Collagen crosslinking (CXL) with riboflavin and ultraviolet-A (UVA) is a new treatment for arresting the progression of keratoconus. It consists of polymerization of the stromal fibers with the combined action of riboflavin (a photosensitizing substance) and UVA rays (riboflavin–UVA), which changes the intrinsic biomechanical properties of corneal collagen by increasing its rigidity.1–3
Collagen crosslinking in cases of keratoconus is generally a safe surgery without sight-threatening complications. Microbial keratitis after CXL has been reported infrequently.4–8 Anecdotal reports of herpetic,4 bacterial,6–8 and Acanthamoeba5 keratitis after CXL appear in the literature (Table 1). A case of polymicrobial keratitis caused by Streptococcus salivarius, Streptococcus oralis, and coagulase-negative Staphylococcus species in a patient who had CXL for keratoconus has also been reported.8 We report a case of Pseudomonas aeruginosa keratitis after CXL with riboflavin–UVA.
A 19-year-old woman presented to the Eye Casualty services of the Rajendra Prasad Centre for Ophthalmic Sciences at All India Institute of Medical Sciences, New Delhi, India, with a 3-day history of pain, redness, and diminution of vision in the right eye. She had had CXL with riboflavin–UVA in the right eye 4 days earlier. The bandage contact lens (BCL), which was inserted immediately after the procedure, had fallen off 1 day previously following excessive rubbing of the eye with unclean fingers.
The protocol used for treatment of keratoconus by CXL included an 8.0mm epithelial debridement, application of riboflavin 0.1% drops before and every 5minutes during irradiation, and UVA light irradiation (370nm) for 30minutes. After the treatment, a BCL (Purevision, Bausch & Lomb) was inserted and the patient was started on prednisolone acetate 1% 4 times a day and moxifloxacin hydrochloride 0.5% (Vigamox) 3 times a day.
At the time of presentation, the corrected distance visual acuity (CDVA) was hand motion in the right eye and 20/30 in the left eye. Slitlamp examination of the right eye showed conjunctival injection along with a corneal ulcer with a central 7.0mm×6.0mm yellow infiltrate with overlying epithelial defect involving 90% of corneal depth. There were mild anterior chamber reactions and 1.5mm of hypopyon (Figure 1). Details of lens and fundus could not be assessed because of hazy media. The cornea was then scraped, and samples were sent for microbiological studies. The BCL was also sent for culture. Ultrasound for posterior segment analysis did not reveal any abnormality.
The patient was admitted and started on fortified cefazolin sodium 5% eyedrops once hourly, tobramycin sulfate 1.5% eyedrops once hourly, and homatropine 2% 4 times a day. Culture results from the BCL and corneal scrapings showed presence of Pseudomonas aeruginosa, which was sensitive to cefazolin, tobramycin, amikacin, chloramphenicol, ciprofloxacin, and ceftazidime.
Following treatment, the infiltrates decreased in size and the hypopyon gradually disappeared, leaving a leucomatous corneal opacification (Figure 2). At 2 months, the CDVA was 20/200. Optical keratoplasty is planned in the future for visual rehabilitation.
Collagen crosslinking with riboflavin–UVA is generally a safe surgical procedure for cases of keratoconus. Microbial keratitis after CXL occurs rarely. Apart from our case, 4 reports of keratitis after CXL have been published.4–8 The age range of the patients varies from 19 to 42 years. Ours is the youngest patient who developed keratitis after CXL. All but 2 of the reported cases occurred in the right eye, and all occurred within the first 5 days of treatment (Table 1). This implies that the infections in these cases occur early in the immediate postoperative period and require strict vigilance during this time.
Varying presentations of keratitis have been reported, depending on the etiologic agent. Keratitis after CXL has occurred due to herpes simplex,4Acanthamoeba,5 and various bacteria (Escherichia coli, Staphylococcus sp, and Streptococcus sp).6–8 Mild anterior chamber inflammation has been reported in all the cases. Although this can be attributed to the keratitis per se, the role of the permeated riboflavin in the anterior chamber should be studied.
Kymionis et al.4 report a case of herpes keratitis with iritis and suggest that UVA light could be a potent stimulus to trigger/induce reactivation of latent herpes simplex virus infections. In the cases reported by Rama et al.5 and Zamora and Males,8 the patients reported self-removal and reapplication of the BCL in the immediate postoperative period, which could be a risk factor for keratitis. In our case, the patient had rubbed her eye excessively, presumably with unclean fingers, following which the BCL came off and led to the infection.
As per the original Wollensak et al.1 protocol, the postoperative treatment in our case consisted of antibiotic ointment. This has been modified by others to include the use of postoperative steroids4 or nonsteroidal antiinflammatory drugs (NSAIDs) with an antibiotic agent.5,8 Both topical corticosteroids9,10 and NSAIDs11 have the potential to exacerbate an infection and corneal melting, especially in the presence of epithelial defects and hypoxic conditions induced by the application of a soft BCL.
In the immediate postoperative period, topical antibiotic agents were prescribed in 4 patients, topical steroids were given in 2 patients, and NSAIDS were given in 1 patient. However, in the case reported by Pérez-Santonja et al.,7 neither topical steroids nor NSAIDs were given in the immediate postoperative period.
The postoperative CDVA in the 5 reported cases ranged from 20/25 to 20/200. In all but 2 eyes, good visual outcome was obtained. The case caused by herpes keratitis had optimal visual outcome.4 Two cases caused by less virulent organisms such as Escherichia coli6 and Staphylococcus epidermidis7 also responded to therapy and achieved CDVA better than 20/60. However, infection due to Acanthamoeba had a fulminating course and a full-thickness keratoplasty was needed to control the infection as well as for visual rehabilitation.5 Similarly, in our case, the CDVA was 20/200 following resolution of infection as the keratitis was caused by P aeruginosa, a more virulent organism. There was also a leucomatous corneal scar following resolution of the keratitis.
The original CXL procedure as described by Wollensak et al.1 and Wollensak2 involves removal of the central 7.0mm of the corneal epithelium before application of the riboflavin solution, allowing better penetration into the corneal stroma. In some studies, a soft therapeutic BCL was used for 4 to 5 days postoperatively. This was believed to aid epithelialization.
In performing this procedure, there are 2 risk factors that may predispose a patient to a corneal infection: corneal epithelium debridement and application of a BCL. It has been suggested that epithelial debridement should be avoided to decrease pain and also help in early epithelialization.6,9 This may reduce the risk for bacterial or fungal infiltration. In cases in which debridement is not performed, the risk factors for the development of keratitis will be eliminated and a BCL will not be necessary. However, adequate stromal absorption of riboflavin may not be achieved without epithelial debridement, as reported by Hayes et al.12
Ironically, although infectious keratitis can occur after CXL, in a few studies, CXL was used to treat sterile as well as infected corneal ulcers.13,14 This is because CXL due to riboflavin–UVA, as well as the free radicals produced during the procedure, result in a marked increase in collagen resistance to digesting enzymes produced by pathogenic bacteria and fungi. Furthermore, UVA (wavelength 315 to 380nm) alone is known to inhibit the growth of these microorganisms.15 However, the exact behavior of these crosslinked corneas to infectious processes should be evaluated in terms of severity as well as the response to treatment.
The potential for using this treatment modality in patients with progressive keratoconus is great and when uneventful, the procedure may spare the patient from a corneal transplant. However, the possibility of secondary infection exists. Even if it is recognized and treated appropriately, a secondary infection may cause corneal opacification and decrease the CDVA. In cases such as ours, the infection may necessitate an early optical keratoplasty. In cases in which the infection becomes severe, a therapeutic keratoplasty may be required.
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