Yoshimasa Kuroda

One-Year Result of Aflibercept Treatment on Age-Related Macular Degeneration and Predictive Factors for Visual Outcome

PURPOSE To investigate the efficacy of periodic injection of aflibercept in each subtype of age-related macular degeneration (AMD) and to explore the predictive factors for visual outcome in clinical settings. DESIGN Prospective nonrandomized interventional case series. METHODS Patients with AMD were recruited and were administered aflibercept injections once a month for 3 months followed by once every 2 months for 8 months. The logarithm of the minimal angle of resolution (logMAR) at 12 months and improvement of vision from baseline were compared among polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP), and typical AMD. Regression rate of polypoidal lesions was assessed. We also performed regression analysis with logMAR at 12 months as the dependent variable. RESULTS The study sample consisted of 98 patients: 46 had typical AMD, 42 had PCV, and 10 had RAP. Mean logMAR improved from 0.36 to 0.21 in 12 months. While there was no difference in visual improvement between typical AMD and PCV, final logMAR was better in PCV (0.32 ± 0.09 vs 0.08 ± 0.04, P = .016). Thirty-nine PCV patients underwent follow-up angiography, and regression of polyps was observed in 27 cases (69.2%). Multiple regression analysis showed that the presence of external limiting membrane (ELM), smaller greatest linear dimension, and the presence of polypoidal lesion were associated with better visual outcome (R(2) = 0.53, P = 2.73 × 10(-14)). CONCLUSIONS Periodic injection of aflibercept is effective for PCV as well as for typical AMD. The statuses of ELM, greatest linear dimension, and polypoidal lesion are predictive for visual outcome.

Factors Associated with Recurrence of Age-Related Macular Degeneration after Anti-Vascular Endothelial Growth Factor Treatment: A Retrospective Cohort Study.

PURPOSE To investigate the predictive factors associated with recurrence after anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (AMD). DESIGN Retrospective cohort study. PARTICIPANTS A total of 343 eyes of 326 patients with subfoveal neovascular AMD who were treated with an as-needed regimen after 3 monthly loading doses of intravitreal ranibizumab. METHODS Patients were followed up by an as-needed regimen for more than 1 year after the first injection. Baseline data and CFH I62V and ARMS2 A69S polymorphisms were analyzed for their association with recurrence after anti-VEGF treatment. Regression analysis was used to identify independent predictors of visual acuity (VA) prognosis. MAIN OUTCOME MEASURES The primary end point was the presence or absence of recurrence. The secondary end point was VA improvement. RESULTS In total, 236 eyes (68.8%) showed complete resolution of retinal exudative change after the 3 loading injections, and 81 eyes (34.3%) experienced no recurrence during the first year. Of the 236 eyes, 139 (58.9%) were followed for more than 2 years and 35 (25.2%) showed no recurrent retinal exudation during 24 months. Visual acuity improvement was significantly better in eyes without recurrence than in eyes with recurrence during the 2-year period. Baseline characteristics and genotypes had no influence on response to ranibizumab loading treatment. Stepwise analysis revealed that age (P<0.001), subtype of AMD (P=0.041), and VA at baseline (P<0.001) were associated with VA at 24 months. Older patients (P=0.006) and male patients (P=0.018) tended to require re-treatment for recurrence during the first year, yet the statistical significance disappeared when evaluated in 2 years. The subtypes of neovascular AMD were solely associated with the interval to the recurrence, which was shorter in eyes with polypoidal choroidal vasculopathy (PCV) than in eyes with typical AMD (P=0.015). CONCLUSIONS Older age and male sex may predict recurrence after 3 monthly ranibizumab injections, and PCV may be associated with shorter interval to recurrence. Predicting the risk of recurrence would help us to choose the most appropriate follow-up treatment strategy for patients with AMD.

Association of focal choroidal excavation with age-related macular degeneration.

PURPOSE To study the prevalence, tomographic features, and clinical characteristics of focal choroidal excavation (FCE) in eyes with exudative age-related macular degeneration (AMD). METHODS We examined 243 consecutive eyes with exudative AMD with a prototype swept-source optical coherence tomography (OCT) system. Three-dimensional images of the macular area, covering 6 × 6 mm(2), were reconstructed by segmentation of the outer surface of the retinal pigment epithelium. RESULTS Three-dimensional swept-source OCT revealed 15 excavations in 12 eyes (4.9%); 10 had a single excavation and 2 had multiple excavations (2 and 3 excavations, respectively). In multiaveraged scans, unusual choroidal tissue was found beneath 5 excavations, bridging the excavation with the outer choroidal boundary. Additionally, the suprachoroidal space was observed beneath 7 excavations-the outer choroidal boundary appeared to be pulled inward by this bridging tissue. In 9 excavations, color fundus photographs showed pigmentary disturbance. Fourteen excavations (93.3%) were located within or adjacent to the choroidal neovascularization area. Compared with eyes without FCE, in eyes with FCE, the mean age was significantly higher (P = 0.040) and mean visual acuity was significantly better (P = 0.014). In addition, polypoidal lesions were observed in 8 of 12 eyes with FCE, but they appeared to have a limited effect on either the rate of FCE (P = 0.44) or the clinical characteristics of the eyes. CONCLUSIONS While FCE may be partially related to the choroidal neovascularization associated with exudative AMD, other factors may also influence this association.

Retinal Pigment Epithelial Atrophy in Neovascular Age-Related Macular Degeneration After Ranibizumab Treatment.

PURPOSE To investigate the risk factors for development and progression of retinal pigment epithelial (RPE) atrophy during ranibizumab treatment for neovascular age-related macular degeneration (AMD) in Japanese patients. DESIGN Retrospective interventional case series. METHODS This study included 195 eyes with treatment-naïve subfoveal neovascular AMD. All patients were treated with an as-needed regimen after 3 monthly ranibizumab treatments. Color fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence were evaluated for RPE atrophy diagnosis. Baseline characteristics and ARMS2 A69S and CFH I62V polymorphisms were analyzed for their association with development and progression of RPE atrophy. RESULTS Ten of 195 eyes (5.1%) had RPE atrophy at baseline; 3 had typical AMD and 7 had polypoidal choroidal vasculopathy (PCV). Among 185 eyes without preexisting RPE atrophy at baseline, 7 (3.8%) developed RPE atrophy at 12 months and 10 (5.4%) during the mean follow-up of 26.7 months. The incidence of newly developed RPE atrophy was lower in PCV than in typical AMD (P = .036), while the progression of the RPE atrophy area was faster in typical AMD than in PCV (0.57 ± 0.35 and 0.31 ± 0.13 mm/year, respectively; P = .018). The ARMS2 A69S and CFH I62V polymorphisms were significantly associated with the baseline RPE atrophy (P = .014 and P = .009, respectively). CONCLUSIONS The RPE atrophy developed in 5.4% of eyes with neovascular AMD during the 26.7 months of ranibizumab treatment. When compared with white individuals, RPE atrophy developed less frequently in Japanese patients, but the progression rate was similar. The subtype of AMD thus affects the development of RPE atrophy.

Dome-Shaped Macular Configuration: Longitudinal Changes in the Sclera and Choroid by Swept-Source Optical Coherence Tomography Over Two Years

PURPOSE To study longitudinal changes in the posterior pole in eyes with dome-shaped macular configuration within the staphyloma. DESIGN Prospective, longitudinal study. METHODS We prospectively examined the macular area in 35 eyes (26 patients) with dome-shaped macular configuration and high myopia (mean spherical equivalent, -14.83 ± 4.50 diopters) using swept-source optical coherence tomography. Scleral and choroidal thicknesses were measured at the fovea and at 4 parafoveal locations 2000 μm from the foveal center. Height of the macular bulge was measured as well. RESULTS During the mean follow-up of 24.8 ± 2.5 months, the scleral thickness significantly decreased at the fovea from 496.1 ± 95.7 μm to 484.7 ± 96.2 μm (P < .001) and at all 4 parafoveal locations (P < .001, respectively). The scleral thinning was asymmetric, with an estimated decrease per year of 5.6 μm at the foveal center, 11.1 μm superiorly, 12.1 μm inferiorly, 10.4 μm temporally, and 5.8 μm nasally. The ocular concavities deepened over time, and mean macular bulge height increased from 136.5 ± 60.9 μm to 157.6 ± 67.0 μm (P < .001). The choroid within the staphyloma showed generalized thinning during follow-up. Mean choroidal thickness decreased significantly at the fovea from 28.3 ± 17.2 μm at baseline to 22.9 ± 17.2 μm (P < .001). CONCLUSIONS Progressive asymmetric scleral thinning occurred in the macular region of eyes with dome-shaped macular configuration. The scleral thinning was more pronounced in the parafoveal area than at the foveal center, resulting in an increase of the macular bulge height.

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.

CHOROIDAL AND RETINAL ATROPHY OF BIETTI CRYSTALLINE DYSTROPHY PATIENTS WITH CYP4V2 MUTATIONS COMPARED TO RETINITIS PIGMENTOSA PATIENTS WITH EYS MUTATIONS.

Purpose: To compare atrophy of the choroid and retina between Bietti crystalline dystrophy (BCD) patients and EYS-related retinitis pigmentosa (RP) patients with a similar degree of central visual field defects, age, and axial length (AL). Methods: Nine eyes of nine BCD patients with CYP4V2 mutations (BCD group) were examined. Moreover, we selected 10 eyes of 10 RP patients with EYS mutations matched for age, axial length, and mean deviation (measured with the 10-2 SITA standard program; EYS-RP group), and 10 eyes of 10 normal volunteers matched for age and axial length (control group). Macular thicknesses of the choroid and retina were measured via swept-source optical coherence tomography. Results: The macular choroid was significantly thinner in the BCD group than in the EYS-RP and control groups, although the thickness did not significantly differ between the EYS-RP and control groups. The macular retina was significantly thinner in the BCD and EYS-RP groups than in the control group, although the thickness did not significantly differ between the BCD and EYS-RP groups at most sites. Conclusion: Bietti crystalline dystrophy patients with CYP4V2 mutations showed more severe macular choroid atrophy as compared to EYS-related RP patients. These different damage patterns suggest differences in choroidal expression between CYP4V2 and EYS.

Morphological features in anterior scleral inflammation using swept-source optical coherence tomography with multiple B-scan averaging

Background/aims To determine the morphological features of anterior scleral inflammation using swept-source optical coherence tomography. Methods In this retrospective observational study, we examined 17 eyes of 14 patients with diffuse anterior scleral inflammation and 13 eyes of 13 young unaffected patients. We compared cross-sectional images of the conjunctiva, episclera and sclera obtained using swept-source optical coherence tomography equipped with a multiple B-scan averaging process between normal eyes and those with episcleritis and scleritis. Results Optical coherence tomography showed that the conjunctival stroma/episclera layer was notably swollen in diseased eyes. The eyes with diffuse anterior scleral inflammation had a significantly thicker conjunctival stroma/episclera than normal eyes (403.0 μm vs 288.0 μm, p=0.002). There was no significant difference in scleral stroma thickness between eyes with anterior scleral inflammation and normal eyes (464.7 μm vs 434.2 μm, p=0.11). We separately analysed 11 eyes with diffuse scleritis and 6 eyes with diffuse episcleritis. While the conjunctival epithelium and conjunctival stroma/episclera were thicker in eyes with diffuse scleritis than in those with diffuse episcleritis (78.9 μm vs 50.4 μm, p=0.003 and 445.5 μm vs 308.8 μm, p=0.033, respectively), the scleral stroma thickness in eyes with diffuse scleritis was comparable with normal eyes (465.5 μm vs 434.2 μm, p=0.43). Conclusions The swelling of diffuse scleritis occurred within the episclera rather than in the scleral stroma. Since optical coherence tomography visualises the morphology of the episclera and sclera, it can be useful for evaluating inflammation activity and therapeutic effects in diffuse scleritis.

Choroidal Vasculature in Bietti Crystalline Dystrophy With CYP4V2 Mutations and in Retinitis Pigmentosa With EYS Mutations

Purpose We compare the choroidal vascular area between Bietti crystalline dystrophy (BCD) patients with CYP4V2 mutations, retinitis pigmentosa (RP) patients with EYS mutations, and normal controls, and investigate the correlation between choroidal vascular area and associated parameters. Methods This prospective case-series study included consecutive nine eyes of nine BCD patients with CYP4V2 mutations (BCD group), 16 eyes of 16 RP patients with EYS mutations (EYS-RP group), and 16 eyes of 16 normal volunteers matched for age and axial length (control group). Using swept-source optical coherence tomography, we obtained en face images of the choroidal vasculature at the midpoint of the choriocapillaris layer-Sattlers layer (inner choroid) and Hallers layer (outer choroid). After binarization, we compared the inner and outer choroidal vascular areas among the three groups and identified associated factors. Results The outer choroidal vascular area was 43.34 ± 5.76%, 53.73 ± 4.92%, and 52.80 ± 4.10% in the BCD, EYS-RP, and control groups, respectively. This value was significantly smaller in the BCD group than in the EYS-RP and control groups (P < 0.001 in both; no significant difference between the EYS-RP and control groups). In the BCD group, the outer choroidal vascular area was correlated strongly with the subfoveal inner choroidal thickness (P = 0.001, r = 0.91, respectively). The inner choroidal vasculature could not be identified in eight of nine eyes in the BCD group. Conclusions The outer choroidal vascular narrowing might progress with the inner choroidal thinning in BCD, and the inner choroidal vasculature might be extinguished in advanced-stage BCD. Our findings may help to clarify the etiology of BCD.

Factors associated with optic nerve head blood flow and color tone: a retrospective observational study.

PurposeTo investigate the relationship between optic nerve head (ONH) blood flow and color tone.MethodsRetrospective observational study conducted between February 2014 and August 2014. We examined 29 eyes of 17 young healthy subjects and 37 eyes of 26 cataract patients undergoing cataract surgery. Blood flow was measured using laser speckle flowgraphy, and color tone was quantified using the public domain ImageJ software. Blood flow and color tone of the ONH before and after cataract surgery were compared. The influence of age, axial length, and color tone on ONH blood flow were also investigated.ResultsMean blur rate (MBR) in the ONH decreased with increasing age (R = –0.437, P < 0.001) and axial length (R = –0.306, P = 0.012). In young subjects, ONH redness had a moderate positive correlation with MBR (R = 0.376, P = 0.044); however, this correlation was not observed in the study population as a whole (R = 0.066, P = 0.601). MBR in the ONH was higher after cataract surgery (P < 0.001). Moreover, the ONH redness reduced postoperatively from that preoperatively (P < 0.001). An increase in MBR after cataract surgery correlated with improved visual acuity (R = –0.399, P = 0.014) and decreased redness the of ONH (R = –0.433, P < 0.01).ConclusionsOcular blood flow decreased in older people and in myopic eyes. The reddish appearance of the ONH was not an indicator of a circulatory condition, particularly in older people. Lens opacity appeared to underestimate hemodynamic quantification using laser speckle flowgraphy.