Subconjunctival Versus Direct Mitomycin C in Trabeculectomy

Subconjunctival Versus Direct Scleral Application of Mitomycin-C in Trabeculectomy

Trabeculectomy is routinely used as a surgical treatment for open angle glaucoma. Success of trabeculectomy is greatly augmented by the use of antimetabolites to inhibit wound healing, specifically Mitomycin C (MMC). MMC can be applied to the eye at various sites, concentrations and times. This study aims to compare the two application routes that are commonly employed: subconjunctival pre-operative injection and intraoperative direct scleral application in terms of IOP lowering effect, bleb appearance and complications.

Study Overview

• Status: Completed
• Conditions: Open Angle Glaucoma
• Intervention / Treatment: Drug: Mitomycin-C injection; Drug: Mitomycin-C sponge

Detailed Description

Trabeculectomy is widely used as a surgical treatment of uncontrolled open glaucoma. Success of trabeculectomy at halting or slowing glaucoma progression primarily relies on the extent of conjunctival and sclera wound healing. The success rates of trabeculectomy increased dramatically with the introduction of anti-metabolites. For more than two decades mitomycin-c (MMC), a chemotherapeutic agent capable of decreasing fibroblast activity and modulating wound healing at the bleb, has been used with trabeculectomy. The complications of MMC are well known and several studies have described various methods of application based on exposure time, dose and surface area. Numerous retrospective and prospective studies have compared the efficacy of MMC applied beneath the conjunctival flap with soaked sponges versus intrascleral application. In 2008, Lee et al. first described an alternative route of application: subconjunctival injection of MMC directly into the intra-Tenon area. Seventy-six eyes with primary and secondary open angle glaucoma underwent trabeculectomy with this approach and were followed for one year post-operatively. Eighty-six percent of eyes achieved an IOP <21 mm Hg and 57% an IOP<14 mm Hg at one year without adjunctive drops. Transient complications included hyphema, bleb leak and choroidal detachment. The advantages of injected MMC are primarily in controlling the exact dosage and area of application and reduced surgical time. Lim et al. retrospectively reviewed the outcomes of trabeculectomy in 57 eyes using sponge application directly to the sclera versus intra-tenon injection. IOP was significantly lower in the injection group at 1 month, 1, 2, and 3 years. Trabeculectomy success (IOP<21mm Hg or IOP >20% below baseline without medications or additional surgery) was greater in the injection group at 3 years. The sponge group experienced more encapsulated blebs but complication rates were similar in both groups. To date, there have been no prospective studies comparing the IOP-lowering efficacy and safety of intra-tenon injection versus direct scleral application of MMC.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• medically uncontrolled glaucoma
• healthy and freely mobile conjunctiva in superior bulbar region

Exclusion Criteria:

• previous incisional glaucoma surgery
• no light perception vision
• pregnant or nursing women
• iris neovascularization or proliferative retinopathy
• iridocorneal endothelial syndrome
• chronic or recurrent uveitis
• steroid-induced glaucoma
• pathologic myopia or refractive error less than -6.00 diopters
• unwillingness or inability to give consent
• inability to return for scheduled protocol visits

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Injection group; MMC delivered by preoperative subconjunctival injection	Drug: Mitomycin-C injection; MMC delivered by preoperative subconjunctival injection
Active Comparator: Sponge group; MMC delivered by intraoperative direct scleral application with impregnated cellulose sponges	Drug: Mitomycin-C sponge; MMC delivered by intraoperative direct scleral application with impregnated cellulose sponges

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Intraocular Pressure Reduction Thresholds	Percentage of patients achieving at least a 30% mean intraocular pressure reductions from baseline and with an intraocular pressure <21 mm Hg. Subjects that met this criteria without the use of intraocular pressure lowering medications were classified as "Complete Success." Subjects that met this criteria but required the use of intraocular pressure lowering medications were classified as "Qualified Success." Subjects that failed to meet this criteria were classified as "Failure." Subjects that failed to meet this criteria and required additional glaucoma surgery were classified as "Complete Failure."	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bleb Morphology	Bleb morphology at 6 months was graded using Indiana Bleb Appearance Grading Scale. Bleb height was graded on a scale of 0 to 3 (0: flat bleb without visible elevation, 1: low bleb elevation, 2: moderate bleb elevation, 3: high bleb elevation). Bleb extent was graded on a scale of 0 to 3 (0: no visible bleb extent to less than 1 clock hour, 1: extent equal to or greater than 1 clock hour but less than 2 clock hours, 2: extent equal to or greater than 2 clock hours but less than 4 clock hours, 3: extent equal to or greater than 4 clock hours). Bleb vascularity was graded on a scale of 0 to 4 (0: avascular/white, 1: avascular/cystic, 2: mild vascularity, 3: moderate vascularity, 4: extensive vascularity). Scales are descriptive and do not necessarily represent better or worse outcomes.	6 months
Medications	Number of intraocular pressure lowering medications used by the patient at follow up visit.	6 months
Visual Acuity	Change in visual acuity from baseline	6 months
Number of Participants With Surgical Complications	Number of eyes that experienced surgical complications following surgery	6 months
Number of Participants Requiring Additional Surgery	Number of eyes requiring additional surgery from each group	6 months
Postoperative Interventions	Mean number of postoperative interventions (needling, antifibrotic injections) performed in each group	6 months

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Investigators: Principal Investigator: Jiun L Do, MD, PhD, UCSD; Principal Investigator: Robert N Weinreb, MD, UCSD; Principal Investigator: Benjamin Xu, MD, PhD, UCSD

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2016
• Primary Completion (Actual): April 14, 2019
• Study Completion (Actual): April 14, 2019

Study Registration Dates

• First Submitted: April 15, 2020
• First Submitted That Met QC Criteria: April 15, 2020
• First Posted (Actual): April 20, 2020

Study Record Updates

• Last Update Posted (Actual): July 2, 2020
• Last Update Submitted That Met QC Criteria: June 14, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: trabeculectomy, mitomycin-C, glaucoma
• Additional Relevant MeSH Terms: Eye Diseases; Ocular Hypertension; Glaucoma; Glaucoma, Open-Angle; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Alkylating Agents; Antibiotics, Antineoplastic; Mitomycins; Mitomycin
• Other Study ID Numbers: 151621

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No