The Layer on Top: Can Epithelium Maps Help Spot Keratoconus Early?

When people picture keratoconus, they usually picture the cone: the cornea slowly thinning and bulging forward. But sitting on top of that tissue is a thin, constantly renewing skin of cells called the epithelium. It is surprisingly clever. As the cornea underneath starts to change shape, the epithelium tends to remodel, thinning over the steepest spot and thickening around it, which smooths the surface. That is good for your vision, but it can also partly hide very early keratoconus from a standard surface map.

A study published in BMC Ophthalmology in 2026 asked a practical question: can mapping the thickness of this top layer help tell early keratoconus apart from ordinary, harmless astigmatism?

What the researchers did

The team worked at the Refractive Surgery Clinic of Moheb Kosar Hospital in Iran during 2023–2024. They scanned 96 eyes from 55 adults aged 18–45. Thirty eyes had early (stage I) keratoconus. The comparison group was 66 eyes with regular astigmatism: 34 with-the-rule, 19 against-the-rule and 13 oblique. Nobody had worn contact lenses for at least three months, and nobody had had corneal surgery or cross-linking.

Each eye was scanned three times on an MS-39, an imager that combines optical coherence tomography (OCT) with a Placido-ring corneal map, by a single experienced operator. The researchers compared epithelial thickness in the centre, in a ring 2–5 mm out, and in an outer ring 5–7 mm out, quadrant by quadrant. It was a one-visit snapshot (a cross-sectional study), and there was no group with completely normal, non-astigmatic corneas.

What they found

First, some scale: a micrometre (µm) is one-thousandth of a millimetre, and the differences here were only a few micrometres.

• The centre looked the same. Central epithelium was 52.8 µm in early keratoconus and 53.1 µm with regular astigmatism (P = 0.779), so a central reading alone was not helpful.
• The top of the cornea was thicker in keratoconus. In the upper 2–5 mm zone, the epithelium averaged 53.9 µm in early keratoconus versus 50.9 µm with regular astigmatism, a difference of +3.0 µm (95% confidence interval 1.3 to 4.6; P < 0.001). The upper 5–7 mm zone showed a similar +2.9 µm difference (1.4 to 4.5).
• The usual top-to-bottom pattern was flatter. In regular astigmatism the epithelium is normally thinner above than below. That gap was smaller in early keratoconus (−1.07 µm versus −2.96 µm; difference +1.89 µm, 0.68 to 3.09; P = 0.002).
• The thinnest spot moved. In 53 of 66 regular-astigmatism eyes (80.3%) the thinnest epithelium was in the upper part of the cornea; in 22 of 30 early keratoconus eyes (73.3%) it was lower down.

Keratoconus corneas were also thinner overall (499.9 µm versus 555.7 µm). After the researchers adjusted for overall thickness, age, sex and amount of astigmatism, the upper-zone thickening remained (+2.776 µm in the 2–5 mm zone, 95% CI 1.147 to 4.405), although some other differences, such as the nasal zone, were no longer statistically significant.

A quick guide to the numbers: a 95% confidence interval is the range of values the true difference plausibly lies in; if it doesn't cross zero, the result is unlikely to be chance alone. A P-value below 0.001 means a difference this large would be very unlikely if there were truly no difference between the groups.

How accurate is it? Understanding the AUC

To judge a test, researchers often use the AUC (area under the curve). Think of it as a score between 0.5 and 1.0: 0.5 is a coin toss, and 1.0 would be a perfect test that never mixes up the two groups.

The upper 2–5 mm thickness scored an AUC of 0.75 (95% CI 0.62–0.87). Using a cut-off of 53.8 µm, it picked up 53.3% of the early keratoconus eyes and correctly cleared 84.8% of the astigmatic eyes. Combining three epithelial measures nudged the AUC to 0.79 (0.67–0.90), catching 83.3% of keratoconus eyes but correctly clearing only 69.7% of the others. The authors describe diagnostic performance as moderate and suggest epithelial mapping be considered an add-on to established tomography, not a replacement.

Where this fits in your care

Catching keratoconus early matters most for teenagers and young adults, and for families where someone already has the condition. We've covered that in why early detection matters for teenagers and screening children with a corneal map, so we won't repeat it here.

The front door to that care is a keratoconus-focused optometrist. At Rose Optometry in Hamilton, our optometrists, including Jagrut Lallu and Jacqueline Rowe, diagnose keratoconus, document any change with repeat corneal maps over time, fit scleral and specialty lenses, and refer to an ophthalmologist for cross-linking at the right moment. An epithelial pattern, where available, is one more clue weighed alongside corneal shape, overall thickness, your history and, above all, how the maps change from visit to visit. You can read more about our keratoconus care in Hamilton.

What the studies can't tell us

• Small and exploratory. Only 30 eyes had keratoconus and just 13 had oblique astigmatism. No sample-size calculation was done, and some people contributed both eyes.
• One clinic, one device. This was a single-centre study in Iran using the MS-39. Results may not transfer to other imaging devices or populations.
• Cut-offs not validated. The thresholds were chosen and tested on the same eyes, so real-world accuracy is likely to be lower.
• A snapshot, not a story. Being cross-sectional, it can't show how epithelial patterns change as keratoconus develops.
• Funding and conflicts unchecked. We read the full text via PubMed Central, but the declarations section (funding and competing interests) was not in the version we retrieved, so we can't say whether the device maker or anyone else was involved. We also couldn't confirm whether the operator knew each eye's diagnosis.

If you or your child has been told about astigmatism that seems to be changing, or keratoconus runs in your family, you're welcome to book a keratoconus assessment with our optometrists in Hamilton.

References

• Hadi Y, Kabood FK, Abdolalizadeh P, Ghiasian L, Mazouchi M. Regional corneal epithelial thickness and asymmetry patterns in early keratoconus versus regular astigmatism using MS-39 anterior segment OCT: a comparative cross-sectional study. BMC Ophthalmol. 2026;26(1). PMID: 42850600. https://doi.org/10.1186/s12886-026-05412-5