Optic nerve head perfusion changes in eyes with proliferative diabetic retinopathy treated with intravitreal ranibizumab or photocoagulation: a randomized controlled trial

Abstract

Background: Proliferative diabetic retinopathy (PDR) is a serious sight-threatening disease, and half of the patients with high-risk PDR can develop legal blindness within 5 years, if left untreated. This study was aimed at comparing panretinal photocoagulation (PRP) and intravitreal ranibizumab injections in terms of radial peripapillary capillary (RPC) density on optical coherence tomography angiography (OCTA) in patients with treatment-naive PDR.

Methods: This open-label, prospective, randomized clinical trial included 50 patients with treatment-naive PDR with optic disc neovascularization and randomized them into two groups: group 1, with patients undergoing two sessions of PRP 2 weeks apart, and group 2, with patients received three intravitreal ranibizumab injections (0.5 mg) 1 month apart for 3 consecutive months. Patients underwent a full ophthalmological examination, including best-corrected distance visual acuity (BCDVA) measurement in the logarithm of minimal angle of resolution (logMAR) notation and OCTA before intervention and monthly after the last laser session or the first intravitreal ranibizumab injection for 3 months of follow-up. Visual field (VF) was tested at the beginning and end of 3 months.

Results: Forty-two (84%) eyes completed the 3-month follow-up, including 22 eyes in the PRP group (88%) and 20 (80%) eyes in the ranibizumab group. The two groups were comparable in terms of demographic characteristics, diabetes duration, baseline BCDVA, glycated hemoglobin level, OCTA parameters, VF indices, and intraocular pressure (all P > 0.05). The RPC density change from baseline to the 3-month follow-up was significantly lower in the PRP group than in the ranibizumab group (mean difference in RPC density change: - 3.61%; 95% confidence interval: - 5.57% to - 1.60%; P = 0.001). The median (interquartile range) logMAR change from baseline to the 3-month follow-up (0.0 [0.2]) was significantly higher in the PRP group than in the ranibizumab group (- 0.15 [0.3]; P < 0.05). The median changes in central foveal thickness from baseline to the 3-month follow-up differed significantly between the two groups (P = 0.001).

Conclusions: In eyes with PDR and neovascularization of the disc RPC density on OCTA increased in the ranibizumab group and decreased in the PRP group. Visual acuity gain was higher in the ranibizumab group than in the PRP group. Future multicenter trials addressing our limitations are required to verify the findings of this study.

Keywords: diabetic retinopathies; intravitreal injection; laser ablation; laser therapies; lucentis; optic nerves; optical coherence tomography; photocoagulation.

Figure 1

Quantitative evaluations of pre- and post-treatment neovascularization and flow areas of neovascularizations of the disc (NVDs) with optical coherence tomography (OCT) angiograms using the OCT-angiography RTVue XR Avanti (AngioVue; Optovue Inc., 2017, Fremont, CA, USA) machine. (A, B) OCT angiograms of treatment-naive NVD in an eye in group 1. (A) Before panretinal photocoagulation, neovascularization and flow areas of NVD were 2.44 and 1.23 mm², respectively. (B) Three months after panretinal photocoagulation, neovascularization and flow areas decreased to 2.18 and 0.83 mm², respectively. (C, D) OCT angiograms of treatment-naive NVD in an eye in group 2. (C) Before intravitreal injections of 0.5 mg ranibizumab (Lucentis, Genetec Inc, San Francisco, CA, USA), neovascularization and flow areas of NVD were 1.08 and 0.68 mm², respectively. (D) After three consecutive intravitreal injections of ranibizumab monthly, neovascularization and flow areas decreased to 0.62 and 0.31 mm², respectively. Note: Eyes in group 1 underwent panretinal photocoagulation divided into two sessions 2 weeks apart; Eyes in group 2 received intravitreal injections of 0.5 mg ranibizumab monthly for 3 consecutive months

Figure 2

CONSORT flow diagram of the study process. Allocation of participants to group 1 or 2. Abbreviations: N, number of eyes; TRD, tractional retinal detachment; NAION, non-arteritic anterior ischemic optic neuropathy. Note: Eyes in group 1 underwent panretinal photocoagulation divided into two sessions 2 weeks apart. Eyes in group 2 received intravitreal injections of 0.5 mg ranibizumab (Lucentis, Genetec Inc., San Francisco, CA, USA) monthly for 3 consecutive months

Figure 3

Typical 4.5 × 4.5-mm optical coherence tomography angiograms using the OCT-angiography RTVue XR Avanti (AngioVue; Optovue Inc., 2017, Fremont, CA, USA) machine of an eye in the panretinal photocoagulation group, show a decrease in radial peripapillary capillary density from (A) 43.4% at baseline to (B) 42.6% at 3-month post-panretinal photocoagulation follow-up. Note: Eyes in group 1 underwent panretinal photocoagulation divided into two sessions 2 weeks apart

Figure 4

Split-plot analysis of variance for repeated measurements of radial peripapillary capillary (RPC) density shows reduced RPC density in group 1 (panretinal photocoagulation group) and increased RPC density in group 2 (ranibizumab group) over a follow-up of 3 months. Note: Eyes in group 1 underwent panretinal photocoagulation divided into two sessions 2 weeks apart; Eyes in group 2 received intravitreal injections of 0.5 mg ranibizumab (Lucentis, Genetec Inc., San Francisco, CA, USA) monthly for 3 consecutive months