Macular Edema Nepafenac vs. Difluprednate Uveitis Trial

Study Overview
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Brief Summary
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Macular edema is a condition in which there is swelling in the macula, the part of the retina that gives you your best vision. This swelling can cause your vision to decline. When diagnosed early and treated, you vision usually can be preserved. However, if the swelling goes untreated for a long time, it can cause permanent vision loss. We think that the three eye drop regimens in this study, difluprednate, difluprednate plus nepafenac, and prednisolone acetate plus nepafenac, might be effective in treating uveitic macular edema. Patients who enter this study are randomized to one of the three regimens and followed for 24 weeks.

Detailed Description
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Trial: Randomized 3 arm (1:1:1) parallel design comparative effectiveness trial Stratification: Systemic corticosteroid/immunosuppressive therapy vs. none Treatments: 1) difluprednate 0.05% 2) combination therapy of prednisolone acetate 1% with nepafenac 0.1% 3) combination therapy of difluprednate 0.05% with nepafenac 0.1% Masking: Unmasked treatment administration; masked outcome assessment (evaluation of OCT and visual acuity) Follow-up: 2, 4, 6, 8, and 24 weeks Treatment protocol: Patients will be randomized at enrollment to either: difluprednate 0.05% 4 drops per day prednisolone acetate 1% 4 drops per day and nepafenac 0.1% 3 drops per day difluprednate 0.05% 4 drops per day and nepafenac 0.1% 3 drops per day If macular edema has not resolved at Week 4, continue study treatment at the same dose until Week 6. If macular edema has resolved at Week 4, reduce study treatment as follows: difluprednate 0.05% 1 drop per day until Week 6, then stop prednisolone acetate 1% 1 drop per day and nepafenac 0.1% 3 drops per day until Week 6, then stop difluprednate 0.05% 1 drop per day and nepafenac 0.1% 3 drops per day until Week 6, then stop If macular edema does not resolve at Week 4 but has resolved at Week 6, reduce study treatment at Week 6 as follows: difluprednate 0.05% 1 drop per day until Week 8, then stop prednisolone acetate 1% 1 drop per day and nepafenac 0.1% 3 drops per day until Week 8, then stop difluprednate 0.05% 1 drop per day and nepafenac 0.1% 3 drops per day until Week 8, then stop If macular edema resolves at Week 4 but reoccurs at Week 6, treat per best medical judgement. After Week 8, there are no restrictions on the treatments patients may receive, and medications can be tapered further, discontinued, or changed at the discretion of the treating physician and patient preference. If a patient with previously resolved macular edema has a recurrence, the physician may treat according to best medical judgement.

Official Title
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Macular Edema Nepafenac vs. Difluprednate Uveitis Trial

Conditions
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Uveitis, Macular Edema

Intervention / Treatment
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* Drug: Difluprednate
* Drug: Nepafenac
* Drug: Prednisolone acetate


Participation Criteria
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Eligibility Criteria
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108 patients with uveitic ME will be enrolled at Aravind Eye Hospital in Madurai, India based on the following eligibility criteria: Patient-level Inclusion criteria: ≥18 years of age Diagnosis of anterior, intermediate, posterior, or panuveitis (can be infectious or non-infectious) Inactive or minimally active inflammation according to Standardization of Uveitis Nomenclature criteria (≤ 0.5+ Anterior Chamber (AC) cells, ≤ 0.5+ vitreous haze and no active retinal/choroidal lesions) If on oral corticosteroids, a stable dose of <10 mg prednisone/day for >4 weeks If on systemic corticosteroid-sparing immunomodulatory therapy, a stable dose for >4 weeks If using prednisolone acetate 1% drops, stable regimen of ≤2 drops per day for >4 weeks If infectious uveitis, inflammation must be inactive or minimally active per definition above and on stable dose of treatment for ≥4 weeks with no anticipated changes to treatment during the trial Eye-level Inclusion Criteria ME defined as thickening of the 1mm central subfield of the macula greater than 2 standard deviations above normal thickness (>320 µm by Heidelberg spectral-domain OCT) with or without the presence of intraretinal cysts. Baseline intraocular pressure >5 mmHg and <21 mmHg (current use ≤3 intraocular pressure-lowering medications and/or prior glaucoma surgery are acceptable) Media clarity and pupillary dilation sufficient to allow OCT testing and retinal photography Best-corrected visual acuity of 5/200 or better Patient-level Exclusion Criteria Use of oral acetazolamide or other systemic carbonic anhydrase inhibitors at baseline Known allergy or hypersensitivity to any component of the study drugs Women who are pregnant or breastfeeding (pregnancy test should be administered prior to baseline fluorescein angiogram) Patients unwilling or unable to not wear contact lenses during the study period History of central serous chorioretinopathy in either eye Eye-level Exclusion Criteria Intravitreal or periocular corticosteroid injection in the past 8 weeks, dexamethasone implant in the past 12 months, or a fluocinolone acetonide implant in the past 3 years Presence of an epiretinal membrane-noted clinically or by OCT-in the study eye, thought to be significant enough to preclude improvement of ME Previous pars plana vitrectomy History of severe glaucoma (C/D ratio > 0.9 or any notching of optic nerve to rim) Prior use of difluprednate or nepafenac in the past 4 weeks

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized 3 arm (1:1:1) parallel design comparative effectiveness trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Difluprednate<br>Difluprednate 0.05% ophthalmic emulsion 4 times a day until Week 4, then decrease according to protocol (if resolution of edema at 4 weeks, decrease to 1 drop per day until Week 6, then stop; if not resolved, continue at 4 times a day until 6 weeks and then decrease to 1 drop per day until Week 8 if resolved, then stop). If macular edema not resolved (or reoccurs) by Week 8, treat per best medical judgement. | Drug: Difluprednate<br>* Difluprednate 0.05% - corticosteroid eyedrop<br>* Other names: Durezol;|
| Experimental: Nepafenac plus Prednisolone acetate<br>Nepafenac 0.1% 3 times a day until resolution; prednisolone acetate 1% 4 times a day until Week 4, then decrease according to protocol (if resolution of edema at Week 4, decrease to 1 drop per day until Week 6, then stop; if not resolved, continue at 4 times a day until Week 6, then decrease to 1 drop per day until Week 8, then stop). If macular edema not resolved (or reoccurs) by Week 8, treat per best medical judgement. | Drug: Nepafenac<br>* Nepafenac 0.1% - NSAID eyedrop<br>* Other names: Nevanac;Drug: Prednisolone acetate<br>* prednisolone acetate 1% - corticosteroid eyedrop<br>* Other names: Pred Forte, Econo Pred;|
| Experimental: Difluprednate plus Nepafenac<br>Nepafenac 0.1% 3 times a day until resolution; Difluprednate 0.05% ophthalmic emulsion 4 times a day until Week 4, then decrease according to protocol (if resolution of edema at 4 weeks, decrease to 1 drop per day until Week 6, then stop; if not resolved, continue at 4 times a day until 6 weeks and then decrease to 1 drop per day until Week 8 if resolved, then stop). If macular edema not resolved (or reoccurs) by Week 8, treat per best medical judgement. | Drug: Difluprednate<br>* Difluprednate 0.05% - corticosteroid eyedrop<br>* Other names: Durezol;Drug: Nepafenac<br>* Nepafenac 0.1% - NSAID eyedrop<br>* Other names: Nevanac;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Central subfield thickness | Central subfield thickness measured by spectral domain optical coherence tomography adjusting for baseline thickness | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resolution | proportion of patients with resolution of macular edema | 4 weeks | 
| Improvement | proportion of patients with improvement in macular edema defined as 20% or greater reduction in central subfield thickness by OCT or resolution of edema | 4 weeks | 
| recurrence | proportion of patients with recurrence of macular edema defined as greater than 20% increase in central subfield thickness to a value >320 microns by OCT or presence of cysts in an eye that previously had resolution of macular edema | 4 weeks | 
| Intraocular pressure (IOP) increase | number of patients with intraocular pressure increase at least 10mmHg over baseline | 4 weeks | 
| High IOP | Number of patients experiencing high intraocular pressure (> 24 mmHg) | 4 weeks | 
| Visual acuity | best-corrected visual acuity (ETDRS protocol) | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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difluprednate, prednisolone acetate, nepafenac