Corneal Collagen Cross-linking With Riboflavin and Ultraviolet-A Irradiation in Patients With Thin Corneas


To report the outcomes after corneal collagen cross-linking (CXL) treatment with riboflavin and ultraviolet-A (UVA) irradiation in patients with thin corneas (minimum corneal thickness less than 400 μm after epithelial removal and before riboflavin instillation).


Prospective case series.


Twelve patients (14 eyes, with minimum corneal thickness less than 400 μm after epithelial removal) were included in the study. All patients underwent riboflavin-UVA-induced CXL using the standard CXL (Dresden) protocol. Uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA) (decimal scale), manifest refraction (diopters, D), and topography were evaluated at baseline and at 1, 3, 6, and 12 months follow-up. Images of the endothelium were acquired with a modified confocal scanning laser ophthalmoscope.


No intraoperative or postoperative complications were observed in this patient series. Mean minimum preoperative corneal thickness at the apex of the cone after epithelial removal and before riboflavin instillation was 373.92 ± 22.92 μm (range 340-399 μm). UDVA and CDVA improved from 0.25 ± 0.15 and 0.40 ± 0.20 to 0.27 ± 0.17 and 0.49 ± 0.20 respectively at the last follow-up examination. There was a reduction of the mean keratometry readings from 51.99 ± 5.57 D to 49.33 ± 4.82 D at the last follow-up. A significant decrease of endothelial cell density was observed (preoperative: 2733 ± 180 cells/mm 2 [range 2467-3016], last follow-up visit: 2441 ± 400 cells/mm 2 [range 1448-2920], P < .01).


CXL in thin corneas with minimum corneal thickness less than 400 μm after epithelial removal seems to result in a significant endothelial cell density decrease postoperatively. This finding was not related to other intraoperative or postoperative complications.

Keratectasia is a condition of progressive thinning and steepening of the cornea, which results in the production of myopia and irregular astigmatism. The most common ectatic disorders of the cornea associated with corneal biomechanical instability are considered to be keratoconus and, especially in the last decade, post–laser in situ keratomileusis (LASIK) ectasia.

Therapeutic solutions proposed for the management of these ectatic disorders are spectacle correction, rigid gas-permeable contact lenses, and intrastromal corneal ring segments, in order to achieve adequate visual rehabilitation. If the disorder continues to advance, lamellar or penetrating keratoplasty are considered the ultimate treatment options.

Corneal collagen cross-linking (CXL) with the use of riboflavin and ultraviolet-A (UVA) irradiation is the latest technique proposed for the stabilization of ectatic disorders such as keratoconus and post-LASIK ectasia. The basic principle of CXL is the induction of cross-links in the corneal stroma, producing a stiffening effect and increasing corneal strength and stability.

The standard protocol of CXL includes, for safety purposes, a minimum corneal thickness of 400 μm after epithelial removal, which is necessary for an effective CXL treatment. This pachymetric limit has been established in order to avoid endothelium damage.

In this prospective study we evaluated the outcomes and possible complications of corneal CXL with the use of riboflavin and UVA irradiation in patients with thinner corneas than the standard protocol (minimum corneal thickness less than 400 μm after epithelial removal).

Patients and Methods

SPSS version 18 (IBM Corporation, New York, New York, USA) was used for the statistical analysis of our data. Meta-analysis for the estimation of the sample size was estimated by G-Power version 3.1.2 (Edgar Erdfelder, Mannheim, Germany). We used paired t test for the estimation of difference between the 2 measurements as the data followed normal distribution according to Shapiro-Wilk W test.

In order to calculate the proper number of eyes needed for our prospective study, we performed an a priori computation of sample size based on preliminary results from 4 eyes. The difference of 495 cells and standard deviation of 605 stated an effect size of 0.82. By selecting a 2-tailed t test for estimation of differences at an error probability of 0.05 and power at 95% of the total sample size was determined to be 25, which is 14 eyes in total, since this is a matched paired test.

In this prospective case series, 12 patients (14 eyes), 10 with keratoconus and 2 with post-LASIK ectasia with minimum corneal thickness less than 400 μm after epithelial removal underwent riboflavin-UVA-induced CXL. Mean patient age was 26.71 ± 6.55 years (range 21-44). Eight patients were male and 4 female. Mean minimum preoperative corneal thickness at the apex of the cone after epithelial removal and before riboflavin instillation was 373.92 ± 22.92 μm (range 340 ± 399 μm).

Patients meeting any one of the following criteria after the preoperative examination were excluded from the study: corneal scars/opacities, pregnancy or lactation, active anterior segment pathology, previous corneal or anterior segment surgery (except LASIK), systemic connective tissue disease, atopic syndrome, ocular or systemic disease that could affect the epithelial healing, or dry eye syndrome. Patients were informed that the nature of the procedure was outside the widely accepted guidelines.

Preoperative data obtained from the case records included patient age and sex, corrected distance visual acuity (CDVA), best spectacle-CDVA, manifest refraction (diopters; D), topography (Technomed C-Scan; Technomed GmbH, Baesweiler, Germany; K-readings preoperatively and postoperatively were assessed as K-readings from topography), corneal thickness at the cone apex using ultrasonic corneal pachymetry (Corneo-Gage Plus; Sonogage Inc, Cleveland, Ohio, USA), slit-lamp biomicroscopy, and fundus examination. Uncorrected visual acuity (UDVA), CDVA, manifest refraction, and topography were also evaluated at 1, 3, 6, and 12 months after surgery.

Images of the endothelium were acquired with a modified confocal scanning laser ophthalmoscope (Heidelberg Retina Tomograph II/Rostock Corneal Module; Heidelberg Engineering GmbH, Dossenheim, Germany). Endothelial cell density was assessed using the software provided by the system used, while repeatability of the measurement was determined using coefficient of repeatability described in a previous study.

Surgical Technique

The surgical procedure was conducted under sterile conditions using the standard CXL protocol. The patient’s eye was anesthetized with proparacaine hydrochloride 0.5% (Alcaine; Alcon Laboratories, Inc, Fort Worth, Texas, USA). An 8.5-mm diameter of the corneal epithelium was mechanically removed using a rotating brush. After epithelial removal, 5 consecutive measurements were obtained at the cone apex using ultrasound pachymetry (Corneo-Gage Plus; Sonogage Inc, Cleveland, Ohio, USA) and the smaller measurement was recorded. Subsequently, single-use isotonic eye drops of riboflavin 0.1% and 20% dextran solution (Medio Cross; Peschke Meditrade GmbH, Huenenberg, Switzerland) were instilled every 3 minutes, for approximately 30 minutes. Penetration of the cornea and presence of riboflavin in the anterior chamber (riboflavin shielding) was monitored by slit-lamp examination. Ultraviolet-A irradiation was performed using an optical system (UV-X; Peschke Meditrade GmbH) with a light source consisting of an array of UV diodes (365 nm). Before treatment, the intended 3-mW/cm 2 surface irradiance (5.4 J/cm 2 surface dose after 30 minutes) was calibrated using the UVA meter YK-34UV (Lutron Electronic Enterprise Co, Ltd, Taipei, Taiwan), which is supplied with the UV-X device. Irradiance was performed for 30 minutes. During treatment, riboflavin solution was applied every 5 minutes to saturate the cornea with riboflavin. At the end of the procedure, a silicon-hydrogel bandage contact lens was applied until full re-epithelialization. Postoperative medication included diclofenac sodium 0.1% (Denaclof; Novartis, Hellas, Athens, Greece) for 2 days as well as antibiotic/corticosteroid (tobramycin/dexamethasone) drops (Tobradex; Alcon Laboratories, Inc) 4 times daily until the removal of the bandage contact lens. After the removal of the contact lens, patients received corticosteroid drops (fluorometholone 0.1%; Falcon Pharmaceuticals, Ltd, Fort Worth, Texas, USA), tapering for the next 2 weeks. Patients were encouraged to use artificial tears at least 6 times per day for 6 months postoperatively.


Patients’ demographic, preoperative, and postoperative data are shown in the Table . All values are expressed as mean ± standard deviation and range. No other intraoperative or early or late postoperative complications (lens or retina damage) were observed in this patient series.


Demographic, Preoperative, and Postoperative Data in Patients (With Keratoconus and Post–Laser In Situ Keratomileusis Ectasia) With Thin Corneas (Under 400 μm After Epithelial Removal) Undergoing Corneal Collagen Cross-linking Treatment

Age Minimum CT a (μm) Preoperative Data Postoperative Data
UDVA (Decimal Scale) CDVA (Decimal Scale) ECD (Cells/mm 2 ) UDVA (Decimal Scale) CDVA (Decimal Scale) ECD (Cells/mm 2 )
Patient 1 22 347 0.2 0.4 2623 0.2 0.3 2592
Patient 2 35 345 0.1 0.1 2708 0.2 0.2 1448
Patient 3 33 365 0.3 0.4 2531 0.5 0.6 2259
Patient 4 28 340 0.5 0.6 2779 0.6 0.7 2362
Patient 5 44 360 CF 0.3 2712 0.1 0.3 2122
Patient 6 23 345 CF 0.3 2563 0.2 0.6 2438
Patient 7 21 373 CF 0.3 2960 0.2 0.4 2880
Patient 7 21 391 CF 0.3 2949 0.1 0.4 2781
Patient 8 24 397 0.3 0.3 2935 0.4 0.6 2920
Patient 9 22 397 0.1 0.3 2523 0.1 0.4 2240
Patient 10 24 399 CF 0.5 2764 CF 0.5 2634
Patient 10 24 397 CF 0.4 2730 CF 0.4 2598
Patient 11 28 388 0.1 1 3016 0.1 1 2829
Patient 12 25 391 0.1 0.4 2467 0.2 0.5 2074

Only gold members can continue reading. Log In or Register to continue

Stay updated, free articles. Join our Telegram channel

Jan 12, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Corneal Collagen Cross-linking With Riboflavin and Ultraviolet-A Irradiation in Patients With Thin Corneas

Full access? Get Clinical Tree

Get Clinical Tree app for offline access