Safety and Efficacy of Intracanalicular Dexamethasone Compared to Loteprednol Etabonate in Patients With Keratoconus

Safety and Efficacy of Intracanalicular Dexamethasone Insert Compared to Loteprednol Etabonate Ophthalmic Gel 0.38% in Patients With Keratoconus Wearing Gas Permeable Contact Lenses Who Have Been Diagnosed With Allergic Conjunctivitis

Drug delivery platforms are an innovative exciting advancement in ophthalmology. They allow patients to eliminate topical medications which are generally associated with lack of compliance, difficulty of use and requiring help from family members. These delivery systems can be applied easily in office, and patients do not have to worry about drop insertion in their post-operative regimen.

The results of this research project should help to answer the following question: Does the use of a physician administered intracanalicular dexamethasone insert improve the signs and symptoms of ocular allergy and dry eye disease in KC patients compared to the use of topical loteprednol etabonate ophthalmic gel 0.38%?

This prospective, open-label, single-center, randomized, fellow-eye, investigator-sponsored clinical study seeks to investigate the safety and efficacy of the dexamethasone insert in the treatment of allergic conjunctivitis and DED signs and symptoms in patients with Keratoconus using RGP contact lenses when compared to topical standard of care loteprednol etabonate ophthalmic gel 0.38%.

Patients with keratoconus who present for their routine visit who have signs and symptoms of dry eye and allergies, will be asked if they want to participate in the study. After screening a given patient for inclusion and exclusion criteria, and gaining informed consent, one eye will be randomized to receive the dexamethasone insert as determined by a coin flip at the screening visit. The remaining eye will be prescribed a loteprednol etabonate ophthalmic gel 0.38% following a 4,3,2,1 weekly taper. Per enrolled eye, the study period will last for approximately 90 days, consisting of five visits. At Screening/ Baseline, Day 0, Day 7, Day 30 and Day 90, primary and secondary endpoints will be assessed alongside standard-of-care procedures. Adjusting for enrollment period, the study will last a total of approximately 3 months

Inclusion Criteria

A patient's study eye must meet the following criteria to be eligible for inclusion in the study:

• 18 years of age or older
• Bilateral Keratoconus
• Bilateral RGP contact lenses
• Bilateral allergic conjunctivitis as determined by the Papillae Efron Scale score of at least 1 and symptoms of itching
• Bilateral underlying dry eye disease as determined by the NEI Fluorescein Staining Scale score of at least 1 and a TBUT of less than 10 and must correlate with dryness on OSDI

Exclusion Criteria

A patient who meets any of the following criteria will be excluded from the study:

• Patients under the age of 18.
• Pregnancy (must be ruled out in women of child-bearing age with pregnancy test)
• Active infectious systemic disease
• Active infectious ocular or extraocular disease
• Obstructed nasolacrimal duct in the study eye(s)
• Hypersensitivity to dexamethasone
• Patients being treated with immunomodulating agents in the study eye(s)
• Patients being treated with immunosuppressants and/or oral steroids Patients with severe disease that warrants critical attention, deemed unsafe for the study by the investigator

Study Procedures Screening/Baseline (Visit 1)

After the patient has provided informed consent, the following information will be collected:

• Inclusion/Exclusion
• Demographics
• Medical History and Concurrent Illnesses
• Concomitant Medications
• Uncorrected and best-corrected visual acuity with manifest refraction as measured by ETDRS chart at 4 meters
• Ophthalmic Examination (with or without dilation)
• QOL assessment as measured by OSDI questionnaire
• Osmolarity (Needs to be done prior to any drop instillation)
• MMP9 (Needs to be done prior to any drop instillation)
• Grading of itching (scale 0-4)
• Papillae conjunctivitis assessment (Efron Scale)
• Conjunctival Injection
• Corneal Staining
• TBUT
• Intraocular Pressure

Insertion Visit/Day 0 (Visit 2)

• Concomitant Medications
• Uncorrected and best-corrected visual acuity with manifest refraction as measured by ETDRS chart at 4 meters
• Ophthalmic Examination (with or without dilation)
• QOL assessment as measured by OSDI questionnaire
• Osmolarity (Needs to be done prior to any drop instillation)
• MMP9 (Needs to be done prior to any drop instillation)
• Grading of itching (scale 0-4)
• Papillae conjunctivitis assessment (Efron Scale)
• Conjunctival Injection
• Corneal Staining
• TBUT
• Intraocular Pressure
• Insertion of Dextenza (intracanalicular dexamethasone insert)
• Insert Visualization
• Subject reported AEs after insertion
• Physician ease of insertion grading

Day 7 (Visit 3)

• Concomitant Medications
• Uncorrected and best-corrected visual acuity with manifest refraction as measured by ETDRS chart at 4 meters
• Ophthalmic Examination (with or without dilation)
• QOL assessment as measured by OSDI questionnaire
• Osmolarity (Needs to be done prior to any drop instillation)
• MMP9 (Needs to be done prior to any drop instillation)
• Grading of itching (scale 0-4)
• Papillae conjunctivitis assessment (Efron Scale)
• Conjunctival Injection
• Corneal Staining
• TBUT
• Intraocular Pressure
• Insert Visualization
• Subject reported AEs after insertion

Day 30 (Visit 4)

• Concomitant Medications
• Uncorrected and best-corrected visual acuity with manifest refraction as measured by ETDRS chart at 4 meters
• Ophthalmic Examination (with or without dilation)
• QOL assessment as measured by OSDI questionnaire
• Osmolarity (Needs to be done prior to any drop instillation)
• MMP9 (Needs to be done prior to any drop instillation)
• Grading of itching (scale 0-4)
• Papillae conjunctivitis assessment (Efron Scale)
• Conjunctival Injection
• Corneal Staining
• TBUT
• Intraocular Pressure
• Insert Visualization
• Subject reported AEs after insertion

Day 90 (Visit 5) or Early Termination

• Concomitant Medications
• Uncorrected and best-corrected visual acuity with manifest refraction as measured by ETDRS chart at 4 meters
• Ophthalmic Examination (with or without dilation)
• QOL assessment as measured by OSDI questionnaire
• Osmolarity (Needs to be done prior to any drop instillation)
• MMP9 (Needs to be done prior to any drop instillation)
• Grading of itching (scale 0-4)
• Papillae conjunctivitis assessment (Efron Scale)
• Conjunctival Injection
• Corneal Staining
• TBUT
• Intraocular Pressure
• Insert Visualization
• Subject reported AEs after insertion
• COMTOL

Inclusion Criteria:

• 18 years of age or older
• Bilateral Keratoconus
• Bilateral RGP contact lenses
• Bilateral allergic conjunctivitis as determined by the Papillae Efron Scale score of at least 1 and symptoms of itching
• Bilateral underlying dry eye disease as determined by the NEI Fluorescein Staining Scale score of at least 1 and a TBUT of less than 10 and must correlate with dryness on OSDI

Exclusion Criteria:

• Patients under the age of 18.
• Pregnancy (must be ruled out in women of child-bearing age with pregnancy test)
• Active infectious systemic disease
• Active infectious ocular or extraocular disease
• Obstructed nasolacrimal duct in the study eye(s)
• Hypersensitivity to dexamethasone
• Patients being treated with immunomodulating agents in the study eye(s)
• Patients being treated with immunosuppressants and/or oral steroids Patients with severe disease that warrants critical attention, deemed unsafe for the study by the investigator