Dr.Radhika Dashputra, R19636, Dr. Ritu Arora, Dr.
Radhika Dashputra, Dr. Goyal J L
INTRODUCTION
Keratoconus is a progressive disorder in which central or paracentral corneal stromal thinning occurs along with apical protrusion and irregular astigmatism. It starts at around puberty and progresses till third or fourth decade after which it arrests.
Clinical diagnosis of moderate to advanced keratoconus is relatively easy as there are present characteristic topographic patterns and classical clinical signs. Diagnosing early keratoconus in patients with minimal or no clinical signs is however challenging.
Corneal thinning is a key pathologic feature of keratoconus, therefore a keratoconus diagnosis based on corneal thickness measurement offers additional information which is not available on topography.
Optical Coherence Tomography is commonly used in ophthalmologic practice and provides quick acquisition. It has been used to do pachymetry mapping and corneal epithelial thickness mapping in patients of keratoconus as well as normal subjects.
In cases of very early keratoconus, epithelial thickness mapping has shown that there occurs thinning of epithelium in the area of the cone with associated peripheral thickening (Doughnut pattern). Thus, epithelial compensation may mask the presence of an early cone on front-surface topography and a diagnosis of keratoconus might be missed by topography alone.1,2,3
A study was therefore conducted to study OCT epithelial mapping and detailed tomography in keratoconus (early to advanced stage). These findings were compared with those in normal corneas.
PATIENTS AND METHODS
This cross-sectional study included eyes with early to advanced keratoconus and eyes with normal corneas. All eyes were assessed using Fourier-domain OCT (RTVue 5.5) and scanning-slit corneal topography (Orbscan IIz), and rotating Scheimpflug camera (Pentacam Comprehensive Eye Scanner). Keratoconus was diagnosed if all of these criteria were found: (1) keratoconic appearance on the topography map (asymmetric bow tie with skewed radial axis, central or inferior steepzone, or clawshape); (2)positive topographic indices on scanning-slit corneal topography assessment (mean keratometry [K]>47.0 diopters [D] or inferior–superior value [I–S] >1.4 D in the central 3.0 mm, according to Rabinowitz and McDonnell criteria); (3) positive rotating Scheimpflug camera assessment (1 or more of a central keratometry index [CKI] >1.03, a keratometry index [KI] >1.07, and a positive topographic keratoconus classification); and (4) at least 1 clinical sign.
Exclusion criteria included previous ocular surgery or trauma; associated corneal pathologic features; a history of collagen cross-linking, intrastromal corneal ring segment implantation, keratoplasty, or other corneal surgery; and contact lens wear during the previous 3 weeks.
A 26 000 Hz Fourier-domain OCT system with a 5 mm axial resolution was used with a corneal adaptor module. The system works at an 830 nm wavelength and has a scan speed of 26 000 axial scans per second. The depth resolution is 5 µm. The wide-angle (corneal long) adaptor lens used in this study provided a 6.0 mm scan width with a transverse resolution of 15 mm. The cornea was mapped using a Pachymetry scan pattern (6.0 mm scan diameter, 8 radials, 1024 axial scans each, and 5 repetitions) centered on the middle of the pupil. The corneal adaptor module software (software version 5.5) automatically processed the OCT scan to provide the pachymetry (corneal-thickness) and the epithelial-thickness maps.
Commercial software of epithelial mapping25 was used to calculate the following corneal-thickness and epithelial thickness parameters: minimum corneal thickness, superonasal– inferotemporal (SN–IT) corneal thickness, I–S corneal thickness, minimum–median (min–med) corneal thickness, I–S epithelial thickness, thinnest epithelial thickness, minimum–maximum (min–max) epithelial thickness, and the standard deviation (SD) of the epithelial thickness. All calculations were performed within the 5.0µm central zone of the cornea. For all analyses, a P value less than 0.05 was considered statistically significant.
RESULTS
The study included 140 eyes of subjects in age group 7 to 30 years. The early keratoconus group included 37 eyes, the moderate keratoconus group 32 eyes, severe keratoconus group 31 eyes while the control group had 40 eyes.
The mean corneal epithelial thickness over the area of minimum pachymetry zone in control eyes was 53.84±3.67µ, 51.27±3.72µ in early keratoconus, 46.04±3.85µ in moderate and 39.83±4.23µ in severe keratoconus.
There was a statistically significant variation in values between the groups. The corneal epithelial thickness over the area of minimum pachymetry zone was statistically significantly less in the early keratoconus group (51.27±3.72µ) than in the control group (53.84±3.67µ) (P < 0.05).
DISCUSSION
In this study we analysed the epithelial thickness corresponding to area of minimum pachymetry. Previous studies3 have commented on minimum epithelial thickness which in our study we found did not always coincide with the area of minimum pachymetry.
Reinstein et al.1,2,3 pioneered the use of corneal epithelial mapping using VHF US (50 MHz) with a 21 µm resolution over the entire corneal surface. They performed a 3-dimensional epithelial thickness analysis for the central 8.0 to 10.0 mm diameter in normal eyes and in keratoconic eyes. The central epithelial thickness in normal eyes in that study was 53.4 ± 4.6 µm. In keratoconic eyes, the corneal epithelium showed an epithelial doughnut pattern characterized by localized central thinning surrounded by an annulus of thick epithelium, and the central epithelial thickness (45.7 ± 5.9 µm) was statistically significantly thinner than in normal eyes. They suggested that in very early keratoconus epithelial compensation could mask the presence the presence of an underlying cone on front-surface topography and a diagnosis of keratoconus might be missed by the use of topography alone.
Using time-domain OCT, Haque et al. reported a central corneal epithelial thickness of 54.7 µm in normal eyes. They also showed that the central epithelial thickness in keratoconic eyes was thinner than in normal eyes (a 4.7 µm average difference).5
Rocha et al. 6 described a regional epithelial thickness profile in keratoconic eyes, eyes with postoperative ectasia, and normal eyes including subjects in the age group 29 to 41yrs. They found that the mean epithelial thickness at the highest point in the meridian was statistically significantly thinner in eyes with keratoconus (P < .0001) and ectasia (P=.0007) than in normal eyes, calculated as 41.18 ± 6.47 µm, 46.5 ± 6.72 µm, and 50.45 ± 3.92 µm, respectively. They reported that total cornea thickness is not predictive of localized regions of stromal thinning or epithelial thickening.
In 2012, Li et al.7,8 developed epithelial-mapping software with Fourier domain OCT to determine the characteristics of the epithelium in keratoconic eyes. Their study found no statistically significant difference in the central epithelial thickness between keratoconic and normal corneas but did find the SI (Superior-Inferior), min–max epithelial thickness differences, and SD (Standard Deviation) to be higher.
In 2015, Temstet et al.4 determined epithelial thickness in the thinnest corneal zone and its location using Fourier-domain OCT in subjects in the age group of 21 yrs to 45.5 yrs. A minimum epithelial thickness from 35.4 ± 9.2 µm to 48.3 ± 3.6 µm was noted in patients of keratoconus. While that in control subjects were noted as 49.1 ± 3.1 µm.
To our knowledge, there are no published studies describing OCT epithelial parameters inclusive of the pediatric age group, even though the prevalence of keratoconus is high in the younger agegroup. In our study we did not observe epithelial thickening in early cases of keratoconus. This finding is similar to that of a study by Temstet et al.4 but differs from that reported by Reinstein et al.1,2,3
OCT epithelial and corneal measurements include the tear film thickness that can lead to potential inaccuracies of the absolute values and this could be a limitation to our study.
In summary, along with complementary tests, corneal/epithelial thickness mapping by OCT could be useful to detect an incipient corneal ectasia in clinically and topographically normal eyes. This finding could have important implications for avoiding keratectasia when refractive surgery is performed on an apparently normal eye
REFERENCES
1.Reinstein DZ, Archer TJ, Gobbe M. Corneal epithelial thickness profile in the diagnosis of keratoconus. J Refract Surg. 2009; 25:604–10
2.Reinstein DZ, Gobbe M, Archer TJ, Silverman RH, Coleman DJ. Epithelial, stromal, and total corneal thickness in keratoconus: three-dimensional display with Artemis very-high frequency digital ultrasound. J Refract Surg. 2010; 26:259–71.
3.Reinstein DZ, Archer TJ, Gobbe M, Silverman RH, Coleman DJ. Epithelial thickness in the normal cornea: three-dimensional display with Artemis very high-frequency digital ultrasound. J Refract Surg. 2008; 24:571–81.
4.Temstet C, Sandali O, Bouheraoua N, Hamiche T, Galan A, Sanharawi ME, et al. Corneal epithelial thickness mapping using Fourier-domain optical coherence tomography for detection of form fruste keratoconus. J Cataract Refract Surg. 2015; 41:812-20.
5.Haque S, Jones L, Simpson T. Thickness mapping of the cornea and epithelium using optical coherence tomography. Optom Vis Sci. 2008; 85:E963–76.
6.Rocha KM, Perez-Straziota CE, Stulting RD, Randleman JB. SD-OCT analysis of regional epithelial thickness profiles in keratoconus, postoperative corneal ectasia, and normal eyes. J Refract Surg. 2013; 29:173–9.
7.Li Y, Meisler DM, Tang M, Lu ATH, Thakrar V, Reiser BJ, et al. Keratoconus diagnosis with optical coherence tomography pachymetry mapping. Ophthalmology. 2008; 115:2159–66.
8.Li Y, Tan O, Brass R, Weiss JL, Huang D. Corneal epithelial thickness mapping by Fourier-domain optical coherence tomography in normal and keratoconic eyes. Ophthalmology. 2012;119:2425–33.
9.Kanellopoulos AJ, Asimellis G. OCT corneal epithelial topographic asymmetry as a sensitive diagnostic tool for early and advancing keratoconus. Clin Ophthalmol. 2014;8:2277-87.
10.Kanellopoulos AJ, Asimellis G. In vivo three-dimensional epithelial imaging of corneal epithelium in normal eyes by anterior segment opti¬cal coherence tomography: a clinical reference study. Cornea. 2013; 32(11):1493–8.

