Targeting Reactive Oxygen Species Production as a Novel Therapeutic in Fuch's Endothelial Corneal Dystrophy

Fuchs Endothelial Corneal Dystrophy (FECD) is the most common corneal endothelial disorder and has been estimated to affect approximately 4% of the US population over the age of 40. Corneal transplantation is currently the primary treatment modality available to treat FECD, and there are no medical therapies that treat the disease or stall its progression. Therefore, there is an unmet need to identify pharmacotherapeutic interventions that would prevent the endothelial cell loss in early through late stages of FECD, as well as after corneal transplantation, aiding in the survival of the corneal grafts.

The investigators know that cell loss in FECD is caused by increased oxidative stress in the CEC and aqueous humor of FECD. The investigators have in vitro and in vivo data showing that the processes involved in the development of FECD can be arrested with administration of N-acetyl cysteine (NAC). Currently topical solutions of NAC are already used in ophthalmology for application in keratoconjunctivitis sicca (using 20% weight/volume solution or 10%), meibomian gland dysfunction (using 5%) and Sjögren's dry eye syndrome (also using 5%).

This is a single center, double-blind, placebo-controlled, randomized trial. Adult participants with advanced FECD and cataracts who qualify for the standard treatment (combined Descemet Membrane Endothelial Keratoplasty (DMEK) and cataract surgery) will be enrolled at Massachusetts Eye and Ear.

After meeting eligibility criteria and completing informed consent, 30 eyes from up to 30 participants with advanced FECD and cataracts with indication for combined DMEK and cataract surgery will be initially enrolled. (NOTE: Some participants may be enrolled twice if they elect to have both eyes treated within the study.) Eyes will be randomized 1:1 to NAC 10% and the placebo, Visine Tears Dry Eye Relief artificial tears ophthalmic solution. Each participant will self-administer 1 drop of study drug four times a day in the planned operative eye for 28 days prior to planned surgery.

After interim analysis of the study with 30 eyes, if a significant difference in the primary endpoint between NAC 10% and placebo is not found, an additional 15 eyes from up to 15 participants will be enrolled and assigned to 20% NAC.

Prior to and after using the study medication, participants will complete patient-reported visual disability questionnaires and have corneal measurements and images taken. Participants additionally will complete a tolerability and medication adherence questionnaire after using the study medication.

In the operating room, a standard incision will be made to collect the fluid from the anterior part of the eye and replaced with a salt solution or viscous agent routinely used during the surgery. This procedure is routinely performed during this type of surgery, however, some of the aqueous fluid will be collected and analyzed rather than being discarded. Additionally, corneal tissue which is normally removed during corneal transplantation surgery and discarded will be kept for further research on FECD.

• Assessment of safety of NAC eye drops in patients with FECD by documenting the number and severity of adverse events. [Срок оценки: Ongoing safety assessment will occur starting on the first day when subjects receive the study drug, through the pre-operative visit, surgery and post-surgical follow-up visits, a period of approximately 6-7 weeks.]
• Assessment of tolerability of N-acetyl cysteine drops in patients with FECD by documenting participants' reports of irritation, burning, itchiness or redness in their eyes while taking the study drug [Срок оценки: Tolerability will be assessed after participants have taken study drug for 28 days or earlier, if the participants report difficulties tolerating the drug.]
• Change in patient-reported visual disability after NAC administration [Срок оценки: Assessed when subject starts study drug and again, 21 to 28 days later.]
• Change in central corneal thickness after NAC administration [Срок оценки: Assessed when subject starts study drug and again, 21 to 28 days later.]
• Change in corneal endothelial cell counts after NAC administration [Срок оценки: Assessed when subject starts study drug and again, 21 to 28 days later.]
• Changes in corneal tomography after NAC administration [Срок оценки: Assessed when subject starts study drug and again, 21 to 28 days later.]