Highlights
- Corneal cross-linking (CXL) is a proven intervention to slow keratoconus progression and reduce corneal transplantation rates.
- Access to FDA-approved epithelium-off CXL in the US is constrained by high cost, insurance coverage gaps, and proprietary treatment protocols.
- The recent FDA approval of epithelium-on Epioxa™ under orphan drug status introduces uncertainty about efficacy and affordability, notably with a high wholesale acquisition cost.
- Phasing out of Photrexa® in 2026 risks exacerbating treatment disparities unless access frameworks and long-term data for Epioxa™ are established.
Study Background and Disease Burden
Keratoconus is a progressive, noninflammatory corneal ectasia characterized by corneal thinning and conical protrusion that leads to irregular astigmatism and vision loss. It affects approximately 1 in 2000 individuals in the United States, causing significant visual impairment, especially in younger populations. The natural history often leads to corneal transplantation in advanced cases, imposing burdens on patients and health systems alike.
Corneal cross-linking (CXL) is the first FDA-approved disease-modifying therapy shown to halt or slow keratoconus progression by increasing collagen cross-links in the corneal stroma, thereby strengthening biomechanical stability. Early CXL intervention can delay or prevent the need for corneal transplant, preserve vision, and improve quality of life.
Study Design
This perspective essay synthesizes clinical experiences from multiple authors involved in keratoconus management, a historical overview of CXL modalities in the US, and a targeted literature review to elucidate current and emerging disparities affecting CXL access and utilization. It addresses regulatory, economic, and clinical factors shaping treatment availability and proposes strategic actions.
Key Findings
The authors highlight that, currently, the only FDA-approved epithelium-off CXL treatment available in the US is the KXL® system utilizing Photrexa® or Photrexa® Viscous. Despite robust evidence supporting its efficacy, access remains limited by the high cost of the therapy, variable insurance reimbursement, and restrictions related to proprietary protocols mandated by the manufacturer.
These barriers disproportionately affect underserved and minority patient populations who are at higher risk for delayed diagnosis and rapid progression. Inequities in CXL availability contribute to worsening visual outcomes and higher rates of keratoplasty in these groups.
In 2025, the FDA approved Epioxa™, an epithelium-on (epi-on) CXL therapy, under an orphan drug designation. This modality promises a less invasive treatment by preserving the corneal epithelium, potentially improving patient comfort and reducing complications. However, the clinical community remains skeptical due to the lack of long-term data confirming non-inferiority in visual acuity stabilization and keratometric outcomes compared to the standard epithelium-off method.
Of particular concern is the reported wholesale acquisition cost of $78,500 for Epioxa™ — a price point posing substantial affordability challenges. Moreover, the manufacturer plans to phase out Photrexa® by 2026, which would eliminate the only approved epithelium-off option in the US.
This planned transition, without adequate demonstration of Epioxa™s durability and without frameworks addressing affordability and access, risks exacerbating existing treatment disparities. The perspective calls for immediate action to pause Photrexa® discontinuation, pending establishment of comprehensive access plans and further clinical validation of Epioxa™.
Expert Commentary
Experts acknowledge that CXL represents a paradigm shift in keratoconus management, enabling disease modification beyond optical correction. However, the balance between innovation, safety, and equitable access remains delicate.
Limitations in current data on Epioxa™ reflect an urgent need for high-quality, long-term randomized controlled trials to evaluate efficacy, safety, and cost-effectiveness. Furthermore, stakeholders, including clinicians, payers, manufacturers, and patient advocacy groups, must collaborate on policies ensuring access irrespective of socioeconomic status.
Emerging health economic analyses suggest that early, equitable access to CXL may reduce lifetime costs by preventing transplants and associated healthcare utilization. This underscores the importance of safeguarding multiple therapeutic options in the US market during transitional regulatory periods.
Conclusion
The approval of Epioxa™ and the forthcoming withdrawal of Photrexa® introduce a precarious moment in US keratoconus care. Without clear evidence supporting Epioxa™s long-term efficacy and without strategic frameworks to address exorbitant costs, the risk of intensifying existing disparities is substantial.
The authors recommend a moratorium on phasing out Photrexa® until (1) comprehensive accessibility solutions are in place to ensure treatment availability for all keratoconus patients and (2) robust data confirms the safety and effectiveness of Epioxa™. Creating an interdisciplinary taskforce dedicated to CXL access could spearhead equitable care models and policy recommendations, adapting to evolving therapeutic landscapes.
Ultimately, maintaining multiple FDA-approved CXL options and addressing financial and structural barriers are critical to preventing avoidable vision loss and improving outcomes for keratoconus patients nationwide.
