Randomized Controlled Trial Comparing Postoperative Topical Nepafenac and Dexamethasone Versus Dexamethasone Alone in Fuchs Dystrophy Patients Undergoing DMEC

The primary objective of this randomized clinical trial is to compare **central macular thickness** and the risk of **cystoid macular edema** between two postoperative medication regimens in patients undergoing corneal endothelial transplantation, specifically Descemet Membrane Endothelial Keratoplasty (DMEC). The study evaluates the efficacy of a combination of topical non-steroidal anti-inflammatory drugs (NSAIDs) and steroids versus the use of only topical steroids. This comparison is clinically relevant as it aims to determine the optimal postoperative treatment strategy to minimize inflammation and the risk of cystoid macular edema, which are significant complications that can affect visual outcomes in patients with **Fuchs dystrophy**. No secondary objectives are specified for this study.

The clinical trial focuses on individuals diagnosed with **Fuchs dystrophy** and aims to compare central macular thickness and the risk of cystoid macular edema between two medication regimens following corneal endothelial transplantation. The study population includes both male and female participants aged 18 years and older, with no upper age limit specified. Participants are required to be scheduled for either Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) or Descemet Membrane Endothelial Keratoplasty (DMEK). The trial does not involve a vulnerable population. Participants must be able to cooperate during examinations and provide informed consent, adhering to the study's requirements and restrictions. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed as a **randomized**, two-arm study to evaluate the efficacy of postoperative topical **NSAIDs** and steroids compared to only postoperative topical steroids in patients undergoing corneal endothelial transplantations, specifically Descemet Membrane Endothelial Keratoplasty (DMEK). The primary objective is to compare central macular thickness and the risk of cystoid macular edema between the two medication regimens. The trial is expected to run from November 25, 2022, to October 1, 2026, with participant involvement lasting up to nine months, depending on the treatment regimen assigned.

Participants will be required to attend several study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age (18 years and older), scheduled DSAEK or DMEK procedures, and the ability to cooperate during examinations. Following the screening, participants will be randomized into one of the two treatment arms. The study will include follow-up visits to monitor primary endpoints, such as central macular thickness and macular cysts using optical coherence tomography, and secondary endpoints, including laser flare, intraocular pressure, and corrected distance visual acuity. The end-of-study visit will conclude the participant's involvement, assessing the overall outcomes and any adverse events.

Participants may be withdrawn from the study early if they fail to comply with the study protocol, experience significant adverse effects, or withdraw consent. The trial is conducted under a double-blind design to ensure unbiased results, with neither participants nor investigators aware of the treatment allocation. The study involves the use of NEVANAC 3 mg/ml eye drops, suspension, and Spersadex 1 mg/ml eye drops, solution, both administered via the ophthalmic route. The maximum treatment period is six months for NEVANAC and nine months for Spersadex, with specific dosing regimens to be followed as per the protocol.

The clinical trial involves the administration of **NEVANAC 3 mg/ml eye drops, suspension**, which contains the active substance **nepafenac**. This medication is formulated as an ophthalmic suspension and is administered via the **ophthalmic** route. The dosage regimen for NEVANAC is one drop per day, with a maximum total dose of 42 drops over a treatment period of up to 6 weeks. The medication is produced by Novartis Europharm Limited and is chemically derived. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

Additionally, the trial includes the use of **Spersadex 1 mg/ml eye drops, solution**, which contains the active substance **dexamethasone**. This medication is provided as an ophthalmic solution and is also administered via the **ophthalmic** route. The dosage for Spersadex is up to five drops per day, with a maximum total dose of 1350 drops over a treatment period of up to 9 weeks. This product is manufactured by Blumont Ofta Trading Limited and is chemically synthesized. As with NEVANAC, participant adherence to the dosing schedule for Spersadex will be closely monitored to ensure compliance with the study protocol.

Both medications are utilized in the trial to compare the effects of postoperative topical NSAIDs and steroids versus only postoperative topical steroids in patients undergoing corneal endothelial transplantations. The primary objective is to assess central macular thickness and the risk of cystoid macular edema between the two medication regimens. No additional non-experimental treatments, such as standard-of-care therapy or placebo, are employed in this study.

Efficacy in this clinical trial will be assessed by comparing two medication regimens in patients undergoing corneal endothelial transplantation. The primary endpoints for evaluating efficacy include **central macular thickness** and the presence of macular cysts, which will be measured using optical coherence tomography. Secondary endpoints will include laser flare, peroperative factors such as operation time and intraocular manipulation, intraocular pressure (IOP) measured in mmHg using applanation and iCare methods, corrected distance visual acuity in logMAR, and corneal endothelial cell density measured with confocal microscopy in cells/mm². These parameters will be collected and analyzed to determine the effectiveness of the postoperative topical NSAIDs and steroids regimen compared to the regimen of only postoperative topical steroids. The trial is designed to provide a comprehensive assessment of the impact of these treatments on inflammation and cystoid macular edema following corneal endothelial transplantation.