 (∼20/96) at month 12 (mean gain 6.5 ETDRS letters, p = 0.002). 34.2% of eyes (38/113 eyes) gained ≥15 ETDRS letters and 14.4% (16/113 eyes) lost ≥15 ETDRS letters. There were no significant differences in visual outcome between AMD-CNV and PCV (p = 0.51). Factors predictive of month 12 visual outcome were baseline VA, baseline OCT central macular thickness, month 3 VA and age. Conclusions There is significant variation in treatment patterns in Asian eyes with exudative maculopathy. There is significant visual improvement in all treatment groups at one year. These data highlight the need for high quality clinical trial data to provide evidence-based management of Asian AMD.

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.

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.

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.

Characterization And Differentiation Of Polypoidal Choroidal Vasculopathy Using Swept Source Optical Coherence Tomography Angiography

Purpose: To determine the correlation and agreement between swept-source optical coherence tomography angiography (SS-OCT-A) with fluorescein angiography (FA), indocyanine green angiography (ICGA) and spectral domain OCT (SD-OCT) in characterizing polypoidal choroidal vasculopathy (PCV) and in differentiating eyes with typical age-related macular degeneration (t-AMD). Methods: This study included 32 and 54 eyes with t-AMD and PCV, respectively, who underwent SS-OCT-A, SD-OCT, fluorescein angiography, and indocyanine green angiography. The images from these four techniques were compared. Results: On SS-OCT-A, flow signals with vascular network configuration were detected in 81.2% and 77.8% of eyes with t-AMD and PCV, respectively. 40.4% of polyps were detected as flow signals with polypoidal configuration. Compared with indocyanine green angiography, SS-OCT-A had sensitivity and specificity of 83.0% and 57.1%, respectively, for vascular network, and 40.5% and 66.7% for polyps. Longitudinal changes were in agreement between SS-OCT-A and SD-OCT in 90% of eyes. 88.2% of eyes with dry retina on SD-OCT had persistent vascular net on SS-OCT-A. In two cases with reactivation of PCV, SS-OCT-A was more sensitive at detecting recurrence than SD-OCT. Conclusion: Swept-source optical coherence tomography angiography is effective at detecting vascular network that correlate to conventional angiography in eyes with t-AMD and PCV. Swept-source optical coherence tomography angiography is inferior to indocyanine green angiography in detecting polyps and cannot replace indocyanine green angiography for differentiating PCV from t-AMD; however, SS-OCT-A may be more sensitive than SD-OCT in detecting early recurrence.

Systemic, Ocular and Genetic Risk Factors for Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy in Singaporeans

To examine the association of systemic, ocular and genetic risk factors in neovascular age-related macular degeneration (nAMD) in a large cohort of Asian patients, and to further compare risk factors between those with typical AMD and polypoidal choroidal vasculoapthy (PCV) subtypes. We recruited 456 cases and 1,824 controls matched for age, gender and ethnicity. Data on systemic and ocular risk factors were collected on questionnaires. In a subgroup of subjects, we included genetic data on four AMD-associated single nucleotide polymorphisms (SNPs). Risk factors for nAMD and subtypes were analyzed. Systemic risk factors for nAMD included older age, male gender, higher BMI and higher HDL-cholesterol. Ocular risk factors included pseudophakic and shorter axial length. Risk factors common to both typical AMD and PCV subtypes included age, BMI and HDL-cholesterol. Shorter axial length was only associated with PCV, while male gender and pseudophakia were only associated with typical AMD. In the subgroup with genotype data, ARMS2 rs10490924 and CFH rs800292 were associated with nAMD. None of the risk factors were significantly different between PCV and typical AMD. Systemic, ocular and genetic risk factors were largely similar for typical AMD and PCV subtypes in this Asian population based in Singapore.

Prevalence and Risk Factors for Nonexudative Neovascularization in Fellow Eyes of Patients With Unilateral Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy

Purpose To determine the prevalence of subclinical nonexudative neovascularization and associated choroidal vascular changes in the fellow eyes of patients presenting with unilateral typical exudative AMD (tAMD) or polypoidal choroidal vasculopathy (PCV) using indocyanine green angiography (ICGA) and swept-source (SS) optical coherence tomography angiography (OCT-A). Methods We recruited patients presenting with tAMD or PCV in a prospective clinical study. The diagnosis in the presenting eye was determined based on clinical, fluorescein angiography (FA), and ICGA findings. We evaluated the contralateral eye for presence of nonexudative neovascularization, choroidal hyperpermeability, and pachyvessels in the outer choroid, based on multimodal imaging which included ICGA, spectral-domain (SD) OCT and OCT-A. We measured subfoveal choroidal thickness in both eyes for each patient. Results We included 76 fellow eyes of 76 patients who presented with unilateral tAMD (n = 33) or PCV (n = 43). Nonexudative neovascularization was present in 18% eyes (14 eyes, 8 in tAMD group, 6 in PCV group; 7 on ICGA, 4 on OCT-A, 3 on both ICGA and OCT-A). Pachychoroid pigment epitheliopathy was present in 13 eyes with nonexudative neovascularization, and was the only risk factor associated with nonexudative neovascularization. Conclusions Approximately one in five fellow eyes with unilateral tAMD and PCV have features of nonexudative neovascularization. The use of multimodal imaging including ICGA and OCT-A can identify these features. The presence of pachychoroid epitheliopathy should alert clinicians to the possibility of underlying neovascularization.

Trends in age-related macular degeneration management in Singapore.

Purpose To describe the trends and patterns of anti–vascular endothelial growth factor (anti-VEGF) therapy and photodynamic therapy (PDT) use for age-related macular degeneration (AMD) in the National Eye Centre in Singapore over a 4-year period. Methods Data on the total number of intravitreal anti-VEGF injections and PDT treatment over a 4-year period at the Singapore National Eye Centre were obtained from centralized electronic records. Patients aged 40 years and older treated for AMD were included. Data retrieved included the annual treatment load in terms of number of new patients and total treatment episodes, and treatment burden for patients was studied in terms of number of injections per year and cumulative injection numbers over 3 years. Potential influence on retreatment by choice of drug, use of adjunct PDT, and diagnosis of polypoidal choroidal vasculopathy were further analyzed. Results From 2009 to 2012, a total of 6157 injections were performed on 1380 unique individual patients. The total number of injections performed per calendar year increased from 962 in 2009 to 2278 in 2012. The number of unique incident cases increased from 287 in 2009 to 446 in 2012. The mean number of injections over the first year increased from 2.62 in 2009 to 3.19 in 2012 (p < 0.001). Choice of anti-VEGF therapy did not significantly alter the cumulative injections required. Patients diagnosed as having polypoidal choroidal vasculopathy had similar injection episodes (p = 0.178), whereas choice of anti-VEGF and adjunct PDT had no effect on the overall treatment. Conclusions Anti-VEGF treatment of AMD continues to increase substantially year on year in the past few years, in alignment with experience from other countries. However, the cumulative number of injections per patient remains low, and many patients discontinue treatment within the first year. These data demonstrate that undertreatment remains a significant concern in clinical settings.

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.

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.