A retrospective case series was conducted at the Department of Ophthalmology, Tishreen University Hospital, Syria. All patients included in this study underwent A-CXL (10 mW/cm² for 9 minutes). This study adhered to the tenets of the Declaration of Helsinki and was approved by the ethics Committee of Tishreen University Hospital, Tishreen University, Syria. Prior to undergoing treatment, written informed consent was obtained from all patients.
The inclusion criteria consisted of patients aged 18 years or older at the time of surgery with progressive KC, clear corneas, minimum corneal thickness of ≥ 400 µm after removal of the epithelium and a minimum follow up duration of at least 12 months after A-CXL. The diagnosis of KC was established in concordance with the Global Consensus on Keratoconus and Corneal Ectatic Diseases Report (9). Progression of keratoconus was defined as: at least 1 diopter increase in the anterior maximum keratometry or in the manifest refraction spherical equivalent (MRSE), a decrease of 5% in the minimum pachymetry, or loss of at least two lines of the corrected distance visual acuity during the past 12 months (10).
Exclusion criteria included pregnancy, central or paracentral corneal opacities or scarring, a clinical history of herpetic keratitis, evidence of active ophthalmic inflammation, autoimmune disease, severe dry eye, and patients with a history of ocular surgery. Patients who developed postoperative scarring or corneal haze were also excluded from the analysis due to the secondary optical abberations that result with both scarring and haze (11).
All keratoconic eyes were classified according to Amsler-Krumeich classification (12). Contact lens-wearing patients were asked to discontinue wearing their lenses for 3-weeks and 1-week for rigid and soft contact lenses, respectively.
Evaluation included the measurement of UDVA, CDVA, manifest refraction spherical equivelant (MRSE), slit-lamp biomicroscopy, retinoscopy and fundoscopy. Topography, tomography and aberrometry data were measured at baseline preoperatively and at 12 months postoperatively using the Sirius Sheimpflug-Placido topographer (Costruzioni Strumenti Oftalmici, Florence, Italy). Anterior corneal higher order aberrations were measured at the central 6.0 mm. Three well-focused, aligned and centred images were obtained for each eye. In order to optimise image quality, patients were asked to blink before each image capture to eliminate the effect of corneal surface dryness. Placido disc mires up to the 17th ring had to be continuous to consider the videokeratography to be of good quality and satisfactory for calculation of the Zernike coefficients for a 6.0 mm simulated pupil. Software acquisition was uniform for all data points for consistency (Phoenix v.2.6).
An epithelium-off A-CXL technique was performed in all subjects. Topical anesthesia consisted of Proparacaine Hydrochloride 0.5% (Proparacain Rama 0.5%, Rama Pharma, Syria) eye drops administered at 2 minute intervals, starting 10-minutes preoperatively. The central 8-9 mm corneal epithelium was removed using a blunt spatula and dry sponge (without alcohol assistance). Twenty minutes prior to irradiance, Riboflavin with Dextran (0.1% Riboflavin in 20% Dextran. Medio Cross, Germany) solution was applied every 2 minutes. The saturation of the anterior chamber with riboflavin was checked with slit-lamp biomicroscopy. The 32 eyes were irradiated with the Vega C.B.M-X Linker (CSO, Italy) using the A-CXL 10 mW/cm² UVA for 9 minutes to achieve a total energy of 5.4 J/cm². During the 9 minutes of irradiance, riboflavin solution was applied every 2 minutes. At the end of the procedure, the corneal surface was irrigated with balanced salt solution (BSS) and a soft contact lens was applied for 5 days. Topical moxifloxacin 0.5% (Megamox, Rama Pharma, Syria) and fluorometholone 0.1% (Methouflor 0.1%, Diamond Pharma, Syria) eye drops were prescribed for 1 week and 2 weeks, respectively. The surgical protocol utilized for accelerated corneal cross-linking was previously described (8, 13).
Mean Outcomes Measures:
Measurements UDVA, CDVA, MRSE, maximum keratometry, mean keratometry, simulated topographic cylinder, symmetry index front (SIf), total Baiocchi-Calossi-Versaci index (BCV) and minimum corneal thickness (ThkMin). Anterior corneal higher order aberrations were collected from the Sirius over the central 6 mm zone. The Sirius Scheimpflug-Placido topographer provides corneal aberrometry using a special algorithm based on the elevation map. Normalized coefficients were used, expressed in microns of wavefront error (root mean square [RMS]), and labeled with International Organization for Standardization (ISO) standardized double-index Zernike symbols (14). The collected HOAs data included: Root mean square (RMS) total HOAs, RMS trefoil Z (3, ±3), RMS trefoil II Z (5, ± 3), RMS coma Z (3, ± 1), RMS coma II Z (5, ± 1) , RMS astigmatism II Z (4, ± 2), and RMS spherical aberration I Z (4, 0).
Visual acuity was converted to a logMAR notation. A paired t-test was used to test the significance between HOAs at baseline and HOAs 1 year after A-CXL. Multivariate regression analysis was used to identify the factors associated with changes in UDVA and CDVA. This analysis was performed using generalized estimating equations to correct for patients in whom both eyes were included in the dataset. Analyses were performed using SPSS software (version 21.0, International Business Machines Corp.). P-values of less than 0.05 were considered significant.