Doric Wong

Polypoidal choroidal vasculopathy and neovascular age-related macular degeneration: Same or different disease?

Neovascular age-related macular degeneration (nAMD) is the commonest cause of severe visual impairment in older adults in Caucasian white populations. Polypoidal choroidal vasculopathy (PCV) has been described as a separate clinical entity differing from nAMD and other macular diseases associated with subretinal neovascularization. It remains controversial as to whether or not PCV represents a sub-type of nAMD. This article summarizes the current literature on the clinical, pathophysiological and epidemiological features and treatment responses of PCV and compares this condition to nAMD. Patients with PCV are younger and more likely Asians, and eyes with PCV lack drusen, often present with serosanguinous maculopathy or hemorrhagic pigment epithelial detachment, and have differing responses to photodynamic therapy and anti-vascular endothelial growth factor (VEGF) agents. There are also significant differences in angiographic and optical coherence tomography features between PCV and nAMD. Histopathological studies suggest differences in the anatomical details of the associated vascular abnormalities in the retina and choroids and the relative role of VEGF. There is emerging evidence of common molecular genetic determinants involving complement pathway and common environmental risk factors (e.g. smoking). Such information could further assist clinicians involved in the care of elderly patients with these conditions.

Association Analysis of CFH, C2, BF, and HTRA1 Gene Polymorphisms in Chinese Patients with Polypoidal Choroidal Vasculopathy

PURPOSE Polypoidal choroidal vasculopathy (PCV) is a major cause of serosanguinous maculopathy in Chinese patients with age-related macular degeneration (AMD). Variants in the CFH and HTRA1/LOC387715 genes are strongly associated with AMD in Caucasians and Chinese. Variants in the C2 and BF genes have been found to confer a significantly reduced risk of AMD. This study was undertaken to determine whether these associations occur in Chinese patients with PCV. METHODS Patients of Chinese ethnicity with clinically and angiographically diagnosed PCV and normal control subjects were recruited from the Singapore National Eye Centre. Five single-nucleotide polymorphisms (SNPs) in the CFH gene, two each within the C2 and BF genes and two variants located in the LOC387715 and HTRA1 genes, were screened in all patients and control subjects. RESULTS Seventy-two patients with PCV and 93 normal control subjects were studied. A significant association was noted with CFH variants rs3753394 and rs800292 among the PCV cases (P = 0.0015 and P = 0.0045, respectively). Individuals homozygous for the TT genotype of rs3753394 had a significantly higher risk (P = 0.0076) of PCV (OR = 4.29; 95% CI: 1.47-12.50) than those carrying a single copy of the T allele (P = 0.3210; OR = 1.69; 95% CI: 0.60-4.78), after adjustment for such risk factors as age and sex. The genotype frequencies of rs11200638 and rs10490924 in HTRA1 and LOC387715, respectively, were also found to be significantly different between patients with PCV and normal control subjects (P = 0.00032 and P = 0.003, respectively). The AA genotype of rs11200638 and TT genotype of rs10490924 conferred a 4.9-fold (95% CI: 1.85-12.95) and 4.89-fold (95% CI: 1.85-12.90) increased risk of PCV, respectively, after adjustment for age and sex. The Y402H variant of CFH (rs1061170) and the BF and C2 variants were not significantly different in patients and normal control subjects. CONCLUSIONS The SNPs rs3753394 and rs800292 of CFH and rs11200638 of HTRA1 are significantly associated with the risk of PCV in Chinese patients.

Correlation of vitreous attachment and foveal deformation in early macular hole states.

PURPOSE To report the foveal anatomy in patients with perifoveal posterior vitreous detachments (PPVD) using optical coherence tomography. DESIGN Retrospective observational case series. METHODS A retrospective study of fellow eyes of patients of patients with macular holes and those with early macular hole states were examined with optical coherence tomography, biomicroscopy, and contact b-scan ultrasonography. Twenty-three eyes of 23 patients were discovered to have PPVD, which was defined as persistent attachment of the vitreous to the central macula with a limited detachment of the posterior vitreous in the perifoveal region. RESULTS The mean diameter of persistent vitreous attachment in eyes with no foveal deformation was 1829 microm, flattening of the foveal depression 840 microm, and with foveal cavitation 281 microm (P < .001, Spearman rank correlation). The difference in the mean diameters was significant (P = .001, Kruskal-Wallis test, all pairwise comparisons showing significant difference using the Mann-Whitney test). CONCLUSIONS This study found that the diameter of the vitreous attachment in eyes with PPVD correlated with induced changes in foveal anatomy. The diameters of vitreous attachment were consistent with known regions of robust attachment of the vitreous determined histologically. Although the actual force loading on the central macula cannot be determined in patients with perifoveal posterior vitreous detachments, the stress, which is force / unit area may well increase with smaller areas of attachment leading to mechanical failure of the macula.

Automated detection of kinks from blood vessels for optic cup segmentation in retinal images

The accurate localization of the optic cup in retinal images is important to assess the cup to disc ratio (CDR) for glaucoma screening and management. Glaucoma is physiologically assessed by the increased excavation of the optic cup within the optic nerve head, also known as the optic disc. The CDR is thus an important indicator of risk and severity of glaucoma. In this paper, we propose a method of determining the cup boundary using non-stereographic retinal images by the automatic detection of a morphological feature within the optic disc known as kinks. Kinks are defined as the bendings of small vessels as they traverse from the disc to the cup, providing physiological validation for the cup boundary. To detect kinks, localized patches are first generated from a preliminary cup boundary obtained via level set. Features obtained using edge detection and wavelet transform are combined using a statistical approach rule to identify likely vessel edges. The kinks are then obtained automatically by analyzing the detected vessel edges for angular changes, and these kinks are subsequently used to obtain the cup boundary. A set of retinal images from the Singapore Eye Research Institute was obtained to assess the performance of the method, with each image being clinically graded for the CDR. From experiments, when kinks were used, the error on the CDR was reduced to less than 0.1 CDR units relative to the clinical CDR, which is within the intra-observer variability of 0.2 CDR units.

A classification system for polypoidal choroidal vasculopathy.

Purpose: To describe the demographic features and clinical characteristics of polypoidal choroidal vasculopathy (PCV) in Chinese patients and define a new classification system. Methods: Retrospective review of 138 eyes of 123 patients presenting to the Singapore National Eye Center with PCV. Patients underwent ophthalmologic examination including digital color fundus photography and stereoscopic indocyanine green angiography. Classification based on indocyanine green angiography findings. Results: Mean age of patient 68.3 years and 62.4% were men. PCV was unilateral in 87.8% cases and age-related maculopathy was present in the unaffected fellow eye in 22.8%. Average largest size of polyp was 207 &mgr;m. PCV lesions were found in multiple discrete areas in 34.8%. Formation of lesion was cluster in 66.7%, single in 27.5%, and string in 5.8%. PCV lesions were found in the extrafoveal area in 63.0%, subfoveal in 29.7%, juxtafoveal in 15.9%, and peripapillary in 8.0%. Conclusions: Demographics of PCV, unilaterality and frequency of age-related maculopathy in fellow eye similar to other reports in Asians. We describe a classification system for PCV comprising polyp size, location, formation, and number of discrete polyp areas, which can be used for prospective interventional clinical studies and may aid in future prognosis and management of this condition.

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.

Foveolitis Associated with Dengue Fever: A Case Series

Background: Dengue fever (DF), a viral infection caused by dengue virus, is characterized by fever, headache, muscle and joint pains. Approximately 50–100 million people are infected annually. Ocular manifestations during DF are uncommon and include intraretinal hemorrhages and cotton wool spots; manifestations predominantly characterized by foveal involvement have not been described before in DF or any other retinopathies. We describe the clinical features of a series of patients with DF-associated foveolitis. Methods: A retrospective review of patients with maculopathy associated with DF was conducted. Patients found to have a yellow-orange lesion at the fovea, supported by a typical optical coherence tomography (OCT) finding of disruption of the outer neurosensory retina, were analyzed. Results: Ten eyes of 6 patients were studied. The mean age was 19.8 years. The mean presenting best corrected visual acuity was 6/45 (range of 6/7.5 to counting fingers). Fundus examination revealed a yellow-orange lesion at the fovea which corresponded to outer neurosensory retina disruption on OCT. Multifocal electroretinography showed decreased foveal and parafoveal responses. Treatment was variable, depended on visual acuity and ranged from observation to immunosuppression. Conclusion: Foveolitis may be associated with DF. OCT is a useful tool for the diagnosis and monitoring of progression of this condition.

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.

Asian age‐related macular degeneration phenotyping study: rationale, design and protocol of a prospective cohort study

Background:  Current knowledge of the phenotypic characteristics (e.g. clinical features, risk factors, natural history and treatment response) of age‐related macular degeneration (AMD) in Asians remains limited. This report summarizes the rationale and study design of a prospective observational study of Asian neovascular AMD, including polypoidal choroidovasculopathy variant.

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.