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Literature review: Corneal crosslinking stops keratoconus progression
By Linda Roach, Contributing Writer
A review of 39 peer-reviewed studies indicates that collagen crosslinking with riboflavin/ultraviolet-A (UVA) stops progression of keratoconus in most patients. Results are stable over the long-term and the most significant risk appears to be loss of BSCVA, which occurred in about 3 percent of patients.
Mohamed Hantera, MD, PhD, FRCS, MBA, presented these findings at the 2010 ISRS Magrabi International Congress in Jeddah, Saudi Arabia. Dr. Hantera, who practices at the Magrabi Eye & Ear Centre in Dammam, used the U.S. National Library of Medicine's MEDLINE/PubMed website to search for studies on corneal crosslinking published from 2004 through 2009.
Fifteen of the 39 papers reported the successful use of riboflavin/UVA to stop the progression of keratoconus. Although only one of the studies was prospective, randomized and controlled1, together the studies suggest that crosslinking is a safe, effective and stable treatment for keratoconus, Dr. Hantera said.
Studies with more than five years of follow-up indicate that the procedure is safe for the endothelium and crystalline lens; does not affect intraocular pressure; and is stable up to 60 months, Dr. Hantera said.
"Collagen crosslinking is a real breakthrough in treatment for sight-threatening keratoconus," Dr. Hantera said. "This is a very important step of clinical management for any refractive or corneal practice where the technique is approved."
He recommends corneal surgeons add it to the list of procedures they offer keratoconic patients.
Dr. Hantera also expects crosslinking to have a global impact because its simplicity and minimal cost make it suitable for use in developing countries, Dr. Hantera said.
Reliability at 48 Months
The authors of one of the longest-running studies, Caporossi et al.,2 reported earlier this year that 44 keratoconic eyes have remained stable 48 to 60 months after treatment, while the patients' untreated fellow eyes showed progression of 2.2 D in the mean K-max.
The mean K-max value was reduced by a mean of 2.26 D in the crosslinked eyes. A reduction in coma aberrations secondary to the improved corneal symmetry were observed in more than 85 percent of treated patients. Mean BSCVA improved by 1.9 Snellen lines and UCVA improved by 2.7 Snellen lines.
In 10 out of 15 clinical trials he reviewed, crosslinking improved BSCVA, while three studies showed no significant changes in BSCVA. Only one study mentioned that 2.9 percent of its crosslinked eyes lost more two Snellen lines.3
Reducing the Risks
The literature also contains information on how to improve the procedure's safety, Dr. Hantera said. He recommended:
- Eyes selected for crosslinking should have K-values of ?58. Koller et al. found that 7.6 percent of eyes (n=117; 99 patients) continued to progress after crosslinking (follow-up: 12 months). A high preoperative K reading was a significant risk factor for treatment failure. They conclude that if K-values were kept at ?58 the failure rate might fall to less than 3 percent.3
- A retrospective case series study found that higher pre-op K was associated with persistent haze (follow-up: 12 months) and losses of UCVA and BSCVA (P=.012 and P=.004, respectively).4 Raiskup et al. suggest that advanced cases of keratoconus, with high corneal curvature, are at a high risk for this persistent, visually significant haze.
- Set the maximum age for crosslinking at 35 years. The Koller study found that patients older than 35 had a greater risk of complications (loss of BSCVA of two or more Snellen lines). Restricting patient age to ?35 might reduce the complication rate to 1 percent, compared to 2.9 percent in their study.3Differential corneal topography maps should be used to confirm the progression of corneal ectasia and the patient's suitability for crosslinking.
- Corneas thinner than 400 microns should be excluded from crosslinking because of the potential for endothelial toxicity.5,6 A stromal thickness of <400 microns would expose the endothelium to 0.36 mW/cm, a cytotoxic dose, researchers in Dresden found.6 Furthermore, in the Raiskup case series,4clinically significant haze at one year occurred in eyes with thinner corneas preoperatively (mean: 420.0±33.9 microns, vs. 478.1+/-52.4 microns in eyes without haze; P=.001).
- Avoid the procedure in patients who have central distance visual acuity (CDVA) of >20/25. Wollensak et al. found that CDVA was a significant risk factor for complications.3
- During UVA irradiation, the surgeon should keep instilling riboflavin drops as well as BSS to avoid stromal dehydration, which could lead to intraoperative stromal thinning and postoperative endothelial damage7and haze.4
Special Relevance for Middle East
Dr. Hantera noted that the availability of crosslinking to treat keratoconus is especially significant for corneal subspecialists who practice in the Middle East.
Both pellucid marginal degeneration and keratoconus are more common in the Mideast due to the cultural custom of consanguine marriage, he said.
"In my tertiary care, referral practice, if I examine 40 eyes per day, 10 of them will have newly diagnosed cases of keratoconus. The associated vernal catarrh and dryness associated with keratoconus in the Middle East also makes crosslinking challenging," Dr. Hantera said.
1. Wittig-Silva C, Whiting M, Lamoureux E, et al. A randomized controlled trial of corneal collagen cross-linking in progressive keratoconus: preliminary results. J Refract Surg. 2008;24(7):S720-725.
2. Caporossi A, Mazzotta C, Baiocchi S, Caporossi T. Long-term results of riboflavin ultraviolet a corneal collagen cross-linking for keratoconus in Italy: the Siena eye cross study. Am. J. Ophthalmol. 2010;149(4):585-593.
3. Koller T, Mrochen M, Seiler T. Complication and failure rates after corneal crosslinking. J Cataract Refract Surg. 2009;35(8):1358-1362.
4. Raiskup F, Hoyer A, Spoerl E. Permanent corneal haze after riboflavin-UVA-induced cross-linking in keratoconus. J Refract Surg. 2009;25(9):S824-828.
5. Wollensak G, Aurich H, Wirbelauer C, Sel S. Significance of the riboflavin film in corneal collagen crosslinking. J Cataract Refract Surg. 2010;36(1):114-120.
6. Wollensak G, Spörl E, Reber F, Pillunat L, Funk R. Corneal endothelial cytotoxicity of riboflavin/UVA treatment in vitro. Ophthalmic Res. 2003;35(6):324-328.
7. Kymionis GD, Portaliou DM, Pallikaris IG. Additional complications of corneal crosslinking. J Cataract Refract Surg. 2010;36(1):185; author reply 186.