Efficacy and Tolerance Comparison Between Subconjunctival Injection of Triamcinolone and Intravitreal Implant of Dexamethasone for the Treatment of Inflammatory Macular Edema

Study Overview
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Brief Summary
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Corticosteroids, whether injected peri- or intra-ocularly, remain indispensable tools of the therapeutic arsenal in treating inflammatory macular edema. However, a few years ago, only triamcinolone acetonide was available to ophthalmologists. This molecule, developed initially for rheumatological or dermatological use, has been increasingly deployed in ophthalmology, while still off-label. In 2011, the delivery system of dexamethasone from biodegradable and injectable implant into the vitreous cavity obtained the label for inflammatory macular edema. This protocol is therefore designed to compare the efficacy and safety of peri- and intra-ocular injections of corticosteroids in the treatment of inflammatory macular edema.

Detailed Description
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This research compares the implantation techniques of corticosteroids in the eye, with two groups of equal size being followed. This is a multi-center, controlled study, with the reference drug being the intravitreal implant of 700μg of dexamethasone (Ozurdex®) compared to subconjunctival injection of triamcinolone (Kénacort retard®). This is an open, prospective, randomized study. It is not possible, for technical reasons, to inject blind two products with different injection routes and that are visible to the investigator during control examinations (sub-conjunctival crystals and intravitreal implant). However, the assessment of visual acuity and central macular thickness will be performed by an uninformed ophthalmologist.

Official Title
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Efficacy and Tolerance Comparison Between Subconjunctival Injection of Triamcinolone and Intravitreal Implant of Dexamethasone for the Treatment of Inflammatory Macular Edema

Conditions
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Inflammatory Macular Edema

Intervention / Treatment
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* Drug: Dexamethasone
* Drug: Triamcinolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient, male or female (under effective contraception if premenopausal) over 18 years old Patient affiliated with a social security plan Patient able to understand and follow the instructions of the study Patient having signed an informed consent Patient having a central macular thickness greater than 320μm (Spectral Domain, 270µm Time Domain) Patient with an inflammatory macular edema, unilateral or bilateral (in the case of a bilateral inflammatory macular edema, the eye most affected will be treated) Exclusion Criteria: Patient with an infectious uveitis Patient with uncontrolled active infection Patient receiving an unbalanced general anti-inflammatory and/or immunosuppressive and/or immunomodulatory therapy (recent modification <1 month) Patient having a history of glaucoma and/or ocular hypertension in the eye studied (intraocular pressure (IOP) > 25 mmHg without antiglaucoma medication or > 21 mmHg with antiglaucoma combination therapy) and/or cortisone-causing-hypertension not controlled by an antiglaucoma dual therapy Patient with uncontrolled diabetes (HbA1c> 8%) or unbalanced hypertension (Systolic Blood Pressure > 160 mmHg and/or Diastolic Blood Pressure > 100mmHg) Edematous diabetic maculopathy Patient who had received triamcinolone (subconjunctivally or sub-tenon) 3 months before randomization, or 700μg dexamethasone intravitreally 6 months before randomization Suspected or active ocular or periocular infection, including most viral diseases of the cornea and conjunctiva, such as active epithelial keratitis with herpes simplex (dendritic keratitis), vaccinia, varicella, mycobacterial infections and mycoses History of ocular herpes infection or central serous chorioretinopathy Aphakic eye with rupture of the posterior lens capsule Eye with implant in the anterior chamber, iris- or transscleral-fixated intraocular implant and rupture of the posterior lens capsule Uncontrolled systemic inflammatory disease. Known hypersensitivity to the active substance or to one of the excipients of Ozurdex®, Kenacort® or injectable fluorescein Pregnant woman or likely to become pregnant or nursing Patient participating in another clinical trial Adult under a legal protection regime (guardianship, trusteeship, sauvegarde de justice)

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Reference Drug<br>Intravitreal implant of 700μg of dexamethasone (Ozurdex®) | Drug: Dexamethasone<br>* Intravitreal implant at D0<br>* Other names: Ozurdex®;|
| Experimental: Tested Drug<br>Subconjunctival injection of 16 mg triamcinolone (Kénacort Retard®) | Drug: Triamcinolone<br>* Subconjunctival injection at 4 mm from the limbus at 6 o'clock<br>* Other names: Kénacort retard®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the effectiveness of a subconjunctival injection of triamcinolone on reducing the central macular thickness versus an intravitreal implant of dexamethasone between patient selection and 2 months after treatment | Difference of the central macular thickness in the treated eye, measured by Optical Coherence Tomography (OCT) spectral domain, for each patient between patient selection and 2 months after treatment | At 2 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the experience of the injection by a questionnaire (tolerable, unpleasant and very unpleasant) and by EVA (0 cm = no pain to 10 cm = extreme pain) | Scale of patient experience the day of the injection (tolerable, unpleasant, very unpleasant) and visual analogue scale (VAS) | At day 0 (= the day of the treatment) | 
| Evaluation of the effectiveness of the studied injection at each visit regarding gain in visual acuity (ETDRS) | Visual acuity (ETDRS) | Up to 6 months | 
| Evaluation of the effectiveness of the studied injection at each visit regarding reduction of the anterior flare | Anterior flare (Lampe A Fente and Laser Flare Meter, if available) | Up to 6 months | 
| Evaluation of the effectiveness of the studied injection at each visit regarding reduction of the vitreous haze | Vitreous flare | Up to 6 months | 
| Evaluation of the effectiveness of the studied injection at each visit regarding central macular thickness measured by OCT, allowing the evaluation of the duration of action of the treatment | Central macular thickness of the eye treated for determining the duration of action | Up to 6 months | 
| Evaluation of the effectiveness of the studied injection at each visit regarding local and general tolerance, by collecting all Adverse Events (AEs) / Serious Adverse Events (SAEs) | Evaluation of tolerance by collecting all AEs / SAEs of randomized patients, such as intra-ocular hypertension, cataracts, endophthalmitis, poor glycemic and/or blood pressure control | Up to 6 months | 
| Evaluation of the effectiveness of the studied injection at each visit regarding patients' quality of life | Patients' quality of life questionnaire (EQ-5D) | Up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ophthalmology, Uveitic macular edema, Triamcinolone subconjunctival injection, Dexamethasone intraocular implant