Mediators of the Effect of Corneal Cross-Linking on Visual Acuity for Fungal Ulcers: A Prespecified Secondary Analysis From the Cross-Linking-Assisted Infection Reduction Trial.

Abstract

PURPOSE:

The purpose of this study was to determine whether astigmatism or corneal scarring is mediating the reduced visual acuity among patients with fungal keratitis randomized to corneal cross-linking (CXL).

DESIGN:

This was a prespecified exploratory outcome from an outcome-masked, 2 × 2 factorial design, randomized controlled clinical trial.

STUDY PARTICIPANTS:

Consecutive patients presented with moderate vision loss from a smear-positive fungal ulcer at Aravind Eye Hospital, Madurai, India.

INTERVENTION:

Study eyes were randomized to one of 4 treatment combinations using an adaptive randomization protocol. The treatment arms included (1) topical natamycin 5% alone, (2) topical natamycin 5% plus CXL, (3) topical amphotericin B 0.15% alone, and (4) topical amphotericin 0.15% plus CXL. Best spectacle-corrected visual acuity (BSCVA), contact lens over-refraction, and scar size and depth as measured by a masked study ophthalmologist using a standardized protocol were recorded at 3 months. Pentacam Scheimpflug imaging was also obtained at 3 months.

MAIN OUTCOME MEASURES:

BSCVA and contact lens over-refraction, infiltrate and/or scar size and depth, total astigmatism of the front and back of the cornea, total lower-order and higher-order aberrations of the anterior and posterior cornea, and total densitometry of the anterior, central, and posterior stroma were recorded. We performed a mediation analysis looking at the proportion of the effect of CXL on BSCVA that was mediated through scar size, scar depth, astigmatism and density.

RESULTS:

BSCVA at 3 months was available for 99 of 111 patients (89%) who had a mean of 0.82-LogMAR (SD 0.68). Three-month infiltrate and/or scar size ( P < 0.001), depth ( P < 0.001), and densitometry ( P = 0.001) were statistically significant predictors of 3-month BSCVA. Astigmatism seemed to mediate 23% of the effect of CXL on BSCVA, whereas scar size mediated 23%, scar depth 17%, and densitometry 7%.

CONCLUSIONS:

Corneal scarring and astigmatism are mediators of worse visual acuity after cross-linking in fungal keratitis. Corneal densitometry may be a helpful cornea-specific variable for clinicians and researchers in determining the effect of corneal scarring on visual acuity in specific patients and as an objective study outcome.

TRIAL REGISTRATION:

NCT02570321.

• Authors: N Venkatesh Prajna, Naveen Radhakrishnan, Prajna Lalitha, Zijun Liu, Jeremy D Keenan, Benjamin F Arnold, Jennifer Rose-Nussbaumer
• Journal: Cornea (Cornea) Vol. 41 Issue 10 Pg. 1217-1221 (Oct 01 2022) ISSN: 1536-4798 [Electronic] United States
• PMID: 35044972 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Chemical References

• Cross-Linking Reagents
• Amphotericin B
• Natamycin

Topics

• Amphotericin B (therapeutic use)
• Astigmatism (pathology)
• Cicatrix (drug therapy)
• Cornea (pathology)
• Corneal Injuries (pathology)
• Corneal Ulcer (microbiology)
• Cross-Linking Reagents (therapeutic use)
• Eye Infections, Fungal (microbiology)
• Humans
• India
• Natamycin (therapeutic use)
• Treatment Outcome
• Ulcer (drug therapy, pathology)
• Visual Acuity