Netarsudil Use After Descemetorhexis Without Endothelial Keratoplasty

Primary aim of the study is to determine whether a rho kinase inhibitor, Netarsudil, can speed corneal clearance after DWEK. Secondary aim of the study is to investigate whether patient factors, such as baseline age, pachymetry, or endothelial cell count influence response to Netarsudil.

Study Overview

• Status: Completed
• Conditions: Cataract; Fuchs' Endothelial Dystrophy
• Intervention / Treatment: Drug: Netarsudil 0.02% Ophthalmic Solution

Detailed Description

Spontaneous corneal clearance after Descemetorhexis without keratoplasty (DWEK) has been documented in several previous trials. One of the largest cohorts at Massachusetts Eye and Ear Infirmary demonstrated spontaneous corneal clearance in about 82% of cases but mean time to clearance was approximately three months after the procedure. During this time period, patients have significantly reduced central vision. Furthermore, some patients fail to have corneal clearance even eight months after DWEK and have to undergo Descemet membrane endothelial keratoplasty (DMEK) to achieve corneal clearance. A recent international case report has documents that the addition of a rho kinase inhibitor, Ripasudil, to two eyes that failed to clear by two to three months after DWEK resulted in corneal clearance within two weeks after the addition of Ripasudil. This finding indicates the possibility that a rho kinase inhibitor can be used to speed corneal clearance after purposeful Descemetorhexis. The only FDA approved rho kinase inhibitor eye drop currently available is Netarsudil, approved in December of 2017 for use in ocular hypertension and primary open angle glaucoma. Investigating whether Netarsudil can speed corneal clearance after DWEK is truly importance as the potential to expand patient eligibility for DWEK is significant. Both patients that had previously not wanted to wait approximately three months after the procedure for corneal clearance as well as patients with lower mid-peripheral endothelial cell counts may now be eligible for a procedure to treat corneal endothelial dysfunction without a corneal transplant. This would reduce risks for corneal transplant rejection and failure, reduce need for long-term steroid eye drop use, and reduce need for frequent corneal screenings to ensure transplant health.

The current study aims to investigate whether the off-label use of Netarsudil can improve corneal clearance after DWEK in Fuchs endothelial dystrophy patients.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts Eye and Ear Infirmary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Cataract in both eyes
• Fuchs endothelial dystrophy in both eyes

Exclusion Criteria:

• History of ocular surgery in one eye and not the other
• History of significant ocular trauma/burn in one eye and not the other
• Inability to provide informed consent
• Inability to undergo eye surgery
• Inablity to use eye drops reliably

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Netarsudil use; Patient eye undergoes cataract surgery + DWEK, immediately after surgery Netarsudil 0.02% ophthalmic 1 drop daily is used in the operative eye until corneal clearance is documented.	Drug: Netarsudil 0.02% Ophthalmic Solution; Use of Netarsudil 0.02% ophthalmic solution daily after surgery
Active Comparator: Standard of care + possible rescue drop; Patient eye undergoes cataract surgery + DWEK, no Netarsudil is used after surgery, if cornea is not cleared in time for first eye Netarsudil 0.02% ophthalmic 1 drop dailyadded daily as possible rescue drop and time to corneal clearance is documented	Drug: Netarsudil 0.02% Ophthalmic Solution; Use of Netarsudil 0.02% ophthalmic solution daily after surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to corneal clearance	Through study completion, an average of 6 months

Collaborators and Investigators

• Sponsor: Massachusetts Eye and Ear Infirmary
• Investigators: Principal Investigator: Emma E Davies, Massachusetts Eye and Ear Infirmary; Principal Investigator: Roberto Pineda, Massachusetts Eye and Ear Infirmary; Principal Investigator: Ula Jurkunas, Massachusetss Eye and Ear Infirmary

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2018
• Primary Completion (Actual): December 20, 2020
• Study Completion (Actual): December 20, 2020

Study Registration Dates

• First Submitted: August 11, 2019
• First Submitted That Met QC Criteria: August 12, 2019
• First Posted (Actual): August 14, 2019

Study Record Updates

• Last Update Posted (Actual): January 26, 2021
• Last Update Submitted That Met QC Criteria: January 24, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: DWEK, Netarsudil
• Additional Relevant MeSH Terms: Eye Diseases; Genetic Diseases, Inborn; Eye Diseases, Hereditary; Lens Diseases; Corneal Diseases; Corneal Dystrophies, Hereditary; Cataract; Fuchs' Endothelial Dystrophy; Pharmaceutical Solutions; Ophthalmic Solutions
• Other Study ID Numbers: 18-101H; 2019P000908 (Other Identifier: MGB IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No