Exploring the genetic diversity of the Japanese population: Insights from a large-scale whole genome sequencing analysis.

The Japanese archipelago is a terminal location for human migration, and the contemporary Japanese people represent a unique population whose genomic diversity has been shaped by multiple migrations from Eurasia. We analyzed the genomic characteristics that define the genetic makeup of the modern Japanese population from a population genetics perspective from the genomic data of 9,287 samples obtained by high-coverage whole-genome sequencing (WGS) by the National Center Biobank Network. The dataset comprised populations from the Ryukyu Islands and other parts of the Japanese archipelago (Hondo). The Hondo population underwent two episodes of population decline during the Jomon period, corresponding to the Late Neolithic, and the Edo period, corresponding to the Early Modern era, while the Ryukyu population experienced a population decline during the shell midden period of the Late Neolithic in this region. Haplotype analysis suggested increased allele frequencies for genes related to alcohol and fatty acid metabolism, which were reported as loci that had experienced positive natural selection. Two genes related to alcohol metabolism were found to be 12,500 years out of phase with the time when they began to increase in the allele frequency; this finding indicates that the genomic diversity of Japanese people has been shaped by events closely related to agriculture and food production.

Perioperative and Postoperative Continuous Nutritional Counseling Improves Quality of Life of Gastric Cancer Patient Undergoing Gastrectomy.

Post-gastrectomy syndrome (PGS) and body weight loss (BWL) decrease quality of life (QOL) and survival of the patient undergoing gastrectomy. We have introduced perioperative and post-discharge continuous nutritional counseling (CNC) to prevent BWL and improve QOL after gastrectomy. In the present study, we evaluated the effect of CNC on QOL using the Post-gastrectomy Syndrome Assessment Scale-45 (PGSAS-45). Eighty-three patients with gastric cancer (GC) who underwent curative gastrectomy between March 2018 and July 2019 were retrospectively analyzed. Patients received either pre-discharge nutritional counseling alone (control group, n = 45) or CNC (CNC group, n = 38) after gastrectomy. QOL at 12 months after gastrectomy was compared between the two groups. In QOL assessment, change in body weight (-7.98% vs. -12.77%, p = 0.0057), ingested amount of food per meal (7.00 vs. 6.07, p = 0.042) and ability for working (1.89 vs. 2.36, p = 0.049) were significantly better in CNC group than control group. Multiple regression analysis showed that CNC was a significantly beneficial factor for abdominal pain subscale (p = 0.028), diarrhea subscale (p = 0.047), ingested amount of food per meal (p = 0.012), Ability for working (p = 0.031) and dissatisfaction at the meal (p = 0.047). Perioperative and postoperative CNC could improve QOL in the patient undergoing gastrectomy in addition to preventing postoperative BWL.

MACULAR CHORIORETINAL ATROPHY AND VISUAL OUTCOMES IN RANIBIZUMAB- OR AFLIBERCEPT-TREATED MYOPIC CHOROIDAL NEOVASCULARIZATION.

PURPOSE: To investigate the predictors of macular chorioretinal atrophy, consisting of patchy atrophy (PA) at the macula and choroidal neovascularization (CNV)-related macular atrophy (CNV-MA), during treatment with ranibizumab or aflibercept for myopic CNV (mCNV) and its impact on visual outcomes. METHODS: This retrospective study included 82 eyes with treatment-naïve mCNV who were treated with pro re nata injections of ranibizumab or aflibercept. RESULTS: Nine eyes (11.0%) presented with macular PA at baseline (PA group), and 73 eyes (89.0%) did not (non-PA group). VA improved during the first year in the non-PA group; a similar trend was noted in the PA group until 3 months after initial treatment. This improvement was maintained until 24 months ( P < 0.001) in the non-PA group, but not in the PA group. In the PA group, macular chorioretinal atrophy progressed faster ( P < 0.0001), and CNV-MA was more frequent during the 2 years of treatments ( P = 0.04). Even non-PA group eyes sometimes developed CNV-MA (42% at Month 24) if they had a larger CNV and thinner subfoveal choroidal thickness at baseline, resulting in poorer visual prognosis ( P < 0.01). CONCLUSION: Macular PA at baseline was a risk factor for CNV-MA development and was associated with poor visual outcomes.

Effect of Patient-Participation Continuous Nutritional Counseling in Gastric Cancer Patients who Underwent Gastrectomy.

BACKGROUND: Body weight loss (BWL) and skeletal muscle loss (SML) are inevitable after gastrectomy for gastric cancer (GC) and can decrease patients' quality of life (QOL) and survival. OBJECTIVE: The aim of this retrospective study was to evaluate the effect of perioperative and post-discharge patient participation in continuous nutritional counseling (CNC) on post-gastrectomy BWL and SML. METHODS: Ninety-three patients with GC who underwent curative gastrectomy between March 2018 and July 2019 were analyzed. Patients received either pre-discharge nutritional counseling alone (control group, n = 49) or patient-participation CNC (CNC group, n = 44) after gastrectomy. Differences between percentage BWL (%BWL), percentage SML (%SML), and nutrition-related blood parameters between the preoperative values and those at 12 months after surgery were compared between the groups. RESULTS: Compared with the control group, %BWL was significantly lower in the CNC group at 1 month (-6.2 ± 2.5% vs. -7.9 ± 3.3%, p = 0.005), 6 months (-7.8 ± 6.6% vs. -12.3 ± 6.4%, p = 0.001) and 12 months (-7.9 ± 7.6% vs. -13.2 ± 8.2%, p = 0.002), and %SML was significantly lower in the CNC group at 12 months (-5.3 ± 10.3% vs. -12.8 ± 12%, p = 0.002). Regarding nutrition-related blood parameters, change in total cholesterol was significantly lower in the CNC group than the control group at 12 months after surgery (p = 0.02). Multivariate analysis identified no CNC as an independent risk factor for severe BWL (p = 0.001) and SML (p = 0.006) at 12 months after surgery. CONCLUSIONS: Following gastrectomy, patient-participation CNC prevented postoperative BWL and SML after surgery. These results support the induction of such a CNC program in these patients.

Novel Manifestation of Retinal Hemangioblastomas Detected by OCT Angiography in von Hippel-Lindau Disease.

PURPOSE: To elucidate the clinical characteristics of atypical retinal vascular proliferation in patients with von Hippel-Lindau (VHL) disease using OCT angiography (OCTA). DESIGN: Prospective, observational study. PARTICIPANTS: Fifty-seven consecutive patients with a diagnosis of VHL disease who visited Kyoto University Hospital between January 2019 and March 2022. METHODS: Retinal hemangioblastomas (RHs) were assessed using multimodal imaging including OCTA. Retinal hemangioblastomas were classified into 2 phenotypes: nodular and flat. Nodular RHs were defined as typical RHs that were globular, well-circumscribed tumors, often accompanied with dilated feeder arterioles and draining venules. Flat RHs lacked a protruded red or colored mass, had variable and indistinct borders, and were not accompanied with feeder and draining vessels. MAIN OUTCOME MEASURES: The prevalence, distribution, and description of atypical flat RHs. RESULTS: Among 57 consecutive patients with VHL disease, 37 patients (64.9%) showed RHs in at least 1 eye. Bilateral RHs were seen in 23 patients (62.2%). Among 58 eyes of 37 patients with RHs, typical nodular RHs were detected in 54 eyes. Nodular RHs were seen mainly in the peripheral retina and occasionally in the peripapillary region, and they showed exudative changes in some cases. Flat RHs were detected in 7 eyes (12.1%). Four eyes showed only flat RHs, and 3 eyes showed both types in the same eye. Most flat RHs appeared as retinal hemorrhages or faint flat abnormal retinal vessels in the inner retina on the fundus examination, often within the macula area or peripapillary. In all eyes with flat RHs, OCTA showed abundant blood flow in the lesions. OCT revealed that flat RHs were seen mainly between the retinal nerve fiber layer and the ganglion cell layer, and occasionally within the inner nuclear layer. During a mean follow-up period of 20.4 ± 15.0 months, no flat RHs accompanied exudative change, tractional retinal detachment, or progression in size. CONCLUSIONS: Patients with VHL disease can demonstrate 2 distinct types of RHs: the classic nodular type and an atypical flat type. OCT angiography can be useful in improving the detection of atypical flat RHs, which can be difficult to detect clinically. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Seven-year outcome after 1-year fixed regimen of intravitreal aflibercept injections followed by pro re nata treatment for neovascular age-related macular degeneration.

PURPOSE: The study aims to investigate the 7-year best-corrected visual acuity (BCVA) course after 1-year fixed regimen of intravitreal aflibercept injection (IVA) for neovascular age-related macular degeneration (nAMD) and to identify factors affecting this BCVA. METHODS: This longitudinal, observational study included 63 treatment-naïve eyes (61 patients) with nAMD, treated with 1-year fixed regimen of IVA-3 monthly injections and 4 subsequent bimonthly injections-essentially followed by PRN regimen of IVA but sometimes followed by agent switching, photodynamic therapy (PDT), or vitrectomy, as needed. We assessed BCVA changes over a 7-year period. Morphologically, we assessed central retinal thickness (CRT), central choroidal thickness (CCT), subfoveal pigment epithelial detachment (PED) height, vitreomacular traction/adhesion (VMT/VMA), epiretinal membrane (ERM), and macular atrophy involving the fovea. RESULTS: Logarithm of the minimum angle of resolution (logMAR) BCVA changed from 0.20 ± 0.24 to 0.29 ± 0.45 over 7 years. BCVA improved significantly after years 1 and 2 (P = 0.002 and 0.001, respectively) and then slowly decreased. BCVA after years 3-7 did not significantly differ from baseline. CRT and CCT decreased significantly during follow-up, while PED height did not. VMT/VMA decreased significantly, whereas ERM and macular atrophy increased significantly. Seven-year and baseline BCVA positively correlated (P = 0.007, ß = 0.35). CONCLUSIONS: BCVA was maintained for 7 years in nAMD eyes after 1-year fixed regimen of IVA, essentially followed by PRN regimen, but sometimes followed by agent switching, PDT, or vitrectomy, without severe drug-induced complications. Thus, early diagnosis and treatment of nAMD are essential for maintaining good long-term BCVA, even in eyes with relatively poor baseline vision.

PREDICTORS OF 3-MONTH AND 1-YEAR VISUAL OUTCOMES AFTER VITRECTOMY WITH SUBRETINAL TISSUE PLASMINOGEN ACTIVATOR INJECTION FOR SUBMACULAR HEMORRHAGE.

PURPOSE: To investigate factors associated with 3-month or 1-year best-corrected visual acuity (BCVA) after vitrectomy with subretinal tissue plasminogen activator injection for submacular hemorrhage (SMH) and to identify the predictors of early displacement. METHODS: This prospective cohort study included consecutive eyes with SMH complicating neovascular age-related macular degeneration or retinal macroaneurysm that underwent vitrectomy with subretinal tissue plasminogen activator injection and were followed up for at least 3 months. Parameters that correlated with 3-month BCVA, 1-year BCVA, and 2-week displacement grade (0-3) were identified. RESULTS: Twenty-nine eyes of 29 patients (73.1 ± 8.4 years; neovascular age-related macular degeneration, 25 eyes) were included. Logarithm of the minimum angle of resolution BCVA improved 3 months after the surgery (baseline, 0.76 [20/115] ± 0.35; 3-month, 0.51 [20/65] ± 0.32; P = 0.006). In multivariable analyses, 1-year logarithm of the minimum angle of resolution BCVA correlated with age ( P = 0.007, ß = 0.39) and SMH recurrence within 1 year after surgery ( P < 0.001, ß = 0.65). Two-week displacement grade correlated with the contrast-to-noise ratio of SMH ( P = 0.001, ß = -0.54). Macular hole occurred in three eyes (10%) with small SMH size and was closed in all eyes via additional vitrectomy with an inverted internal limiting membrane flap technique. CONCLUSION: The recurrence of SMH negatively affected the 1-year visual outcome after vitrectomy with subretinal tissue plasminogen activator injection for SMH. The contrast-to-noise ratio was a useful predictor of early SMH displacement, but not of 1-year BCVA. Further research is necessary to determine the optimal treatment to prevent SMH recurrence.

TEN-YEAR VISUAL OUTCOME AND CHANGE IN CHORIORETINAL ATROPHY AFTER INTRAVITREAL RANIBIZUMAB FOR MACULAR NEOVASCULARIZATION IN PATHOLOGIC MYOPIA.

PURPOSE: To investigate the 10-year visual outcome and chorioretinal atrophy after a single intravitreal ranibizumab injection followed by a pro re nata regimen for myopic macular neovascularization in pathologic myopia, and to identify the factors associated with 10-year best-corrected visual acuity (BCVA). METHODS: This retrospective observational study evaluated 26 consecutive treatment-naïve eyes (26 patients) with myopic macular neovascularization in pathologic myopia who underwent a single intravitreal ranibizumab followed by a pro re nata regimen of intravitreal ranibizumab and/or intravitreal aflibercept injection and observed over 10 years. We assessed changes in BCVA and morphological parameters, including the META-PM Study category as a chorioretinal atrophy index. RESULTS: The logarithm of the minimum angle of resolution BCVA changed from 0.36 (Snellen, 20/45) ± 0.39 to 0.39 (20/49) ± 0.36 over 10 years of observation. Compared to baseline, 1-year BCVA improved ( P = 0.002), whereas 2 to 10-year BCVA was not significantly different. Total injection frequency was 3.8 ± 2.6. In none of the eyes, 10-year BCVA was 20/200 or less. Ten-year BCVA correlated with baseline BCVA ( P = 0.01, r = 0.47). The META-PM Study category progressed in 60% of eyes. There were no drug-induced complications. CONCLUSION: Best-corrected visual acuity in eyes with myopic macular neovascularization in pathologic myopia was maintained for 10 years after a single intravitreal ranibizumab followed by a pro re nata regimen without drug-induced complications. The META-PM Study category progressed in 60% of eyes, especially those with older baseline age. Early diagnosis and treatment of myopic macular neovascularization are essential to maintain good long-term BCVA.

Genome-wide Survival Analysis for Macular Neovascularization Development in Central Serous Chorioretinopathy Revealed Shared Genetic Susceptibility with Polypoidal Choroidal Vasculopathy.

PURPOSE: To identify susceptibility genes for macular neovascularization (MNV) development in central serous chorioretinopathy (CSC). DESIGN: Genome-wide survival analysis using a longitudinal cohort study. PARTICIPANTS: We included 402 and 137 patients with CSC but without MNV at their first visit from the Kyoto CSC Cohort and Kobe CSC dataset, respectively. All patients underwent detailed ophthalmic examinations, including multimodal imaging, such as fundus autofluorescence, spectral-domain OCT, and fluorescein angiography/indocyanine green angiography or OCT angiography. METHODS: We conducted a genome-wide survival analysis using the Kyoto CSC Cohort. We applied the Cox proportional hazard model to adjust for age, sex, and the first principal component. Single nucleotide polymorphisms (SNPs) with P values < 1.0 × 10-5 were carried forward to the replication in the Kobe CSC dataset. Moreover, we evaluated the contribution of previously reported age-related macular degeneration (AMD) susceptibility loci. We used FUMA and ToppFun for the functional enrichment analysis. MAIN OUTCOME MEASURES: The association between SNPs and MNV development in patients with CSC. RESULTS: Rs370974631 near ARMS2 displayed a genome-wide significant association in the meta-analysis of discovery and replication result (hazard ratio [HR]meta, 3.63; Pmeta = 5.76 × 10-9). Among previously reported AMD susceptibility loci, we additionally identified CFH rs800292 (HR, 0.39, P = 2.55 × 10-4), COL4A3 rs4276018 (HR, 0.26, P = 1.56 × 10-3), and B3GALTL rs9564692 (HR, 0.56, P = 8.30 × 10-3) as susceptibility loci for MNV development in CSC. The functional enrichment analysis revealed significant enrichment of 8 pathways (GO:0051561, GO:0036444, GO:0008282, GO:1990246, GO:0015272, GO:0030955, GO:0031420, and GO:0005242) related to ion transport. CONCLUSIONS: ARMS2, CFH, COL4A3, and B3GALTL were identified as susceptibility genes for MNV development in CSC. These 4 genes are known as susceptibility genes for AMD, whereas COL4A3 and B3GALTL were previously reported to be polypoidal choroidal vasculopathy (PCV)-specific susceptibility genes. Our findings revealed the shared genetic susceptibility between PCV and MNV secondary to CSC.

PREDICTORS OF RETINAL PIGMENT EPITHELIUM TEAR DEVELOPMENT AFTER TREATMENT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION USING SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: The purpose of this study was to investigate the predictors of retinal pigment epithelium (RPE) tear development after treatment for neovascular age-related macular degeneration using swept source optical coherence tomography angiography. METHODS: This prospective study included 152 treatment-naïve eyes with neovascular age-related macular degeneration without high myopia that were followed up for 1 year after treatment. Eligible eyes were classified into eyes with or without RPE tear development. They were matched in a 1:2 ratio. The areas of choroidal neovascularization (CNV) and RPE detachment (pigment epithelial detachment [PED]) were measured from optical coherence tomography angiography and OCT en face images, respectively. The optical coherence tomography angiography-specific parameters representing CNV status were analyzed. RESULTS: Eight (5.3%) of the 152 eyes developed RPE tears (RPE tear group). After matching, 16 eyes without RPE tears were analyzed (non-RPE tear group). The ratio of the CNV/PED area was lower in the RPE tear group than that in the non-RPE tear group (P = 0.007). The PED area was broader (P = 0.008), and PED height was greater in the RPE tear group (P = 0.04). Optical coherence tomography angiography-specific parameters did not differ between the two groups. CONCLUSION: Neovascular age-related macular degeneration with pretreatment broad PED, high PED, and small CNV area relative to the PED area has a high risk of RPE tear development after therapy. However, CNV status may not have an association.

CONTRAST-TO-NOISE RATIO IS A USEFUL PREDICTOR OF EARLY DISPLACEMENT OF LARGE SUBMACULAR HEMORRHAGE BY INTRAVITREAL SF6 GAS INJECTION.

PURPOSE: To investigate predictors of early displacement of submacular hemorrhage (SMH) by simple intravitreal SF6 gas injection. METHODS: This retrospective study included 16 eyes of 16 consecutive patients (age: 74.5 ± 7.7 years; 15 men) with large SMH treated with simple intravitreal SF6 gas before inception of subretinal tissue plasminogen activator injection at our institution. The SMH displacement was graded at 1-week posttreatment as 0, 1, or 2. Central retinal thickness, central choroidal thickness, SMH height, SMH area, disease duration, use of anticoagulant or antiplatelet drugs, and contrast-to-noise ratio (CNR) of SMH on optical coherence tomography images were recorded. Correlations between displacement grading and baseline parameter were analyzed. RESULTS: Univariable correlation analysis revealed association of the 1-week displacement grading with the CNR (P = 0.004; r = -0.68) and SMH height (P = 0.03; r = -0.55). The CNR was most strongly associated with 1-week displacement on multivariable correlation analysis (P = 0.01; ß = -0.60). CONCLUSION: Findings of the present study showed that the CNR of SMH was a useful predictor of early displacement of large SMH after simple intravitreal SF6 gas injection. When vitrectomy with subretinal injection of tissue plasminogen activator is difficult in patients with large SMH, with low CNR on optical coherence tomography, simple intravitreal SF6 gas injection may be a treatment option.

Myopia Prevalence and Ocular Biometry Features in a General Japanese Population: The Nagahama Study.

PURPOSE: To describe the distribution of ocular biometry and refraction in Japanese adults. DESIGN: Cross-sectional analysis of a prospective cohort study. PARTICIPANTS: A total of 9850 individuals participated in the first follow-up of the Nagahama Prospective Cohort for Comprehensive Human Bioscience (the Nagahama Study) conducted between 2013 and 2016. Participants were between 34 and 80 years of age. METHODS: All participants underwent axial length (AL; in millimeters), anterior chamber depth (ACD; in millimeters), corneal diameter (white to white; in millimeters), and central corneal thickness (CCT; in micrometers) measurement (IOL Master; Carl Zeiss Meditec, Dublin, CA) and refraction (spherical equivalent [SE]; in diopters [D]) and corneal curvature (CC; in millimeters) measurement (ARK-530A; Nidek, Aichi, Japan). Distribution of these ocular biometric parameters and prevalence of myopia, high myopia, and extreme myopia were summarized. MAIN OUTCOME MEASURES: Distribution of ocular biometry and refraction. RESULTS: After standardization to the national population of 2015, estimates of mean AL and SE were 24.21 mm and -1.44 D, respectively. Estimates of mean CC, corneal diameter, CCT, and ACD were 7.69 mm, 12.01 mm, 543.96 µm, and 3.21 mm, respectively. After standardization of age and gender, the prevalence of myopia (SE, ≤-0.5 D) and high myopia (SE, ≤-6.0 D) were 49.97% and 7.89%, respectively. Approximately 70% of the younger participants (34-59 years of age) showed myopia, whereas high myopia was observed in approximately 10%. Although the number of individuals with myopia or high myopia was higher in the younger age groups, the prevalence of more extreme phenotypes remained stable across all ages, especially in women. Axial length of more than 30 mm was observed only in older women (n = 5 [0.05%]). CONCLUSIONS: We showed detailed distributions of various ocular biometry and refraction parameters using a large general Japanese cohort. Prevalences of myopia and high myopia from 2013 through 2016 were higher than those in earlier studies, which reflects recent environmental change. However, constant prevalence of extreme myopia across all ages suggests high genetic predisposition of the extreme phenotype.

MACULAR ATROPHY AND MACULAR MORPHOLOGY IN AFLIBERCEPT-TREATED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To investigate the incidence and predictors of macular atrophy during treatment with aflibercept for neovascular age-related macular degeneration in Japanese patients. METHODS: This study included patients with treatment-naive subfoveal neovascular age-related macular degeneration treated from December 2012 through January 2015. Patients were treated with bi-monthly aflibercept injections after 3 monthly loading injections for the first year. Diagnosis of retinal pigment epithelial atrophy was made based on color fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence. Baseline characteristics and morphological features were analyzed for their association with the development of macular atrophy. RESULTS: This study included 123 eyes that had no baseline macular atrophy and treated with aflibercept injections for 12 months. Thirteen eyes (10.6%) developed new macular atrophy at 12 months. Logistic regression analysis showed that the presence of intraretinal fluid and thinner subfoveal choroidal thickness at baseline were associated with the development of macular atrophy after aflibercept treatment. CONCLUSION: Macular atrophy developed in about 10% of eyes with neovascular age-related macular degeneration during 12 months of treatment with a fixed regimen of aflibercept. Intraretinal fluid and subfoveal choroidal thickness seem to be predictors for development of macular atrophy after anti-vascular endothelial growth factor (VEGF) therapy.

RECURRENCE OF CHOROIDAL NEOVASCULARIZATION LESION ACTIVITY AFTER AFLIBERCEPT TREATMENT FOR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To examine the recurrence rate of choroidal neovascularization (CNV) lesion activity in age-related macular degeneration (AMD) and associated factors after 1-year aflibercept treatment. METHODS: Age-related macular degeneration eyes with 1-year aflibercept fixed-regimen treatment and a follow-up period of at least 18 months from the initial aflibercept injection for treatment-naive exudative AMD were retrospectively evaluated. The recurrence rate was examined. Age, gender, visual acuity, AMD subtype, greatest linear dimension, and retinal and choroidal thicknesses at the 12th month examination were compared between eyes with and without recurrence. Presence of remnant polyps and pigment epithelial detachment (PED) morphology were also compared in polypoidal choroidal vasculopathy (PCV) eyes. RESULTS: Of the 98 eyes studied, 69 displayed a dry macula at the 12th month examination; 43.7% exhibited recurrence during the subsequent 12-month period in Kaplan-Meier analysis. Although no factors associated with recurrence were detected in AMD, remnant polyps and pigment epithelial detachment morphology at the 12th month examination were significantly associated with recurrence in polypoidal choroidal vasculopathy (P = 0.018 and 0.048, respectively). CONCLUSION: Continuous, proactive treatment would be considered overtreatment for more than half of the AMD eyes that achieved a dry macula. Angiography and optical coherence tomography analyses may be useful for predicting recurrence in polypoidal choroidal vasculopathy eyes.

RETINAL PIGMENT EPITHELIAL ATROPHY AFTER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTIONS FOR RETINAL ANGIOMATOUS PROLIFERATION.

PURPOSE: To investigate the incidence rate and risk factors for development of retinal pigment epithelial (RPE) atrophy during anti-vascular endothelial growth factor (anti-VEGF) treatment for retinal angiomatous proliferation. METHODS: This study included 46 eyes with treatment-naive retinal angiomatous proliferation. All patients were treated with ranibizumab or aflibercept injections. Color fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence were evaluated for RPE atrophy diagnosis. Baseline characteristics and gene polymorphisms of ARMS2 A69S, and CFH I62V were analyzed for association with development and progression of RPE atrophy. RESULTS: Among 21 eyes treated with ranibizumab without preexisting RPE atrophy at baseline, 5 eyes (23.8%) developed RPE atrophy at 12 months. Among 20 eyes treated with aflibercept without preexisting RPE atrophy at baseline, 10 eyes (50.0%) developed RPE atrophy at 12 months. Refractile drusen at baseline was associated with RPE atrophy development at 12 months (P = 0.014), and the progression rate of RPE atrophy area was negatively correlated with subfoveal choroidal thickness at baseline (R = -0.595, P = 0.019). Gene polymorphisms were not associated with RPE atrophy. CONCLUSION: Retinal pigment epithelial atrophy developed in 36.6% during 12 months after anti-VEGF treatment for retinal angiomatous proliferation. The presence of refractile drusen at baseline was identified as a novel significant risk factor for RPE atrophy development.

ASSOCIATIONS BETWEEN MACULAR EDEMA AND CIRCULATORY STATUS IN EYES WITH RETINAL VEIN OCCLUSION: An Adaptive Optics Scanning Laser Ophthalmoscopy Study.

PURPOSE: To investigate associations between parafoveal microcirculatory status and foveal pathomorphology in eyes with macular edema (ME) secondary to retinal vein occlusion (RVO). METHODS: Ten consecutive patients (10 eyes) with acute retinal vein occlusion were enrolled, 9 eyes of which received intravitreal ranibizumab (IVR) injections. Foveal morphologic changes were examined via optical coherence tomography (OCT), and parafoveal circulatory status was assessed via adaptive optics scanning laser ophthalmoscopy (AO-SLO). RESULTS: The mean parafoveal aggregated erythrocyte velocity (AEV) measured by adaptive optics scanning laser ophthalmoscopy in eyes with retinal vein occlusion was 0.99 ± 0.43 mm/second at baseline, which was significantly lower than that of age-matched healthy subjects (1.41 ± 0.28 mm/second, P = 0.042). The longitudinal adaptive optics scanning laser ophthalmoscopy examinations of each patient showed that parafoveal AEV was strongly inversely correlated with optical coherence tomography-measured central foveal thickness (CFT) over the entire observation period. Using parafoveal AEV and central foveal thickness measurements obtained at the first and second examinations, we investigated associations between differences in parafoveal AEV and central foveal thickness, which were significantly and highly correlated (r = -0.84, P = 0.002). CONCLUSION: Using adaptive optics scanning laser ophthalmoscopy in eyes with retinal vein occlusion macular edema, we could quantitatively evaluate the parafoveal AEV. A reduction or an increase in parafoveal AEV may be a clinical marker for the resolution or development/progression of macular edema respectively.

ASSOCIATION BETWEEN RETINAL HEMORRHAGIC PATTERNS AND PERFUSION STATUS IN EYES WITH ACUTE CENTRAL RETINAL VEIN OCCLUSION.

PURPOSE: To evaluate peripheral retinal hemorrhagic patterns in eyes with acute central retinal vein occlusion, and to explore their clinical relevance in differentiating for the retinal perfusion status, through a prospective, and cross-sectional study. METHODS: Fifty eyes with acute central retinal vein occlusion were included. Retinal hemorrhagic patterns at the equator and retinal perfusion status were evaluated by ultra-wide field fundus photography and fluorescein angiography. RESULTS: Retinal perfusion was categorized as nonischemic in 29 eyes, ischemic in 18 eyes, and undeterminable in 3 eyes. None of the examined eyes had flame-shaped retinal hemorrhages in the periphery. All hemorrhages were rounded-dot or blot and were variable in size. Particle analysis was performed to quantify hemorrhage size, and showed higher values in eyes having larger blot hemorrhages, and lower values in eyes having dot or smaller blot hemorrhages. Mean size of maximum peripheral dot or blot hemorrhage was larger in eyes classified as ischemic (10,763.0 ± 5,946.3 pixels) than as nonischemic (2,839.9 ± 1,153.6 pixels, P < 0.001). The authors calculated area under the curve to investigate the ability of continuous variables to discriminate retinal perfusion status, which was 0.963 (P < 0.001) for mean size of maximum peripheral blot hemorrhages. CONCLUSION: The authors objectively evaluated retinal hemorrhagic patterns at the equator in eyes with acute central retinal vein occlusion using particle analysis. The resulting hemorrhage size measurement was considered to be often useful in determining retinal perfusion status. Because they can be noninvasively evaluated with readily available equipment, peripheral hemorrhagic patterns might be good clinical markers of retinal perfusion.

INCIDENCE AND CAUSES OF VISION LOSS DURING AFLIBERCEPT TREATMENT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: One-Year Follow-up.

PURPOSE: To investigate the incidence rate, risk factors, and final outcomes of patients with age-related macular degeneration (AMD) who have experienced vision loss despite periodic aflibercept treatment. METHODS: Subjects with treatment-naive AMD were prospectively recruited and treated with three monthly injections followed by two monthly injections of aflibercept. The incidence rate and risk factors of more than two lines of vision loss at any visit were investigated. RESULTS: We included 196 eyes of 196 patients. Vision loss was observed in 16 patients (8.2%). Eleven of 16 patients developed vision loss during the initial 3 months (68.8%). Vision loss remained in 11 eyes (68.8%) at the final visit. The maximum pigment epithelium detachment (PED) height (odds ratio = 1.46 for a 100-µm increase in the PED height) and disruption of the external limiting membrane (odds ratio = 4.45) were identified as risk factors for developing vision loss on logistic regression analysis. CONCLUSION: The incidence rate of vision loss during aflibercept treatment was relatively low. Identifying high-risk patients, those with a high PED height and disruption of the external limiting membrane, would be helpful in ensuring appropriate informed consent before treatment. Further studies are needed to establish optimal treatment for these patients.

RANIBIZUMAB FOR MACULAR EDEMA AFTER BRANCH RETINAL VEIN OCCLUSION: One Initial Injection Versus Three Monthly Injections.

PURPOSE: To compare the 12-month-efficacy of 1 initial intravitreal ranibizumab injection (IVR) followed by pro re nata (PRN) dosing with that of three initial monthly IVR followed by PRN dosing in patients with macular edema (ME) after branch retinal vein occlusion. DESIGN: Prospective, interventional study. METHODS: Of 81 eyes, 42 received 1 initial IVR injection (1+PRN group) and 39 eyes received 3 monthly IVRs (3+PRN). Pro re nata injections were performed when fovea exudative changes were evident. RESULTS: At Month 12, the visual acuity (VA) changes from baseline were -0.245 ± 0.227 and -0.287 ± 0.222, in the 1+PRN and 3+PRN groups, respectively; there were no significant difference between groups (P = 0.728). The stratified analysis showed that patients with better VA (baseline VA >20/40) had similar significant improvement in VA at Month 12 (P < 0.001) to that of those with poorer VA (≤20/40). Better VA at Month 12 was significantly associated with younger age, better baseline VA, and thinner baseline central foveal thickness (P = 0.003, < 0.001, and < 0.001, respectively). Mean total number of IVR injections in the 1+PRN and 3+PRN groups were 3.8 ± 1.8 and 4.6 ± 1.4, respectively (P = 0.060). In both groups, shorter durations to the first PRN injection were associated with greater total PRN injection number (1+PRN, P = 0.006; 3+PRN; group, P < 0.001). CONCLUSION: In IVR treatment for ME after branch retinal vein occlusion, 1+PRN and 3+PRN regimens achieved similar 12-month functional outcomes. Patients with shorter durations to initial PRN injection may require more PRN treatments.