Findings from a recent study published in the American Journal of Ophthalmology compared the efficacy and safety of combining customized photorefractive keratectomy (cPRK) with cross-linking (CXL) to CXL alone in improving visual outcomes for patients with progressive keratoconus (KC).
Give me some background.
While CXL is considered a first-line therapy for corneal ectasia due to KC, it does not adequately address irregular astigmatism—leaving many patients dependent on rigid contact lenses to attain satisfactory visual quality.
More recently, however: Progress in excimer laser technology has allowed surgeons to treat some extent of irregular astigmatism by selectively targeting the most prominent higher-order aberrations (HOAs) on a cornea to enhance visual outcomes.
Bring it back to this study.
Previous studies have explored treating progressive KC by adding customized excimer ablations (i.e., topography- or wavefront-guided) before same-day CXL (CXL+cPRK).
The findings thus far have demonstrated promising outcomes in providing patients with both enhanced visual acuity (VA) improvement and same corneal stability compared to CXL alone.
Considerations for CXL+cPRK include:
- Benefits:
- Minimized time-off work
- Accelerated visual rehabilitation
- Preservation of crosslinked corneal tissue
- Unaltered tissue ablation rates
- Risks:
- Potential for corneal stromal tissue removal during PRK, which may compromise the corneal biomechanical stability
Now, talk about the study.
In this systematic review and meta-analysis, investigators searched the following databases up to September 2024 for relevant studies:
- MEDLINE
- PubMed
- Cochrane Library
- EMBASE
Note: While the research team originally sought to include randomized controlled trials (RCTs) and comparative non-randomized prospective or retrospective studies, they were only able to retrieve non-randomized studies.
And what was studied?
- Primary outcome measures: Uncorrected-distance visual acuity (UDVA) and corrected-distance visual acuity (CDVA)
- Secondary outcome measures: Refraction, corneal structure, and HOAs
Findings?
In total, eight non-randomized studies of 731 eyes from 706 patients were included in the analysis.
Compared to CXL alone, CXL+cPRK significantly improved postoperative UDVA (standardized mean difference [SMD]: -0.39, 95% confidence interval [CI] -0.69 to -0.08, P=0.01) and CDVA (SMD: -0.57, 95% CI: -0.96 to -0.18, P=0.004).
Simultaneously, CXL+cPRK led to reductions in:
- Refractive cylinder error
- Coma
- Total HOA
- Coma-like aberrations
- Mean keratometry (KM)
- Central corneal thickness (CCT)
Anything else?
No significant differences were observed between the groups in endothelial cell count (ECC).
The rate of postoperative ectasia progression was comparable between both groups.
Talk about potential bias in the included studies.
All included studies exhibited at least one Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) domain at high risk of bias, particularly related to confounding.
What ROBINS-1 is: As the name suggests, it evaluates the risk of bias by posing questions that assess seven domains where bias may be introduced in studies that did not use randomization to determine cohorts to controls.
Expert opinion?
CXL+cPRK could provide earlier and more substantial improvements in VA and quality of vision for the more functionally impaired eyes, the study authors noted.
- What is required: A minimum corneal thickness necessary to support the ablation (typically ≥450μm preoperatively, ensuring a residual stromal bed of ≥400μm), thus optimizing visual rehabilitation for these patients.
They also compared topography- and wavefront-guided PRK for patients with KC, explaining:
- Topography-guided cPRK is generally preferred for patients with pronounced anterior corneal irregularities—particularly those with significant coma-like aberrations, as it aims to regularize the anterior corneal surface
- Wavefront-guided cPRK is more suitable for cases where preserving corneal tissue is a priority while still addressing HOAs
- This makes it a safer option for patients with more advanced KC.
Limitations?
These included:
- The inclusion of only non-randomized studies, all of which had at least one ROBINS-1 domain at high risk of bias
- High heterogeneity in the data, which was largely due to differences in surgical techniques, patient selection criteria, and study designs
- Lack of long-term follow-up data (beyond 5 years) limited the ability to fully evaluate the sustained effects of CXL+cPRK
Take home.
These findings suggest that cPRK+CXL provided superior postoperative visual acuity (UDVA, CDVA) and visual quality compared to CXL alone while maintaining the same corneal stability in the management of progressive KC.
Of note: Only nonrandomized studies could be retrieved for the purpose of the study, which may have introduced bias to the results.
Next steps?
Future studies with extended follow-up periods and standardized assessment protocols are essential to confirm the durability and safety of CXL+cPRK.