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    Detecting Keratoconus Progression

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    Researchers have found that corneal epithelial thickness measure­ments may be useful in detecting actively progressing versus stable keratoconus (KC). This work builds on previous research that showed epithe­lial analysis can increase the sensitivity for early diagnosis of KC.1,2

    “With comprehensive mapping through spectral-domain (SD) OCT, it is possible to reproducibly measure parameters of epithelial thickness,” said Marcony Santhiago, MD, PhD, at the University of São Paulo in Brazil.

    Map of keratoconus progression.

    MIN-MAX. KC progression documented in one year. Red arrow = high variability of the min-max parameters.

    Study details. The researchers enrolled 50 patients with progressive KC (maximum keratometry [Kmax] increase of 1 D per year), 50 with stable KC, and 50 healthy controls. All indi­viduals underwent SD-OCT imaging to obtain epithelial thickness maps and pachymetry. Minimum and maximum epithelial thicknesses of the map and the difference between the thicknesses (min-max) were compared between the groups. “We aimed to identify mea­sures of corneal epithelium that behave differently in stable keratoconus from those in progression,” Dr. Santhiago said.

    Results. Epithelium min-max was the only epithelial parameter with a statisti­cally significant difference between the stable and progressive KC groups. Eyes with stable KC presented min-max mean values of –18.2 ± 6.6 μm. In contrast, progressing KC eyes presented mean values of –23.4 ± 10.3 μm (p < .0001).

    Findings assessed. “We found that epithelial measures are useful to iden­tify eyes with progressing KC and that the variation between the minimum and maximum epithelial points was significantly greater in progressing KC eyes,” said Dr. Santhiago. “A possible ex­planation for the min-max difference in progression is that the corneal epitheli­um has rapid cell turnover and is highly reactive to asymmetries in the shape of the underlying stromal surface.”

    In addition, he said, “This study confirms that metrics associated with the asymmetric reactive capacity of the epithelium are capable of detecting subtle differences between groups,” which he described as “more mean­ingful than values such as epithelial thinnest point.”

    A substantial aspect of the research team’s methodology is that “we iden­tified eyes that have progressed based on the limits that would make them candidates for corneal crosslinking (1 D over a year), regardless of their final KC stage,” Dr. Santhiago noted. “Only grouping these eyes in stages, regardless of progression, creates a bias for analyzing any variable role in relevant KC progression.”

    Next steps. An important part of the group’s research involves the iden­tification of inflammatory biomarkers possibly correlated with structural impairment in eyes with KC, Dr. San­thiago said. Their next step: publishing their latest work, which “showed that progressing KC eyes have a higher concentration of interleukin 6 [IL-6] and cortisol” versus that observed in eyes with stable KC, he said. He added, “There is a significant correlation be­tween increased IL-6 and cortisol with corneal structural change in keratome­try and pachymetry.”

    Takeaway for clinicians. “Combined with the topography of the cornea, the epithelial map helps to understand structural alterations that represent the disease,” Dr. Santhiago said. “It can be a promising complementary tool both in the follow-up of a patient with KC and in the preoperative course of a patient who is a candidate for refractive sur­gery. In this group, we want to identify KC in its early forms.”

    —Patricia Weiser, PharmD


    1 Santhiago M et al. Ophthalmol Science. 2023;3:100256.

    2 Wang Y et al. J Refrac Surg. 2018;34(3):201-211.


    Relevant financial disclosures: Dr. Santhiago—None.

    For full disclosures and the disclosure key, see below.

    Full Financial Disclosures

    Dr. Chaudhary Bayer: C,L,S; Boehringer Ingelheim: C; Novartis: C,S; Roche: L,S.

    Dr. Santhiago Alcon: C; Ziemer: C.

    Dr. Skowronska-Krawczyk Visgenx: C.

    Disclosure Category



    Consultant/Advisor C Consultant fee, paid advisory boards, or fees for attending a meeting.
    Employee E Hired to work for compensation or received a W2 from a company.
    Employee, executive role EE Hired to work in an executive role for compensation or received a W2 from a company.
    Owner of company EO Ownership or controlling interest in a company, other than stock.
    Independent contractor I Contracted work, including contracted research.
    Lecture fees/Speakers bureau L Lecture fees or honoraria, travel fees or reimbursements when speaking at the invitation of a commercial company.
    Patents/Royalty P Beneficiary of patents and/or royalties for intellectual property.
    Equity/Stock/Stock options holder, private corporation PS Equity ownership, stock and/or stock options in privately owned firms, excluding mutual funds.
    Grant support S Grant support or other financial support from all sources, including research support from government agencies (e.g., NIH), foundations, device manufacturers, and\or pharmaceutical companies. Research funding should be disclosed by the principal or named investigator even if your institution receives the grant and manages the funds.
    Stock options, public or private corporation SO Stock options in a public or private company.
    Equity/Stock holder, public corporation US Equity ownership or stock in publicly traded firms, excluding mutual funds (listed on the stock exchange).


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