Automated quantification of macular edema in patients with diabetic macular edema and their response to anti-VEGF: A study protocol

Introduction

According to World Health Organization (WHO) figures, the number of people affected by diabetes have increased by 114% by 2030 compared to the year 2000.¹ India has the world’s second-highest number of diabetes cases (77 million in 2019), after China.²

Diabetes is characterized by hyperglycemia in conjunction with hypo-insulinemia or insulin resistance, and this chronic metabolic disorder can lead to a variety of consequences, including kidney failure, heart attacks, and retinal degeneration.

Diabetic retinopathy is further subdivided into:

Diabetic macular edema (DME) is the leading cause of vision loss among individuals with diabetes. This disease is marked by changes in the blood-retinal barrier, which includes the loss of pericytes and the breakdown of junctions between endothelial cells. Retinal blood flow and vascular permeability change, in addition to basement membrane thickening and pericyte loss.³ The formation of acellular capillaries causes non-proliferative diabetic retinopathy (NPDR) lesions that are visible in clinical settings; some signs of diabetic retinopathy include microaneurysms, venous beading, and intraretinal microvascular abnormalities.⁴ Ischemia worsening can lead to proliferative diabetic retinopathy, which poses vision threats due to complications caused by neovascularization like vitreous hemorrhage or retinal detachment. As a consequence of ischemia, there is an increase in the permeability of the capillaries and the microaneurysms of the retinal vessels which results in the cumulation of fluid outside the cell and d increase in the thickness of the dense tissue in the macula. The risk of macular edema increases with the severity of diabetic retinopathy.⁵

DME attacks the macular zone of the retina. To comprehend the anatomic alterations in DME. We discuss retinal anatomy using optical coherence tomography (OCT) a technique used to comprehend the different layers of the retina and choroid. This method helps detect and monitor DME.

At the onset, edema affects the cells intracellularly, with the Müller cells being the first to swell. As it progresses, it leads to the apoptosis of affected cells, including ganglion cells, bipolar cells, and photoreceptors Presynaptic elongation and prolongation decrease until the edema is reversed. As the metabolic state improves, at this stage, the fluid passes through the cell membrane and accumulates in the interstitial space, resulting in the formation of cysts.⁶ Cyst formation in DME begins in small cysts in the inner layers and moves towards the outer layers, creating bigger cysts that can be seen through retinal biomicroscopy and fluorescein angiography.

The peripheral deposition of lipids in the plexiform layer due to the edema is called the Hard exudates. The rupture of the retinal pigment epithelium permits fluids to gather and the neurosensory retina to detach, resulting in edema.

In DME the central height of cystoid spaces correlates with poor vision.⁷ Spectral domain-optical coherence tomography (SD-OCT) is the foundation of clinical evaluation of DME. Intra-retinal fluid and subretinal fluid are the key OCT biomarkers for diagnosing macular edema and their impact on visual function has been extensively studied in retinal diseases like diabetic retinopathy.⁸

If macular thickness changes by more than 11%, it’s likely a real change, not just due to measurement variability.

The basic therapeutic principle is metabolic management of hyperglycemia and blood pressure.

Until recently, diabetic macular edema was primarily treated by laser photocoagulation; it was observed that with the r photocoagulation, the risk of loss of vision was reduced by 50%. In recent years, the availability of intravitreal anti-VEGF medicines and good data to support their efficacy has radically transformed the approach to care.

In a retrospective claims analysis of 2,733 newly diagnosed DME patients from 2008 to 2010, the mean annual number of bevacizumab injections was 2.2, 2.5, and 3.6 for the years 2008, 2009, and 2010, respectively, which was lower than in major clinical trials of anti-VEGF agents. Similarly, a retrospective investigation of 121 eyes from 110 patients with a new diagnosis of DME who received anti-VEGF injectable therapy for the first time between 2007 and 2012 from the Geisinger Health System database found that a mean of 3.1 2.4 injections was administered per study eye in the first year of treatment. The mean change in corrected visual acuity was 4.7 estimated ETDRS letters, which is determined from Snellen visual acuity. The greater number of anti-VEGF injections in the first 12 months after diagnosis correlated with improved visual outcomes, implying that real-world outcomes usually lag those in randomised clinical trials (RCTs).⁹

Patients without SRF at the start of DME treatment had worse visual outcomes, according to a study by Roberts et al.¹⁰

Protocol

This will be a hospital-based non-randomized one-arm interventional study.

All procedures will be carried out at the Department of Ophthalmology, Acharya Vinobha Bhave Hospital Sawangi, Meghe, after obtaining approval from the institutional ethical committee of Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra. The participants will be enrolled for study after considering the inclusion and exclusion criteria. The study will take place over two years, from September 2022 to August 2024.

After apprehending inclusion and exclusion criteria, all patients over the age of 18 with diabetic retinopathy who present to the Ophthalmology OPD at AVBRH will be offered to take part in the study. The central foveal thickness will be recorded by optical coherence tomography by Topcon Cirrus HD OCT before and after each intravitreal injection for every patient.