Efficacy of Topical Hydrocortisone Sodium Phosphate and Dexamethasone Phosphate Versus Povidone in Treating Inflammatory Conjunctival Secretions in Ocular Prosthesis Patients

The primary objective of this study is to evaluate the **efficacy** of two topical treatments, hydrocortisone and dexamethasone, in comparison to a tear substitute, DULCILARMES®, on the **inflammatory secretions** of the conjunctiva in patients with ocular prostheses. This is clinically relevant as it aims to determine the most effective treatment for managing inflammation and secretions, which can significantly impact patient comfort and ocular health.

Secondary objectives include assessing the effect of these treatments on:

• Conjunctival **inflammation**
• Secretions
• Quality of life

The clinical trial involves participants diagnosed with **inflammatory secretions of the conjunctiva**, commonly associated with eye disease. The study population includes both male and female subjects aged 18 years and older. Participants are required to have been wearing a permanent prosthesis for more than six months and must have a modified OSDI score of 13 points or higher out of 40. All participants are affiliated with a health insurance scheme and have provided free, informed, and written consent. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. The selection criteria ensure that participants are consultants in the ophthalmology department, which may imply a certain level of health awareness and access to healthcare resources. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of two **topical** treatments, **hydrocortisone sodium phosphate** and **dexamethasone phosphate**, compared to a tear substitute, DULCILARMES®, in managing inflammatory secretions of the conjunctiva in patients with ocular prostheses. This is a prospective, randomized, double-blind, controlled trial. The trial is expected to commence on May 12, 2023, and conclude by June 1, 2026. The study will involve a series of visits, starting with an inclusion visit where participants will be screened based on specific criteria, including age (18 years or older), duration of prosthesis wear (more than 6 months), and a modified OSDI score of 13 or higher. Participants must also be affiliated with a health insurance scheme and provide informed consent.

Following the inclusion visit, participants will undergo a baseline assessment and be randomly assigned to one of the treatment groups. The trial will include follow-up visits to monitor the primary endpoint, which is the Secretion Self-Rating Scale score, and secondary endpoints such as bulbar and tarsal conjunctival inflammation scores, secretion frequency, and OSDI quality of life score. The treatment period for each participant is set at 14 days, with the possibility of early termination if adverse effects occur or if the participant withdraws consent. The end-of-study visit will involve a final assessment of the endpoints and overall health status of the participants. The expected length of participant involvement is approximately 14 days, with additional time for follow-up assessments as needed. Conditions leading to early termination include significant adverse reactions or non-compliance with the study protocol.

The clinical trial involves the use of three different **eye drops** solutions, each with a specific role in the study. The first experimental medication is **DEXAFREE 1 mg/ml**, an eye drop solution containing **dexamethasone phosphate** as the active substance. This medication is administered via **topical administration** directly into the eye cavity. The maximum daily dose is 360 µg, with a total maximum dose of 5040 µg over a treatment period of up to 14 days. The primary purpose of DEXAFREE is to utilize its anti-inflammatory properties to manage inflammatory secretions in patients with ocular prostheses.

The second experimental medication is **SOFTACORT 3.35 mg/ml**, also an eye drop solution, which contains **hydrocortisone sodium phosphate** as the active ingredient. Similar to DEXAFREE, SOFTACORT is administered topically in the eye cavity. The maximum daily dose is 0.48 mg, with a total maximum dose of 6.72 mg over a 14-day treatment period. SOFTACORT is used for its anti-inflammatory action, aiming to reduce inflammation in the conjunctiva of patients with ocular prostheses.

The comparator treatment in this trial is **DULCILARMES 1.5%**, an eye drop solution containing **povidone**. This solution is also administered topically in the eye cavity. The maximum daily dose is 4 units, with a total maximum dose of 56 units over a 14-day treatment period. DULCILARMES serves as a tear substitute and is used to evaluate the efficacy of the experimental treatments against a standard comparator in managing secretions in patients with ocular prostheses.

All medications are provided in single-dose containers to ensure precise dosing and minimize contamination risk. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment regimen. The trial aims to compare the efficacy of the two experimental anti-inflammatory treatments against the tear substitute in managing inflammatory secretions in the conjunctiva of patients with ocular prostheses.

Efficacy in the clinical trial titled "CRYSTAL: Comparison of topical hydrocortisone versus dexamethasone treatment for inflammatory secretions of the conjunctiva in patients with ocular prostheses" will be assessed using both primary and secondary endpoints. The primary endpoint is the Secretion Self-Rating Scale score, a 40-point score calculated as the sum of four criteria, each scored on 10 points. This scale is based on the methodologies of Jacobs et al. and Maucourant et al.

Secondary endpoints include several measures: the bulbar conjunctival inflammation score and tarsal conjunctival inflammation score, both evaluated according to the grades of Saini et al. Additionally, the secretion frequency, color, amount, and thickness/viscosity will be assessed using a secretion analysis scale, each scored out of 10 points as per Jacobs et al. Furthermore, the OSDI quality of life score, adapted for prosthesis wearers, will be used, which is scored on 40 points across 10 items, with a maximum of 4 points per item, following the methodology of Maucourant et al.