Pathogenesis Of Polypoidal Choroidal Vasculopathy Research Articles

Relationship between pulsation of posterior vortex vein, choroidal thickness, and choroidal vascular hyperpermeability in polypoidal choroidal vasculopathy.

Posterior vortex vein pulsation on Heidelberg indocyanine green angiography (HRA-IA) video is reported to indicate the presence of congestion in these vessels. This study aimed to determine the relationship between posterior vortex vein pulsation, choroidal thickness, and choroidal vascular hyperpermeability (CVH) in polypoidal choroidal vasculopathy (PCV). Forty-three eyes of 43 patients who had not received previous treatment and were diagnosed with PCV using multimodal imaging were included and retrospectively investigated. On initial visit, presence or absence of pulsation in the posterior vortex vein was analysed using HRA-IA. Subfoveal choroidal thickness (SFCT) was assessed, and patients were divided into the SFCT ≥ 200μm and < 200μm (P and NP, respectively) groups. Presence or absence of CVH was investigated using IA in the late phase, and the associations between the three parameters were analysed. Posterior vortex vein pulsation was detected in 24/43 eyes (55%). There were 27 eyes in the P group (mean SFCT, 286 ± 48μm) and 16 eyes in the NP group (mean SFCT, 143 ± 41μm). Pulsation was detected in 10 eyes (37%) in the P group and 14 eyes (88%) in the NP group. Incidence of pulsation was significantly higher in the NP group (P < 0.05). There were 17 (40%) patients with CVH-13 (48%) and four (25%) in the P and NP groups, respectively (P = 0.1994). There was no correlation between the presence or absence of pulsation and CVH (P = 0.1994). Congestion of the vortex vein is potentially associated with the pathogenesis of PCV with a thin choroid.

Clinical implications of choroidal vascular brightness using ultra-widefield indocyanine green angiography in polypoidal choroidal vasculopathy

Polypoidal choroidal vasculopathy (PCV) is characterized by choroidal vascular abnormalities including polypoidal lesion and branching vascular networks. Not only choroidal structural changes, but also choroidal hyperpermeability and congestion are also thought to be involved in pathogenesis of PCV. We investigated choroidal vascular brightness intensity (CVB) using ultra-widefield indocyanine green angiography (UWF-ICGA) images and analyzed its association with clinical features in patients with PCV. In this study, 33 eyes with PCV and 27 eyes of age-matched controls were included. CVB was measured by extracting the enhanced pixels of choroidal vessels after the reference brightness across the images was adjusted to be uniform. Associations between choroidal vascular features and the clinical features of PCV were also determined. The mean CVB was higher in PCV than control eyes, regardless of the segmented region (all p < 0.001). CVB was also higher at the posterior pole than at the periphery, and the inferior quadrants were brighter than the superior quadrants in both the PCV and control group (all p < 0.05). In affected eyes, CVB was higher than in unaffected fellow eyes at the posterior pole, whereas there was no difference at the periphery. Posterior pole CVB correlated significantly with subfoveal choroidal thickness (r = 0.502, p = 0.005), polyp number (r = 0.366 p = 0.030), and the greatest linear dimension (r = 0.680, p = 0.040). Greatest linear dimension was positively correlated with CVB at posterior pole (p = 0.040), whereas SFCT or CVD in all regions didn't show the significant correlation. The UWF ICGA results showed an increase in CVB at the inferior quadrants and posterior pole, suggesting venous outflow congestion in PCV eyes. CVB might provide more substantial information on the phenotype than other choroidal vascular features.

Clinical features of pachyvessels associated with polypoidal choroidal vasculopathy in chronic central serous chorioretinopathy

To investigate the association between clinical features of chronic central serous chorioretinopathy (CSC) and subsequent development of polypoidal choroidal vasculopathy (PCV). Characteristics and treatment response of PCV secondary to CSC were described. This retrospective observational study included 18 patients with chronic CSC (18 eyes) with subsequent PCV and 36 controls (36 eyes) with chronic CSC without PCV development during follow-up. Clinical features were compared between the two groups. A logistic regression model was used to evaluate the risk factor of PCV formation. Treatments for PCV included anti-vascular endothelial growth factor (VEGF) monotherapy, photodynamic therapy (PDT), or PDT and anti-VEGF combination treatment. Subretinal fluid on optical coherence tomography images were assessed after treatments. Significant between-group differences were observed in best-corrected visual acuity after disease resolution and presence of pachyvessels (P = .001 and P = .003, respectively). The presence of pachyvessels in chronic CSC was associated with subsequent PCV (odds ratio = 6.00; 95% CI, 1.74–20.68; P = .005). CSC recurrence and subfoveal choroidal thickness (SFCT) were not significantly associated with subsequent PCV development (P = .393 and P = .911, respectively). The mean age of PCV diagnosis was 51 years, and the mean time from CSC diagnosis to PCV confirmation was 77.8 months. The mean (range) SFCT of PCV was 327.7 (134–599) μm. Nine patients received anti-VEGF monotherapy and 5 had disease remission. Four patients received PDT and anti-VEGF combination treatment and all of the 4 had disease remission. In chronic CSC, pachyvessel characteristics are associated with subsequent PCV development. This result will assist clinicians to evaluate CSC in clinical practice and provide insights into the pathogenesis of PCV.

Quantitative analysis of choroidal vasculature in polypoidal choroidal vasculopathy using ultra-widefield indocyanine green angiography

Polypoidal choroidal vasculopathy (PCV) is a common choroidal vascular disease particularly in Asians. However, the underlying pathogenesis of PCV is still yet to be fully elucidated, and the correlation between choroidal vasculature and treatment response of PCV are poorly understood. Accordingly, we sought to find clues to understand the pathogenesis and prognosis of PCV by quantitatively evaluating choroidal vasculature from the entire fundus using ultra-widefield (UWF) indocyanine green angiography (ICGA). In this study, 32 eyes from 29 patients with treatment naïve PCV and 30 eyes from 30 healthy control participants were enrolled. Choroidal vascular density (CVD) of PCV eyes was higher than normal eyes in majority regions including the periphery. CVD was positively correlated with choroidal thickness and choroidal hyperpermeability, supporting that the pathogenesis of PCV may include choroidal congestion and dilatation. Thicker choroid and higher CVD were also correlated with poor treatment response after anti-VEGF injections. The CVD, quantified from UWF ICGA can also be used as an effective image biomarker to predict the treatment response in PCV.

Age-Related Scattered Hypofluorescent Spots on Late-Phase Indocyanine Green Angiography as Precursor Lesions of Polypoidal Choroidal Vasculopathy.

Age-related scattered hypofluorescent spots on late-phase indocyanine green angiography (ASHS-LIA) might represent lipid accumulation in Bruch's membrane in the form of basal linear deposits (BlinD). The present study was conducted to describe the clinical characteristics of polypoidal choroidal vasculopathy (PCV) associated with ASHS-LIA. Consecutive patients with treatment-naïve PCV who underwent color fundus photography (FP), fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), and spectral-domain optical coherence tomography (SD-OCT) at the Zhongshan Ophthalmic Center from June 2016 through May 2018, were reviewed. ASHS-LIA and choroidal vascular hyperpermeability (CVH) were evaluated by ICGA. Subfoveal choroidal thickness (SFCT) was assessed by SD-OCT. A total of 187 patients were eligible for inclusion in this study (mean, 63.2 ± 7.6 years; range, 41-85 years). Of these patients, 117 (62.6%) showed ASHS-LIA, 57 (30.5%) had bilateral lesions and 70 (37.4%) showed CVH. Moreover, compared with patients without ASHS-LIA, PCV patients with ASHS-LIA were older (P = 0.001), more frequently had bilateral lesions (P = 0.001), and less frequently showed CVH (P = 0.006). SFCT in eyes with ASHS-LIA was significantly greater than that in eyes without ASHS-LIA after adjusting for age, sex, and CVH (P = 0.026). Nevertheless, there was no significant difference in best-corrected visual acuity or lesion characteristics between the two groups. ASHS-LIA, which is very common in PCV patients, might be involved in the pathogenesis of PCV. PCV with ASHS-LIA was more frequently associated with bilateral involvement, less CVH, and a thicker choroid than PCV without ASHS-LIA.

Polypoidal Choroidal Vasculopathy.

The aim of this review is to summarize developments in the treatment of active polypoidal choroidal vasculopathy (PCV). PCV is associated with a poor visual prognosis as a consequence the condition's hallmark polypoidal dilatation and a branching network resulting in recurrent hemorrhages and serous leakage. Recent research has provided new insights into the pathogenesis of PCV. While still considered a subtype of age-related macular degeneration, suggestions that PCV belongs to a spectrum of conditions that present with a pachychoroid are increasingly well accepted. Treatment remains challenging. Combination therapy (photodynamic therapy (PDT) and intravitreal anti-vascular endothelial growth factor (VEGF)) is associated with higher polyp closure rate, but polyp closure rate has not been correlated with superior visual outcomes. Current data points to non-inferiority of anti-VEGF alone versus combined with PDT when final vision acuity is the study outcome. PCV remains a clinical challenge. Classification and treatment of the condition continues to evolve. Combination therapy may not be superior to anti-VEGF treatment alone in terms of visual acuity outcome, however data on long-term recurrence should be compared in formulating preferred treatment plans.

Current management strategy of polypoidal choroidal vasculopathy.

Polypoidal choroidal vasculopathy (PCV) is a retinal disorder commonly found in Asians presenting as neovascular age-related macular degeneration and is characterized by serous macular detachment, serous or hemorrhagic pigment epithelial detachment, subretinal hemorrhage, and occasionally visible orange-red subretinal nodular lesions. PCV is diagnosed using indocyanine green angiography (ICGA), and the lesions appear as polypoidal aneurysmal vascular lesions with or without abnormal branching vascular network. Although ICGA remains the gold standard for the diagnosis of PCV, various imaging modalities have also facilitated the diagnosis and monitoring of PCV. Recent advances in imaging technology including the use of high resolution spectral domain optical coherence tomography (OCT) and OCT angiography have provided new insights on the pathogenesis of PCV, suggesting a link between PCV and pachychoroid spectrum of macular disorders. With the evolving understanding on the pathogenesis and clinical characteristics of PCV, different therapeutic options have been proposed. These include intravitreal anti-vascular endothelial growth factor (anti-VEGF) monotherapy, combination therapy with anti-VEGF and verteporfin photodynamic therapy, and thermal laser photocoagulation. In recent years, major multi-center randomized clinical trials such as EVEREST, EVEREST II, and PLANET studies have been conducted to compare the efficacy and safety of various treatment options for PCV. This review aims to summarize the results of recent literature, clinical trials and studies to provide an update on the management options of PCV. An overall management strategy for PCV will also be proposed.

Optical Coherence Tomography Angiography for Assessment of the 3-Dimensional Structures of Polypoidal Choroidal Vasculopathy

Investigating the quantitative 3-dimensional (3-D) anatomy of polypoidal complex is important for a better understanding of the pathogenesis of polypoidal choroidal vasculopathy (PCV). To quantitatively evaluate the 3-D characteristics of polypoidal structures, branching vascular networks (BVNs), and origin of PCV using optical coherence tomography angiography (OCTA) and multiple image systems. A prospective, observational study was conducted in 47 consecutive Taiwanese patients (47 eyes) from May 21, 2015, to April 30, 2017. All participants were scanned with the Optovue-RTVue-XR-Avanti OCTA system. Patients in whom PCV was identified on OCTA were examined to define characteristics and structures of the original spouting vessels (stalks) from the choroid, polypoidal structures, and BVNs on OCTA. Quantitative analysis of 3-D structures of the polypoidal complex. Among the 47 patients, the mean (SD) patient age was 68.9 (8.0) years, and 28 (59.6%) men were included. Clear images of polypoidal structures could be detected in 17 eyes (36.2%, 22 polypoidal structures), BVNs in 26 eyes (55.3%, 26 tufts of BVNs), and stalks of origin from the choroid in 26 eyes (55.3%, 26 stalks) on the en face plane on OCTA. All polypoidal structures were found at a mean (SD) height of 45.3 (36.1) μm above the retinal pigment epithelium (RPE) reference plane that was preset by the machine, while the BVNs were found at a mean (SD) depth of 28.6 (14.2) μm below the RPE reference plane and the choroidal stalks at 80.4 (24.4) μm below RPE reference plane. The mean (SD) thickness of polypoidal structures was 38.4 (15.5) μm and of BVNs, 60.2 (25.0) μm. The polypoidal structures were all above the Bruch membrane within the dome of the RPE detachment, the choroidal stalks were all in the choroid layer. The BVNs could be either above (up to 18 μm), within, or below (up to 28 μm) the Bruch membrane and were in proximity to the double layers of flattened RPE detachment. These results demonstrate a 3-D architecture of PCV that may be helpful for a better understanding of the anatomy, pathophysiology, and pathogenesis of PCV.

CLINICAL RELEVANCE OF AQUEOUS VASCULAR ENDOTHELIAL GROWTH FACTOR LEVELS IN POLYPOIDAL CHOROIDAL VASCULOPATHY.

To investigate vascular endothelial growth factor (VEGF) level according to the clinical and imaging features, and to explore its relationship with the responsiveness to anti-VEGF treatment in eyes with polypoidal choroidal vasculopathy. Aqueous samples were collected from 62 eyes of 62 patients with treatment-naïve polypoidal choroidal vasculopathy. Vascular endothelial growth factor levels were measured using enzyme-linked immunosorbent assay. Baseline best-corrected visual acuity, central macular thickness, subfoveal choroidal thickness, greatest linear dimension of the lesion, and the presence of hemorrhage were included in the analysis. The effects of 3 monthly intravitreal ranibizumab injections on best-corrected visual acuity and central macular thickness were assessed. Baseline VEGF level was negatively correlated with subfoveal choroidal thickness (r = -0.33, P = 0.01). Other variables had no correlation with VEGF level. The mean change in central macular thickness after anti-VEGF treatment was -51 ± 64 μm, which is positively correlated with VEGF concentration (r = 0.30, P = 0.04) and negatively correlated with subfoveal choroidal thickness (r = -0.35, P = 0.02). Vascular endothelial growth factor level demonstrated a negative correlation with baseline subfoveal choroidal thickness and was associated with response to anti-VEGF treatment. These findings suggest that VEGF has a variable contribution to the pathogenesis of polypoidal choroidal vasculopathy depending on choroid thickness.

Gender specific association of a complement component 3 polymorphism with polypoidal choroidal vasculopathy.

Neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are leading causes of irreversible blindness in developed countries. In this study, we investigated the associations of haplotype-tagging single nucleotide polymorphisms (SNPs) in the complement component 3 (C3) gene with both neovascular AMD and PCV, and potential epistatic effects on C3. Eight tagging SNPs in C3 were genotyped in 708 unrelated study subjects: 200 neovascular AMD patients, 233 PCV patients and 275 controls. Among the eight C3 SNPs, rs17030 was associated with PCV after adjusted for gender and SNP-gender interaction (P = 0.008, OR = 2.94; 95% CI: 1.32-6.52). Moreover, an interaction between rs17030 and gender was identified in PCV (P = 0.02). After stratification by gender, the rs17030 G allele was found to confer an increased risk for PCV in male (P = 0.010, OR = 1.56) but not in female. The haplotype AG defined by the major alleles of rs17030 and rs344555 was also associated with PCV in male (P = 0.010, OR = 0.64). In contrast to PCV, none of the eight SNPs was significantly associated with neovascular AMD. This study shows an association of C3 rs17030 with PCV in male, indicating that C3 may have an epistatic effect with gender in the pathogenesis of PCV.

Hyperhomocysteinemia in patients with polypoidal choroidal vasculopathy: a case control study.

PurposeTo determine whether elevated plasma homocysteine and serum high sensitivity C-reactive protein (hsCRP) levels, two established risk factors of vascular diseases, are associated with polypoidal choroidal vasculopathy (PCV).DesignRetrospective case-control study.MethodsOne hundred and nineteen consecutive patients with PCV and 119 matched controls were enrolled in a tertiary hospital from September 2008 to June 2013. Plasma homocysteine and serum hsCRP levels were measured. Associations among plasma homocysteine, serum hsCRP levels and PCV were further evaluated using multivariable logistic regression analysis.ResultsThe median plasma homocysteine level was significantly higher in patients with PCV than in the controls (12.20 µmol/L vs. 9.80 µmol/L, p<0.001). The median serum hsCRP level was slightly higher in the PCV group (0.16 mg/dl vs. 0.11 mg/dl in control group, p = 0.07). After multivariable logistic regression analysis, each 1 µmol/L increase of plasma homocysteine was associated with a 1.5-fold increase in likelihood of having PCV (OR, 1.54; 95% confidence interval (CI), 1.33–1.79, p<0.001).ConclusionsHyperhomocysteinemia was associated with PCV and might play a role in the pathogenesis of PCV.

Different impact of high-density lipoprotein-related genetic variants on polypoidal choroidal vasculopathy and neovascular age-related macular degeneration in a Chinese Han population

Neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) are both major serosanguinous maculopathies among the Asian elderly. They are similar in phenotype. Genetic variants in high-density lipoprotein (HDL) pathway were discovered to be associated with AMD in two genome-wide association studies. In this study with a Chinese Han cohort, we investigated the impacts of these genetic variants on nAMD and PCV separately. The missense coding variants and previously identified variants at LIPC, ABCA1, CETP, LPL and FADS1 loci were genotyped in 157 nAMD patients, 250 PCV patients and 204 controls without any macular abnormality. The known variants in CFH, ARMS2 and near HTRA1 were also genotyped. Fasting serum cholesterol levels were determined. The variants in CFH, ARMS2 and near HTRA1 were strongly associated with both PCV (P < 10−6, 10−7 and 10−7 respectively) and nAMD (P < 10−6, 10−16 and 10−17 respectively). None of the studied HDL-related variants were significantly associated with nAMD. A missense variant in CETP, rs5882, was significantly associated with PCV (P = 2.73 × 10−4). The rs5882 GG genotype had a 3.53-fold (95% CI: 1.93–6.45) increased risk for PCV, and conferred a significantly lower serum HDL-cholesterol level for PCV patients than the AA genotype (P = 0.048). These results suggest the need to separate PCV from nAMD in association studies especially with Asian cohorts, and that the HDL pathway may involve in the pathogenesis of PCV and nAMD differently.

Coding Variant I62V in the Complement Factor H Gene Is Strongly Associated with Polypoidal Choroidal Vasculopathy

To investigate whether variants in the complement factor H (CFH) gene are associated with polypoidal choroidal vasculopathy (PCV). Cross-sectional study. A case-control group of 130 PCV subjects and 173 unrelated controls. We conducted an association analysis between CFH variants and PCV in a Japanese population, genotyping 12 tag single nucleotide polymorphisms (SNPs)-including rs3753394, rs800292 (I62V), and rs1061170 (Y402H)-that are highly representative of the common genetic variation in the CFH region. Genotyping was performed using TaqMan technology. Allele and haplotype frequencies of the CFH variants. A highly significant association with PCV was observed across the CFH region. The strongest association was observed at I62V (P = 1.7 x 10(-7)). Six other SNPs (rs3753394, rs6680396, rs1410996, rs2284664, rs1329428, and rs1065489) also showed significant association (10(-3) < P < 10(-6)). These associations became nonsignificant after accounting for rs800292 in a conditional logistic regression analysis. A significant omnibus haplotype association was detected in the entire CFH region (omnibus P = 1.6 x 10(-5) at 7 degrees of freedom). Conditional haplotype-based likelihood ratio tests revealed that the significant omnibus haplotype association disappeared when it was estimated conditional on I62V (omnibus P = 0.20, 6 degrees of freedom, post-I62V dependency), whereas the omnibus haplotype association remained significant when it was estimated conditional on any SNP other than I62V. These findings indicate that multiple observed effects were caused by linkage disequilibrium with I62V, and that this variant fully accounts for the association signals observed at the set of SNPs examined at this locus. The present study provides evidence that the complement pathway plays a substantial role in the pathogenesis of PCV. The nonsynonymous variant I62V is a plausible candidate for a causal polymorphism leading to the development of PCV, given its potential for functional consequences on the CFH protein and our own statistical evidence. The authors have to proprietary or commercial interest in any materials discussed in this article.

Nasal and independent polypoidal lesions in polypoidal choroidal vasculopathy

Polypoidal vessels in polypoidal choroidal vasculopathy (PCV) are known to occur frequently in the macular and peripapillary regions. The aim of this study is to describe patients with polypoidal vessels that are nasal to the optic disc, being independent of macular polypoidal lesions. A 75-year-old man and a 65-year-old man with polypoidal vessels in the macula of both eyes were followed up through routine examinations including indocyanine green angiography and optical coherence tomography. A polypoidal vessel located 1.5 disc diameters to the nasal margin of the disc was found in the right eye during the first examination in one case, and in the other case it developed during the follow-up period, after successful treatment using photodynamic therapy for the polypoidal lesion in the macula of the left eye. Indocyanine green angiography disclosed no continuity between the polypoidal vessels nasal to the disc and the polypoidal vessels in the macula region in either case. The nasal polypoidal vessels were not associated with exudative changes in either case, and the vessel in one case disappeared spontaneously without any treatment. The findings of this study demonstrate that PCV could involve regions outside the macula and occur in multiple areas independently. The results also indicate the dynamic nature and transitory appearance of polypoidal vessels. Polypoidal vessels nasal to the disc might be overlooked, especially in cases that are not associated with exudative changes, and careful examination might disclose more subclinical nasal polypoidal vessels. Further detailed examination would be helpful to gain a better understanding of the pathogenesis of PCV.

Clinical features of early and late stage polypoidal choroidal vasculopathy characterized by lesion size and disease duration

The pathogenesis of polypoidal choroidal vasculopathy (PCV), and even its clinical features, are controversial. Previous histopathological studies have identified different features; either dilated choroidal vessels or intra-Bruch's neovascularization. These differences might be partly attributable to the influence of the disease stage. We therefore evaluated the clinical features of early and late stage PCV. The medical records of 110 eyes of 97 PCV patients were retrospectively reviewed. The time between the subjective onset of visual abnormality and examination at our clinic and the greatest linear dimension of the total lesion at the first examination were investigated. The period of disturbed vision and lesion size data were placed in ascending order to determine the first quartile point. Eyes with both values at or below the first quartile point were classified as 'small-short' (early stage). Eyes with both values equal to at least the third quartile point were classified as 'large-long' (late stage). Fundus photography, indocyanine green and fluorescein angiography, visual acuity, and clinical course were compared. Twelve eyes from 12 patients were small-short cases (period of disturbed vision of 1 month or less, lesion size 2.0 disc diameters or less). Eleven eyes from ten patients were large-long cases (period of disturbed vision 36 months or more, lesion size at least 5.0 disc diameters). The large-long eyes were characterized by occult choroidal neovascular membrane or scar tissue secondary to exudative age-related macular degeneration. Noticeable in the small-short eyes were atrophic changes in the retinal pigment epithelium, choroidal vessel hyperpermeability and pulsation. The visual prognosis and clinical course were different between the groups. The difference of clinical features between the groups might reflect different disease stages, although not all of the features observed in the small-short group appeared to represent the early stages of those recorded in the large-long group. Thus, the variation in histopathologic features among previous reports might be partly attributable to differences in disease stage.

Elevated C-Reactive Protein Levels in Patients with Polypoidal Choroidal Vasculopathy and Patients with Neovascular Age-Related Macular Degeneration

To determine the relationship between systemic C-reactive protein (CRP) levels and polypoidal choroidal vasculopathy (PCV) and advanced neovascular age-related macular degeneration (AMD) in Japanese patients. Case-control study. Ninety-seven patients with PCV, 176 with advanced neovascular AMD, and 262 control subjects without any macular abnormality were studied. Color fundus photographs of the macular area were taken from both eyes in all subjects. Indocyanine green angiography and fluorescein angiography were performed for diagnosis. The CRP level was measured by a high-sensitivity assay using a latex aggregation immunoassay, and the levels in patients with PCV and neovascular AMD were compared with that in the control group using the Kruskal-Wallis test. Associations between CRP and PCV or neovascular AMD were compared using logistic regression analysis by computing the odds ratios (ORs) and 95% confidence intervals (CIs) after the study populations were divided into quartiles. The CRP levels in patients with PCV, patients with neovascular AMD, and control subjects. Standard univariate and multivariate analyses between groups. Median CRP levels were significantly higher in cases with PCV (0.94 mg/l) or with advanced neovascular AMD (0.95 mg/l) than in control subjects (0.43 mg/l) (P<0.001 for Kruskal-Wallis test). After adjusting for baseline characteristics such as age, gender, smoking status, alcohol use, body mass index, history, and use of antiinflammatory drugs, the increase in risk was significant for the highest quartile of CRP for both PCV (OR, 3.53; 95% CI, 1.49-8.40) and neovascular AMD (OR, 4.08; 95% CI, 1.94-8.56), and for the third quartile of CRP for neovascular AMD (OR, 2.29; 95% CI, 1.07-4.91). The trends for an increase in risk of disease with increase in CRP were statistically significant for both PCV (P = 0.001) and neovascular AMD (P<0.001). The significant associations between elevated serum CRP levels and PCV or neovascular AMD in the Japanese strongly suggest that inflammatory processes are involved in the pathogenesis of PCV and neovascular AMD.