Safety and efficacy of corneal cross-linking for progressive keratoconus in patients with corneal thickness less than 400 μm
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2025
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Melbourne Authors
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Ophthalmology (Eye & Ear Hospital)
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Masters Research thesis
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Open Access
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© 2025 FARZANEH MOHAMMADI
Abstract
Purpose: Historically, corneal collagen cross-linking (CXL) was contraindicated for
people with thin corneas due to the potential for damage to the corneal stroma and
endothelium from ultraviolet radiation. We aimed to assess the long-term safety and
effectiveness of CXL in corneal thickness (CT) less than 400 micron for slowing the
progression of keratoconus among people with thin corneas (intraoperative CT <400
micron after epithelium removal) by assessing change in corneal topography parameters
and visual acuity.
First, we conducted a systematic review and meta-analysis of outcomes from CXL
protocols modified for thinner corneas. MEDLINE Ovid, Embase Ovid, and SCOPUS
were searched for English-language studies published in peer-reviewed journals.
Eligible studies included prospective and retrospective case series, cohort studies,
and randomised clinical trials in keratoconus patients with CT <400 micron, regardless of
CXL approach. A random-effects meta-analysis was conducted to pool average
changes in corrected visual acuity (CVA), refractive cylinder, endothelial cell density,
and corneal curvature (Kmax) at key time points. Study quality was assessed using the
JBI Critical Appraisal Checklist for Case Series.
Twenty-nine records published between 2011 and 2024 were included. Average Kmax
decreased at 6 (n = 15/330 studies/eyes, mean change: -1.4D, 95% CI [-2.1, -0.6],
I2=94%) and 12 months (n=17/402 studies/eyes, mean change: -1.4D, 95% CI [-2.0, -0.9], I2=92%) from baseline. CVA also improved at 6 (n=14 studies/317 eyes, mean -0.10 log MAR units, 95% CI [-0.14, -0.05], I2=76%) and 12 months (n = 19/443
studies/eyes, mean change -0.09 log MAR units, 95% CI [-0.13, -0.06], I2=67%). No
study reported major complications.
To focus further, we performed a retrospective study of patients with keratoconus who
underwent CXL procedures at an Australian public subspecialty hospital and a private
day surgery between 1st April 2017 and 1st April 2022. Uncorrected visual acuity,
CVA, CT, and keratometry values (K1, K2, Kmax) were extracted before surgery and at
1, 3-, 6-, 9-, and 12-months; complications occurring up to 3 years post-operation were
also extracted. Outcomes were compared between participants with CT < 400 micron after epithelium removal who underwent CXL with hypotonic riboflavin and those with CT > 400 micron using Isotonic riboflavin.
A total of 237 eligible patients were included. Eyes with CT >400 micron had more
flattening of the cornea one year post-operatively compared to those with CT <400 micron.
on average, although attrition was substantial at that time. Other changes observed
were within the range of normal variation. No meaningful differences were observed
in post-operative keratometry readings and visual acuity between the two groups,
except for pre-operative values in corneal thickness, which showed some significant
differences.
In conclusion, CXL appears safe and effective among people with keratoconus who
have CT between 365 micron and 400 micron with epithelium. Additional work is required to
determine new safety thresholds for CT and which surgical modifications produce
optimal outcomes.
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Keywords
Keratoconus, Corneal Collagen Cross-linking, CXL, Thin cornea, Hypotonic Riboflavin, Systematic Review