Pharmacogenomics of antiVEGF in Patients With Age-Associated Macular Degeneration (AMD)

A cycle of 3 intravitreal injections every 4-6 weeks of BVZ

Drug: Bevacizumab

A cycle of 3 intravitreal injections every 4-6 weeks of RBZ

Drug: Ranibizumab Ophthalmic

The dosage for each intravitreal injection is 1.25mg of BVZ in 0.05ml

The dosage for each intravitreal injection contains 0.5mg of RBZ in 0.05ml

Plazo: From baseline, first dose, up to 3 years

Proportion of patients carrying the VEGFA genetic polymorphism (VEGFA, CFH, CTFG, ARMS2, HTRA1, OR52B4, LOC387715, LOC100287225, LEPR, SERPINF1), as determined by genotyping of DNA extracted from saliva samples.

This measure will be correlated with response to anti-VEGF therapy (ranibizumab or aflibercept).

Unit of Measure: % of participants with polymorphism. Measurement Tool: Genotyping assay on saliva-derived DNA (e.g., TaqMan PCR-based method).

Plazo: Baseline, 6 months, 12 months, 24 months, 36 months

Visual acuity (VA), measured in number of letters read on the ETDRS chart, at baseline and at months 6, 12, 24, and 36. The change from baseline will be analyzed to assess treatment response over time.

Unit of Measure: Number of letters (ETDRS scale). Measurement Tool: ETDRS (Early Treatment Diabetic Retinopathy Study) visual acuity chart.

Plazo: Baseline, 6 months, 12 months, 24 months, 36 months

Retinal anatomical changes assessed by OCT, including presence and amount of intraretinal and/or subretinal fluid, and central foveal thickness (in microns), measured at baseline and at months 6, 12, 24, and 36. Differences between treatment arms (ranibizumab vs. bevacizumab) will be evaluated over time.

Unit of Measure: Microns for foveal thickness; qualitative presence/absence or categorical grading of retinal fluid Measurement Tool: Spectral-domain Optical Coherence Tomography (SD-OCT)

Plazo: At baseline

Proportion of male and female participants in the study population, analyzed in relation to treatment response to anti-VEGF drugs.

Unit of Measure: % of participants by sex. Measurement Tool: Demographic data collected via clinical records.

Plazo: At baseline

Age in years at time of AMD diagnosis for each participant. Age will be analyzed as a continuous variable in relation to treatment response.

Unit of Measure: Years. Measurement Tool: patient-reported age or medical record.

Plazo: At baseline

Proportion of participants with a history of tobacco use at baseline, categorized as current, former, or never smokers.

Unit of Measure: % of participants by smoking status. Measurement Tool: Patient-reported history via questionnaire or clinical interview.

Plazo: At baseline

Mean weight of participants measured at baseline. Weight will be used both as a descriptive baseline characteristic and as part of the BMI calculation.

Unit of Measure: Kilograms (kg) Measurement Tool: Calibrated digital scale

Plazo: At baseline

Mean height of participants measured at baseline. Height will be used both as a descriptive baseline characteristic and as part of the BMI calculation.

Unit of Measure: Meters (m) Measurement Tool: Stadiometer

Plazo: At baseline

Proportion of participants with obesity, defined as BMI ≥ 30 kg/m² at baseline. Unit of Measure: % of participants with BMI ≥ 30 kg/m². Measurement Tool: Body Mass Index (BMI) calculated from measured height and weight.

Plazo: At baseline

Proportion of participants with a diagnosis of hypertension at baseline. Unit of Measure: % of participants with hypertension. Measurement Tool: Clinical diagnosis from patient medical records or blood pressure measurement (≥140/90 mmHg).

Plazo: From intravitreal injection, up to 3 years

Total number of participants experiencing ocular or systemic adverse events, including cardiovascular events (e.g., myocardial infarction, stroke), following intravitreal injection of ranibizumab or bevacizumab. Events will be assessed cumulatively from the third intravitreal injection through the 3-year follow-up.

Unit of Measure: Number of participants with at least one adverse event. Measurement Tool: Clinical assessment and adverse event reporting as per standard pharmacovigilance procedures.

Plazo: From baseline up to 1 year

Total direct healthcare cost per patient treated with ranibizumab or bevacizumab over a 1-year period, based on a cost minimization analysis assuming similar clinical efficacy. Costs will be calculated from the perspective of the Spanish National Health System (SNS) and will include drug acquisition (considering container cost and fractionation), number of intravitreal injections, pharmacogenomic testing, and clinical monitoring. The NEI VFQ-25 composite score will be used to contextualize quality-of-life outcomes within the economic evaluation.

Unit of Measure: Euros per patient. Measurement Tool: Cost minimization analysis based on administrative and billing records; NEI VFQ-25 (National Eye Institute Visual Function Questionnaire) for quality-of-life scoring.

Multicentre, Randomised, Double-blind, Parallel-group, Phase III Study to Evaluate the Genetic Polymorphism Influence in the Response to Ranibizumab and Bevacizumab Treatment in Patients With Age-Associated Macular Degeneration.