Association of polymorphisms rs10410996, rs6677604 of the CFH gene, rs10490924 of the ARMS2 gene and rs11200638 of the HTRA1 gene with clinical-tomographic findings in neovascular age-related macular degeneration

Abstract

Introduction

Currently, the first line of treatment for neovascular AMD is antiangiogenic therapy. Recently, immunotherapy has been used, and anti-Vascular Endothelial Growth Factor (VEGF) drugs have been developed for the treatment of this disease. These have proven to be more cost-effective and have reduced adverse effects.

This proposal aims to develop new forms of diagnosis and prevention of the disease through the individual's own information, paving the way for personalized and precision medicine that improves treatment response rates, as well as reduces the prevalence of AMD and reduces costs and optimal treatment times.

General Objective

To identify the association of polymorphisms rs10410996 and rs6677604 of the CFH gene, rs10490924 of the ARMS2 gene, and rs11200638 of the HTRA1 gene with clinical and computed tomographic findings in neovascular age-related macular degeneration.

Specific Objectives

To characterize patients as responders or non-responders to anti-VEGF treatment based on clinical and computed tomographic findings.
To determine the polymorphisms rs10410996 and rs6677604 of the CFH gene, rs10490924 of the ARMS2 gene, and rs11200638 of the HTRA1 gene.
To evaluate the association of the studied polymorphisms with treatment response.
Methodology

Study Design
A longitudinal study will be conducted from August 2024 to January 2026, using non-probability sampling. These patients are being recruited from the Ophthalmology Department at the National Institute of Rehabilitation (LGII). Patients will be diagnosed with neovascular AMD and begin treatment. Data will be collected from their medical records, and a previously validated smoking questionnaire will be administered.

Study Population:
Inclusion Criteria:
The inclusion criteria are: a clinically confirmed diagnosis of neovascular AMD, treatment-naive, starting anti-VEGF therapy, of both sexes, aged 60 years and older, who agree to participate by signing an informed consent form, are not receiving any other treatment for AMD, and have no family members participating in the study.

Exclusion Criteria:
Withdrawal from the study (missing more than two appointments) and incomplete data for logistical or personal reasons will be excluded.

Exclusion Criteria:
All patients with glaucoma or prior ocular anti-angiogenic therapy will be excluded.

An exploratory and descriptive analysis of the study variables will be performed. The Shapiro-Wilk test will be used to evaluate data distribution. If the data are parametric, the Student t-test will be used, and the data will be presented with mean and standard deviation. If the data are nonparametric, the Mann-Whitney U test will be performed and the data will be presented as median and interquartile range (IQR). Differences between responders and non-responders will be assessed. Receiver operating curves (ROC) will be performed to evaluate the predictive capacity of oxidative stress variables to predict whether the individual is a responder or non-responder. Statistical analysis will be performed using STATA version 16 software.