Yasuo Kurimoto

Autologous Induced Stem-Cell–Derived Retinal Cells for Macular Degeneration

We assessed the feasibility of transplanting a sheet of retinal pigment epithelial (RPE) cells differentiated from induced pluripotent stem cells (iPSCs) in a patient with neovascular age‐related macular degeneration. The iPSCs were generated from skin fibroblasts obtained from two patients with advanced neovascular age‐related macular degeneration and were differentiated into RPE cells. The RPE cells and the iPSCs from which they were derived were subject to extensive testing. A surgery that included the removal of the neovascular membrane and transplantation of the autologous iPSC‐derived RPE cell sheet under the retina was performed in one of the patients. At 1 year after surgery, the transplanted sheet remained intact, best corrected visual acuity had not improved or worsened, and cystoid macular edema was present. (Funded by Highway Program for Realization of Regenerative Medicine and others; University Hospital Medical Information Network Clinical Trials Registry [UMIN‐CTR] number, UMIN000011929.)

The significance of cone outer segment tips as a prognostic factor in epiretinal membrane surgery.

PURPOSE To evaluate the prognostic value of the cone outer segment tips (COST) and other features using spectral-domain optical coherence tomography (SD-OCT) in patients undergoing epiretinal membrane (ERM) surgery. DESIGN Retrospective observational case series. METHODS Fifty eyes of 49 patients that underwent vitrectomy for idiopathic ERM were studied. Best-corrected visual acuity (BCVA) and SD-OCT images were examined preoperatively and at 1 and 6 months postoperatively. The SD-OCT features evaluated included central foveal thickness (CFT) and the status and defect diameter of the external limiting membrane (ELM), the photoreceptor inner/outer segment (IS/OS) junction, and the COST line. The associations between SD-OCT parameters and BCVA were analyzed. RESULTS There was no ELM disruption found, and thus the eyes were categorized into 3 groups: Group A, with a continuous IS/OS and COST line; Group B, with a continuous IS/OS but disrupted COST line; and Group C, with a disrupted IS/OS and COST line. At 6 months, Group A showed a significantly better BCVA than Group B (P<.005), and poorer BCVA was noted in Group C (P=.034). Defect diameters of IS/OS and COST line were also significantly correlated with BCVA postoperatively. The BCVA at 6 months was better in order of Group A, B, and C as assigned at baseline (P<.05) or 1 month (P<.001). There was no significant correlation between CFT and BCVA. CONCLUSIONS The status of the COST line, in conjunction with the IS/OS junction, is a useful prognostic factor after ERM surgery.

The Significance of External Limiting Membrane Status for Visual Acuity in Age-Related Macular Degeneration

PURPOSE To evaluate status of the external limiting membrane (ELM) as a contributor of visual acuity (VA) in age-related macular degeneration (AMD). DESIGN Hospital-based, cross-sectional study. METHODS We retrospectively reviewed spectral-domain optical coherence tomography images of 158 patients with AMD who had undergone photodynamic therapy and classified them based on the status of the ELM: absent, discontinuous, or complete. We simultaneously assessed foveal thickness, presence or absence of subretinal fluid/mass, presence or absence of subretinal pigment epithelium fluid/mass, status of the inner segment/outer segment (IS/OS) junction, and status of the intermediate line between the IS/OS junction and retinal pigment epithelium. Correlation coefficients between each parameter and VA were analyzed. RESULTS There was a strong correlation between ELM status and VA (r = -0.75, P < .001), and that was higher than that of the IS/OS (r = -0.69, P < .001). Multivariate analysis showed that ELM status is the most important factor for VA. Other parameters that correlated with VA included age, status of the intermediate line, and presence of subretinal or subretinal pigment epithelium fibrosis. Foveal thickness showed V-shaped correlation, with the dividing line around 200 mum. CONCLUSION ELM status may be more useful than is IS/OS status in evaluation of retinal morphology and function in patients with AMD.

Transplantation of adult rat hippocampus-derived neural stem cells into retina injured by transient ischemia

Neural stem cells are capable of differentiating along multiple central nervous system cell-type lineages, and their use as graft material has provided new strategies for the treatment of neuronal damage. We transplanted adult rat hippocampus-derived neural stem cells into eyes of adult rats that underwent ischemia-reperfusion injury. As control, the cells were also injected into normal rats eyes without ischemic insult. The rats were sacrificed at 1, 2, 4, and 8 weeks, and the eyes were examined histochemically. In eyes with the insult, the transplanted cells were well integrated into the host retinas and expressed Map2ab. In the control, none of the cells migrated into the retina. These results suggest that neural stem cells may be used as donor cells for transplantation to repair ischemic-injured retina.

Changes in the anterior chamber configuration after small-incision cataract surgery with posterior chamber intraocular lens implantation

PURPOSE To report quantitative changes in the anterior chamber configuration after small-incision cataract surgery with implantation of a posterior chamber intraocular lens by means of ultrasound biomicroscopy. METHODS We examined the anterior chamber configuration of 20 eyes of 20 patients before and 3 months after small-incision cataract surgery (phacoemulsification and aspiration plus foldable intraocular lens implantation through a 3.0- to 4.0-mm self-sealing wound) by means of ultrasound biomicroscopy. The following variables were measured: the anterior chamber depth at the center of the cornea, the angle-opening distance 250 microns from the scleral spur (AOD250), the angle-opening distance 500 microns from the scleral spur (AOD500), and the trabecular-iris angle. RESULTS The anterior chamber depth at the center of the cornea, AOD250, AOD500, and trabecular-iris angle increased significantly after surgery. The preoperative anterior chamber depth at the center of the cornea and trabecular-iris angle were negatively correlated with the differences between the postoperative and preoperative values (P < .01). The preoperative values of all variables examined were negatively correlated with the ratios of the postoperative value to the preoperative value (P < .002). CONCLUSIONS The present results showed that small-incision cataract surgery significantly deepened the anterior chamber and widened its angle. The more shallow the preoperative anterior chamber was, the greater the postoperative change of the chamber was; and the more narrow the preoperative angle was, the greater the postoperative change of the angle was.

Comparison of the Effect of Ranibizumab and Verteporfin for Polypoidal Choroidal Vasculopathy: 12-Month LAPTOP Study Results

PURPOSE To compare the effect of photodynamic therapy (PDT) and intravitreal ranibizumab in patients with polypoidal choroidal vasculopathy (PCV). DESIGN Randomized clinical trial. METHODS SETTING Multicenter. STUDY POPULATION Total of 93 patients with treatment-naïve PCV. INTERVENTION Patients were randomized to 2 arms. Patients in the PDT arm underwent a single session of PDT with verteporfin, and patients in the ranibizumab arm received 3 monthly ranibizumab injections at baseline. Additional treatment was performed as needed in each arm. MAIN OUTCOME MEASURES Primary outcome measurement was the proportion of patients gaining or losing more than 0.2 logarithm of minimal angle of resolution (logMAR) units from baseline. Mean change of logMAR and central retinal thickness (CRT) were also evaluated. RESULTS In the PDT arm (n = 47), 17.0% achieved visual acuity gain, 55.3% had no change, and 27.7% experienced visual acuity loss. The results were 30.4%, 60.9%, and 8.7%, respectively, in the ranibizumab arm (n = 46), significantly better than the PDT arm (P = .039). In the PDT arm, mean CRT improved (366.8 ± 113.6 μm to 289.1 ± 202.3 μm, P < .001), but logMAR was unchanged (0.57 ± 0.31 to 0.62 ± 0.40). The ranibizumab arm demonstrated improvement in both CRT (418.9 ± 168.6 μm to 311.2 ± 146.9 μm, P < .001) and logMAR (0.48 ± 0.27 to 0.39 ± 0.26, P = .003). Mean change of logMAR was also greater in the ranibizumab arm (P = .011). CONCLUSION Intravitreal injection of ranibizumab is more effective than PDT for treatment-naïve PCV.

Prognostic Factor Analysis in Pars Plana Vitrectomy for Retinal Detachment Attributable to Macular Hole in High Myopia: A Multicenter Study

PURPOSE To detect the prognostic factors associated with initial reattachment after primary pars plana vitrectomy (PPV) with gas tamponade for retinal detachment attributable to macular hole (MHRD). DESIGN Retrospective, multicenter, interventional case series. METHODS This study included 49 eyes of 48 patients with MHRD in high myopia (axial length more than 28.0 mm). All eyes underwent PPV with gas tamponade. We retrospectively reviewed the medical records and performed univariate analysis to detect the presence of any difference between eyes with a successful initial reattachment and those that failed. We performed multivariate logistic regression analysis to assess the influence of each preoperative factor on initial success. RESULTS Success rate of initial reattachment was 69%. Postoperative best-corrected visual acuity (BCVA) of 34 eyes with initial success was significantly better than those of 15 eyes with initial failure (P < .05); preoperative BCVA was not significantly different (P = .43). The axial length of eyes with initial success (29.26 +/- 0.94 mm) was shorter than that of eyes with initial failure (30.04 +/- 1.49 mm) with borderline significance (P = .049). There were no significant differences noted for other factors such as use of ILM peeling (P = .43) or type of tamponade gas (P = .99). Multiple logistic regression analysis using preoperative factors indicated that only axial length was significantly associated with initial success (odds ratio, 0.49; 95% confidence interval, 0.26 to 0.93; P < .05). CONCLUSIONS Initial reattachment is important for visual prognosis, and axial length is a prognostic factor for initial reattachment after PPV with gas tamponade for MHRD in high myopia.

Comparative Assessment of Photodynamic Therapy for Typical Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy: A Multicenter Study in Hyogo Prefecture, Japan

Purpose: We aimed to evaluate the effects of photodynamic therapy (PDT) on different phenotypes of age-related macular degenerations (AMD): typical AMD (tAMD) and polypoidal choroidal vasculopathy (PCV). Procedures: 246 eyes from 242 patients (tAMD: 139, PCV: 107 eyes) were recruited. Gender, age, best-corrected visual acuity (BCVA) before treatment, greatest linear dimension before treatment, lesion phenotype and PDT frequency were evaluated for predicting the BCVA at 12 months after PDT using stepwise multiple regression analyses. Additionally, 125 eyes with tAMD and 97 eyes with PCV followed up for more than 12 months after the final PDT were compared for the recurrence period. Results: In the stepwise analysis, a younger age, better pretreatment BCVA, lower PDT frequency, lesions with PCV and a smaller pretreatment greatest linear dimension were all significantly beneficial for a better BCVA at 12 months after PDT. PCV showed a significantly lower PDT frequency and greater improvement in the BCVA than tAMD. The recurrence period of PCV was significantly later than that of tAMD. Conclusions: The phenotype of AMD is significantly correlated with its prognosis after PDT. PCV showed a significantly better response to PDT in terms of BCVA improvement and effect durability.

Successful Transplantation of Retinal Pigment Epithelial Cells from MHC Homozygote iPSCs in MHC-Matched Models

Summary There is an ongoing controversy as to whether major histocompatibility complex (MHC) matching is a solution for allogeneic stem cell transplantation. In the present study, we established retinal pigment epithelial (RPE) cells from induced pluripotent stem cells (iPSCs) in MHC homozygote donors. We observed no rejection signs in iPSC-derived RPE allografts of MHC-matched animal models without immunosuppression, whereas there were immune attacks around the graft and retinal tissue damage in MHC-mismatched models. In an immunohistochemical examination of MHC-mismatched allografts, the transplanted RPE sheets/cells were located in the subretinal space, but the RPE exhibited inflammatory and hypertrophic changes, and many inflammatory cells, e.g., Iba1+ cells, MHC class II+ cells, and CD3+ T cells, invaded the graft area. Conversely, these inflammatory cells poorly infiltrated the area around the transplanted retina if MHC-matched allografts were used. Thus, cells derived from MHC homozygous donors could be used to treat retinal diseases in histocompatible recipients.

Joint effect of cigarette smoking and CFH and LOC387715/HTRA1 polymorphisms on polypoidal choroidal vasculopathy.

PURPOSE To investigate whether the major genetic and environmental risk factors of age-related macular degeneration (AMD)-CFH Y402H and LOC387715 A69S and cigarette smoking-are also associated with polypoidal choroidal vasculopathy (PCV) and whether the associations of CFH Y402H and LOC387715 A69S with PCV are modified by smoking. METHODS Three hundred seventy-five Japanese patients with PCV and 847 Japanese who served as population-based control subjects, all ≥55 years of age, were studied. CFH Y402H (rs1061170) and LOC387715 A69S (rs10490924) were genotyped with a single-nucleotide polymorphism (SNP) assay. An unconditional logistic regression model was used to analyze the association between age, sex, smoking status, CFH Y402H, LOC387715 A69S, and PCV. The synergy index (SI) was measured to assess gene-smoking and gene-gene interaction as a departure from additivity. RESULTS CFH Y402H, LOC3387715 A69S, and cigarette smoking status were all significantly associated with PCV; for CFH Y402H, the adjusted odds ratio (OR) for the number of copies of the allele was 1.63 (95% confidence interval [CI], 1.12-2.36; P < 0.05); for LOC387715 A69S, the adjusted OR was 2.26 (95% CI, 1.83-2.78; P < 0.0001); and for smoking status (ever versus never smoked), the adjusted OR was 1.45 (95% CI, 1.00-2.10; P < 0.05). The joint effect of CFH Y402H and smoking was significantly greater than the additive scale, with an SI of 2.41 (95% CI, 1.14-5.10). CONCLUSIONS CFH Y402H and LOC387715 A69S are both significantly associated with PCV. Cigarette smoking is an environmental risk factor for PCV. The findings suggest interactions between CFH 402H and cigarette smoking in PCV.