EyeWorld is the official news magazine of the American Society of Cataract & Refractive Surgery.
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72 | EYEWORLD | MARCH 2021 R EFRACTIVE by Liz Hillman Editorial Co-Director About the physicians Francesco Carones, MD Carones Vision Milan, Italy Arthur Cummings, MD Wellington Eye Clinic Dublin, Ireland Dan Reinstein, MD London Vision Clinic London, U.K. References 1. Reinstein DZ, et al. Epithelial thickness in the normal cornea: three-dimensional display with Artemis very high-frequency digital ultrasound. J Refract Surg. 2008;24:571–581. 2. Li Y, et al. Corneal epithelial thickness mapping by Fourier- domain optical coherence tomography in normal and keratoconic eyes. Ophthalmolo- gy. 2012;119:2425–2433. 3. Reinstein DZ, et al. Epithe- lial and corneal thickness measurements by high-fre- quency ultrasound digital signal processing. Ophthalmology. 1994;101:140–146. 4. Reinstein DZ, et al. Corneal epithelial thickness profile in the diagnosis of keratoconus. J Refract Surg. 2009;25:604–610. 5. Reinstein DZ, et al. Com- parison of corneal epithelial thickness measurement between Fourier-domain OCT and very high-frequency digital ultrasound. J Refract Surg. 2015;31:438–445. E pithelial thickness mapping was FDA approved in the U.S. in 2017, but awareness about its utility—and in some minds, its necessity—is growing. Three international ophthalmologists— Francesco Carones, MD, Arthur Cummings, MD, and Dan Reinstein, MD—shared their experi- ence with the technology and offered insights on where they think it fits in ophthalmic practic- es now and in the future. Dr. Carones said he has been using epi- thelial mapping for 4 years. It's a routine part of his practice, and he thinks it will become routine for anterior segment ophthalmology in the future. "Many anterior segment surgeons are not doing this on a routine basis yet because anterior segment OCT technology being able to map epithelial thickness became available only recently, and this kind of technology has some significant cost. We are still in that phase of early adoption where surgeons have to buy the instrument," Dr. Carones said. Dr. Reinstein developed epithelial mapping and applications as a bioengineering research fellow working in D. Jackson Coleman's lab with Ronald Silverman, PhD. Dr. Reinstein was the first to measure the epithelium of the cornea in vivo in 1991 using very high frequency (VHF) digital ultrasound and the first to produce a map of the epithelium in 1993. He went on to develop the first method of mapping the full epithelial profile of the cornea by 1997 when he began scanning and elucidating the epithelial changes in LASIK and analyzing the compli- cations of corneal refractive surgery. With this work and the commercialization of the first epithelial mapping device (ArcScan Insight 100 VHF and other anterior segment OCT devices with this capability), Dr. Reinstein is considered to be the "father" of this new diagnostic field of layered corneal diagnostics. "Having developed and worked with VHF digital ultrasound for 20 years prior, I was excit- ed to help Optovue develop the first OCT pro- totype device to map the corneal epithelium in 2012 and commercially launched in 2015. Most anterior segment OCT manufacturers are now developing this capability for their devices," Dr. Reinstein said. "This is becoming the standard of care for refractive surgery diagnostics." Dr. Carones described epithelial mapping as a diagnostic and screening tool that can help ensure the right treatment is pursued in certain cases. It's first important to understand what a normal epithelial map looks like so it can be used as a baseline for comparison. Dr. Reinstein and colleagues published in 2008 that normal epithelium was 5.7 µm thicker inferiorly than superiorly and 1.2 µm thicker nasally than temporally. 1 The mean central thickness was 53.4 µm. According to Dr. Reinstein's work, the av- erage central epithelial thickness was 53.4 µm with a standard deviation of 4.6 µm. "This indicated that there was little vari- ation in central epithelial thickness in the population," he said. "The thinnest epithelial point within the central 5 mm of the cornea was displaced on average 0.33 mm (±1.08) tem- porally and 0.90 mm (±0.96) superiorly with reference to the corneal vertex. Studies using OCT have confirmed this superior-inferior and nasal-temporal asymmetric profile for epithelial thickness in normal eyes." 2 Dr. Reinstein first postulated in 1994 that this inferior/superior asymmetry is produced by the balance of forces of epithelial outward growth and the combined inward forces pro- duced by the eyelids, the upper eyelid produc- ing more inward force than the lower lid, he explained. 3 A diagnostic and screening tool Epithelial mapping has been described by Dr. Reinstein and colleagues as a very sensitive and specific method to detect keratoconus even ear- lier than topographic and tomographic devices. 4 "If the keratoconus is early enough, it cannot be detected on topography or tomogra- phy," Dr. Cummings said. "If the epithelial maps show a thinning of the epithelium, however, that would indicate that the stroma beneath the thinned epithelium may be bulging or ectatic. The epithelium has the ability to mask corneal irregularities when they are sufficiently subtle." Diagnosing keratoconus early can ensure patients are being monitored closely for pro- gression. If progression is observed, crosslink- ing could be performed to stop it before there are significant visual impacts. Dr. Reinstein The utility of epithelial mapping