# Longitudinal analysis of XEN45 gel stent bleb morphology using bleb grading scales, anterior segment-OCT, in vivo confocal microscopy, and impression cytology

## TL;DR

This study examines the characteristics of blebs formed after XEN45 Gel Stent surgery using multiple imaging techniques to determine factors associated with successful outcomes.

## Contribution

The study introduces a multi-modal approach combining AS-OCT, IVCM, and ICA to evaluate XEN45 Gel Stent bleb morphology and function.

## Key findings

- Successful blebs showed higher preoperative goblet cell density and mucin expression.
- AS-OCT metrics like BECSA were significantly higher in successful cases.
- AS-OCT was found to be the most clinically useful tool for monitoring bleb function.

## Abstract

To characterize bleb morphology and conjunctival features after XEN45 Gel Stent surgery (XGS) using slit-lamp bleb grading, anterior segment optical coherence tomography (AS-OCT), in vivo confocal microscopy (IVCM), and impression cytology analysis (ICA), in both success and failure cases.

Twenty-four eyes (24 patients) underwent XGS, with 20 included in the final analysis. In addition to a full ophthalmic exam, blebs were evaluated using Moorfield’s Bleb Grading System (BGS), AS-OCT, IVCM, and ICA. AS-OCT metrics included bleb-wall and subepithelial cyst-like structure area and density (BECSA/BECSD, BSCSA/BSCSD), bleb height (BH), bleb thickness (BT), and epithelial thickness (BET). IVCM parameters included stromal meshwork reflectivity (SMR), goblet cell density (GCD), epithelial microcyst density and area (EMD, EMA), and dendritic cell density (DCD). ICA assessed MUC5AC and HLA-DR/cell area ratio. Success was defined as an IOP < 21 mmHg and ≥ 20% reduction at six months. Imaging parameters were correlated with surgical outcomes.

At six months, 11 (55%) cases were classified as successful and 9 (45%) as failures. BGS showed significantly larger blebs in the success group (88.9% with maximal diffusion area grade ≥ 3 vs. 22.1%, p < 0.05). AS-OCT detected persistent epithelial and subepithelial changes in successful blebs, with significantly higher BECSA (0.11 vs. 0.02 mm², p < 0.02). Preoperatively, successful cases showed higher GCD on IVCM (67.3 vs. 39.2 cells/mm², p = 0.25) and mucin expression on ICA (MUC5AC/cell ratio: 1.28 vs. 0.01, p = 0.11). Postoperative IVCM also showed trends toward increased EMD in both groups, though not statistically significant.

Successful XGS blebs were associated with higher preoperative goblet cell density (IVCM) and mucin expression (ICA). Postoperatively, AS-OCT parameters—especially epithelial and subepithelial changes—showed the strongest correlation with IOP, highlighting AS-OCT as the most clinically applicable tool for monitoring bleb function.

ClinicalTrials.gov Identifier NCT04727411, January 22, 2021.

The online version contains supplementary material available at 10.1007/s00417-025-06952-0.

Bleb-forming devices (such as XEN45 Gel Stent, XGS) have been characterized as flatter, less extensive blebs compared to other filtering procedures (trabeculectomy, deep sclerectomy)The characteristics of functioning XGS blebs have been scarcely described, and the preoperative characteristics and changes during the bleb maturation that might conform to a successful bleb have not been detailed.

Bleb-forming devices (such as XEN45 Gel Stent, XGS) have been characterized as flatter, less extensive blebs compared to other filtering procedures (trabeculectomy, deep sclerectomy)

The characteristics of functioning XGS blebs have been scarcely described, and the preoperative characteristics and changes during the bleb maturation that might conform to a successful bleb have not been detailed.

The conjunctival bleb characteristics of the successful cases resemble those of the traditional glaucomaIncorporating bleb-wall epithelium cyst-like structure area measurements (BECSA) with anterior-segment optical coherence tomography or mucin level expression with impression cytology analysis could help to differentiate between functioning and failed blebs instead of solely relying on clinical evaluation

The conjunctival bleb characteristics of the successful cases resemble those of the traditional glaucoma

Incorporating bleb-wall epithelium cyst-like structure area measurements (BECSA) with anterior-segment optical coherence tomography or mucin level expression with impression cytology analysis could help to differentiate between functioning and failed blebs instead of solely relying on clinical evaluation

The online version contains supplementary material available at 10.1007/s00417-025-06952-0.