Riboflavin-UVA treatment for nonhealing ulcers of the cornea.

To the Editor: The case series study by Ehlers et al,1 which appeared in the September 2009 issue of the Journal of Refractive Surgery, presented the results of ribofl avin-ultraviolet A (UVA) treatment in the management of edema and nonhealing ulcers of the cornea. Both the effi cacy and safety of this method in the treatment of persisting nonhealing corneal ulcers were remarkable; 6 of 14 eyes with chronic nonhealing ulceration were healed after ribofl avin-UVA application, while no complication occurred in any case subjected to the treatment mentioned above. The antimicrobial effi cacy of ribofl avin/UVA for bacterial and fungal isolates was fi rst documented in vitro by Martins et al2 in 2008. Ehlers et al, based on this evidence, tested the clinical effi cacy of ribofl avinUVA irradiation in the treatment of nonhealing corneal ulcers and yielded most promising results. Nevertheless, we would like to emphasize some critical points which, in our opinion, should be further clarifi ed. The authors should elucidate whether ribofl avin-UVA treatment was applied as a sole therapeutic method or if an adjuvant topical antimicrobial treatment was administered as well. If the latter is true, it would be extremely diffi cult for the clinician to evaluate the contribution of each therapeutic measure to the fi nal outcome. It would also be of importance for the authors to report whether ribofl avin-UVA treatment had an effect on the anterior chamber infl ammation (cells, fl are, hypopyon, etc), if any was observed. We would also like to underscore the necessity for a proper evaluation of the corneal thickness and especially the depth of the corneal ulcer before any treatment with ribofl avin-UVA irradiation. It is well established that during as well as after cross-linking induced by ribofl avin-UVA in patients with keratoconus (thin corneas), corneal thickness is signifi cantly reduced.3 The same effect on corneal thickness may be induced by the application of ribofl avin-UVA in patients with corneal edema, as reported in the above mentioned study by Ehlers et al.1 Moreover, the recommendation for a minimum corneal thickness of 400 μm is considered to be essential to minimize the risk for potential endothelium impairment by direct UVA damage or by induced free radicals (photochemical damage).4 Would it not be reasonable to postulate that cross-linking in a patient with deep corneal ulcer may increase the risk for damage of corneal endothelium in this distinct area or even cause corneal perforation? The authors do not provide data regarding the central corneal thickness or the depth and morphology (total size, vertical and horizontal diameter) of the corneal ulcers in the patients who were studied. Moreover, it is not clear whether the debris in the area of corneal ulcer was removed during the abrasion of corneal epithelium before ribofl avin-UVA application. In 3 of 14 patients, a corneal grafting procedure/enucleation was required. Was the indication for corneal grafting in these cases an underlying pre-perforation condition or even corneal perforation? If not, why did the authors not use another therapeutic measure (amniotic membrane transplantation, autologous serum drops, etc) before proceeding with corneal grafting? If yes, would it not be possible that ribofl avin-UVA treatment in distinct patients with extensive and deep corneal ulcers may have induced focal endothelial damage or even precipitated the development of corneal perforation? We believe ribofl avin-UVA irradiation in patients with corneal ulcers should be performed only after adequate morphological analysis of the ulcer area by anterior segment imaging (eg, anterior segment optical coherence tomography) and most important by precise evaluation of corneal thickness in the ulcer area. In patients with extensive deep corneal ulcers, other therapeutic options may represent more rational approaches, such as amniotic membrane transplantation, which is an effective and safe therapy of choice in persisting corneal epithelial defects, after the underlying infection has resolved.5 Zisis Gatzioufas, MD Berthold Seitz, MD Homburg/Saar, Germany