Our study was performed according to the ethical standards of the Declaration of Helsinki. The institutional review board of Osaka University Hospital approved the study protocol. Informed consent was obtained in the form of an opt-out option on the website.
We retrospectively studied 78 eyes of 46 consecutive patients with high myopia who underwent OCTA between September 2014 and March 2015 at Osaka University Hospital. The inclusion criteria were the presence of high myopia (defined as −6.0 D or an axial length of ≥26 mm) and a history or presence of mCNV. The exclusion criteria were the presence of punctate inner choroidopathy, CNV owing to diseases other than myopia, poor fixation, CNV outside a 3 × 3 mm2 square on an SSADA image, and CNV too large to fit within the 3 × 3 mm2 area.
Retina specialists (Y.I. and S.U. with 25 years and 10 years of professional experience, respectively) diagnosed mCNV based on the findings of fundus photographs, conventional OCT images, and FA images. BCVA was measured and converted to logMAR for analysis. The Zeiss IOL Master (Carl Zeiss Meditec, Oberkochen, Germany) was used for measuring the axial length.
FA, IA (Heidelberg Retina Angiograph 2; Heidelberg Engineering, Dossenheim, Germany), and OCT B-scans were used to diagnose mCNV.
The study included patients with active and inactive mCNVs. Inactive CNV was defined as CNV that had been detected or treated previously, with no active signs on examination in the present study. Active signs were defined as dye leakage on FA images using the Heidelberg Retina Angiograph 2 or the presence of subretinal fluid or intraretinal cysts on OCT images (Cirrus HD-OCT, Carl Zeiss Meditec, Dublin, CA, USA) or on a swept-source OCT system (Topcon, Tokyo, Japan). Early-phase FA images (within 2 mins after the start of imaging) were used to locate mCNV on OCTA images.
CNV flow signal and CFD measurements
RTVue XR Avanti (Optovue, Fremont, CA, USA) with the AngioVue mode was used to obtain 3 × 3 mm2 and 6 × 6 mm2 OCTA images. Four layers of en-face vessel images were generated (e.g., superficial retinal layer, deep retinal layer, outer retinal layer, and choroidal capillary layer) using the AngioVue mode, as previously described by the SSADA algorithm31. Three examiners (S.U., K.S., and A.Y.) measured the flow signal area of CNV (area A) using ImageJ software (National Institute of Health, Bethesda, MD, USA) in the choriocapillaris layers of OCTA images. Area B included both CFD, defined as a dark hypo-signal area around CNV, and CNV, which was measured in a similar manner. The size of the CFD around CNV was calculated by subtracting area A from area B. The number of pixels was used to calculate the area. When the OCTA images of multiple visits were available, images from the first visit were used for all analyses. The average values from the three examiners were used in this study.
The study included both naïve patients and patients that had been treated with anti-VEGF agent injections. Retina specialists administered the following intravitreal injections of anti-VEGF treatment to patients with mCNV: 1.0 mg of bevacizumab (Avastin, Genentech, San Francisco, CA, USA), ranibizumab (0.5 mg), or aflibercept (2.0 mg) according to a pro re nata regimen when mCNV was diagnosed as active. Bevacizumab was used between May 2006 and August 2013 before the Japanese government approved ranibizumab or aflibercept for mCNV treatment; ranibizumab was used after August 2013, and aflibercept was used after September 2014. The use of bevacizumab was approved by the institutional review board of Osaka University Hospital.
Statistical analyses were performed using the JMP statistical software (SAS Institute, Cary, NC, USA). Fisher’s exact test was used for analyzing the non-parametric data. Student’s t-test and one-way analysis of variance were used for parametric numerical data, and the Wilcoxon t-test and Kruskal-Wallis test were used for nonparametric numerical data. A P-value of <0.05 was considered significant. The multivariate linear regression analysis was used when multiple variables were found to be statistically significant.
All data generated or analyzed during this study are included in this published article.