Keratoconus is a noninflammatory progressive corneal thinning and ectasia of unknown etiology in which the cornea assumes a conical shape. It is associated with irregular astigmatism, central corneal scarring, and progressive myopia resulting in impaired visual acuity.1 Various treatment modalities have been described including spectacles, contact lenses, and keratoplasty, none of which alter the natural course of the disease.1,2 Corneal collagen crosslinking (CXL) is a relatively new approach to increase the mechanical and biochemical strength of the corneal tissue, thereby halting the disease process.3,4
Based on the current protocol for performing CXL,4 the effect is limited to the anterior 300 μm of the corneal stroma.5,6 Both corneal stromal thickness (at least 400 μm) and the presence of riboflavin are of critical importance to the procedure because they prevent ultraviolet-A (UVA) from reaching deep stroma, the corneal endothelium, and the crystalline lens. Corneal thickness is often a limiting factor as many patients with corneal ectasia have thin corneas. To increase the intraoperative corneal thickness, we performed CXL in 3 patients using refractive lenticules removed during small-incision lenticule extraction. The safety and efficacy of the procedure were assessed.
Preoperative progression of keratoconus with steepening on corneal topography was documented in 3 patients over a 6-month period. Pachymetric analysis revealed corneal thickness of less than 400 μm at the area of maximum steepening (380 μm, 370 μm, and 374 μm, respectively, determined by Scheimpflug imaging). The patients had CXL with tailored stromal expansion using refractive lenticules obtained from patients having small-incision lenticule extraction for myopia without astigmatism. The center of the cone was predetermined, enabling correct placement of the thickest area of the refractive lenticule.
The tailored stromal expansion procedure was planned along with refractive lenticule extraction in another patient with moderate myopia. Based on the technique described by Shah et al.,7 small-incision lenticule extraction using the Visumax femtosecond laser (Carl Zeiss Meditec AG) was performed under topical anesthesia. The refractive lenticule with an estimated central thickness of 80 to 100 μm (predetermined by the Visumax laser system) was extracted as a whole and stored in McCarey-Kaufman media to be used subsequently for CXL.
The stromal expansion procedure was performed under aseptic precautions. The eye was cleaned and draped. Proparacaine 0.5% (Alcaine) was instilled 3 times at 5-minute intervals, 15 minutes prior to the procedure. A blunt spatula was used to debride the central 8.0 mm of corneal epithelium. Deepithelialization was followed by intraoperative pachymetry to determine the required thickness of the refractive lenticule. The central area of the 6.2 mm lenticule was placed over the predetermined area of the apex of the cone (Figure 1). The augmented stromal thickness was confirmed to be more than 400 μm by intraoperative ultrasonic pachymetry, allowing CXL to be performed within the required safety protocol guidelines.
One drop of riboflavin (0.1% solution of 10 mg riboflavin-5-phosphate) was instilled every 5 minutes for 30 minutes and 1 drop every 5 minutes under UVA radiation for the next 30 minutes. Slitlamp examination was performed in all cases to confirm the presence of yellow flare in the anterior chamber and ascertain adequate penetration of the dye. Anterior segment optical coherence tomography (AS-OCT) images were taken after placement of the stromal lenticule and initial riboflavin instillation (Figure 2). Ultraviolet-A radiations of 365 nm with desired irradiance of 3 mW/cm2 were used at a distance of 5 cm (UV-X, IROC Innocross AG). On completion of the procedure, the refractive lenticule was peeled off the stromal bed and the surface was irrigated with normal saline. The refractive lenticule showed increased rigidity, and histopathologic examination revealed CXL (Figure 3). A bandage contact lens was applied and was removed on the fifth postoperative day. Postoperative medications included gatifloxacin 0.3% eyedrops 4 times daily for 7 days, loteprednol etabonate 0.5% eyedrops (L-Pred) 3 times daily for 20 days, and hypromellose 0.3% eyedrops (Genteal) 6 times daily for 45 days.
No intraoperative or postoperative complications were noted. The epithelium healed completely within 3 to 5 days of the procedure, following which the bandage contact lens was removed. Corneal stability was demonstrated on topography at the 6-month follow-up (Figure 4A and 4B). Specular microscopy revealed no significant endothelial cell loss (Table 1). In all cases, a demarcation line was observed postoperatively on corneal AS-OCT imaging at a depth ranging from 280 to 300 μm (Figure 5).
When performed according to the standard protocol, CXL with riboflavin and UVA is a safe and effective treatment for the management of keratoconus and other corneal ectasias.4,8 Corneal thickness plays a significant role in this procedure. According to the standard Dresden protocol,3 the cornea is photosensitized with isoosmolar riboflavin (0.1% solution in 20% dextran) for 30 minutes, following which it is exposed to UVA radiation (370 nm, 3 mW/cm2) for 30 minutes. Because the absorption coefficient of the human cornea is 70 cm−1 and the intended surface irradiance is 3.0 mW/cm2, the 0.37 mW/cm2 irradiance is reached at the 300 μm depth. In a 400 μm thick cornea saturated with riboflavin, the irradiance at the endothelial level is 0.18 mW/cm2, which is a factor of 2 smaller than the damage threshold. Therefore, a corneal thickness of 400 μm is considered the safe limit to protect the endothelium and intraocular structures from the adverse effects of UV irradiation and has been established as a clinical standard.5,9,10 Unfortunately, the patients who are in need of CXL have thin corneas that are often below the threshold considered to be safe for the treatment. In developing Asian countries such as ours, keratoconus has an earlier onset and is often detected at a later stage, making the disease not amenable to traditional CXL.
Various techniques to overcome the limitations of reduced corneal thickness have been described. Hafezi et al.11 describe a CXL technique using hypoosmolar riboflavin in which the deepithelialized cornea swells to twice its normal thickness when irrigated with a hypoosmolar solution because of the hydrophilic property of the stromal proteoglycans. One-year results were satisfactory. However, it is not clear whether artificially swollen corneas behave the same as nonswollen keratoconic corneas. Crosslinking might be expected to have a smaller effect on the biomechanics of an artificially swollen cornea because of a relatively lower concentration of collagen in the hydrated stroma.
Transepithelial CXL was introduced to prevent the complications associated with epithelial debridement, for use in pediatric cases, and for its possible role in treating thinner corneas. Filippello et al.12 report a series of 20 patients with bilateral progressive keratoconus who had transepithelial CXL using enhanced riboflavin solution containing trometamol and ethylenediaminetetraacetic acid sodium salt. They report a statistically significant improvement in visual and topographic parameters. Spadea and Mencucci13 report a similar technique of transepithelial CXL in ultrathin corneas (thinnest pachymetry 331 to 389 μm). Although both studies report no endothelial toxicity, this issue remains a concern because an improper stromal concentration of riboflavin may not be effective in absorbing all the UV radiation.
Kymionis et al.14 describe custom pachymetry-guided epithelial debridement in 2 patients with progressive keratoconus. Central 8.0 mm epithelial debridement was done while preserving a small localized island corresponding to the thinnest area or the area of maximum topographic steepening. Postoperative stabilization of ectasia was noted with no significant endothelial cell loss. Preserving epithelium over the thinnest area also has the potential advantages of preventing local stromal dehydration and blocking the excessive UV radiations in this susceptible area. In a study using anterior segment OCT and confocal microscopy,15 stromal haze and demarcation lines were seen in areas corresponding to deepithelialized stroma and were not evident in areas with an intact epithelium.15 Moreover, the efficacy of custom pachymetry-guided epithelial debridement is doubtful as it spares the thinnest area with the maximum need for CXL.
Jacob et al.16 describe the use of a riboflavin-soaked bandage contact lens of negligible power to artificially increase the corneal thickness for CXL. Long-term results of this procedure are not available. The inability to customize the thickness of the contact lens, varied hydration states of different contact lens materials, difference in UV-light transmission properties of contact lenses and corneal stroma, and uneven adherence to the underlying stromal bed causing irregular interface and subsequent pooling of riboflavin are some drawbacks of this innovative technique. Intraoperative buckling of the contact lens might also create an uneven precorneal riboflavin film and consequently lead to hot or cold spots.16
Small-incision lenticule extraction is a new refractive surgery that involves the extraction of a femtosecond laser–constructed corneal lenticule through a single small incision without raising a flap.7 The lenticular thickness depends on the refractive error of the patient. Also, the thickness of the lenticule is maximum in the center and decreases toward the periphery, as described in a study by Tay et al.17 In that study, preoperative and postoperative stromal bed morphology was evaluated using AS-OCT. In our modified technique of CXL using the refractive lenticule, the thickness of the cornea is increased in the most physiologic manner by adding stromal tissue, whose biologic and absorptive properties are the same as those of the cornea to be treated. Refractive lenticules of variable thickness (20 to 140 μm) can be obtained following femtosecond lenticule extraction depending on the extent of the refractive error to be corrected. Placing the central lenticule over the apex of the cone enables us to augment the corneal thickness where required while sparing the remaining stroma to be crosslinked normally. Moreover, the relatively rough host stromal surface makes it easy to spread the lenticule and prevents buckling. Also, after the application of riboflavin 0.1% for 30 minutes, the lenticule was well-attached; it had to be peeled off the bed after the procedure. An even demarcation line indicative of CXL was seen in all cases, as described previously.18 In our technique, both femtosecond lenticule extraction and CXL were performed in the same sitting in adjacent operation rooms, thereby maintaining sterility. Long-term preservation of myopic lenticules would enable more widespread use of this technique.
To summarize, we describe a technique of tailored stromal expansion for performing CXL in thin and ultrathin corneas by adding a myopic lenticule to the ectatic corneal surface following epithelial debridement. The technique was found to be safe and effective in our initial few cases. Long-term studies are required to further establish the efficacy and feasibility of this procedure.
What Was Known
- Corneal CXL is a safe and effective way to prevent progression of keratoconus but cannot be performed in ultrathin corneas (<400 μm).
- Several modifications have been proposed to enable performance of CXL in ultrathin corneas, each fraught with its own limitations.
What This Paper Adds
- Intraoperative stromal augmentation with refractive lenticules obtained after small-incision lenticule extraction for myopia allowed safe and effective CXL in keratoconic eyes with ultrathin corneas.
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