Fuchs Endothelial Corneal DystrophyPhase 2NCT04440280
Targeting Reactive Oxygen Species Production as a Novel Therapeutic in Fuch's Endothelial Corneal Dystrophy
A Phase 2 study testing N-acetyl cysteine (NAC) 10% solution, N-acetyl cysteine (NAC) 20% solution and Visine Dry Eye Relief eye drops in people with Fuchs Endothelial Corneal Dystrophy, run by Massachusetts Eye and Ear Infirmary at 1 site in United States.
Trial summary
This protocol will investigate whether topical application of N-acetyl cysteine (NAC) eye drops decreases oxidative stress and confers cytoprotection in patients with FECD. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Fuchs Endothelial Corneal Dystrophy
- What is being tested?
- N-acetyl cysteine (NAC) 10% solution, N-acetyl cysteine (NAC) 20% solution and Visine Dry Eye Relief eye drops
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Sep 2020to 30 Apr 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female ≥21 years of age at time of surgical evaluation.
- Diagnosis of advanced FECD and visually significant cataract
- Indication for DMEK (Descemet Membrane Endothelial Keratoplasty) with concurrent cataract surgery
- Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
- Willingness and ability to adhere to medication regimen
Who cannot join
- Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
- History of prior intraocular surgery in study eye including cataract, glaucoma and/or retina surgery
- History of other corneal diseases, such as severe dry eye, corneal scars, pseudophakic bullous keratopathy, corneal degenerations, corneal infections
- Use of ocular prescription medications except for lubricants, hyperosmotic agents, or ocular hypotensive agents
- History of ocular surface infection within the past 30 days
- Use of systemic, inhalational, or topical N-Acetylcysteine within the past 30 days
Show all 9Show fewer
- History of intolerance to topical N-Acetylcysteine
- Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
- -
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Massachusetts Eye and Ear Infirmary
Boston, Massachusetts, 02114
Ula Jurkunas, MD, 6175734330, Ula_Jurkunas@meei.harvard.edu
Michael Cheung, MSc. CCRP, 6175736060 ext. Cheung, mcheung0@meei.harvard.edu
About this study
This protocol will investigate whether topical application of N-acetyl cysteine (NAC) eye drops decreases oxidative stress and confers cytoprotection in patients with FECD.
Read the detailed description
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.
- Conditions
- Fuchs Endothelial Corneal Dystrophy
- Being tested
- N-acetyl cysteine (NAC) 10% solution, N-acetyl cysteine (NAC) 20% solution, Visine Dry Eye Relief eye drops
- Keywords
- Fuchs, Fuchs Endothelial Corneal Dystrophy, oxidative stress, N-Acetylcysteine ophthalmic drops, Descemet Membrane Endothelial Keratoplasty, DMEK
- Medical subject headings
- Fuchs' Endothelial Dystrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetyl cysteine (NAC) 10% solutionDrug
Also called acetylcysteine
N-acetyl cysteine is a sterile, unpreserved eye drop containing 10% (100 mg/mL) of acetylcysteine.
N-acetyl cysteine (NAC) 20% solutionDrug
Also called acetylcysteine
N-acetyl cysteine is a sterile, unpreserved eye drop containing 20% (200 mg/mL) of acetylcysteine.
Visine Dry Eye Relief eye dropsDrug
Visine Tears Dry Eye Relief artificial tears ophthalmic solution
| Study group | Role | What they receive |
|---|---|---|
| NAC 10% group | Active comparator | Subjects in this group will be treated with eye drops containing a 10% solution of N-acetyl cysteine. Topical NAC is a well-tolerated medication that has many applications in ophthalmology including dry eye disease and meibomian gland dysfunction. Receives: Drug: N-acetyl cysteine (NAC) 10% solution |
| NAC 20% group | Active comparator | Subjects in this group will be treated with eye drops containing a 20% solution of N-acetyl cysteine. Topical NAC is a well-tolerated medication that has many applications in ophthalmology including dry eye disease and meibomian gland dysfunction. Receives: Drug: N-acetyl cysteine (NAC) 20% solution |
| Placebo group | Placebo comparator | Subjects in this group will be treated with a placebo (Visine Tears Dry Eye Relief artificial tears ophthalmic solution.) Receives: Drug: Visine Dry Eye Relief eye drops |
What is being measured
The primary outcome is the main question the study is designed to answer.
Level of H2O2 in the aqueous humor
The primary endpoint is the level of H2O2 in the aqueous humor obtained at time of DMEK surgery.
Measured: DMEK Surgery occurs 28 to 42 days after participant enrollment
Secondary outcomes (6)
Assessment of safety of NAC eye drops in patients with FECD by documenting the number and severity of adverse events.
Safety assessment will be ongoing for the entire 28 days that study participants take study drug (prior to surgery) and in all post surgical follow-up visits. Assessment will be based on the number and severity of adverse events, with specific scrutiny for evidence of severe ocular adverse reactions such as ocular chemosis, severe injection, presence or worsening of corneal epithelial staining and/or epithelial defects.
Measured: 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
Participants will be asked to fill out a tolerability and medication adherence questionnaire where they will rate the irritation, burning, itchiness and redness they experience after using the medication on a scale of 1 to 100.
Measured: 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
Change in patient-reported visual disability will be obtained using the previously validated questionnaire, V-FUCHS instrument 10 before and after the study drug is administered. Participants will be asked how often they experience specific visual difficulties selecting from the following choices: never, rarely, sometimes, most of the time or all of the time. Participants will also be asked how much difficulty they have performing certain visual tasks. Options for the answers are: No difficulty, a little difficulty, moderate difficulty, a lot of difficulty or extreme difficulty.
Measured: Assessed when subject starts study drug and again, 21 to 28 days later.
Change in central corneal thickness after NAC administration
Change in central corneal thickness as measured by CCT; decrease by >30 µm before and after NAC drop administration period.
Measured: Assessed when subject starts study drug and again, 21 to 28 days later.
Change in corneal endothelial cell counts after NAC administration
Change in the number of corneal endothelial cells as determined by HRT3 with Rostock Corneal Module (Heidelberg Engineering, Heidelberg, Germany) before and after NAC drop administration period. If central counts are unattainable due to end-stage of FECD, then peripheral counts will be obtained.
Measured: Assessed when subject starts study drug and again, 21 to 28 days later.
Changes in corneal tomography after NAC administration
Corneal tomography is a three-dimensional imaging technique that characterizes the anterior/posterior corneal surfaces. Participants will have corneal tomography twice: first before they start the study drug, and then again, 28 to 42 days later when the drug treatment has concluded. Change in corneal tomography imaging will be assessed qualitatively.
Measured: Assessed when subject starts study drug and again, 21 to 28 days later.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2020
- Study start16 Sep 2020
- Primary completion29 Apr 2027 (estimated)
- Study completion30 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fuchs Endothelial Corneal DystrophyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Initially, 30 eyes from up to 30 participants will be randomized 1:1 to one of two groups, a group administering N-acetyl cysteine (NAC) 10% and a group administering Visine Tears Dry Eye Relief artificial tears ophthalmic solution (the placebo). 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 to investigate 20% NAC.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts Eye and Ear Infirmary
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ula Jurkunas, Massachusetts Eye and Ear Infirmary
- Investigators
- Ula Jurkunas, MD, Principal investigator, Mass Eye and Ear
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04440280
- Sponsor's protocol ID
- 2020P001909
- Status last verified
- Sep 2025
- First submitted
- 11 Jun 2020
- Last updated
- 2 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Reactive Oxygen Species Production as a Novel Therapeutic in Fuch's Endothelial Corneal Dystrophy
- ClinicalTrials.gov ID
- NCT04440280
- Acronym / sponsor ID
- 2020P001909
- Conditions
- Fuchs Endothelial Corneal Dystrophy
- Keywords
- Fuchs, Fuchs Endothelial Corneal Dystrophy, oxidative stress, N-Acetylcysteine ophthalmic drops, Descemet Membrane Endothelial Keratoplasty, DMEK
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Massachusetts Eye and Ear InfirmaryUniversity, hospital or other
- Study start
- 16 Sep 2020 (actual)
- Primary completion
- 29 Apr 2027 (estimated)
- Study completion
- 30 Apr 2027 (estimated)
- First posted
- 19 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This protocol will investigate whether topical application of N-acetyl cysteine (NAC) eye drops decreases oxidative stress and confers cytoprotection in patients with FECD.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
- Model description
- Initially, 30 eyes from up to 30 participants will be randomized 1:1 to one of two groups, a group administering N-acetyl cysteine (NAC) 10% and a group administering Visine Tears Dry Eye Relief artificial tears ophthalmic solution (the placebo). 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 to investigate 20% NAC.
| Arm | Type | Receives |
|---|---|---|
| NAC 10% group | Active comparator | Drug: N-acetyl cysteine (NAC) 10% solutionSubjects in this group will be treated with eye drops containing a 10% solution of N-acetyl cysteine. Topical NAC is a well-tolerated medication that has many applications in ophthalmology including dry eye disease and meibomian gland dysfunction. |
| NAC 20% group | Active comparator | Drug: N-acetyl cysteine (NAC) 20% solutionSubjects in this group will be treated with eye drops containing a 20% solution of N-acetyl cysteine. Topical NAC is a well-tolerated medication that has many applications in ophthalmology including dry eye disease and meibomian gland dysfunction. |
| Placebo group | Placebo comparator | Drug: Visine Dry Eye Relief eye dropsSubjects in this group will be treated with a placebo (Visine Tears Dry Eye Relief artificial tears ophthalmic solution.) |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female ≥21 years of age at time of surgical evaluation.
- Diagnosis of advanced FECD and visually significant cataract
- Indication for DMEK (Descemet Membrane Endothelial Keratoplasty) with concurrent cataract surgery
- Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
- Willingness and ability to adhere to medication regimen
Key exclusion criteria (9 listed)
- Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
- History of prior intraocular surgery in study eye including cataract, glaucoma and/or retina surgery
- History of other corneal diseases, such as severe dry eye, corneal scars, pseudophakic bullous keratopathy, corneal degenerations, corneal infections
- Use of ocular prescription medications except for lubricants, hyperosmotic agents, or ocular hypotensive agents
- History of ocular surface infection within the past 30 days
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-acetyl cysteine (NAC) 10% solutionAlso: acetylcysteineN-acetyl cysteine is a sterile, unpreserved eye drop containing 10% (100 mg/mL) of acetylcysteine. | Drug | NAC 10% group |
| N-acetyl cysteine (NAC) 20% solutionAlso: acetylcysteineN-acetyl cysteine is a sterile, unpreserved eye drop containing 20% (200 mg/mL) of acetylcysteine. | Drug | NAC 20% group |
| Visine Dry Eye Relief eye dropsVisine Tears Dry Eye Relief artificial tears ophthalmic solution | Drug | Placebo group |
Primary outcome
Level of H2O2 in the aqueous humor
Time frame: DMEK Surgery occurs 28 to 42 days after participant enrollment
The primary endpoint is the level of H2O2 in the aqueous humor obtained at time of DMEK surgery.
6 secondary outcomes
Assessment of safety of NAC eye drops in patients with FECD by documenting the number and severity of adverse events.
Time frame: 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
Time frame: 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
Time frame: Assessed when subject starts study drug and again, 21 to 28 days later.
Change in central corneal thickness after NAC administration
Time frame: Assessed when subject starts study drug and again, 21 to 28 days later.
Change in corneal endothelial cell counts after NAC administration
Time frame: Assessed when subject starts study drug and again, 21 to 28 days later.
Changes in corneal tomography after NAC administration
Time frame: Assessed when subject starts study drug and again, 21 to 28 days later.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ula Jurkunas, MD principal investigator
Mass Eye and Ear
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing N-acetyl cysteine (NAC) 10% solution, N-acetyl cysteine (NAC) 20% solution and Visine Dry Eye Relief eye drops in people with Fuchs Endothelial Corneal Dystrophy, run by Massachusetts Eye and Ear Infirmary at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Michael Cheung, MSc, CCRP (6175736060, mcheung0@meei.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Level of H2O2 in the aqueous humor (time frame: DMEK Surgery occurs 28 to 42 days after participant enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2026.