Clinical Study of Mitomycin C in Reducing Haze Formation After Ultraviolet A/Riboflavin Crosslinking for Keratoconus.

OBJECTIVES: To evaluate the safety and efficacy of mitomycin C (MMC) in haze formation after ultraviolet A/riboflavin corneal crosslinking (CXL) for progressive keratoconus. METHODS: A total of 60 keratoconic eyes of 48 patients were enrolled in this prospective comparative study after obtaining informed consent. In the CXL group, standard corneal CXL was performed, whereas in the CXL+MMC group, 0.02% MMC was used for 30 s soon after CXL. Comprehensive ophthalmologic examinations were performed on all patients before surgery and at 1, 3, 6, and 12 months after surgery. RESULTS: The epithelium recovered within 3 to 4 days after CXL, and the healing time was comparable in the two groups. There was no significant endothelial cell density loss after CXL in both groups. Eyes in both groups showed improvement of uncorrected distance visual acuity (Snellen) and best-corrected visual acuity (Snellen; P<0.05), and there was a decrease in K-max, cylinder degree, and central corneal thickness (CCT) (P<0.05). There was no significant statistical difference between the groups regarding postoperative K-max reduction, refraction, and CCT (P>0.05). Corneal haze scores were significantly higher in the CXL group at 1 and 3 months after CXL (P=0.012 and P=0.028, respectively), but were similar to the MMC group at 6 and 12 months after surgery (P=0.329 and P=0.543, respectively). CONCLUSIONS: Prophylactic intraoperative use of 0.02% MMC can significantly reduce CXL-associated haze formation, especially in the early postoperative period, and no signs of weakening CXL efficacy were observed.

Therapeutic and inducing effect of corneal crosslinking on infectious keratitis.

The corneal crosslinking (CXL) with riboflavin and ultraviolet-A (UVA) is a new therapy method to successfully treat infectious keratitis in clinical practice. However, there are rare reports on the complications of CXL such as the secondary keratitis. The diverse clinical outcomes on keratitis have highlighted the necessity to further evaluate the efficacy and complications of CXL. We reviewed the positive and negative reports on UVA/riboflavin related with keratitis and provided our opinion on the therapeutic and side effect of UVA/riboflavin crosslinking on keratitis.

Corrigendum to "A Review of Collagen Cross-Linking in Cornea and Sclera".

[This corrects the article DOI: 10.1155/2015/289467.].

Combining corneal crosslinking and phakic toric Implantable Collamer Lenses for the treatment of keratectasia: A case report.

The present study reports the use of a phakic toric Implantable Collamer Lens (ICL) that improved the refraction correction of high myopia and astigmatism in a case of keratectasia following corneal cross-linking. A 31-year-old male was diagnosed with keratectasia 12 years after laser-assisted in situ keratomileusis (LASIK). Following LASIK, the manifest refraction was -3.50-2.25×90 [0.1 logarithmic expression (LogMAR) best corrected visual acuity (BVCA)] in the right eye and -8.00-3.50×175 (0.3 LogMAR BCVA) in the left eye, with a LogMAR uncorrected distance visual acuity (UDVA) of 0.8 and a 'counting fingers' value of 3 ft (CF @3 ft) in the left and right eyes, respectively. Riboflavin/ultraviolet A light (UVA) corneal crosslinking (CXL) was conducted on both eyes. Seven months after cross-linking, LogMAR UDVA was 0.4, the manifest refraction was -2.75-2.50×85 and LogMAR BCVA was 0.1 in the right eye. In the left eye, LogMAR UDVA was CF @3 ft, the manifest refraction was -15.00 and LogMAR BCVA was 0.3. The corneal topography was stable 7 months after CXL. Phakic toric ICL was implanted to correct the refractive error, following which the LogMAR UDVA improved to 0.1 in the right eye and 0.3 in left eye, and visual acuity remained stable for 6 months after ICL implantation. In conclusion, combining riboflavin/UVA corneal cross-linking and phakic toric ICL implantation may be an alternative in the correction of high refractive error in patients with keratectasia.

Corneal ectasia 6.5 months after small-incision lenticule extraction.

Our case involves a 19-year-old patient with forme fruste keratoconus. Small-incision lenticule extraction was performed, and 6.5 months after surgery, corneal ectasia was diagnosed. Preoperatively, the minimum central corneal thickness was 546 µm in the right eye and 542 µm in the left eye; the refractive correction was -6.75 -1.00 × 45 and -6.75 -0.75 × 140, respectively; the lenticular thickness was 137 µm and 135 µm, respectively. At 6.5 months, ectasia was diagnosed based on anterior and posterior surface keratometry of 38.4/39.5 diopters (D) and -6.3/-6.8 D, respectively, in the right eye and 38.6/40.8 D and -7.1/-6.6 D, respectively, in the left eye. The keratometry increased gradually and the corneal thickness decreased after surgery, and these trends continued during the 13-month follow-up. This report documents corneal ectasia as a complication of small-incision lenticule extraction and highlights the importance of preoperative evaluation and the need for long-term follow-up.

A review of collagen cross-linking in cornea and sclera.

Riboflavin/UVA cross-linking is a technique introduced in the past decades for the treatment of keratoconus, keratectasia, and infectious keratitis. Its efficacy and safety have been investigated with clinical and laboratory studies since its first clinical application by Wollensak for the treatment of keratoconus. Although its complications are encountered during clinical practice, such as infection inducing risk, minimal invasion merits a further investigation on its future application in clinical practice. Recently, collagen cross-linking in sclera shows a promising prospect. In present study, we summarized the representative studies describing the clinical and laboratory application of collagen cross-linking published in past decades and provided our opinion on the positive and negative results of cross-linking in the treatment of ophthalmic disorders.

A short-term study of corneal collagen cross-linking with hypo-osmolar riboflavin solution in keratoconic corneas.

AIM: To report the 3mo outcomes of collagen cross-linking (CXL) with a hypo-osmolar riboflavin in thin corneas with the thinnest thickness less than 400 µm without epithelium. METHODS: Eight eyes in 6 patients with age 26.2±4.8y were included in the study. All patients underwent CXL using a hypo-osmolar riboflavin solution after its de-epithelization. Best corrected visual acuity, manifest refraction, the thinnest corneal thickness, and endothelial cell density were evaluated before and 3mo after the procedure. RESULTS: The mean thinnest thickness of the cornea was 408.5±29.0 µm before treatment and reduced to 369.8±24.8 µm after the removal of epithelium. With the application of the hypo-osmolar riboflavin solution, the thickness increased to 445.0±26.5 µm before CXL and recover to 412.5±22.7 µm at 3mo after treatment, P=0.659). Before surgery, the mean K-value of the apex of the keratoconus corneas was 57.6±4.0 diopters, and slightly decreased (54.7±4.9 diopters) after surgery (P=0.085). Mean best-corrected visual acuity was 0.55±0.23 logarithm of the minimal angle of resolution, and increased to 0.53±0.26 logarithm after surgery (P=0.879). The endothelial cell density was 2706.4±201.6 cells/mm(2) before treatment, and slightly decreased (2641.2±218.2 cells/mm(2)) at last fellow up (P=0.002). CONCLUSION: Corneal collagen cross-linking with a hypo-osmolar riboflavin in thin corneas seems to be a promising treatment. Further study should be done to evaluate the safety and efficiency of CXL in thin corneas for the long-term.

Corneal collagen cross-linking with hypoosmolar riboflavin solution in keratoconic corneas.

PURPOSE: To report the 12-month outcomes of corneal collagen cross-linking (CXL) with a hypoosmolar riboflavin and ultraviolet-A (UVA) irradiation in thin corneas. METHODS: Eight eyes underwent CXL using a hypoosmolar riboflavin solution after epithelial removal. The corrected distance visual acuity (CDVA), manifest refraction, the mean thinnest corneal thickness (MTCT), and the endothelial cell density (ECD) were evaluated before and 6 and 12 months after CXL. RESULTS: The MTCT was 413.9 ± 12.4 µm before treatment and reduced to 381.1 ± 7.3 µm after the removal of the epithelium. After CXL, the thickness decreased to 410.3 ± 14.5 µm at the last follow-up. Before treatment, the mean K-value of the apex of the keratoconus corneas was 58.7 ± 3.5 diopters and slightly decreased (57.7 ± 4.9 diopters) at 12 months. The mean CDVA was 0.54 ± 0.23 logarithm of the minimal angle of resolution before treatment and increased to 0.51 ± 0.21 logarithm at the last follow-up. The ECD was 2731.4 ± 191.8 cells/mm(2) before treatment and was 2733.4 ± 222.6 cells/mm(2) at 12 months after treatment. CONCLUSIONS: CXL with a hypoosmolar riboflavin in thin corneas seems to be a promising method for keratoconic eyes with the mean thinnest corneal thickness less than 400 µm without epithelium.

Evaluation of the in vitro antimicrobial properties of ultraviolet A/riboflavin mediated crosslinking on Candida albicans and Fusarium solani.

AIM: To evaluate the antimicrobial properties of ultraviolet A (UVA) (365 nm)/riboflavin against Candida albicans and Fusarium solani. METHODS: Two fungus isolates were cultured in vitro and prepared with 10-fold serial PBS dilutions of cell concentration. For each dilution of fungus suspension, the concentration (colony-forming units/mL, CFU/mL) and the inactivation ratio of fungal cells were evaluated under 4 conditions: no treatment (control), UVA (365 nm)/riboflavin, riboflavin, and UVA (365 nm). RESULTS: The cell concentration decreased in UVA (365 nm)/riboflavin group for Candida albicans at each dilution and Fusarium solani at dilutions of 10(4), 10(3), 10(2) CFU/mL, when compared with that in control, riboflavin, and UVA (365 nm) groups (P<0.01). No difference of cell concentration was detected amongst the culture of control, riboflavin, and UVA (365 nm) groups for the two fungus. There is a negative correlation between suspension concentration (log-transformed) and the inactivation ratio in UVA (365 nm)/riboflavin group for Candida albicans and Fusarium solani (P<0.01). CONCLUSION: According to the standard protocol of corneal collagen cross-linking, UVA (365 nm)/riboflavin combination treatment is found to moderately inactivate the viability of Candida albicans and Fusarium solani in vitro. The inactivation ratio was found to increase with the decrease of cell concentration under UVA (365 nm)/riboflavin condition.

Role of corneal epithelium in riboflavin/ultraviolet-A mediated corneal cross-linking treatment in rabbit eyes.

PURPOSE: To evaluate the role of corneal epithelium in riboflavin/ultraviolet-A (UVA) mediated corneal collagen cross-linking treatment. METHODS: Fifty New Zealand rabbits were divided into 5 groups: UVA treatment with or without corneal epithelium, UVA+riboflavin treatment with or without corneal epithelium, and control without any treatment. All rabbits were sacrificed after irradiation and subsequently 4 mm × 10 mm corneal strips were harvested for biomechanical evaluation. RESULTS: UVA irradiation alone did not enhance the maximal stress and Young's modulus of corneal specimens with (3.15 ± 0.56 mpa, 1.00 ± 0.09 mpa) or without (3.53 ± 0.85 mpa, 0.94 ± 0.21 mpa) the corneal epithelium, compared to specimens in the control group (4.30 ± 0.68 mpa, 1.03 ± 0.24 mpa). However, UVA irradiation combined with riboflavin significantly increased the maximal stress and Young's modulus of corneal specimens with (5.27 ± 1.09 mpa, 1.23 ± 0.23 mpa, P < 0.05) or without (7.16 ± 1.88 mpa, 1.42 ± 0.16 mpa, P < 0.05) corneal epithelium when compared to the control group. The maximal stress and Young's modulus of cornea in UVA+riboflavin and "epithelium-off" group were 35.9% and 15.4% higher compared to the UVA+riboflavin and "epithelium-on" group, respectively (P < 0.05). CONCLUSIONS: Our study shows that UVA+riboflavin treatment significantly affects the biomechanical properties of the cornea with and without epithelial removal. However, corneas without epithelium seem to benefit more compared to corneas with the epithelium.