Methotrexate Infusion and Intrasilicone Injection During Diabetic Vitrectomy

Study Overview
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Brief Summary
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The goal of this interventional clinical trial is to assess anatomical and functional outcomes of methotrexate use in irrigating fluid during parsplana vitrectomy combined with intrasilicone injection at end of surgery in patients with advanced proliferative diabetic retinopathy. The main questions it aims to answer are: Does methotrexate use in irrigating fluid during parsplana vitrectomy combined with intrasilicone injection at end of surgery decrease the post operative vitreoretinal proliferation after vitrectomy in patients with advanced proliferative diabetic retinopathy? Does methotrexate use in irrigating fluid during parsplana vitrectomy combined with intrasilicone injection at end of surgery improve post operative functional outcome after vitrectomy in patients with advanced proliferative diabetic retinopathy? Researchers will compare the anatomical and functional outcomes after vitrectomy in patients with advanced proliferative diabetic retinopathy without using methotrexate.

Detailed Description
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Tractional macular detachment (TMD) or macula threatening tractional retinal detachment (TRD) and combined tractional-rhegmatogenous retinal detachment (TRD/RRD) are considered as important indications for vitreoretinal intervention. Although a growing number of eyes with TMD and TRD/RRD are successfully treated with a single procedure, retinal re-detachment associated with fibrovascular proliferation or proliferative vitreoretinopathy (PVR) is still a major cause of failure of the surgery. Previous studies have shown increased expression of inflammatory cytokines and growth factors in both proliferative diabetic retinopathy (PDR) and PVR. Methotrexate (MTX) is an anti-neoplastic and anti-inflammatory agent used to treat a variety of malignancies and rheumatologic diseases. In ophthalmology, systemic and intraocular MTX has been successfully used for indeterminate uveitis, sarcoid uveitis and intraocular lymphoma. MTX has been recently found to inhibit PVR by stopping cellular proliferation and promoting organized apoptosis. MTX has also been found to be effective in lowering the incidence of PVR when used as an adjunct in irrigation fluid during vitrectomy for retinal detachment.

Official Title
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Anatomical and Functional Outcomes of Use of Methotrexate Infusion and Intrasilicone Injection During Diabetic Vitrectomy

Conditions
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Diabetic Retinopathy, Vitreomacular Traction

Intervention / Treatment
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* Drug: Methotrexate 25 MG/ML
* Procedure: parsplana vitrectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Patients with diabetic tractional macular detachment or combined tractional- rhegmatogenous retinal detachment Exclusion Criteria: Previous vitreoretinal surgery. Pregnant or lactating female. Co-existing pathology that might induce PVR such as penetrating ocular trauma or uveitis, co-existing congenital anomalies or hereditary vitreoretinopathies

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methotrexate group<br>methotrexate group will receive 40 mg of MTX in 500 ml of irrigation fluid during vitrectomy and 250 ug intra-silicone oil injection at the end of vitrectomy | Drug: Methotrexate 25 MG/ML<br>* Methotrexate is a folate derivative that inhibits several enzymes responsible for nucleotide synthesis. This inhibition leads to suppression of inflammation as well as prevention of cell division.<br>* Other names: Methotrexate Mylan 50 mg/2 mL;Procedure: parsplana vitrectomy<br>* Pars plana vitrectomy (PPV) is a technique in vitreoretinal surgery that enables access to the posterior segment for treating tractional retinal detachment in advanced proliferative diabetic retinopathy, in a controlled, closed system.<br>|
| Placebo Comparator: Control group<br>control group will not receive MTX in irrigation fluid during vitrectomy nor intra-silicone at the end of vitrectomy | Procedure: parsplana vitrectomy<br>* Pars plana vitrectomy (PPV) is a technique in vitreoretinal surgery that enables access to the posterior segment for treating tractional retinal detachment in advanced proliferative diabetic retinopathy, in a controlled, closed system.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| assess retinal layers by optical coherence tomography | presence of epiretinal membrane, cystic changes in retina, central macular thickens | one month after pars plana vitrectomy and one month after silicone oil evacuation | 
| assess functional outcomes by multifocal electroretinogram | latency and amplitude of main P wave | one month after pars plana vitrectomy and one month after silicone oil evacuation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anterior segment slit lamp biomicroscopic examination | assess anterior segment inflammation as iritis or posterior synechia | one month after pars plana vitrectomy | 
| visual acuity | by logMAR (Logarithm of the Minimum Angle of Resolution) | one month after pars plana vitrectomy and one month after silicone oil evacuation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Methotrexate, proliferative diabetic retinopathy