In a busy cornea practice, keratoconus (KC) certainly doesn’t feel like a rare disease, but that’s how it is classified under the Orphan Drug Act—a law that helps incentivize treatments for rare diseases with faster Food and Drug Administration (FDA) review and lower regulatory costs. We can debate whether KC really occurs in 1 in 2,000 people, as is classically reported, or at a higher rate, as studies that relied upon tomographic screening in a Chicago-based pediatric population¹ have suggested. Whatever the exact prevalence numbers for KC, we know for certain that prompt diagnosis and treatment is rare. About 70% of patients have already reached the moderate to advanced stages of the disease when they are diagnosed² and only about 12% of newly diagnosed patients get cross-linking therapy,³ which has been proven to slow or halt worsening of KC.

The reason for such low treatment rates has nothing to do with clinical efficacy or the strength of the scientific data, but rather much more to do with how challenging it has been historically to detect early-stage KC. The most effective method for early detection is topography/tomography, which has not been widely available in primary care. Compared to more widespread eye diseases like macular degeneration or cataract, there just isn’t much public awareness about KC. It affects younger people who are otherwise healthy and may go several years between eye exams—if they get eye exams at all.

On the treatment side, there have not been enough doctors to provide cross-linking care, which has led to long wait times and, sometimes, the need for patients to travel to see a cornea specialist. Doctors sometimes misdiagnose KC, manage it with vision correction only, or in some cases, delay treatment until they can document a certain level of progression for insurance coverage. Patients have been hesitant to move forward with cross-linking or to have their second eye treated after epi-off cross-linking in the first eye due to fear of pain or discomfort, or the inconvenience of not being able to wear their normal vision correction for weeks or months. In fact, pain and recovery time are some of the most common topics optometrists see discussed in online patient forums about keratoconus.

These delays can lead to heartbreaking consequences. One patient who comes to mind was 13 or 14 years old and was still seeing well: 20/20 in one eye and 20/25 in the other. The parents were hesitant to treat him right away, so we recommended that he come back in 6 months for follow-up. Life got busy and he instead came back almost a year later, at which point the worse eye was 20/400. Looking back, it would have been great to have had the opportunity to treat him right away to likely prevent that dramatic change in vision. It is critical to emphasize to patients with keratoconus the severity of the disease and the importance of keeping follow-up appointments. We tell them, “The changes can be so gradual that you don’t notice them until suddenly there is a dramatic loss of vision. Ideally, we should treat it right away. If you are going to wait, you really need to come in regularly for detailed imaging of the eye so we can detect change before it is severe.”

Conversely, there are many patients who have been treated in our practice since the early days of cross-linking. They have maintained stable topography with no further vision loss (Figures 1 and 2) and no need for a corneal transplant—proof that these patients benefit for many years from cross-linking therapy.

Better Screening Needed

There are certain groups of patients who have an elevated risk for KC, including those with sleep apnea, Down syndrome, connective tissue disorders, severe ocular allergies, and those with a close family relative with KC.^4-8 In our experience, there is good awareness in the medical community of the relationship between Down syndrome and KC, and those patients do get referred for eye care and screening. Other risk factor categories are less well known and less likely to be routinely referred for screening, which suggests that more education within our communities is needed.

Most states require vision screening for all 5-year-olds prior to entering kindergarten. From a public health perspective, it would be ideal if screening for keratoconus was mandatory before entering or at some point during high school, because the teen years are when early onset symptoms of KC are most likely to develop. In clinical practice, although it may not be practical to screen all vision care patients for KC, we strongly recommend screening any young person who is difficult to refract or has other early signs of KC (see sidebar).

Simple portable topography devices that could be used in widespread screening are in development.^9-11 Early results for a portable screening device that would leverage machine learning to flag patients for further testing were promising: The device projects mire rings onto the cornea, captures images of the anterior corneal surface to reconstruct the anterior surface map, and then applies a real-time classifier algorithm to aid in the detection of keratoconus. In a feasibility study of 140 eyes, including 28 with keratoconus, 99.3% were successfully captured with the handheld screening device; further studies are ongoing.⁹

Facilitating Early Intervention

The recent FDA approval of epithelium-on, oxygen-enriched corneal cross-linking can help to change the paradigm of delayed diagnosis and treatment toward a more interventional keratoconus approach that broadens access to cross-linking. The FDA’s approval of Epioxa (Glaukos) did not include progression in the label, which means that patients can potentially be treated earlier without needing documented progression. Epioxa is a streamlined treatment and, because the epithelium is left intact, it is designed for improved patient comfort and fast recovery. Some of the patients in the clinical trial for Epioxa were able to have both eyes treated within 1 week of each other,⁸ as opposed to the usual interval of several months between eyes with epi-off cross-linking.

Recent evidence also suggests that younger patients have approximately double the treatment effect (a 2.0-D vs a 1.0-D change in Kmax from baseline) with Epioxa compared with the study group as a whole.^8,9 Moreover, significant progression was observed in untreated eyes in younger patients, which reinforces the importance of early treatment in young people.^8,9 All of these features of the new therapy will be beneficial, especially for young patients.

We have personally seen that early diagnosis and treatment of KC can completely change a patient’s life trajectory. Instead of losing vision and facing a potential future corneal transplant, early-stage cross-linking reduces the burden of their disease and makes it less likely that poor vision will limit performance in school or at work. KC patients still need vision correction after cross-linking, but with early treatment, they may be able to wear glasses or soft contact lenses instead of specialty lenses. Future contact lens fitting should also be easier once the cornea has been stabilized.

With epithelium-on cross-linking, we hope to see many more patients with KC gravitate toward and be willing and able to undergo sight-saving cross-linking. The ultimate goal of interventional keratoconus is to diagnose KC in the early stages before vision has been lost, cross-link quickly to stabilize the cornea and prevent the disease from worsening, and then rehabilitate the patient’s vision with glasses, contact lenses (including specialty lenses), or refractive surgical options, as needed. This process can be best handled through a collaborative approach.OM

References

1. Block SS, Harthan J, Zhuang X, et al. Prevalence of abnormal corneas in the United States based on Scheimpflug tomography analytics of a pediatric population. Invest Ophthalmol Vis Sci. 2022;63(7):2415.

2. Kreps EO, Claerhout I, Koppen C. Diagnostic patterns in keratoconus. Cont Lens Anterior Eye. 2021;44(3):101333. doi:10.1016/j.clae.2020.05.002

3. Syed ZA, Tomaiuolo M, Zhang Q, et al. Trends and sociodemographic patterns in keratoconus management 2015-2020: An American Academy of Ophthalmology IRIS Registry analysis. Ophthalmology. 2024;131(8):892-901. doi:10.1016/j.ophtha.2024.01.036

4. Hefley BS, Ali AA, Bhattacharya P, Hjortdal J, Walker MK, Karamichos D. Systemic and ocular associations of keratoconus. Expert Rev Ophthalmol. 2024;19(5):379-391. doi:10.1080/17469899.2024.2368801

5. Santodomingo-Rubido J, Carracedo G, Suzaki A, Villa-Collar C, Vincent SJ, Wolffsohn JS. Keratoconus: an updated review. Cont Lens Anterior Eye. 2022;45(3):101559. doi:10.1016/j.clae.2021.101559

6. Gordon-Shaag A, Millodot M, Shneor E, Liu Y. The genetic and environmental factors for keratoconus. Biomed Res Int. 2015;2015:795738. doi:10.1155/2015/795738

7. Akoto T, Li JJ, Estes AJ, Karamichos D, Liu Y. The underlying relationship between keratoconus and Down syndrome. Int J Mol Sci. 2022;23(18):10796. doi:10.3390/ijms231810796

8. Safir M, Satanovsky A, Heckht I, Heller D, Einan-Lifshitz A, Pras E. The association between keratoconus and systemic manifestations of connective tissue hyperlaxity. Cont Lens Anterior Eye. 2023;46(5):101892. doi:10.1016/j.clae.2023.101892

9. Raizman MB, Tran DB, Usher D, et al. Design review and clinical plan for novel keratoconus screening device. Paper presented at: 2026 American Society of Cataract and Refractive Surgery Annual Meeting; April 10-13, 2026; Washington, DC.

10. Askarian B, Askarian A, Tabei F, Chong JW. An IoT-enabled mHealth sensing approach for remote detection of keratoconus using smartphone technology. Sensors (Basel). 2025;25(5):1316. doi:10.3390/s25051316

11. Abou Said AG, Gispets J, Shneor E. Strategies for early keratoconus diagnosis: a narrative review of evaluating affordable and effective detection techniques. J Clin Med. 2025;14(2):460. doi:10.3390/jcm14020460

12. Epioxa HD and Epioxa. Prescribing information. Glaukos; 2026. Accessed May 19, 2026. https://www.epioxa.com/prescribing-information/

13. Raizman MB. Non-invasive epithelium-on oxygen-enriched corneal collagen crosslinking for the treatment of pediatric patients with keratoconus. Presented at: 51^st American Association for Pediatric Ophthalmology and Strabismus Annual Meeting; March 18-22, 2026; Boston, MA.

The authors are in private practice at Chicago Cornea Consultants. Dr. Majmudar is a consultant for Glaukos and a consultant and shareholder in Epion Therapeutics. Dr. Andrzejewski has no relevant financial disclosures. Contact them at tma@chicagocornea.com and pamajmudar@chicagocornea.com.