Analysis of Conjunctival Changes as Indicators for Ab-interno Gelatin Microstent Implantation Surgery Outcomes
Condition: Glaucoma; Glaucoma Open-Angle Primary
MeSH terms: Glaucoma; Glaucoma, Open-Angle
Study type: Interventional

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.
    

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
    

Intervention name(s): XEN45 Gel stent; Trabeculectomy
Intervention type(s): Procedure; Procedure
Intervention description(s): XEN Gel stent implantation either combined or as a stand-alone procedure; XEN Gel stent implantation either combined or as a stand-alone procedure
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Gel stent; Trabeculectomy; In vivo confocal microscopy; Conjunctival impression cytology; Anterior segment optical coherence tomography