Background To evaluate the correlation between visual acuity improvement and vision-related QOL after ranibizumab treatment in Japanese patients with AMD. Methods In this one-year prospective, interventional, open-label, multicenter study involving four sites, patients with neovascular AMD were enrolled and observed for 12 months. Treatment-naïve patients received 0.5 mg ranibizumab as needed after three initial monthly doses. The best corrected visual acuity (BCVA) and central macular thickness (CMT) were measured at every visit. Evaluations with the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and patient satisfaction questionnaire were performed at baseline and 3 and 12 months after initial treatment. The primary endpoint was change in BCVA and QOL 3 months after ranibizumab treatment. QOL outcomes were also assessed in the better and poor BVCA subgroups. Results The study enrolled 100 patients. The mean logMAR BCVA after treatment improved significantly from 0.43 to 0.30 at 3 months (p< 0.0001), and 0.28 at 12 months (p< 0.0001). The mean NEI-VFQ-25 composite scores improved from 79.48 to 84.13 at 3 months (p< 0.0001), and 86.0 at 12 months (p< 0.0001). The 3 and 12-month changes in NEI-VFQ-25 score and BCVA showed significant correlation. In the poor baseline visual acuity group (decimal BCVA ≤0.5), there was a significant correlation between the changes in the NEI-VFQ-25 score and BCVA (p=0.02) but not in the better baseline visual acuity group (decimal BCVA > 0.6, p=0.1) at 3 months. There were no significant differences in the satisfaction questionnaire score from baseline to at 3 months (p=0.54) and 12 months (p=0.23). The average CMT improved significantly from 340 to 264 μm at 3 months (p< 0.0001) and to 268 μm at 12 months (p< 0.0001). Conclusions Intravitreal ranibizumab treatment resulted in improvement in visual acuity, anatomical change, and visual function change in Japanese AMD patients. Significant improvement was seen in patient visual function, and this was correlated with changes in VA, except immediately after loading dose treatment in patients with higher baseline VA. The patients’ satisfaction with the treatment remained unchanged during the study period. Trial registration This study is registered at UMIN Clinical Trials Registry (UMIN000012013). Registered October 10, 2013, as prospective study.

Objective: The purpose of our study was to determine the 4-year visual and anatomic outcomes of intravitreal aflibercept treatment for neovascular age-related macular degeneration (AMD) using a treat-and-extend (TAE) regimen. Methods: We retrospectively reviewed the medical records of 39 patients with neovascular AMD who were treated continuously with intravitreal aflibercept injections using the TAE regimen for at least 4 years. The outcome measures were the best-corrected visual acuity (BCVA) and central macular thickness (CMT) on spectral-domain optical coherence tomography. The BCVAs were measured as decimal values and converted to the corresponding Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores for statistical analysis. The Wilcoxon signed-rank test was used to compare the differences in BCVAs and CMTs. Results: The mean ETDRS letter scores improved significantly from 63.9 at baseline to 70.4, 67.8, 67.2, and 67.3 at 1, 2, 3, and 4 years, respectively. The mean baseline CMT was 380 µm, which decreased significantly to 229, 231, 221, and 210 µm at 1, 2, 3, and 4 years, respectively. The mean numbers of injections were 7.9, 6.0, 5.5, and 5.4 at 1, 2, 3, and 4 years, respectively. The percentages of patients with a treatment interval of 12 weeks or more were 46.2%, 46.2%, 43.6%, and 46.2% at 1, 2, 3, and 4 years, respectively. At year 4, 30.8% of the patients had a treatment interval of 7 weeks or less, whereas 25.6% had 16 weeks or more. Conclusion: Intravitreal aflibercept TAE treatment may be an effective and efficient method for treating patients with neovascular AMD up to 4 years of follow-up. The TAE regimen is a potential tool to optimize appropriate treatment intervals, avoiding both undertreatment and overtreatment of neovascular AMD.

Purpose: Patients with polypoidal choroidal vasculopathy (PCV) may develop large submacular hemorrhages (SMHs), which may result in severe visual loss. This study was performed to determine the visual outcomes and prognostic factors of large SMHs secondary to PCV. Patients and Methods: We retrospectively reviewed the medical records of patients diagnosed with PCV who developed a large SMH. The best-corrected visual acuity (BCVA) data were collected at the SMH development, 1 month, 1 year after the SMH development, and at the final visit. Patients' medical information also were collected and included age, gender, systemic hypertension, current regular use of an anticoagulant or antiplatelet medication, the initial area of the SMH, breakthrough vitreous hemorrhage, ocular treatment, and fellow eye status. Univariate and multiple regression analyses were performed to determine the prognostic factors for the BCVA 1 year after the development of large SMHs. Results: Thirty eyes of 29 patients were included in this study. The mean area of the SMHs at the development was 17.0 disc areas. The mean follow-up period after the development of SMHs was 53.5 months. The mean BCVA at the development, 1 month, and 1 year after the development, and at the final visit were 20/151, 20/263, 20/138, and 20/152, respectively. Multiple regression analyses indicated that a SMH 20 disc areas or larger was a significant negative factor, and the BCVA 1 month after the development was a significant positive factor affecting the BCVA 1 year after the development of large SMHs. Conclusion:The increase in the initial area of SMH was correlated inversely with the BCVA 1 year after the development of SMH. The BCVA 1 month after the development may predict the BCVA 1 year after the development of a large SMH.

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Nudix hydrolases typically catalyze the hydrolysis of nucleoside diphosphate linked to moiety X and yield nucleoside monophosphate and X-phosphate, while some of them hydrolyze a terminal diphosphate group of non-nucleosidic compounds and convert it into a phosphate group. Although the number of Nudix hydrolases is usually limited in archaea comparing with those in bacteria and eukaryotes, the physiological functions of most archaeal Nudix hydrolases remain unknown. In this study, a Nudix hydrolase family protein, MM_2582, from the methanogenic archaeon Methanosarcina mazei was recombinantly expressed in Escherichia coli, purified, and characterized. This recombinant protein shows higher hydrolase activity toward isopentenyl diphosphate and short-chain prenyl diphosphates than that toward nucleosidic compounds. Kinetic studies demonstrated that the archaeal enzyme prefers isopentenyl diphosphate and dimethylallyl diphosphate, which suggests its role in the biosynthesis of prenylated flavin mononucleotide, a recently discovered coenzyme that is required, for example, in the archaea-specific modified mevalonate pathway.