Laser Photocoagulation and Ranibizumab Treatment in Proliferative Diabetic Retinopathy

The global prevalence of diabetes mellitus (DM) in 2019 is estimated to be 9.3% (463 million people). Diabetic retinopathy represents the fifth cause of blindness globally and the commonest visual impairing condition in working-age people.

Diabetic retinopathy (DR) is microangiopathy characterized by capillary non-perfusion, microaneurysms (MAs), and retinal ischemia. It may cause many complications, such as diabetic macular edema (DME) and diabetic macular ischemia (DMI).

Capillary ischemia decreases the nutrition of the retina and causes of hypoxia which results in increased level vascular endothelial growth factor (VEGF), which promotes angiogenic responses causing both neovascularization (proliferative diabetic retinopathy, PDR) and vascular permeability (macular edema).

Pan-retinal photocoagulation (PRP) is the standard treatment for proliferative diabetic retinopathy (PDR). It improves oxygenation of the ischemic retina. Destruction of the highly active photoreceptor cells is the suggested mechanism of action for PRP. Subsequently, production of VEGFs, the key player in neovascularization process, is reduced leading to regression of new vessels.

However, the use of intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents as (Ranibizumab, Bevacizumab and Aflibercept) for the treatment of PDR has provided encouraging results in the last decade, with better functional outcomes compared to PRP.

Both treatments have a positive effect in delaying progression of DR, and they also have been combined many times in clinical practice. However the efficacy of monotherapy and combined treatment may be different. Many studies concluded that PRP and Anti VEGF treatment can achieve the ideal efficacy on DR by improving visual acuity and neovascularization regression.

PDR eyes have an overall lower blood flow than normal or non-PDR eyes, parallel to the higher level of retinal ischemia and disease severity. With regression of these neovascular and shunt vessels theoretically increase blood flow in the macula and may reverse the ischemia flow.

While most previous studies have explored the large vessel effects of PRP, the development of optical coherence tomography angiography (OCTA) allowed the study of microvascular retinal changes in a detailed manner. It is a non-invasive modality that allows vascular mapping with high speed and quality and promotes visualization of vascular system in different retinal and choroidal levels. Several studies have demonstrated the competence of OCTA in the quantification of microvascular density, choroidal flow area, and foveal avascular zone (FAZ) area in diabetic patients.

Unlike other studies that focused only on the effect of PRP alone on macular vascular flow, our study will focus on the additional effect of intravitreal Anti-VEGF (Ranibizumab) with PRP on the macula of eyes with PDR using OCTA.

Inclusion criteria

• PDR patients diagnosed clinically and by the presence of neovascularization on optic disc (NVDs) or elsewhere (NVEs) on fluorescein angiography.

Exclusion criteria

• a) History of previous intra ocular surgery, uveitis, glaucoma and significant eye trauma.

b) Significant media opacity decreasing image quality (corneal opacity, dense cataract, and vitreous hemorrhage)

c) Significant macular edema to overcome errors in segmentation

d) Scans with low signal strength index (SSI; < 50), presence of blink artifacts, and poor fixation leading to motion artifacts.

e) History of previous treatment for diabetic retinopathy including intravitreal injection of anti-VEGFs, laser, or vitrectomy

f) Presence of vitreo-macular traction