Mitsuhiro Imasawa

Association of LOC387715 A69S with vitreous hemorrhage in polypoidal choroidal vasculopathy.

PURPOSE To investigate whether the LOC387715 polymorphism is associated with polypoidal choroidal vasculopathy (PCV) and with vitreous hemorrhage (VH), one of the most severe clinical phenotypes, in the Japanese population. DESIGN Cross-sectional case-control association study. METHODS One hundred and nine Japanese patients with PCV, composed of nine patients associated with VH (VH group) and 100 patients without VH (non-VH group), and 85 control subjects were analyzed for the LOC387715 polymorphism (rs = 10490924), using denaturing high-performance chromatography. RESULTS There was a significant difference in the T allele frequency between PCV patients and control subjects (P < .0001). In comparison with wild-type homozygosity (GG), homozygosity for the at-risk allele genotype (TT) increased the likelihood for PCV 8.4-fold (3.6 to 19.5, 95% confidence interval [CI]) and heterozygosity for the at-risk allele genotype (TG) increased the likelihood for PCV 4.0-fold (1.9 to 8.4, 95% CI). There was a significant difference in the genotypic frequency at the LOC387715 site between the VH and non-VH groups (P = .0099, Chi-square test) with the TT genotype occurring in 88.9% in the VH group and 37.0% in the non-VH group. The frequency of the T allele in the VH group was significantly greater than that in the non-VH group (0.944 vs 0.610; P = .0039, Fisher exact test). CONCLUSIONS The LOC387715 polymorphism is associated with PCV and clinical severity in the subgroups of PCV in the Japanese population.

Association of LOC387715 A69S genotype with visual prognosis after photodynamic therapy for polypoidal choroidal vasculopathy.

Purpose: To investigate whether there is an association of the LOC387715 A69S genotype with visual prognosis after photodynamic therapy in eyes with polypoidal choroidal vasculopathy (PCV). Methods: Photodynamic therapy was repeated every 3 months until the disappearance of angiographic signs of active lesions in 71 eyes of 71 patients with PCV who were followed-up for at least 12 months. All patients were genotyped for LOC387715 A69S polymorphism (rs10490924, risk-allele T). Results: Although there was no statistically significant difference in the mean baseline visual acuity (P = 0.53) among the 3 genotypes, there was a statistically significant difference in the visual acuity both at the 12-month and final visits (P = 0.002 and P < 0.001, respectively) with the poorer acuity in patients with the higher “T-”allele frequency. “T” allele was more frequently observed in those with the recurred PCV lesions (odds ratio: 5.8, 95% confidential interval: 2.3-15.1, T vs. G). Conclusion: There is a pharmacogenetic association between the LOC387715 A69S variant and the long-term results after photodynamic therapy in eyes with PCV. The LOC387715 A69S genotype is of clinical importance to predict the visual prognosis after photodynamic therapy in eyes with PCV. These results should be confirmed or refuted by replication studies.

Angiographic lesion size associated with LOC387715 A69S genotype in subfoveal polypoidal choroidal vasculopathy.

Purpose: To investigate whether the LOC387715/ARMS2 variants are associated with an angiographic phenotype, including lesion size and composition, in subfoveal polypoidal choroidal vasculopathy. Methods: Ninety-two subjects with symptomatic subfoveal polypoidal choroidal vasculopathy, whose visual acuity was from 0.1 to 0.5 on the Landolt chart, were genotyped for the LOC387715 polymorphism (rs10490924) using denaturing high-performance chromatography. The angiographic phenotype, including lesion composition and size, was evaluated by evaluators who were masked for the genotype. Lesion size was assessed by the greatest linear dimension based on fluorescein or indocyanine green angiography. Results: Although there was no statistically significant difference in lesion size on indocyanine green angiography (P = 0.36, Kruskal-Wallis test) and in lesion composition (P = 0.59, chi-square test) among the 3 genotypes, there was a statistically significant difference in lesion size on fluorescein angiography (P = 0.0022, Kruskal-Wallis test). Conclusion: The LOC387715 A69S genotype is not associated with lesion composition or size on indocyanine green angiography but with lesion size on fluorescein angiography in patients with subfoveal polypoidal choroidal vasculopathy. Because fluorescein angiography findings represent secondary exudative changes, including subretinal hemorrhages and retinal pigment epithelial detachment, the results in the present study likely indicate that the T allele at the LOC387715 gene is associated with the exudative activity of polypoidal lesions.

Role of Complement Factor H I62V and Age-Related Maculopathy Susceptibility 2 A69S Variants in the Clinical Expression of Polypoidal Choroidal Vasculopathy

PURPOSE To investigate the role of complement factor H (CFH) I62V (rs800292) and age-related maculopathy susceptibility 2 (ARMS2) A69S (rs10490924) variants in the clinical characteristics of polypoidal choroidal vasculopathy (PCV). DESIGN Cross-sectional study. PARTICIPANTS A total of 226 Japanese patients with PCV in both eyes (44 cases) or in 1 eye (182 cases). METHODS Genotyping was performed in all cases for CFH I62V using TaqMan technology and for ARMS2 A69S by denaturing high-performance chromatography. The incidence of 5 characteristic funduscopic findings was studied, including serous retinal detachment, subretinal hemorrhage, serous pigment epithelial detachment (PED), hemorrhagic PED, and classic choroidal neovascularization (CNV). MAIN OUTCOME MEASURES The association of clinical phenotypes, including the incidence of each of 5 specific fundus findings, bilaterality of the disease, and age at onset, with variants of CFH I62V or ARMS2 A69S. RESULTS Although there was no association of CFH I62V variants with any of the phenotypes in PCV, at-risk variants of ARMS2 A69S were associated with higher incidences of subretinal hemorrhage, serous PED, and hemorrhagic PED. In particular, the at-risk allele homozygosity of ARMS2 A69S increased the likelihood for hemorrhagic PED by 12.4-fold compared with non-carriers of the allele (confidence interval, 1.60-95.1, P = 0.0001). However, the at-risk allele of ARMS2 A69S was associated with a lower incidence of serous retinal detachment (P = 0.0092). Classic CNV was not associated with either variant. The mean age at the onset of PCV was significantly younger (68.8 years) in those with homozygosity of the at-risk allele of ARMS2 A69S than in those with heterozygosity (71.6 years) or in non-carriers (72.6 years) (P = 0.026). Moreover, the at-risk allele frequencies of the ARMS2 A69S were significantly higher in bilateral cases than in unilateral cases (75.0% vs. 59.3%, P = 0.007). CONCLUSIONS ARMS2 A69S variants were significantly associated with hemorrhagic or subpigment epithelium lesions of PCV, and with earlier onset and bilateral involvement. The genotyping of ARMS2 A69S is more informative than that of CFH I62V in understanding the clinical features in patients with PCV.

Systemic risk factors associated with polypoidal choroidal vasculopathy and neovascular age-related macular degeneration.

Purpose: To compare the association of systemic risk factors between neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). Methods: Seven hundred and three patients (235 with nAMD and 468 with PCV) were included. Associated systemic conditions, including hypertension, cardiovascular disease, stroke, diabetes mellitus, and end-stage renal disease, were investigated through an interview and questionnaire. Results: The prevalence of diabetes mellitus and end-stage renal disease in nAMD was significantly higher than that in PCV (P < 0.001 and P = 0.021, respectively, multivariate logistic regression analysis). Moreover, in diabetic patients with nAMD or PCV, the more severe form of diabetic retinopathy was more prevalent in nAMD cases than in PCV cases (P = 0.006, multivariate logistic regression analysis). Conclusion: Diabetes mellitus and end-stage renal disease are more prevalent in patients with nAMD than in those with PCV. Specific systemic conditions might be associated with the development of nAMD.

Perimetric sensitivity and retinal thickness in eyes with macular edema resulting from branch retinal vein occlusion.

PURPOSE To document and study the relationship between perimetric sensitivity and retinal thickness at the foveal and parafoveal points in eyes with macular edema associated with branch retinal vein occlusion. METHODS A prospective study was performed using the central 10-2 Humphrey perimetry program and optical coherence tomography. Seventeen eyes with branch retinal vein occlusion were eligible showing macular edema without macular nonperfusion or massive retinal hemorrhage. RESULTS The sensitivity and retinal thickness were significantly correlated at the fovea (r = -0.629, P =.006) as well as 1 (r = -0.656, P <.0001) and 3 (r = -0.885, P <.0001) degrees apart from the fovea. The visual acuity that is expressed as a logarithm of the minimum angle of resolution (LogMAR) also correlated with retinal thickness (r = 0.591, P =.011). CONCLUSION The increased retinal thickness resulting from macular edema is closely correlated with retinal sensitivity as measured by automated static perimetry both at the fovea and parafovea. Measuring the retinal thickness using optical coherence tomography may be useful in monitoring macular edema in eyes with branch retinal vein occlusion.

Multiple retinal vein occlusions in essential thrombocythemia

PURPOSE To report the ophthalmoscopic and angiographic evidence of both temporally and spatially independent multiple occlusions of the retinal veins in a patient with essential thrombocythemia. METHODS Observational case report. Ophthalmic examinations, including fluorescein fundus angiogram, were performed on a 77-year-old male, who was found to have essential thrombocythemia. RESULTS An acute impending central retinal vein occlusion in the left eye was diagnosed with coexisting old retinal vein occlusions evidenced by white vessels and capillary nonperfusion in both eyes. Peripheral retinal capillary dropout was also found angiographically in the right eye. CONCLUSION Bilateral multiple occlusions of retinal veins in the present case suggest a prothrombotic tendency in retinal circulation in essential thrombocythemia.

Spontaneous closure of stage 2 macular hole observed with optical coherence tomography

PURPOSE To report the clinical course and images of optical coherence tomography of an eye with a stage 2 macular hole which closed spontaneously. DESIGN Observational case report. METHODS Serial optical coherence tomographic images were obtained. RESULTS A 67-year-old woman received a diagnosis of stage 2 idiopathic macular hole in her right eye. The diagnosis was made with a tomographic image of a full-thickness dehiscence of the neurosensory retina at the fovea. The posterior hyaloid membrane was adhering to the edge of the dehiscence. Four weeks later, the closure of the macular hole was ascertained with optical coherence tomography. The posterior hyaloid membrane was fully separated from the fovea. CONCLUSION A stage 2 macular hole may close spontaneously with the separation of the hyaloid membrane.

Reappraisal of Spontaneous Closure Rate of Idiopathic Full-Thickness Macular Holes

We retrospectively reviewed the records of 142 eyes of 138 patients with idiopathic full-thickness macular hole. Spontaneous closure of idiopathic full-thickness macular hole was observed in five eyes (3.5%) of four patients before the planned vitrectomy. In the era when surgical treatment was not available for macular hole, the rate of spontaneous closure of idiopathic full-thickness macular hole was reported as 6.2%. Among several case reports on spontaneous closure of idiopathic full-thickness macular hole based on the optical coherence tomography images only one study reported the rate of spontaneous closure as 2.7%. According to the previous reports and our results, small idiopathic full-thickness macular holes may close spontaneously in a few percent of all macular hole cases. The rate of spontaneous closure may be affected by the waiting time before vitrectomy.

Retinal thickness and perimetric sensitivity in central serous chorioretinopathy

PurposeTo investigate the relationship between anatomical changes and visual sensitivity in eyes with central serous chorioretinopathy (CSC).MethodsTwenty-one eyes with CSC were retrospectively studied using optical coherence tomography (OCT) retinal maps, line scan mode, and the Humphrey perimetry central 10-2 program.ResultsTotal retinal thickness (TRT), including the neurosensory retina and subretinal fluid, correlated significantly with the sensitivity loss in the corresponding visual field in the central macula within a circle 6 mm in diameter. Differential analysis of the TRT, separating it into neurosensory retinal thickness (NRT) and subretinal thickness (SRT), revealed that only SRT correlated well with perimetric sensitivity at 1°, 3°, 5°, 7°, and 9° from the fovea along horizontal and vertical lines crossing at the fovea.ConclusionsVisual sensitivity measured with automated static perimetry is further attenuated by increasing distance between the photoreceptor and retinal pigment epithelium (RPE) in areas of serous retinal detachment in eyes with CSC.