Acute and subacute intraocular pressure and macular microvascular structure changes after intravitreal ranibizumab injection in eyes with branch retinal vein occlusion

This prospective observation study was performed from September, 2016 to October, 2017. The research protocols were approved by the Ethics Committee of Beijing Hospital, carried out in accordance with the tenets of the Declaration of Helsinki. Written informed consent was obtained from each participant. Thirty eyes of 30 patients (one eye per patient) who were ultimately diagnosed with ME due to BRVO were enrolled.

All patients underwent an ophthalmological examination with best-corrected visual acuity (BCVA), IOP measurements, slit lamp examination, fluorescein fundus angiography (FFA), dilated fundoscopic examinations and OCTA. Additionally, vital signs, such as systolic and diastolic blood pressures were also acquired. IOP, OCTA, and blood pressure, including systolic blood pressure (SBP)and diastolic blood pressure (DBP) were acquired at baseline, 30 min, and 1-month post-injection.

Patients were excluded if they met the following criteria: (1) hemi-CRVO or CRVO; (2) diabetic maculopathy and/or retinopathy; (3) any other BCVA compromising ocular disease; (4) any prior intravitreal anti-VEGF or corticosteroid injections; (5) any prior retinal laser photocoagulation; (6) IOP higher than 21 mmHg; (7) history of vitrectomy; (8) history of myocardial infarction or stroke within three months; and (9) other major systemic disorders. The inclusion and exclusion criteria were similar to Song’s study [17].

Each patient received intravitreal ranibizumab injection at a dose of 0.5 mg/ 0.05 ml. After instilling topical 0.4% oxybuprocaine chloride eye drops for topical anesthesia, the eye was irrigated with 5% povidone-iodine and opened using a lid retractor, and the drug was injected through the pars plana 3.5 mm posterior to the limbus in the inferotemporal quadrant in pseudophakic eyes and 4.0 mm posterior to the limbus in phakic eyes using a 30 G needle. The treatment protocol was similar to Song’s study [17].

IOP was measured with Goldmann applanation tonometry(Haag-Streit AT 900) at least twice in each eye at each visit. The average of the measurements wastaken. The baseline IOP was measured at the visit before the injection. We also examined the IOP 30 min and 1 month after the injection.

All patients had macular OCT-A performed before and 30 min, and 1-month post-IVI treatment by spectral-domain OCT (RTVue XR Avanti, Optovue, Inc., Fremont, CA, USA). We only chose OCTA images with an image quality score of 6 or more. For each patient, 3 × 3 mm scans centered on the fovea were acquired. Macular scans were segmented into superficial and deep OCT-A layers. The OCT system’s Angio Analytics software (version 2017.1.0.151, Optovue, Inc.) performs automatic segmentation of vessel layers. Based on the default setting of the OCTA system, the SCP of the retina included blood vessels from the internal limiting membrane (ILM) to − 10 μm below the inner plexiform layer (IPL). DCP of the retina included blood vessels from − 10 μm below the IPL to 10 μm below the outer plexiform layer (OPL). The SCP, DCP as described as the whole macula, the fovea and parafovea which were measured automatically by OCTA built-in software. The fovea was defined as the area within the central 1-mm ring of the Early Treatment Diabetic retinopathy Study (ETDRS) grid. Parafovea was considered as the area between the central 1- and the 3-mm ring of the ETDRS grid. (Fig. 1) FAZ was defined as a capillary-free area in the central macular region on traditional FFA analysis of the retina. FAZ measurements include the following parameters: the FAZ area; the FAZ perimeter (PERIM); the acircularity index (AI), which is defined as the ratio of the perimeter of the FAZ and the perimeter of a circle with equal area, AI = PERIM/equal area standard circumference; and the FD300, which refers to the blood vessel density within a 300 μm wide ring around the FAZ. The FAZ area, PERIM, AI, and FD-300 were used to evaluate the hemodynamics of the FAZ [17]. We recorded the VD of the whole macula, fovea, parafovea of the SCP and DCP, FAZ area, perimeter (PERIM), FD-300 and AI and also their relationships with IOP were observed.

Continuous variables with normal distribution were presented as mean ± standard deviation and with nonnormal distribution were presented as median (interquartile range). Paired t-test and Wilcoxon paired signed rank test were used to compare changes pre- and post-IVI of ranibizumab in BRVO eyes. Normality of errors (residuals) was checked while modeling (histograms and P–P plots). Pearson correlation analyses were adopted to study the correlations among IOP and OCTA findings 30 min and 1 month post-injection. Statistical analyses were performed with the IBM SPSS Statistics for Windows, Version 28.0 (IBM Corp., Armonk, NY, USA), and statistical significance was established at two-tailed P < 0.05.