Evaluation of Spontaneous Retinal Arterial Pulsations as Prognostic Indicators in Central Retinal Vein Occlusion with Aflibercept Treatment

The primary objective of this study is to compare the evolution of **visual acuity** between the time of inclusion and the one-year follow-up visit in patients with **central retinal vein occlusions** (CRVO) who exhibit spontaneous retinal arterial pulsations (PARS) versus those who do not. This objective is clinically relevant as it aims to determine the prognostic value of PARS in predicting visual outcomes in CRVO patients, which could influence treatment strategies and patient management.

Secondary objectives include:

• Comparison of the percentages of PARS+ and PARS- patients at inclusion who develop macular edema during the first year of follow-up.
• Comparison of changes in macular thickness between diagnosis and the one-year visit in PARS+ and PARS- patients.
• Comparison of the occurrence of CRVO-related complications, such as neovascular glaucoma or intravitreal hemorrhage, during the first year of follow-up between PARS+ and PARS- patients.
• Comparison of the mean time between the last two aflibercept injections in PARS+ and PARS- patients, specifically for those treated with aflibercept.

The clinical trial focuses on patients diagnosed with **central retinal vein occlusion** (CRVO), with or without macular edema. The study population includes both male and female participants over the age of 18, who are naïve to intravitreal injection and intravitreal corticosteroid implant. Participants must be members or beneficiaries of a health insurance scheme and have experienced the onset of symptoms within the previous month, with a maximum of 30 days prior to inclusion. Women of childbearing age are required to commit to effective contraception during aflibercept treatment and for at least three months after the last intravitreal injection. The sponsor has not provided information regarding the total number of participants. The trial does not involve a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted. Participants were selected based on their diagnosis and consent to participate, having received informed information about the study. The trial aims to compare the evolution of visual acuity between inclusion and the one-year visit in CRVO patients with PARS versus those without PARS.

The clinical trial is designed to evaluate the prognostic value of **spontaneous retinal arterial pulsations** in patients with **central retinal vein occlusions** (CRVO) treated with or without intravitreal injections of **aflibercept**. This is a phase 4, randomized, double-blind, controlled trial with an estimated duration from March 2021 to March 2025. The primary objective is to compare the evolution of visual acuity between the inclusion and the one-year visit in CRVO patients with and without pulsations. The primary endpoint is the change in visual acuity, measured in letters read on the ETDRS scale, from the start of treatment to one year. Secondary endpoints include the assessment of macular edema, measurement of macular thickness, collection of CRVO complications, and documentation of the number and timing of aflibercept injections over the first year.

Participants will be involved in the study for a maximum of 12 months. The study begins with an inclusion visit, where eligibility is confirmed based on criteria such as age over 18, diagnosis of CRVO, and naivety to intravitreal injections. Participants must have experienced symptom onset within the previous month and provide informed consent. Women of childbearing age must commit to effective contraception during treatment and for three months after the last injection. Follow-up visits will occur periodically to monitor visual acuity, macular condition, and treatment administration. The end-of-study visit will conclude the trial, assessing the primary and secondary endpoints.

Participants may be terminated early from the study if they withdraw consent, experience adverse effects, or fail to comply with study protocols. The trial will utilize **Eylea 40 mg/mL solution for injection in pre-filled syringes**, administered via intravitreal use, with a maximum daily dose of 2 mg. The trial is not classified as low intervention and is conducted under the sponsorship of Bayer AG. The study aims to provide confirmatory data on the efficacy and safety of aflibercept in the treatment of CRVO, contributing to the understanding of its role in managing this condition.

The clinical trial involves the administration of **Eylea**, a pharmaceutical product containing the active substance **aflibercept**. Eylea is formulated as a **solution for injection** in a pre-filled syringe, with a concentration of 40 mg/mL. The medication is administered via **intravitreal use**, which involves injecting the solution directly into the eye. The maximum daily dose is 2 mg, and the treatment period can extend up to 12 months. Aflibercept is a protein-based therapeutic agent, specifically categorized under "Protein - Other," and is produced by Bayer AG. The product is identified by the marketing authorization number EU/1/12/797/001 and is approved for use in the European Union.

In this study, Eylea is used to evaluate its efficacy in patients with Central Retinal Vein Occlusions (CRVOs), with a focus on comparing visual acuity outcomes between patients exhibiting Spontaneous Retinal Arterial Pulsations (SRAPs) and those without. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the prescribed treatment regimen.

Efficacy in this clinical trial will be assessed primarily through the change in visual acuity, measured by the Best Corrected Visual Acuity (BCVA) on the ETDRS scale, in letters read and validated between the start of treatment and one year. This primary endpoint will provide a quantitative measure of visual improvement or decline in patients with Central Retinal Vein Occlusion (CRVO) treated with **aflibercept**.

Secondary endpoints include the determination of macular edema by an ophthalmologist using Optical Coherence Tomography (OCT) examination, and the measurement of macular thickness in micrometers (µm) using OCT-integrated measurement software. Additionally, the trial will collect data on CRVO complications, the number of aflibercept injections during the first year, and the time between the last two injections of aflibercept, all recorded at one year from the patient's file. These secondary endpoints will provide further insights into the treatment's impact on retinal health and the management of CRVO.