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.

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.

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.

Pachychoroid-phenotype effects on 5-year visual outcomes of anti-VEGF monotherapy in polypoidal choroidal vasculopathy.

PURPOSE: To investigate whether the efficacy of anti-vascular endothelial growth factor (VEGF) monotherapy for polypoidal choroidal vasculopathy (PCV) differs between pachychoroid and non-pachychoroid phenotypes in the long term. METHODS: This retrospective longitudinal study included 115 treatment-naïve eyes in 115 consecutive patients with symptomatic PCV who were treated with anti-VEGF monotherapy and were followed up for 5 years. Eligible eyes were assigned to either a pachy-PCV group, with a pachychoroid phenotype, or a non-pachy-PCV group, without a pachychoroid phenotype. Best-corrected visual acuity (BCVA) and other parameters over a 5-year period were compared between the groups. RESULTS: Forty-eight eyes and 67 eyes were classified into the pachy-PCV and non-pachy-PCV groups respectively. Baseline and 5-year BCVA (logarithm of the minimum angle of resolution) were 0.19 ± 0.20 and 0.16 ± 0.28 in the pachy-PCV group, respectively, and 0.25 ± 0.26 and 0.26 ± 0.36 in the non-pachy-PCV group respectively. BCVA did not change significantly in either group (p = 0.18 and 0.08 respectively). BCVA did not differ between the groups at any observation time-point. Subfoveal choroidal thickness (SFCT) at baseline and at 5 years was significantly higher in the pachy-PCV group than in the non-pachy-PCV group (both p < 0.001); however, the mean rate of decrease in SFCT did not differ in either group over the 5-year period (22% vs. 23%, p = 0.81). CONCLUSION: Our findings suggest that anti-VEGF monotherapy was similarly effective for pachychoroid- and non-pachychoroid-phenotype eyes with PCV, for at least 5 years, although further studies are required.

Long-Term Visual Outcome in Inferior Posterior Staphyloma and Efficacy of Treatment for Complicated Choroidal Neovascularization.

PURPOSE: To investigate long-term visual outcome in inferior posterior staphyloma (IPS) in each group classified based on macular complications and to examine the treatment effect for eyes with IPS with choroidal neovascularization (CNV). DESIGN: Prospective clinical cohort study. PARTICIPANTS: We analyzed 56 eyes of 43 consecutive patients with IPS who were followed for 4 years. METHODS: We classified eligible eyes into 3 groups based on baseline findings: eyes without CNV or retinal exudate (no-exudate group), eyes without CNV and with retinal exudate (exudate group), and eyes with CNV (CNV group). We investigated the best-corrected visual acuity (BCVA) and associated parameters for 4 years. RESULTS: BCVA declined during 4 years only in the exudate group (P = .002), whereas it was maintained for 4 years in the no-exudate and CNV groups (P = .53 and .20, respectively). Baseline BCVA was lower in the CNV group than in the exudate group (P = .004); however, the 4-year BCVA was not (P = .84). The 4-year BCVA was associated with baseline BCVA in all groups. Eyes in the CNV group required 9.0 ± 8.7 anti-vascular endothelial growth factor therapy in 4 years. CONCLUSIONS: Better baseline BCVA in eyes with exudative IPS without CNV spontaneously declined in 4 years, whereas worse baseline BCVA in eyes with IPS with CNV did not, probably because of treatment for retinal exudate from CNV. Anti-vascular endothelial growth factor therapy would be effective for long-term maintenance of BCVA in eyes with IPS with CNV, similar to other diseases with CNV.

Time-Course Change in Eye Shape and Development of Staphyloma in Highly Myopic Eyes.

Purpose: To quantitatively assess the posterior pole shape change in highly myopic eyes and to investigate the factors determining the speed of shape change. Methods: Local curvature of the Bruch's membrane on the optical coherence tomography image was measured at intervals of 1 µm, and the mean curvature and curvature variance were calculated for 1094 eyes with an axial length of ≥26 mm. Speed of shape change was calculated using two points of mean curvature and curvature variance, and compared according to age, sex, axial length, and baseline eye shape. Results: The posterior pole shape of females changed significantly greater than males (P < 0.01). Protruding change through the mean curvature was the greatest in the eyes with an axial length of ≥28 mm and <29 mm, while undulating change through the curvature variance became greater with axial length elongation in the eyes with an axial length of <29 mm and showed similar change in the eyes with an axial length of ≥29 mm. The eyes with a flatter shape at baseline tended to show a slow shape change, whereas those with moderate shape deformation at baseline showed faster shape change. Conclusions: Quantitative evaluation of posterior pole eye shape clearly demonstrated significant time-dependent protruding and undulating changes in highly myopic eyes. Sex, axial length, and baseline posterior pole eye shape significantly affected speed of the posterior pole shape change. Our findings will facilitate risk assessment of staphyloma-associated complications in highly myopic eyes through measurement of speed of the posterior pole shape change.

Prevalence of posterior staphyloma and factors associated with its shape in the Japanese population.

Myopia is increasing rapidly worldwide. We performed a cross-sectional study to investigate the prevalence of posterior staphyloma, a complication of myopia, and its shape characteristics in relation to age, sex, and axial length (AL) in a Japanese community-based cohort. The right eyes of 3748 participants who underwent fundus photography and optical coherence tomography (OCT) examination were evaluated. Posterior staphyloma prevalence was evaluated using fundus photographs and OCT images. Furthermore, fundus shapes were analyzed by measuring local fundus curvatures on 6 mm cross-line OCT images at intervals of 1 µm. The mean and variance of the curvatures were calculated to represent the fundus shape of each eye for investigation of the relationship between fundus curvature and age, sex, and AL. Seventy-seven eyes (2.05%) had posterior staphyloma. The mean and variance of the fundus curvatures were significantly greater in women than in men and became greater with age, suggesting that the shape of the staphyloma was steeper and less smooth in women and elderly subjects. AL and mean curvature showed a significant correlation (P = 2 × 10-16, R = 0.480), which was significantly affected by age (P < 2 × 10-16). Quantitative analysis of fundus shapes was useful for statistical analysis of posterior staphyloma in relation to age, sex, and AL.

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.

Association between SCO2 mutation and extreme myopia in Japanese patients.

PURPOSE: To investigate the role of SCO2 in extreme myopia of Japanese patients. METHODS: In total, 101 Japanese patients with extreme myopia (axial length of ≥30 mm) OU at the Kyoto University Hospital were included in this study. Exon 2 of SCO2 was sequenced by conventional Sanger sequencing. The detected variants were assessed using in silico prediction programs: SIFT, PolyPhen-2 and MutationTaster. To determine the frequency of the mutations in normal subjects, we referred to the 1000 Genomes Project data and the Human Genetic Variation Database (HGVD) in the Human Genetic Variation Browser. RESULTS: The average age of the participants was 62.9 ± 12.7 years. There were 31 males (30.7 %) and 70 females. Axial lengths were 31.76 ± 1.17 mm OD and 31.40 ± 1.07 mm OS, and 176 eyes (87.6 %) out of 201 eyes had myopic maculopathy of grade 2 or more. Among the 101 extremely myopic patients, one mutation (c.290 C > T;p.Ala97Val) in SCO2 was detected. This mutation was not found in the 1000 Genomes Project data or HGVD data. Variant type of the mutation was nonsynonymous. Although the SIFT prediction score was 0.350, the PolyPhen-2 probability was 0.846, thus predicting its pathogenicity to be possibly damaging. MutationTaster PhyloP was 1.268, suggesting that the mutation is conserved. CONCLUSIONS: We identified one novel possibility of an extreme myopia-causing mutation in SCO2. No other disease-causing mutation was found in 101 extremely myopic Japanese patients, suggesting that SCO2 plays a limited role in Japanese extreme myopia. Further investigation is required for better understanding of extreme myopia.

Detection of Myopic Choroidal Neovascularization Using Optical Coherence Tomography Angiography.

PURPOSE: To assess whether optical coherence tomography angiography (OCTA) can be used as an alternative to conventional fundus fluorescein angiography (FFA) for the detection of myopic choroidal neovascularization (CNV). DESIGN: Validity and reliability analysis. METHODS: Twenty-eight eyes of 26 consecutive Japanese patients with exudative lesions associated with pathologic myopia were included in this institutional study. Myopic CNV was detected in 23 eyes of 22 patients; 5 eyes exhibited simple hemorrhage. The main outcome measure was CNV detection by OCTA and FFA. The CNV area was individually measured by FFA and OCTA. Intraclass correlation coefficients (ICCs) for the CNV area, independently measured by 2 investigators using OCTA and FFA, were determined. RESULTS: OCTA images with sufficient quality for CNV assessment were obtained for 17 eyes with CNV and 4 without. FFA alone detected CNV in all 17 eyes, while OCTA alone detected CNV in 16 (94.1%). The 1 eye for which CNV was not detected by OCTA exhibited a 0.01 mm(2) area on FFA. Both FFA and OCTA did not detect CNV in eyes with simple hemorrhage. The mean CNV areas on FFA and OCTA were 0.59 ± 0.56 mm(2) and 0.51 ± 0.55 mm(2), respectively; the 2 values were significantly correlated (P < .001, r = .86). The ICC (2, 1) values for FFA and OCTA were 0.944 and 0.997, respectively. CONCLUSIONS: Our results indicate that OCTA can detect most myopic CNVs if high-quality images are acquired and can preclude the requirement for FFA in these settings.

Photoreceptor outer segment abnormalities and retinal sensitivity in acute zonal occult outer retinopathy.

PURPOSE: To investigate the relationship between retinal function and photoreceptor abnormalities in eyes with acute zonal occult outer retinopathy. METHODS: Five patients with acute zonal occult outer retinopathy underwent complete ophthalmologic examination, including spectral-domain optical coherence tomography. Spectral-domain optical coherence tomography findings were compared with retinal sensitivity measured by microperimetry. RESULTS: Spectral-domain optical coherence tomography images revealed disruptions in the inner segment/outer segment junction line in four of five eyes and disruptions in the outer segment (OS) tip lines in all eyes. Mean retinal sensitivity was 15.1 ± 3.6 dB in the intact OS tip regions and 6.0 ± 6.3 dB in disrupted regions (P < 0.001). In all eyes, disruption of the OS tip lines was also seen in regions of reduced retinal sensitivity, although the inner segment/outer segment was intact. Within the intact inner segment/outer segment regions, mean retinal sensitivity was 7.5 ± 6.7 dB at locations of OS tip disruption and 15.1 ± 3.6 dB at intact OS tip locations (P < 0.001). CONCLUSION: Structural abnormalities in the photoreceptors were correlated with visual function in eyes with acute zonal occult outer retinopathy. Loss of photoreceptor OS, as indicated by disruptions of the OS tip lines on spectral-domain optical coherence tomography, may represent the primary lesion in acute zonal occult outer retinopathy.