Keiko Azuma

A prospective multicenter study on genome wide associations to ranibizumab treatment outcome for age-related macular degeneration

We conducted a genome-wide association study (GWAS) on the outcome of anti-VEGF treatment for exudative age-related macular degeneration (AMD) in a prospective cohort. Four hundred and sixty-one treatment-naïve AMD patients were recruited at 13 clinical centers and all patients were treated with 3 monthly injections of ranibizumab followed by pro re nata regimen treatment for one year. Genomic DNA was collected from all patients for a 2-stage GWAS on achieving dry macula after the initial treatment, the requirement for an additional treatment, and visual acuity changes during the 12-month observation period. In addition, we evaluated 9 single-nucleotide polymorphisms (SNPs) in 8 previously reported AMD-related genes for their associations with treatment outcome. The discovery stage with 256 patients evaluated 8,480,849 SNPs, but no SNPs showed genome-wide level significance in association with treatment outcomes. Although SNPs with P-values of <5 × 10−6 were evaluated in replication samples of 205 patients, no SNP was significantly associated with treatment outcomes. Among AMD-susceptibility genes, rs10490924 in ARMS2/HTRA1 was significantly associated with additional treatment requirement in the discovery stage (P = 0.0023), and pooled analysis with the replication stage further confirmed this association (P = 0.0013). ARMS2/HTRA1 polymorphism might be able to predict the frequency of injection after initial ranibizumab treatment.

ANGIOGRAPHIC FINDINGS OF RANIBIZUMAB-RESISTANT POLYPOIDAL CHOROIDAL VASCULOPATHY AFTER SWITCHING TO A TREAT-AND-EXTEND REGIMEN WITH INTRAVITREAL AFLIBERCEPT.

Purpose: The aim of this study was to study the angiopathic findings of ranibizumab-resistant polypoidal choroidal vasculopathy after switching to a treat-and-extend regimen with intravitreal aflibercept. Methods: The authors retrospectively reviewed 17 eyes of 17 Japanese patients with polypoidal choroidal vasculopathy (10 men and 7 women, age: 73.8 ± 7.4 years) who were treated with intravitreal aflibercept (2 mg/0.05 mL) injections from February 2013 to August 2014 at Tokyo University Hospital. All patients had switched to aflibercept because their polypoidal choroidal vasculopathy had been refractory to ranibizumab. Results: The mean logMAR best-corrected visual acuity at baseline and after 12 months of therapy was 0.30 ± 0.29 (Snellen equivalent: 20/40) and 0.17 ± 0.26 (20/30) (paired t-test P < 0.001). Visual acuity remained stable in 5 cases (29%), deteriorated in 3 (18%), and improved in 9 (53%). Branching vascular networks persisted in all 17 eyes but shrank in 15 (88%). The mean lesion diameter was 3329 ± 1261 &mgr;m at baseline and 3180 ± 1247 &mgr;m after 12 months (P = 0.0002). Conclusion: A treat-and-extend regimen with intravitreal aflibercept for ranibizumab-resistant patients resulted in branching vascular network shrinkage over a 1-year period.

Changes of outer retinal microstructures after photodynamic therapy for chronic central serous chorioretinopathy

Purpose To evaluate the morphological changes in retinal microstructures following modified photodynamic therapy (PDT) for chronic central serous chorioretinopathy. Subjects and methods Retrospective study of 21 consecutive eyes (age, 59±8.0 years [mean ± SD]) of 21 patients with chronic central serous chorioretinopathy. Inner foveal thickness (the distance between the internal limiting membrane and external limiting membrane), photoreceptor outer segment (PROS) length at the point without serous retinal detachment and choroidal thickness were assessed with enhanced depth imaging optical coherence tomography before treatment and at 1, 3 and 6 months after modified PDT. Results Six eyes had half-dose and 15 eyes had half-fluence PDT. PROS length within the irradiated area was significantly decreased by 3.9% at 1 month compared with that before modified PDT (43.5±5.72 and 40.5±7.53, P=0.020 [paired t-test]) and returned to baseline length at 3 and 6 months (43.0±5.42 and 43.5±4.33 μm [mean ± SD]; P=0.53 and 1.00 [paired t-test]). PROS length of the nonirradiated area at 1, 3 and 6 months after modified PDT did not significantly differ from that before PDT (41.8±6.35, 41.4±5.33, 41.9±4.67 and 42.3±4.26 μm [mean ± SD]; P=0.66, 0.90 and 0.60, respectively [paired t-test]). There was no significant change in inner foveal thickness during the observation period. At all time points, choroidal thickness was significantly thinner than it was before PDT (P<0.001, paired t-test). Conclusion Modified PDT may cause mild temporary microstructural changes.

Corneal biomechanical properties are associated with the activity and prognosis of Angioid Streaks

The aim of the current study is to investigate corneal biomechanical properties in detail using Ocular Response Analyzer (ORA) and Corvis ST (CST) tonometry and to analyze the association between corneal biomechanical properties and the frequency of intravitreal anti-vascular endothelial growth factor (VEGF) injections (FIV) in AS eyes with choroidal neovascularization (CNV). Twenty-eight eyes of 15 patients with AS were enrolled. Mean age of AS patients was 67.9 ± 9.8 years. ORA and CST measurements were carried out, in addition to comprehensive ophthalmic examinations. LogMAR visual acuity (VA) and ΔVA (the change of VA from baseline to the final visit) were calculated in each eye. Also, the relationships between FIV, and the variables of initial age at the observation period, axial length, and corneal biomechanical properties were investigated in eyes with AS using linear mixed model with model selection using AICc. In 28 AS eyes, 16 eyes underwent intravitreal anti-VEGF injections during follow-up period. Lower corneal hysteresis (CH), higher corneal resistant factor (CRF) and higher CST measured the DA ratio were associated with the increase of FIV in AS eyes (p = 0.01, p = 0.002, p = 0.027, respectively), suggesting the usefulness for monitoring of corneal biomechanical properties.

Choroidal structure as a biomarker for visual acuity in intravitreal aflibercept therapy for polypoidal choroidal vasculopathy

Purpose To investigate the relationship between choroidal structure and visual acuity after intravitreal aflibercept therapy for polypoidal choroidal vasculopathy (PCV). Methods We conducted a retrospective, single-centre and observational study including 18 eyes of 18 patients with PCV (73.8 ± 10.2 years of age) who were treated with three monthly intravitreal aflibercept injections followed by additional treatments in a treat-and-extend protocol. The cross-sectional images of the macula were obtained with enhanced depth imaging optical coherence tomography at baseline, at 3 months, and at 12 months. The choroidal layer was divided into luminal or stromal segments by applying binarization processing to calculate these areas. The relationships between age, spherical equivalent, best-corrected visual acuity (BCVA), baseline value, or changes in the luminal or the stromal areas, and the BCVA change at 12 months were analysed using multiple regression analyses and model selection procedures. Results Both stromal and luminal areas were decreased at 3 and 12 months compared to baseline areas (5% and 9% at 3 months, 6% and 12% at 12 months, p < 0.0001, p < 0.0001, p < 0.0001 and p < 0.0001, respectively). Greater improvement of visual acuity (VA) at 12 months was significantly associated with younger age, greater spherical equivalent, worse baseline BCVA, greater baseline luminal area, and smaller baseline stromal area. Conclusions Choroidal structure might be useful as a new biomarker for potential Visual outcomes after intravitreal aflibercept therapy for PCV.

Observation of Outer Retinal Tubulation Using En face Optical Coherence Tomography

要 約 【目的】Outer Retinal tubulation(ORT)は、加齢黄斑変性のほか様々な網膜疾患の網膜外層にみ られる管状病変である。今回、光干渉断層計(OCT)を用いてORTを撮像し、En face画像におけ る病変の形状を観察した。 【対象と方法】2015年12月から2016年4月までに東京大学医学部附属病院を受診し、黄斑変性に ORTを認めた15例15眼を対象とした。Optovue社RTVueXRを使用し、En face画像でORTの形 状を後ろ向きに検討した。 【結果】En face画像では、ORTは外網状層に存在し、内部が低反射で外壁が網膜血管より肥厚し た管状組織として認められた。ORTの形状は、分岐のない比較的小さな型(散在型 11眼)と分 岐を認める比較的大きな型(分岐型 4眼)の2種に分類された。散在型と分岐型の間には、年齢、 視力、屈折値の有意差は認められなかったが、ORTの存在期間は、分岐型が散在型に比べて有意 に長かった(平均57.7ヵ月対31.9ヵ月、p<0.05)。 【結論】OCTのEn Face画像を用いてORTを観察した。散在型と分岐型の2種の形状に特徴づけら れた。分岐型ORTは、経過観察中にその形状が変化した。