Microbial keratitis following accelerated corneal collagen cross-linking.

A deep stromal infiltrate with hypopyon appeared in central cornea of right eye of a 15-year-old boy postoperatively after 2 days, who underwent uneventful accelerated corneal collagen crosslinking (C3R) with riboflavin and ultraviolet-A (UVA) for the treatment of keratoconus. Staphylococcus aureus keratitis was confirmed by the microbiological studies, which guided intense treatment with topical and systemic antibiotics. Before C3R, the best corrected visual acuity (BCVA) in the ocular dexter was 20/30 with the refraction of - 1.00 DS/-5.00 DC × 30° with drop to 20/400 following the infection. After intensive treatment BCVA recovered to 20/40 with the refraction of -4.0 DC × 60° at 6 months postprocedure. Slit lamp examination at this stage revealed a faint nebulo-macular grade scar in the central cornea involving visual axis. Collagen crosslinking with riboflavin-UVA is a minimally invasive method, but traditionally requires epithelial removal, which could be a predisposing factor to bacterial keratitis.

Introduction

Keratoconus is progressive, noninflammatory ectatic disorder of the cornea that's, usually, bilateral. The onset is typically at puberty, with ectasia progressing in approximately 20% of cases to the extent that keratoplasty is necessary.[1] Various treatment modalities are available for the treatment of keratoconus. Of these, hard contact lenses and corneal grafting have been major treatment modalities for many years, and now some patients can also benefit from intracorneal ring segment [Intacs] implantation. However, none of these techniques treat the underlying cause of ectasia and thus cannot stop the progression of keratoconus.[2]

The advent of minimally invasive and safer treatment option of corneal collagen crosslinking (C3R) with ultraviolet-A (UVA) light-Riboflavin in last few years has been a major breakthrough in the management of keratoconus.[2] This technique increases the rigidity of treated corneas and many clinical studies have shown improvement and stabilization of keratectasia in patients with keratoconus.[34]

We report a case of unilateral microbial keratitis that developed after uneventful accelerated C3R procedure with UVA-riboflavin.

Case Report

A 15-year-old male, came to Cornea Department of our hospital (Tertiary Eye Care Center) for an opinion on keratoconus. There was no history of using any glasses or contact lenses previously. His best spectacle-corrected visual acuity (BSCVA) in ocular dexter (OD) was 20/30 with refraction of − 1.00 DS/−5.00 DC × 30° and in ocular sinister (OS) was 20/30 with refraction of 1.00 DS/−4.50 DC × 100°. Slit lamp examination of anterior segment showed keratoconus in oculus utro (OU). Topography showed a pattern consistent with keratoconus in OU (asymmetric bowtie with skewing of the radial axis above and below the horizontal meridian and inferior steepening in OS > OD). His optical pachymetry at thinnest point was 456 μm and 448 μm in OD and OS, respectively. Based on these data, Krumeich stage 1 keratoconus was diagnosed in OD and Krumeich stage 2 keratoconus in OS. Patient was advised accelerated C3R with UVA treatment in OU.

He underwent uneventful accelerated C3R in OS (0.1% riboflavin + hydroxypropyl methyl cellulose, irradiance of 30 mW/cm2 at 370 nm wavelength, 3 min of UVA exposure with energy of 7.2 J/cm2) using Avedro system, which is significantly faster treatment when compared with the conventional C3R treatment (0.1% riboflavin + 20% dextran, irradiance of 3 mW/cm2 at 370 nm wavelength, 30 min of UVA exposure with energy of 5.4 J/cm2). Postoperatively, he was doing very well in OS. He underwent uneventful accelerated C3R in OD after 2 weeks. On first postoperative, he was doing well in OD so was advised to continue routine postoperative medications. On the 3rd postoperative day, he presented with a sudden decrease of vision in OD associated with pain and redness. On examination, visual acuity in OD was 20/400. The slit lamp examination showed central 3.5 mm × 3 mm deep stromal infiltrate with surrounding corneal edema and 1 mm hypopyon [Figure 1].

Figure 1

Central deep stromal infiltrate with surrounding corneal edema and hypopyon on 3rd day postoperatively

Corneal scraping of the infiltrate was done, followed by Gram's-staining and KOH mount examination. No fungal filaments were observed on KOH mount and inflammatory cells with few Gram-positive cocci were seen on Gram's-stain. The corneal scrapings, bandage contact lens (BCL) were sent for culture and antibiotic sensitivity. Bacterial culture showed scanty growth of Staphylococcus aureus and fungal culture report came negative for any fungal growth. BCL culture report also came negative for any growth. Patient was started topically on preservative free Moxifloxacin drops 1 h, tobramycin drops 6 times/day, atropine drops 3 times/day, preservative free lubricating drops 6 times/day, timolol drops 2 times/day and systemic sustained release acetazolamide tablets 2 times/day. On postoperative 5th day followup, he was doing better in OD and was started on tablet amoxicillin-clavulinic acid BD orally for 5 days based upon culture sensitivity reports. On postoperative 10th day followup, there was a significant decrease in stromal infiltrate, resolution of hypopyon and decrease in corneal edema [Figure 2].

Figure 2

Decrease in stromal infiltrate, resolution of hypopyon and decrease in corneal edema on 10th day postoperatively after starting the treatment

On 21st day postoperatively, slit lamp examination showed relatively quiet eye along with central macular grade corneal opacity of 3.5 mm × 3 mm, indistinct borders and surrounding clear cornea with uncorrected visual acuity of 20/80 [Figure 3]. At his stage, topical loteprednol drops were started 3 times/day.

Figure 3

Relatively quiet eye with central macular grade corneal opacity with indistinct borders and surrounding clear cornea on 3 weeks postoperatively

At 1 month followup postoperatively, slit lamp examination showed completely quiet eye with a central 3 mm macular grade anterior stromal opacity with distinct borders, surrounding clear cornea [Figure 4] with a BSCVA of 20/60. At this stage, patient was asked continue loteprednol drops in OD.

Figure 4

Completely quiet eye with a macular grade anterior stromal opacity with distinct borders, surrounding clear cornea at 1 month postoperatively

At 6 month followup postoperatively, his BSCVA was improved to 20/40 with correction of −4.0 DC × 60°. Slit lamp examination showed faded nebulo-macular grade opacity in the visual axis with surrounding clear cornea [Figure 5].

Figure 5

Faded nebulo-macular grade opacity in visual axis at 6 months

Discussion

Corneal collagen crosslinking with riboflavin-UVA is a minimally invasive procedure and seems to be the first approach to stop or even reduce the progression of keratoconus.[23] Multiple preliminary clinical studies have shown long-term stabilization and improvement of keratoconus after C3R with no vision threatening complications.[23]

This procedure requires epithelial removal, before corneal stromal irradiation by UVA is done. The resultant epithelial defect, usually, takes from 2 to 5 days to heal completely. An intact corneal epithelium is an important defense barrier and cannot be penetrated by majority of the bacteria, except neisseria gonorrhea, corynebacterium diphtheriae and listeria monocytogenes, which can penetrate intact epithelium.

We emphasize that strict aseptic precautions were maintained intra-operatively. Also, UVA irradiation is known to kill bacteria and fungi so it has been used as effective adjuvants in cases of infective stromal keratitis along with antimicrobial therapy.[5] In our case, clinically the lesion was suspected of being microbial keratitis. The patient did give a history of entry of some dust in OD while travelling. The compromised corneal epithelial integrity caused by C3R was probably the predisposing factor to bacterial keratitis in our patient in the same way as corneal epithelial damage caused by contact lens wear, corneal trauma or any other corneal surgical procedures is a predisposing factor to microbial keratitis.[6] Coagulase-negative staphylococci, including Staphylococcus epidermidis are, usually, present in normal ocular flora and can cause opportunistic infection when the epithelium is compromised.

There has been some case reports of post C3R infectious keratitis reported in the literature. Bacterial keratitis has been reported 3 days following treatment in which scraping revealed an Escherichia coli infection.[7] Poor contact lens hygiene resulting in polymicrobial keratitis caused by Streptococcus salivarius, Streptococcus oralis, and coagulase negative Staphylococcus species has been reported.[8] Staphylococcus epidermidis keratitis has also been reported 2 days after treatment.[9] Severe keratitis with patient's contact lens and cornea scrapings positive for Pseudomonas aeruginosa has also been reported recently.[10] One study has reported four cases of severe keratitis in a group of 117 keratoconic eyes treated with standard C3R.[11]

A prompt and proper microbiologic workup was undertaken which enabled appropriate treatment in our case. The routine use of antibiotic agents after surgery was unable to prevent bacterial keratitis development in our patient. Although the patient gave a history of dust exposure in early postoperative period, the negative BCL culture reports ruled out this contamination. Despite the prompt treatment, there was significant corneal scarring in the visual axis which faded with timely starting of topical steroids with recovery of BSCVA almost fully to the preoperative level.

This case illustrates the risk for microbial keratitis after uneventful accelerated C3R for the treatment of keratoconus. The case also emphasizes the need of good postoperative surveillance, use of postoperative topical antibiotics and judicious use of topical steroids at the appropriate stage if required for optimal clinical outcome. Furthermore, the compromised epithelial integrity during the procedure makes the eye vulnerable to infections despite maintaining strict aseptic precautions intraoperatively.