CASE REPORT

Herpetic keratitis after corneal collagen cross-linkingwith riboflavin and ultraviolet-A for progressivekeratoconus

Nilay Yuksel • Kamil Bilgihan •

Ahmet M. Hondur

Received: 14 October 2011 / Accepted: 22 November 2011 / Published online: 3 December 2011

� Springer Science+Business Media B.V. 2011

Abstract To describe a case of herpetic keratitis

after corneal collagen cross-linking (CXL) with ribo-

flavin and ultraviolet-A for progressive keratoconus.

A 31-year-old woman with rapidly progressive

keratoconus in the left eye was treated with CXL.

Four days postoperatively, a dendritic ulcer developed

in the treated eye. The diagnosis was confirmed with

polymerase chain reaction analysis of the corneal

swab for herpes simplex. The patient had no prior

history of herpetic eye disease or cold sores. The

keratitis resolved in 10 days with treatment. At

1 month, the visual acuity was stable, but a mild

superficial opacity was noted. Herpetic keratitis can be

induced by CXL even in patients with no history of

previous herpetic eye disease. Early diagnosis and

proper treatment can facilitate successful management

of this rare but important complication.

Keywords Cornea � Cross linking �Herpes simplex �Keratoconus � Polymerase chain reaction

Introduction

Corneal collagen cross-linking (CXL) with riboflavin

and ultraviolet A (UV-A) is currently the only

treatment that can block or delay progression of

keratoconus. In this technique, the combined action of

riboflavin and UV-A rays is utilized to increase the

corneal strength and integrity by polymerization of the

stromal fibers [1, 2].

With more widespread application of the technique,

reports of side-effects and complications are increas-

ing [3–7]. In this case report, we present a patient who

developed herpetic keratitis in the early postoperative

period after CXL.

Subject and methods

A 31-year-old woman presented at our clinic with

rapidly progressive keratoconus in her left eye. The

uncorrected visual acuity (UCVA, Snellen) was 0.3

and the best-corrected visual acuity (BCVA, Snellen)

was 0.8 with rigid gas permeable (RGP) contact lens

correction. The maximum K value and the central

corneal thickness were 55.3 diopters and 458 lm,

respectively. The patient did not have a history of any

herpetic eye disease or cold sores, or any previous

intraocular or corneal surgery.

The surgical procedure was performed under sterile

conditions in an operating room environment. After

topical anesthesia with topical 0.5% proparacaine, the

N. Yuksel (&)

Department of Ophthalmology, Kahramanmaras State

Hospital, Yorukselim Mah. Gazi Mustafa Kuscu Cad.,

Merkez, 46100 Kahramanmaras, Turkey

e-mail: ozturk.nilay@gmail.com

K. Bilgihan � A. M. Hondur

Department of Ophthalmology, Gazi University Medical

School, Ankara, Turkey

123

Int Ophthalmol (2011) 31:513–515

DOI 10.1007/s10792-011-9489-x

corneal epithelium was removed using ethanol (20%

for 20 s) in the central 8.0 mm. A solution of

riboflavin (0.1%) in dextran (20%) was instilled every

5 min for 30 min. An optical system with a light

source consisting of UV diodes (365 nm) was used

for UV-A irradiation. An intended 3.0 mW/cm2 of

surface irradiance (5.4 J/cm2 surface dose) was cali-

brated using a UV light meter at a distance of 1.0 cm at

the beginning of the irradiation. Irradiance was

performed for 30 min; meanwhile the riboflavin

solution was applied every 5 min. Postoperatively, a

bandage contact lens was placed.

The patient was examined daily until epithelial

closure. The postoperative medication consisted of

topical antibiotic/corticosteroid drops (netilmycin

0.3%/dexamethasone 0.1%) five times daily.

During the first 3 days, the examinations were

uneventful, the bandage contact lens was in place, and

the level of pain was as expected. Four days postop-

eratively, the patient presented with increased pain

and redness. Slit-lamp examination revealed a den-

dritic ulcer over the treated zone (Fig. 1). Polymerase

chain reaction (PCR) analysis of the corneal swab

proved to be positive for herpes simplex virus (HSV).

Results

Topical corticosteroid drops were discontinued, top-

ical antiviral ointments (acyclovir 5%) and antibiotic

drops (netilmycin 0.3%) were given five times daily.

Over 10 days, the ulcer resolved. Artificial tears were

prescribed while topical antiviral and antibiotic drops

were tapered slowly.

At 1 month postoperatively, a mild paracentral

subepithelial opacity was noted (Fig. 2), as well as the

typical haze after CXL. UCVA was 0.4 and BCVA

was 0.8 with RGP lens correction.

Discussion

In this case report, we describe a patient who developed

herpetic keratitis 4 days after CXL (Fig. 1). Despite

rapid initiation of appropriate treatment the ulcer

healed slowly over 10 days, and resulted in a mild

subepithelial opacity at 1 month (Fig. 2). Fortunately,

the opacity was small and mild, and therefore did not

affect visual acuity.

Recently, Kyminonis et al. [3] also reported a case

of HSV keratitis and iritis after CXL. Their diagnosis

was also confirmed with PCR tear analysis for HSV in

their case. Despite rapid closure of the epithelium in

2 days and initiation of topical steroids, they also

noted a mild central corneal scar at 2 months.

HSV reactivation in the cornea can be triggered by

various stimuli including trauma, fever, emotional

stress, corneal surgery and UV light. CXL comprises

epithelial and stromal trauma, damage to the subep-

ithelial nerve plexus, UV-A irradiation and use of

topical corticosteroids; all of which can act as triggers.

In our case, the patient did not have a history of

previous herpetic eye disease or cold sores. Otherwise,

we would have carried out the treatment under

systemic antiviral prophylaxis. Similarly, in the case

reported by Kyminonis et al. [3] a history of previous

herpetic keratitis or cold sores was not present. CXL

seems to include potent stimuli which can lead to

Fig. 1 Dendritic ulcer 4 days after cross-linking Fig. 2 A mild paracentral subepithelial opacity 1 month later

514 Int Ophthalmol (2011) 31:513–515

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reactivation of herpetic eye disease, even in patients

with no prior history of the disease.

As CXL is becoming a more extensively applied

treatment for progressive keratoconus, new side-effects

and complications are emerging. It seems that herpetic

keratitis may be triggered by CXL, even in the absence

of a history of previous disease. Close follow-up of

patients after CXL appears to be important, as early

diagnosis and proper treatment can facilitate successful

management of early and late complications.

Acknowledgement None of the authors has a financial support

or proprietary interest in any method or material mentioned.

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