Analysis of Conjunctival Changes as Indicators for Ab-interno Gelatin Microstent Implantation Surgery Outcomes (IIT_XEN)

• ClinicalTrials.gov Identifier: NCT04727411
• Recruitment Status: Recruiting
• First Posted: January 27, 2021
• Last Update Posted: January 27, 2021
• Sponsor: Hospital Clinic of Barcelona
• Information provided by (Responsible Party): Néstor Ventura, Hospital Clinic of Barcelona

Study Description

Brief Summary:

Trabeculectomy and XEN45 gel stent implantation are glaucoma surgeries that creates an aqueous humor (AH) shunt towards the subconjunctival space (filtration bleb). Once the AH reaches the subconjunctival space, it is removed by different paths such as the trans-bleb wall route. For this reason, the conjunctiva is considered an essential structure that may condition the glaucoma filtering procedures outcomes. As part of the inflammatory response, an unbalanced fibrosis during the postoperative period may lead to a bleb cavity scarring and failure; for this reason, bleb massage and antifibrotic injections (i.e., 5-Fluoruracil) are frequently required as part of the postoperative care of these procedures. There have been described several risk factors, such as intraocular pressure (IOP) lowering medications, previous surgical interventions or ocular surface disease that may predispose to an early failure. These preoperative factors fail to aim to predict the surgical outcomes.

However, ocular biomarkers may overcome this limitation. There are promising studies that have analyzed the role of in vivo confocal microscopy (IVCM), anterior-segment optical coherence tomography (AS-OCT) and conjunctival cytology impression as clinical tools that may improve the filtration bleb assessment at a cellular level.

Condition or disease	Intervention/treatment	Phase
Glaucoma; Glaucoma Open-Angle Primary	Procedure: XEN45 Gel stent; Procedure: Trabeculectomy	Not Applicable

Detailed Description:

Detailed description Hypothesis

• Conjunctival biomarkers may represent a predictive factor to determine the XEN45 and trabeculectomy surgical success and outcomes
• A cellular-based analysis may help to predict postoperative pro-fibrotic changes that may lead to an early or mid-term surgery failure, and therefore it could help to improve the postoperative care of the filtering bleb.

Objective

• To evaluate the preoperative and postoperative conjunctival factors that may influence in the surgical outcomes of XEN45 gel stent compared to trabeculectomy using in vivo confocal microscopy, anterior segment optical coherence tomography and conjunctival cytology impression
• To assess the efficacy of XEN Gel stent and trabeculectomy to predict IOP, based on the morphologic characteristics of the filtering bleb
• To analyze the needling rate during the postoperative bleb management and the potential correlation to the pre and postoperative conjunctival changes and surgical success outcomes

Design Single-center, prospective, simple-blind study

Primary outcomes All the outcomes are measured pre and postoperative at each follow-up time

• In vivo confocal microscopy images: goblet cells density, dendritic cell density and stromal fibrosis
• Anterior segment optical coherence tomography: wall thickness and epithelium thickness
• Conjunctival cytology impression: dendritic cells, goblet cells

Secondary outcomes

• Intraocular pressure
• Number of IOP lowering medications
• Number of postoperative needling

Sample size calculation Based on the most assessed outcome in glaucoma surgeries and the only pilot study aiming to determine a similar outcome, to detect IOP differences between both procedures that may reflect the surgical outcomes of both procedures and therefore reflect the subconjunctival changes, accepting an alfa risk of 0.05 and a beta risk of 0.20 in a two-sided Student's T-test, 40 subjects are necessary in each group to recognize as statistically significant a difference greater than or equal to - 13,38 mm Hg in IOP, with a common standard deviation of 17%. A drop-out rate of 15% has been anticipated. If no drop-out rate is considered, the number of needed subjects is 68 (34 per group)

Method Single center, prospective, observational study of primary open angle glaucoma and uncontrolled intraocular pressure, progression of the disease confirmed by visual field examination that require either XEN gel stent implantation or trabeculectomy.

Preoperative examinations

• Medial records including ophthalmic procedures, other ocular diseases, intraocular pressure while on treatment, target pressure, visual field, detailed description of the optic disc, both preoperative and postoperative
• Glaucoma staging: peripapillary retinal nerve fiber layer, visual field (baseline, 3 moths and 6 months)

• Ocular biomarkers

  • In vivo confocal microscopy (baseline, 3 moths and 6 months)
  • Conjunctival impression cytology (baseline, 3 moths and 6 months)

A specific case report form (CRF) was designed with all variables and data required for the study, including potential complications

Surgery. Patients were assigned either to trabeculectomy or XEN stent implantation

Trabeculectomy: the surgical technique is as follows: retro/peribulbar o subtenon's anesthesia, superior corneal traction suture, phacoemulsification through 2.2 with in-the-bag IOL implantation, a fornix-based conjunctival flap, sufficient but not excessive cauterization, application mitomycin-C (MMC) 0,2 mg/ml for 2 minutes under the conjunctiva, then MMC was washed out with 100 ml of saline solution, then a scleral flap (4x3 mm in the trabeculectomy) is dissected. A sclerectomy with punch and peripheral iridectomy were performed, and suture nylon 10/00 sutures was used to place 3 or 4 stiches in the scleral flap

XEN gel stent: a clear cornea incision in the inferotemporal quadrant was performed, injecting the XEN 45 device into the superonasal quadrant using an ab interno approach. Approximately 15 min before inserting the implant, 0.1 ml of a MMC solution (0.01%) was injected into the superior conjunctiva. Both stand-alone and combined phaco-glaucoma procedures were used.

Post-operative treatment. All patients instilled ofloxacin antibiotic every 6 hours for 1 week, dexamethasone (every 2 hours for 1 month, every 4-6 hours on the second month and tapered during the third month according to surgeon's instructions). Atropine was also used when clinical finds recommended its use. Subconjunctival injections of anti-fibrotic agents (5-FU) and/or bleb needling were allowed and performed at the discretion of the surgeon

Statistical analysis

• Descriptive statistics, including mean and standard deviation for normally distributed variables and median and interquartile range for non-normally distributed variables, previous checked using Shapiro-Wilk test.
• Logistic regression models to evaluate the correlation with preoperative and postoperative factors and needling rate, surgical success (IOP < 18 mm Hg), and ocular biomarkers. The results will be reported as odds ratio (OR).
• All the reported values will be considered statistically significant at two-tailed p <0.05

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: In Vivo Imaging and Impression Cytology Analysis of Conjunctival Changes as Potential Indicators for Ab-interno Gelatin Microstent Implantation Surgery Outcomes
• Actual Study Start Date: January 1, 2021
• Estimated Primary Completion Date: December 31, 2021
• Estimated Study Completion Date: June 30, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Gel Stent implantation; XEN gel stent: a clear cornea incision in the inferotemporal quadrant was performed, injecting the XEN 45 device into the superonasal quadrant using an ab interno approach. Approximately 15 min before inserting the implant, 0.1 ml of a MMC solution (0.01%) was injected into the superior conjunctiva. Both stand-alone and combined phaco-glaucoma procedures were used.	Procedure: XEN45 Gel stent; XEN Gel stent implantation either combined or as a stand-alone procedure
Experimental: Trabeculectomy; Trabeculectomy: the surgical technique is as follows: retro/peribulbar o subtenon's anesthesia, superior corneal traction suture, phacoemulsification through 2.2 with in-the-bag IOL implantation, a fornix-based conjunctival flap, sufficient but not excessive cauterization, application MMC 0,2 mg/ml for 2 minutes under the conjunctiva, then MMC was washed out with 100 ml of saline solution, then a scleral flap (4x3 mm in the trabeculectomy) is dissected. A sclerectomy with punch and peripheral iridectomy were performed, and suture nylon 10/00 sutures was used to place 3 or 4 stiches in the scleral flap	Procedure: Trabeculectomy; XEN Gel stent implantation either combined or as a stand-alone procedure

Outcome Measures

Primary Outcome Measures :

1. In vivo confocal microscopy of the filtering bleb [ Time Frame: Preoperative to 6 months operative ]
   Increase of the mean microcysts density (MMD): number of cysts/mm2
2. Anterior segment optical coherence tomography microscopy of the filtering bleb [ Time Frame: Preoperative to 6 months operative ]
   Differences in thickness of the conjunctival epithelial surface and the bleb wall, in micrometers
3. Conjunctival impression cytology of the filtering bleb [ Time Frame: Preoperative to 6 months operative ]
   Increase in the percentage of goblet cells biomarkers

Secondary Outcome Measures :

1. Intraocular pressure [ Time Frame: Preoperative to 6 months visit, at each follow-up visit ]
   Difference of intraocular pressure, in mm Hg
2. Glaucoma medications [ Time Frame: Preoperative to 6 months visit, at each follow-up visit ]
   Difference between the number of glaucoma medications before and after each surgery

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Primary open angle glaucoma
• Written informed consent
• Older than 18 years old

Exclusion Criteria:

• Patients that don't fully understand the purpose and the postoperative care
• Severe or end-stage glaucoma
• Patients with prior ocular surgery, excluding uncomplicated phacoemulsification 6 months prior to the inclusion in the study

Contacts and Locations

Contacts

Contact: Néstor V Ventura Abreu, MD; +34697292698; neventura@clinic.cat

Locations

Spain

Hospital Clínic - ICOF; Recruiting

Barcelona, Spain, 08028

Contact: Nestor Ventura Abreu, MD +34 69629268 neventura@clinic.cat

Sponsors and Collaborators

Hospital Clinic of Barcelona

Investigators

• Principal Investigator: Marta Pazos, MD, PhD; Hospital Clinic

More Information

• Responsible Party: Néstor Ventura, Investigator, Glaucoma Department, Hospital Clinic of Barcelona
• ClinicalTrials.gov Identifier: NCT04727411
• Other Study ID Numbers: HCB/2019/0035
• First Posted: January 27, 2021
• Last Update Posted: January 27, 2021
• Last Verified: January 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Néstor Ventura, Hospital Clinic of Barcelona:

Gel stent; Trabeculectomy; In vivo confocal microscopy; Conjunctival impression cytology; Anterior segment optical coherence tomography

Additional relevant MeSH terms:

Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Eye Diseases