Ocular Involvement Preceded the Onset of Cutaneous Lesions in Hydroa Vacciniforme-Like Lymphoproliferative Disorder: A Case Report.

PURPOSE: To report a case of ocular involvement associated with hydroa vacciniforme-like lymphoproliferative disorder (HVLPD). CASE REPORT: A 10-year-old HVLPD boy suffered conjunctivitis, interstitial keratitis, and anterior uveitis sequentially during the whole course. Interestingly, this case manifested initially only with ocular findings, which preceded 1 year earlier than the onset of cutaneous lesions. And his later ocular findings occurred simultaneously with cutaneous lesions. The patient was treated with oral prednisone, ganciclovir, and light protection. Topical corticosteroid drops used to control ocular inflammation. Since then, he has not had any flares of ocular inflammation, and the cutaneous lesions improved. Although corneal nebula had been formed, the vision was still good. CONCLUSION: Our case was supportive of ocular involvement in HVLPD. Ophthalmologists should be aware of ocular involvement in HVLPD could be preceded the onset of cutaneous lesions, and prudently perform a careful ophthalmic examination at regular intervals to limit long-term sequelae.

Pilot study of inactive polypoidal lesions in polypoidal choroidal vasculopathy.

PURPOSE: This pilot study was conducted to describe the angiographic characteristics of inactive polypoidal lesions that were observed during indocyanine green angiography (ICGA) in polypoidal choroidal vasculopathy (PCV). METHODS: This was a retrospective study involving 40 eyes of 39 consecutive Chinese patients with PCV with inactive polypoidal lesions. All patients underwent fundus fluorescein angiography and ICGA examinations. We used ICGA to make a definitive diagnosis of PCV in each patient. The clinical and angiographic characteristics of inactive polypoidal lesions were recorded and analyzed. RESULTS: In the 40 eyes that were studied, the time between receiving an injection of indocyanine green and the initial appearance of inactive polypoidal lesions ranged from 8.2 minutes to 25.1 minutes, with a mean time of 15.1 ± 5.6 minutes. Inactive polypoidal lesions were divided into 4 groups: 5 eyes (12.5%) in the asymptomatic group; 8 eyes (20.0%) in the atrophic and/or cicatricial group; 24 eyes (60.0%) in the combined group (coexisting with active polypoidal lesions); and 3 eyes (7.5%) in the mixed group (coexisting with choroidal neovascularization). Twelve of the 40 eyes were followed up for 9 to 29 months (mean 12.4 ± 5.3 months). Over this time period, inactive polypoidal lesions completely regressed (not observed in ICGA) in 3 eyes (25.0%), partially regressed in 3 eyes (25.0%), and were stable (the same as the first visit) in 6 eyes (50.0%). CONCLUSIONS: Inactive polypoidal lesions in patients with PCV most commonly appeared during the middle phase of ICGA and were manifested in 4 groups. These lesions represented the sites of PCV in a regressed or quiescent stage.

MMP9 gene polymorphism is not associated with polypoidal choroidal vasculopathy and neovascular age-related macular degeneration in a Chinese Han population.

BACKGROUND: Recently, one of our studies has revealed that the serum matrix metalloproteinase 9 (MMP9) level is elevated in polypoidal choroidal vasculopathy (PCV) but not in age-related macular degeneration (AMD). Previous studies have demonstrated that abnormal extracellular matrix (ECM) metabolism plays an important role in the pathogenesis of AMD and PCV. MMP9 is an important regulating enzyme in ECM metabolism, and the MMP9 gene may be a candidate gene for the susceptibility of PCV and AMD. In this study, we aimed to investigate whether the MMP9 gene polymorphism is associated with PCV and neovascular AMD (nAMD) in a Chinese Han population. METHODS: We performed a case-control study in a Chinese Han population. Three tag single nucleotide polymorphisms (SNPs) (rs17576, rs3787268 and rs2274755) of the MMP9 gene were genotyped in 251 patients with PCV, 157 patients with nAMD, and 204 control individuals using the Multiplex SNaPshot system and the direct DNA sequencing technique. The three SNPs genotypes and allele frequencies in the PCV, nAMD and control groups were evaluated using PLINK software and binary logistic regression analysis. RESULTS: In the PCV, nAMD, and control groups, the minor allele frequencies were 0.2099, 0.2070 and 0.2108 for the rs17576 variant; 0.4442, 0.4522 and 0.4461 for the rs3787268 variant; and 0.1036, 0.1338 and 0.1225 for the rs2274755 variant, respectively. The three tag SNPs were not significantly associated with susceptibility to PCV (p = 0.9524, 0.9553, and 0.3672, respectively) or nAMD (p = 0.9015, 0.8692, and 0.6543, respectively). None of the p values for the additive, dominant, or recessive models were statistically significant in the PCV or nAMD group. CONCLUSIONS: No evidence was found to support an association between the MMP9 gene variants and susceptibility to either nAMD or PCV in a Chinese Han population.

The noninvasive retro-mode imaging modality of confocal scanning laser ophthalmoscopy in polypoidal choroidal vasculopathy: a preliminary application.

PURPOSE: To evaluate the validity of the novel and noninvasive retro-mode imaging modality of confocal scanning laser ophthalmoscopy (cSLO) for detecting the morphological features of polypoidal choroidal vasculopathy (PCV). DESIGN: Prospective, observational, consecutive case series. METHODS: Twenty-six patients (29 eyes) with PCV were enrolled in this study. All patients underwent comprehensive ophthalmologic examinations and imaging studies, including retro-mode imaging, fundus autofluorescence (FAF), fundus photography, fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA) and spectral-domain optical coherence tomography (SD-OCT). We investigated the retro-mode images and compared the results with those of SD-OCT, FFA and ICGA. RESULTS: In the 29 PCV eyes, the retro-mode images clearly revealed polypoidal lesions in 27 (93.1%) eyes as well as branching vascular networks in 16 (55.2%) eyes. Others findings, including pigment epithelial detachment (PED) in 20 (69.0%) eyes, neuroretinal detachment (NRD) in 3 (10.3%) eyes, cystoid macular edema (CME) in 3 (10.3%) eyes, drusen in 4 (13.8%) eyes and minute granular changes of the retinal pigment epithelium (RPE) in 12 (41.3%) eyes, were also clearly visualized. When we compared the results with those of SD-OCT, FFA and ICGA, there was no significant difference between ICGA and retro-mode imaging for finding polypoidal lesions and (or) branching choroidal vascular networks (P>0.05). However, the rate of PED detection was significantly better with retro-mode imaging than with the ICGA (P<0.05). The differences were not statistically significant between SD-OCT and retro-mode imaging for detecting PED, NRD, CME, drusen and minute granular RPE changes (P>0.05). The differences were not statistically significant between FFA and retro-mode imaging for detecting PED, NRD, CME (P>0.05). CONCLUSIONS: The novel and noninvasive retro-mode imaging by cSLO is able to clearly visualize the morphological features of PCV.

Serum levels of matrix metalloproteinase 2 and matrix metalloproteinase 9 elevated in polypoidal choroidal vasculopathy but not in age-related macular degeneration.

PURPOSE: Age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are the leading causes of vision loss in the elderly Asian population. Previous studies have confirmed that abnormal extracellular matrix (ECM) metabolism plays an important role in the pathogenesis of AMD and PCV. However, the dynamic metabolism of the ECM is closely regulated by matrix metalloproteinases (MMPs) and tissue metalloproteinase inhibitors (TIMPs). Whether MMPs and TIMPs participate in the pathogenesis of AMD and PCV remains unclear. The aim of this study was to investigate the correlation between circulating MMP and TIMP levels and AMD and PCV. METHODS: The serum levels of MMPs (MMP1, MMP2, MMP3, and MMP9) and TIMPs (TIMP1 and TIMP3) were quantified using enzyme-linked immunosorbent assays in four groups of subjects (n=342): early AMD (group 1, n=75), neovascular AMD (group 2, n=89), PCV (group 3, n=98), and age- and gender-matched controls (group 4, n=80). RESULTS: The mean concentrations of the two gelatinases, MMP2 and MMP9, in the PCV group were significantly higher than that of the control (p=0.001, p<0.001, respectively), early AMD (both p<0.001), and neovascular AMD (p=0.005, p=0.001, respectively) groups. Moreover, the serum MMP2 concentration was positively correlated with the serum MMP9 concentration in the PCV group (r=0.822, p<0.001). However, the mean concentrations of MMP2 and MMP9 in the early AMD and neovascular AMD groups were not significantly different from that of the control group (p>0.05). The mean serum levels of MMP1, MMP3, TIMP1, and TIMP3 were not significantly different among the four groups. CONCLUSIONS: This pilot study first reveals a link between increased levels of circulating gelatinases (MMP2 and MMP9) and PCV but not AMD, which may provide a biologically relevant marker of ECM metabolism in patients with PCV. This finding suggests that the two disorders may have different molecular mechanisms.

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.

COL1A2 polymorphic markers confer an increased risk of neovascular age-related macular degeneration in a Han Chinese population.

PURPOSE: We have previously documented that neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) have multiple different clinical and genetic characteristics. In this study, we investigated the association of rs42524 in the alpha-2 type I collagen (COL1A2) gene, which has been identified as a risk variant for intracranial aneurysm, with nAMD and PCV in a Han Chinese population. METHODS: The study prospectively recruited 195 patients with PCV, 136 patients with nAMD, and 181 control individuals. We genotyped the rs42524 polymorphism of COL1A2 using the Multiplex SNaPshot System and direct DNA sequencing. Genotype and allele frequencies were evaluated with PLINK software. RESULTS: The rs42524 polymorphism was modestly significantly associated with nAMD [minor allele: G, p(allelic)=0.04253, odds ratio=0.5285 (95% confidence interval: 0.2832-0.9866)], but not with PCV [minor allele: G, p(allelic)=0.4164, odds ratio=1.2110 (95% confidence interval: 0.7631-1.9210)]. The pvalues for the additive model were significant for nAMD but not for the dominant or recessive models. None of the models for PCV were statistically significant. The size of our sample cohort resulted in a post hoc power of more than 80% to detect associations of rs42524 with nAMD and PCV. CONCLUSIONS: The rs42524 polymorphism is a risk allele for nAMD in a Han Chinese population. rs42524 in COL1A2 confers different levels of susceptibility to nAMD and PCV.

An rs9621532 variant near the TIMP3 gene is not associated with neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in a Chinese Han population.

BACKGROUND: Recently, two genome-wide association studies with large cohorts both identified rs9621532, a new single nucleotide polymorphism (SNP) that is associated with advanced age-related macular degeneration (AMD) and located near the TIMP3 gene. Previous studies have demonstrated that AMD and polypoidal choroidal vasculopathy (PCV) share some common genetic background and that the incidence of PCV is higher in Asian populations than Caucasian populations. In this study, we aimed to investigate whether the rs9621532 SNP is associated with neovascular AMD (nAMD) and PCV in a Chinese Han population. METHODS: We performed a case-control study in a Chinese Han population. The rs9621532 SNP was genotyped in 136 patients with nAMD, 195 patients with PCV, and 181 control individuals using the Multiplex SNaPshot system and the direct DNA sequencing technique. Rs9621532 genotypes and allele frequencies in the nAMD, PCV and control groups were evaluated using PLINK software. RESULTS: In the nAMD, PCV, and control groups, the minor allele frequencies of the rs9621532 variant were 0.05147, 0.02564, and 0.03039, respectively. The rs9621532 SNP was not significantly associated with susceptibility to nAMD (p = 0.1773) or PCV (p = 0.6933). None of the p-values for the additive or dominant models were found to be statistically significant in the nAMD or PCV groups. No recessive homozygotes were genotyped in any of the three groups. CONCLUSIONS: No evidence was found to support an association between the rs9621532 variant and susceptibility to either nAMD or PCV in a Chinese Han population.

Lack of association with PEDF Met72Thr variant in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in a Han Chinese population.

PURPOSE: To investigate whether Met72Thr (rs1136287), a common single nucleotide polymorphism (SNP) variant of the pigment epithelium-derived factor (PEDF) gene, is associated with neovascular age-related macular degeneration (nAMD) or polypoidal choroidal vasculopathy (PCV) in a Han Chinese cohort. METHODS: We genotyped Met72Thr (rs1136287) in persons of Han Chinese descent: 177 PCV patients, 131 nAMD patients, and 182 control persons. Genotyping was accomplished using the Multiplex SNaPshot system and by direct DNA sequencing. Genotypes and allele frequencies of patients and controls were evaluated for the SNP using PLINK software. RESULTS: The minor allele frequency of the PEDF Met72Thr variant did not differ significantly between either PCV or nAMD and the control group: p = 0.3822 and p = 0.9822, respectively. The p-values for the additive, dominant, and recessive models were not statistically significant for PCV or nAMD. CONCLUSIONS: No evidence was found to support a role for the Met72Thr variant in susceptibility to either PCV or nAMD in a Han Chinese cohort.