Longitudinal changes in the peripapillary retinal nerve fiber layer thickness in the fellow eyes of unilateral retinal vein occlusion

www.nature.com/scientificreports OPEN Longitudinal changes in the peripapillary retinal nerve fiber layer thickness in the fellow eyes of unilateral retinal vein occlusion Yong-Il Shin, Hyung-Bin Lim, Hyungmoon Koo, Woo-Hyuk Lee & Jung-Yeul Kim ✉ To analyze longitudinal changes in peripapillary retinal nerve fiber layer (pRNFL) thicknesses over time in the fellow eyes of patients with unilateral retinal vein occlusion (RVO). A total of 47 patients with unilateral RVO and 47 healthy controls were enrolled. The mean and sectoral pRNFL thicknesses were measured using spectral domain-optical coherence tomography at 1 year intervals, and followed for 3 years. Linear mixed models were performed to calculate and compare the reduction rates of pRNFL thicknesses over time. The mean pRNFL thickness decreased significantly during the 3-year follow-up, with a significant decrease over time in both groups. The reduction rate in mean pRNFL thicknesses was −0.41 μm/year in the control group and −0.68 μm/year in the fellow eyes of RVO group, and the decrease was significantly higher in the fellow eyes of RVO group than in the control group (p < 0.001). Using a multivariate linear mixed model, age (estimate: −0.41, p = 0.011) and hypertension (HTN) (estimate: −6.51, p = 0.014) were significantly associated with the reduction in mean pRNFL thicknesses in fellow eyes of RVO group. The fellow eyes of RVO patients showed a greater reduction in pRNFL thickness over time than normal controls. Age and HTN should be considered as factors to decrease the pRNFL thickness over time in fellow eyes of RVO group. Retinal vein occlusion (RVO) is a common cause of retinal vascular disease. Branch retinal vein occlusion (BRVO) is 4–6 times more prevalent than central retinal vein occlusion (CRVO). Various systemic diseases such as hypertension (HTN), diabetes mellitus (DM), hyperlipidemia, and arteriosclerosis are considered risk factors for RVO1–5, so it is also important to detect and treat these systemic diseases associated with life-threatening cerebrovascular and cardiovascular diseases. The Beijing Eye Study reported that the 10-year incidence of BRVO is 1.6%, and the incidence of CRVO was 0.3%6. The Beaver Dam Study estimated that the 15-year cumulative incidences of BRVO and CRVO were 1.8% and 0.5%, respectively7. At baseline, 5–6% of eyes had bilateral BRVO8, and the cumulative probability of developing a second episode of RVO in fellow eye was 7.7% within 2 years and 11.9% within 4 years9. Therefore, we should always consider the possibility of disease in the fellow eyes of patients with RVO. Optical coherence tomography (OCT), developed in 1991 by Huang et al.10, is now widely used by ophthalmologists. OCT has undergone many advances in technology, with improved resolution and speed. OCT can has the advantage that it is possible to observe the change of retinal cross-section according to disease progression and treatment in high resolution. In addition, the measurement show good reproducibility and repeatability, so objective and quantitative measurements can be conducted in a short time. OCT is also widely used to quantitatively measure the thickness of the peripapillary retinal nerve fiber layer (pRNFL) during the diagnosis and treatment of glaucoma. Several studies have reported that high intraocular pressure (IOP) and/or glaucoma were associated with the development of RVO11–13. Previous studies of structural changes in the fellow eyes of unilateral RVO patients have shown that the pRNFL is thinner compared to normal eyes, which suggests the possibility that RVO and glaucoma share common systemic risk factors14. In addition, the possibility of vascular dysfunction was reported by showing decreased perfusion of optic nerve head (ONH) measured by OCTA15. However, no studies have investigated longitudinal changes in pRNFL of the fellow eyes of patients with unilateral RVO. Therefore, in this study, we characterized longitudinal changes in the rate of pRNFL loss over time during a 3-year period in the fellow eyes of patients with unilateral RVO. Department of Ophthalmology, Chungnam National University College of Medicine, Daejeon, Republic of Korea. ✉e-mail: Scientific Reports | (2020) 10:7708 | https://doi.org/10.1038/s41598-020-64484-5 1 www.nature.com/scientificreports/ www.nature.com/scientificreports Methods Participants. This prospective, longitudinal, observational study was approved by the Institutional Review Board of Chungnam National University Hospital, Daejeon, Republic of Korea. The study adhered to the tenets of the Declaration of Helsinki. Patients with unilateral RVO who visited our retina clinic were enrolled between January 2014 and July 2016, and the last examination was performed in August 2019. Written informed consent was obtained from each participant. The sample size was calculated using G*Power version 3.1.9.2 sample size package (http://www.gpower.hhu.de/); α = 0.05, power = 95%, effect size = 0.188 (calculate from our previous study16). Considering the expectable dropout, we decided to enroll at least forty participants in each group. A retinal specialists (JYK) diagnosed unilateral RVO via dilated fundus examinations, fundus photography, and fluorescein angiography. The healthy fellow eyes of unilateral RVO patients who exhibited a best-corrected visual acuity (BCVA) of 20/25 or better were enrolled. Among the subjects who visited our clinic for various reasons (health screening checkup, work-up for ocular disease, and so forth), those who met inclusion and exclusion criteria were recruited as controls. The exclusion criteria for fellow eyes and controls were as follows: a history of retinal or optic nerve disease such as glaucoma; an IOP ≥ 21 mmHg at baseline and during the follow-up period; glaucomatous optic disc (increased cup/disc ratio, neuroretinal rim loss, disc hemorrhage, etc17); intraocular surgery; high myopia (spherical equivalent [SE] > −6 diopters or axial length [AL] ≥ 26.0 mm); and significant media opacity. Normal subjects (control group) also had no history of diabetes and hypertension. All patients underwent a comprehensive ophthalmic examination, including measurement of the BCVA using a Snellen chart, slit-lamp examination, dilated fundus examination, IOP, SE, AL measurement using an IOL Master version 5.0 (Carl Zeiss, Jena, Germany), and spectral domain-optical coherence tomography (SD-OCT). After the initial visit, the examinations were performed at 1 year intervals between examinations for 3 years. Optical coherence tomography measurements. SD-OCT imaging was performed using a Cirrus HD-OCT version 10.0 (Carl Zeiss Meditec, Dublin, CA, USA), by a single experienced examiner. The pRNFL thickness was measured using an optic disc cube (200 × 200) scan mode. This mode scanned a 6 × 6 mm area and measured the pRNFL thickness of a 3.46 diameter circle from the optic disc center. The average and four quadrant sectors (superior, nas (...truncated)