Methotrexate Infusion and Intrasilicone Injection During Diabetic Vitrectomy

Diabetic Retinopathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06038968
• Other study ID #: MTX DM vitrectomy
• Status: Completed
• Phase: Early Phase 1
• Start date: September 1, 2022
• Est. completion date: January 1, 2024

Study information

• Verified date: September 2023
• Source: Minia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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:

1. 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?

2. 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: January 1, 2024
• Est. primary completion date: November 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetic Retinopathy
• Retinal Diseases
• Vitreomacular Traction

Intervention

Drug:
• Methotrexate 25 MG/ML
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.

Procedure:
• parsplana vitrectomy
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.

Locations

Country	Name	City	State
Egypt	ophthalmology department, Minia university hospital	Minya	Minia

Sponsors (1)

Lead Sponsor	Collaborator
Minia University

Country where clinical trial is conducted

Egypt, 

References & Publications (8)

Amarnani D, Machuca-Parra AI, Wong LL, Marko CK, Stefater JA, Stryjewski TP, Eliott D, Arboleda-Velasquez JF, Kim LA. Effect of Methotrexate on an In Vitro Patient-Derived Model of Proliferative Vitreoretinopathy. Invest Ophthalmol Vis Sci. 2017 Aug 1;58(10):3940-3949. doi: 10.1167/iovs.16-20912. — View Citation

Gologorsky D, Thanos A, Vavvas D. Therapeutic interventions against inflammatory and angiogenic mediators in proliferative diabetic retinopathy. Mediators Inflamm. 2012;2012:629452. doi: 10.1155/2012/629452. Epub 2012 Sep 17. — View Citation

Meleth AD, Carvounis PE. Outcomes of vitrectomy for tractional retinal detachment in diabetic retinopathy. Int Ophthalmol Clin. 2014 Spring;54(2):127-39. doi: 10.1097/IIO.0000000000000021. No abstract available. — View Citation

Newman DK. Surgical management of the late complications of proliferative diabetic retinopathy. Eye (Lond). 2010 Mar;24(3):441-9. doi: 10.1038/eye.2009.325. Epub 2010 Feb 5. — View Citation

Ricker LJ, Kijlstra A, Kessels AG, de Jager W, Liem AT, Hendrikse F, La Heij EC. Interleukin and growth factor levels in subretinal fluid in rhegmatogenous retinal detachment: a case-control study. PLoS One. 2011 Apr 27;6(4):e19141. doi: 10.1371/journal.pone.0019141. — View Citation

Samson CM, Waheed N, Baltatzis S, Foster CS. Methotrexate therapy for chronic noninfectious uveitis: analysis of a case series of 160 patients. Ophthalmology. 2001 Jun;108(6):1134-9. doi: 10.1016/s0161-6420(01)00576-0. — View Citation

Smith JR, Rosenbaum JT, Wilson DJ, Doolittle ND, Siegal T, Neuwelt EA, Pe'er J. Role of intravitreal methotrexate in the management of primary central nervous system lymphoma with ocular involvement. Ophthalmology. 2002 Sep;109(9):1709-16. doi: 10.1016/s0161-6420(02)01125-9. — View Citation

Zhou J, Wang S, Xia X. Role of intravitreal inflammatory cytokines and angiogenic factors in proliferative diabetic retinopathy. Curr Eye Res. 2012 May;37(5):416-20. doi: 10.3109/02713683.2012.661114. Epub 2012 Mar 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Anterior segment slit lamp biomicroscopic examination	assess anterior segment inflammation as iritis or posterior synechia	one month after pars plana vitrectomy
Secondary	visual acuity	by logMAR (Logarithm of the Minimum Angle of Resolution)	one month after pars plana vitrectomy and one month after silicone oil evacuation