Letter to the Editor

Presumed herpetic keratitis and topical anesthetic abuse Abraham Solomon, Charalambos S. Siganos and Joseph Frucht-Pery

Dear Sir,

opical anesthetic abuse may cause T severe corneal damage, including epithelial defects, stromal edema and infiltration. We report a rare case of presumed recurrent epithelial herpetic keratitis, that had rapid progression secondary to a topical anesthetic abuse. This patient had a regression of the herpetic manifestations following the cessation of the topical anesthetic and treatment with local acyclovir.

Topical ocular anesthetics are used in ophthalmology mainly for diagnos- tic purposes. Their abuse by patients seeking pain relief following ocular trauma or various infections may cause severe toxicity to the cornea and delay of the healing of the epithelium (Ep- stein & Paton 1968; Rosenwasser 1990). Uncontrolled use of topical an- esthetics decreases the efficacy of the drugs and increases the frequency of their administration, thus inducing corneal damage.

We report here on a healthy 19- year-old male who had a history of a red and painful right eye 8 years pre- viously, that resolved with topical Idoxuridine. In February 1993 he had an episode of upper respiratory tract infection with fever. During the next 4 days he started to complain of redness, discomfort and foreign body sensation in the right eye. A general practitioner prescribed topical Chloramphenicol 0.3% drops three times daily and Oxy- buprocaine hydrochloride 0.2% (Be- noxinate) for pain. For a period of 60 h the patient applied a drop of Oxybu- procaine hydrochloride every 2 h into his right eye, however, the pain and redness increased. Examination by an ophthalmologist revealed a corneal epithelial defect of 3.5 x 5.0 mm with stromal edema at the upper temporal cornea, and diffuse punctate kerato-

pathy. In the anterior chamber cells (+ 2) and flare (+ 2) were observed. The patient was instructed to stop using the local anesthetic. For the next 2 days the patient was treated with chloramphenicol 5% ointment once daily, topical cyclopentolate 1% three times daily and eye patching. However, the epithelial defect and stromal edema increased and the patient was referred to our clinic.

On examination the best corrected visual acuity was 20/400 in the right eye and 6/6 in the left eye. A round ve- sicular lesion of 6 x 6 mm was found under the right lower lid. The right upper lid was edematous. A geogra- phic epithelial defect of 10 x 4.5 mm was found in the upper half of the cor- nea. The upper two-thirds of the stroma were edematous with a dense haze. Superficial stromal scars with mild to moderate infiltration were ob- served 2 to 3 mm from the limbus be- tween 10 and 12 o'clock. The rest of the corneal epithelium presented punctate keratopathy. Cells (+ 2) and flare (+ 2) were still present in the anterior cham- ber. Microbiologic work-up was nega- tive for bacteria and fungi. A clinical diagnosis of geographic and stromal herpetic keratitis was made, and the patient was treated with acyclovir 1% ointment 5 times daily, chlorampheni- col 0.3% twice a day and cyclopento- late 1 o/o three times daily.

After 48 h, the epithelial defect dra- matically decreased to 4.0 x 1.5 mm, on the seventh day it measured 1.0 x 0.2 mm, and within the next week it healed completely. The stroma re- mained edematous and slightly infil- trated. Topical dexamethasone 0.1% three times daily was added and after 10 days the edema finally resolved, leaving diffuse stromal scars typical of

herpetic keratitis. Visual acuity in the right eye recovered to 6/6.

Our patient presents a rare case of presumed recurrent herpetic keratitis aggravated by topical anesthetic abuse. All topical anesthetics have been shown in the past to inhibit corneal epithelial healing in animal models (Gundersen & Liebman 1944; Marr 1957; Smith 1973). Abuse of topical anesthetics may cause epithelial cor- ned defects, stromal edema and infil- tration, and intraocular inflammatory response. These severe manifestations were described following frequent ad- ministration of topical anesthetic for a week or longer (Epstein & Paton 1968; Rosenwasser 1990). The large epithe- lial defects usually include the inter- palpebral corneal surface where con- tact with the medication is most pro- longed. Discontinuation of the anes- thetic drug is followed by a slow heal- ing process with subsequent epithelial- ization and stromal scarring. Clinical manifestations of topical anesthetic abuse may simulate any infectious ker- atitis, including severe herpetic ker- atitis. However, progressive herpetic keratitis, to our knowledge, has not been reported in association with abuse of topical anesthetics.

No laboratory studies were per- formed to substantiate the diagnosis of recurrent herpes keratitis. However, the diagnosis in our patient is sup- ported by several manifestations. This patient had a past history of ocular her- petic disease with typical superficial stromal scars. The first symptoms ap- peared following a febrile disease. The epithelial defect that was initially lo- cated in the area of herpetic scars, pro- gressed into a typical geographic epi- thelial lesion that continuously en- larged despite discontinuation of topi- cal anesthetic. Finally, the process was dramatically arrested following ad- ministration of topical acyclovir, with rapid epithelialization of the cornea.

Reactivation of herpetic keratitis can be induced by some agents such as epinephrine and prostaglandins (Blyth 1976; Laibson & Kibrick 1966), but the effect of topical anesthetic on the

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ACTA OPHTHALMOLOGICA SCANDINAVICA 1996 -

recurrence of herpetic keratitis is not known. In one laboratory study, in vitro topical anesthetic suppressed the proliferation of the virus, but this could not be related to a direct effect of the drug on the virus. On the other hand, administration of the anesthetic in vivo did not affect the virus (Weinberg 1977). This is the only reference in the ophthalmic literature on the effect of a topical anesthetic on the herpes sim- plex virus.

Rapid progression of an epithelial herpetic lesion into a large geographic herpetic lesion is uncommon, and usually follows a misdiagnosed her- petic disease treated with medications other than antivirals, particularly topi- cal steroids. The surprisingly rapid for- mation of geographic herpetic keratitis was probably induced by toxicity of the anesthetic to the epithelial cells con- taining a replicating virus, allowing fas- ter destruction of cells and viral spread to surrounding tissue.

This case indicates that topical an-

esthetics should not be given to take home. The possibility of herpetic in- fection should be suspected in the presence of large corneal lesions, after short-term abuse by topical anesthe- tics.

Key words herpes simplex keratitis - topical anesthetic - cornea.

References Blyth WA, Hill TJ & Harbour DA (1976):

Reactivation of herpes simplex virus in- fection by ultraviolet light and possible in- volvement of prostaglandins. J Gen Virol

Epstein DL & Paton D (1968): Keratitis from misuse of corneal anesthetics. N Engl J Med 279: 396-399.

Gundersen T & Liebman SD (1944): Effect of local anesthetics on regeneration of corneal epithelium. Arch Ophthalmol3 1 :

Laibson P & Kibrick S (1966): Reactivation

33: 547-550.

29-33.

of herpetic keratitis by epinephrine in the rabbit. Arch Ophthalmol75: 254-260.

Man WG, Wood R, Senterfit L & Sigelman S (1957): Effect of topical anesthetics on regeneration of the corneal epithelium. Am J Ophthalmol43: 606-610.

Rosenwasser GO, Holland S, Ptlugfelder SC, Lug0 M, Heidemann DG, Culbertson W & Kattan H (1990): Topical anesthetic abuse. Ophthalmology 9 7 967-972.

Smith RF3 & Everett WG (1973): Physiology and pharmacology of local anesthetic agents. Int Ophthalmol Clin 13(2): 35-60.

Weinberg RJ & Oh JO (1977): The effect of a topical anesthetic on the recovery of her- pes simplex virus. Ann Ophthalmol9(8): 977-983.

Corresponding author: Joseph Frucht-Pery. MD Department of Ophthalmology Hadassah University Hospital PO Box 12000 91 120 Jerusalem, Israel Tel 972-2-341538 (home)

972-2-777692 (office) F~M 972-2-434434.