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Canalicular stenosis due to topical use of fortified antibiotics
CASE REPORTS
Canalicular stenosis due to topical use of fortified antibiotics Bonnie C. Weston,* MD, FRCSC; James W. Loveless,t MD he recent availability of broad-spectrum antibiotics for topical use has led to debate regarding the standard of care for the treatment of corneal ulceration. The epithelial toxicity of topically administered antibiotics and preservatives can lead to significant problems with surface healing, thus increasing both morbidity and the cost of care. We describe a patient in whom canalicular stenosis developed after treatment of a corneal ulcer with topically administered natamycin, fortified gentamicin and fortified vancomycin.
T
CASE REPORT
A 48-year-old white woman presented with pain and photophobia in her right eye. She had been trimming weeds 2 days earlier. On examination there was purulent discharge on her right upper and lower eyelids. A small foreign body was embedded in the corneal stroma, surrounded by a dense white infiltrate. Corneal edema, anterior chamber inflammation and keratic precipitates were present. The foreign body was removed at the slit lamp. Corneal scrapings were obtained for culture. The woman was admitted to hospital, where she received fortified vancomycin (50 mg/mL) and fortified gentamicin (14 mg/mL), both instilled on the right eye every half hour around the clock, and 5% natamycin, instilled hourly for 8 hours a day. Culture gave negative results. The infiltrate resolved quickly, and the corneal epithelium was healed by day 5. Natamycin treatment was stopped, and the antibiotics were From *the Department of Ophthalmology and tthe College of Medicine, University of South Alabama, Mobile, Ala. Accepted for publication July 5, 2000 Reprint requests to: Dr. Bonnie C. Weston, Department of Ophthalmology, University of South Alabama, HSB Rm. 2500, 307 University Blvd., Mobile AL 36688, USA Can j Ophthafmol 2000;35:334-5
334
reduced to every hour on day 5 and every 2 hours while awake on day 6. The patient was discharged the next day. At that time the infiltrate had almost resolved, the epithelium was healed, and the vision in the right eye was 20/80. Antibiotic therapy was stopped on day 10. On day 13 a pseudomembrane developed. Topical therapy with 0.1% fluorometholone was started, and the conjunctival inflammation resolved within 1 week. The visual acuity was now 20/20. One month later the patient experienced right epiphora. Symblepharon had formed superonasally, and the puncta were stenosed. The symblepharon was lysed, and topical therapy with 1% prednisolone acetate was started. A three-snip punctoplasty procedure was attempted 1 week later. No puncta or canaliculi could be identified owing to complete fibrosis. A bypass procedure was recommended. One year later the patient underwent canalicular dacryocystorhinostomy with lacrimal intubation, middle turbinectomy and implantation of a Jones tube. Extensive scarring of the canaliculi was confirmed intraoperatively. Despite a successful initial result, the tube extruded repeatedly. At the time of writing, the patient had required three reinsertions, with excision of extensive intranasal scar tissue at the second revision. COMMENTS
The standard of care for the treatment of bacterial corneal ulcers is to use both a cephalosporin and an aminoglycoside to cover gram-positive and gramnegative bacteria respectively. Therapy is modified according to the clinical response and culture results. We chose to add natamycin to the patient's therapeutic regimen because of the foreign body acquired outdoors in an area endemic for fungal keratitis. Difficulty with corneal healing owing to the toxicity of such frequently applied eyedrops is a common problem during the treatment of corneal ulcers. The toxic effects of topically administered aminoglycosides include delayed epithelial healing, contact dermatoconjunctivitis, punctate keratopathy, papillary conjunctivitis and pseu-
Canalicular stenosis and antibiotics-Weston et al
Canalicular stenosis and antibiotics-Weston et al
domembrane formation. 1 Topically given vancomycin can be toxic to the corneal epithelium owing to its low pH, particularly in unbuffered preparations. 2 Natamycin appears to be well tolerated by the corneal epithelium. 3 Most commercially available ophthalmic medications contain benzalkonium chloride as a preservative, which also has significant epithelial toxicity. The symblepharon and canalicular stenosis in our patient are presumed to be the result of apposition of two injured epithelial surfaces during healing. Canalicular stenosis has been reported in association with topical use of antiglaucoma medications4•5 and antivirals. 3•5 Antibiotics have only recently been identified as a cause. McNab 5 reported three cases of canalicular obstruction due to topical use of tobramycin and three due to topical use of chloramphenicol. However, to our knowledge, stenosis due to natamycin, gentamicin or vancomycin has not previously been reported. We chose to use vancomycin in our patient because of the severity of the infiltrate at presentation. We suspect that the epithelial toxicity of gentamicin combined with the acidic pH of vancomycin was responsible for the stenosis in our patient. Our patient experienced considerable long-term morbidity from treatment of a corneal ulcer. There is good evidence that topical fluoroquinolone treatment is adequate single-agent therapy for many corneal ulcers because of the broad spectrum of activity and low ocular toxicity of these drugs. 6 We have replaced
gentamicin with ciprofloxacin in treating most cases of corneal ulcer. For vision-threatening ulcers we add a cephalosporin for gram-positive coverage but avoid vancomycin unless clinical and laboratory sensitivity results support its use. We no longer use antifungals unless there is more definitive clinical evidence of fungal keratitis. With this approach we hope to reduce toxicity during the treatment of corneal ulcers. REFERENCES
1. Bullard SR, O'Day DM. Pseudomembranous conjunctivitis
2. 3. 4. 5.
6.
following topical gentamicin therapy. Arch Ophthalmol 1997;115:1591-2. Barron B. Corneal toxicity from acidic vancomycin solution [letter]. Arch Ophthalmo/1993;111:18. Stem GA, Killingsworth DW. Complications of topical antimicrobial agents. lnt Ophthalmol Clin 1989;29:137-42. Wilson PM II. Adverse external ocular effects of topical ophthalmic medications. Surv Ophthalmoll979;24:57-88. McNab AA. Lacrimal canalicular obstruction associated with topical ocular medication. Aust N Z J Ophthalmol 1998;26:219-23. O'Brien TP, Maguire MG, Fink NE, Alfonso E, McDonnell P. Efficacy of ofloxacin vs cefazolin and tobramycin in the therapy for bacterial keratitis. Report from the Bacterial Keratitis Study Research Group. Arch Ophthalmol 1995; 113:1257-65.
Key words: canalicular stenosis, corneal ulcer, antibiotics, topical administration
CAN J OPHTHALMOL-VOL. 35, NO.6, 2000
335
Canalicular stenosis due to topical use of fortified antibiotics Bonnie C. Weston,* MD, FRCSC; James W. Loveless,t MD he recent availability of broad-spectrum antibiotics for topical use has led to debate regarding the standard of care for the treatment of corneal ulceration. The epithelial toxicity of topically administered antibiotics and preservatives can lead to significant problems with surface healing, thus increasing both morbidity and the cost of care. We describe a patient in whom canalicular stenosis developed after treatment of a corneal ulcer with topically administered natamycin, fortified gentamicin and fortified vancomycin.
T
CASE REPORT
A 48-year-old white woman presented with pain and photophobia in her right eye. She had been trimming weeds 2 days earlier. On examination there was purulent discharge on her right upper and lower eyelids. A small foreign body was embedded in the corneal stroma, surrounded by a dense white infiltrate. Corneal edema, anterior chamber inflammation and keratic precipitates were present. The foreign body was removed at the slit lamp. Corneal scrapings were obtained for culture. The woman was admitted to hospital, where she received fortified vancomycin (50 mg/mL) and fortified gentamicin (14 mg/mL), both instilled on the right eye every half hour around the clock, and 5% natamycin, instilled hourly for 8 hours a day. Culture gave negative results. The infiltrate resolved quickly, and the corneal epithelium was healed by day 5. Natamycin treatment was stopped, and the antibiotics were From *the Department of Ophthalmology and tthe College of Medicine, University of South Alabama, Mobile, Ala. Accepted for publication July 5, 2000 Reprint requests to: Dr. Bonnie C. Weston, Department of Ophthalmology, University of South Alabama, HSB Rm. 2500, 307 University Blvd., Mobile AL 36688, USA Can j Ophthafmol 2000;35:334-5
334
reduced to every hour on day 5 and every 2 hours while awake on day 6. The patient was discharged the next day. At that time the infiltrate had almost resolved, the epithelium was healed, and the vision in the right eye was 20/80. Antibiotic therapy was stopped on day 10. On day 13 a pseudomembrane developed. Topical therapy with 0.1% fluorometholone was started, and the conjunctival inflammation resolved within 1 week. The visual acuity was now 20/20. One month later the patient experienced right epiphora. Symblepharon had formed superonasally, and the puncta were stenosed. The symblepharon was lysed, and topical therapy with 1% prednisolone acetate was started. A three-snip punctoplasty procedure was attempted 1 week later. No puncta or canaliculi could be identified owing to complete fibrosis. A bypass procedure was recommended. One year later the patient underwent canalicular dacryocystorhinostomy with lacrimal intubation, middle turbinectomy and implantation of a Jones tube. Extensive scarring of the canaliculi was confirmed intraoperatively. Despite a successful initial result, the tube extruded repeatedly. At the time of writing, the patient had required three reinsertions, with excision of extensive intranasal scar tissue at the second revision. COMMENTS
The standard of care for the treatment of bacterial corneal ulcers is to use both a cephalosporin and an aminoglycoside to cover gram-positive and gramnegative bacteria respectively. Therapy is modified according to the clinical response and culture results. We chose to add natamycin to the patient's therapeutic regimen because of the foreign body acquired outdoors in an area endemic for fungal keratitis. Difficulty with corneal healing owing to the toxicity of such frequently applied eyedrops is a common problem during the treatment of corneal ulcers. The toxic effects of topically administered aminoglycosides include delayed epithelial healing, contact dermatoconjunctivitis, punctate keratopathy, papillary conjunctivitis and pseu-
Canalicular stenosis and antibiotics-Weston et al
Canalicular stenosis and antibiotics-Weston et al
domembrane formation. 1 Topically given vancomycin can be toxic to the corneal epithelium owing to its low pH, particularly in unbuffered preparations. 2 Natamycin appears to be well tolerated by the corneal epithelium. 3 Most commercially available ophthalmic medications contain benzalkonium chloride as a preservative, which also has significant epithelial toxicity. The symblepharon and canalicular stenosis in our patient are presumed to be the result of apposition of two injured epithelial surfaces during healing. Canalicular stenosis has been reported in association with topical use of antiglaucoma medications4•5 and antivirals. 3•5 Antibiotics have only recently been identified as a cause. McNab 5 reported three cases of canalicular obstruction due to topical use of tobramycin and three due to topical use of chloramphenicol. However, to our knowledge, stenosis due to natamycin, gentamicin or vancomycin has not previously been reported. We chose to use vancomycin in our patient because of the severity of the infiltrate at presentation. We suspect that the epithelial toxicity of gentamicin combined with the acidic pH of vancomycin was responsible for the stenosis in our patient. Our patient experienced considerable long-term morbidity from treatment of a corneal ulcer. There is good evidence that topical fluoroquinolone treatment is adequate single-agent therapy for many corneal ulcers because of the broad spectrum of activity and low ocular toxicity of these drugs. 6 We have replaced
gentamicin with ciprofloxacin in treating most cases of corneal ulcer. For vision-threatening ulcers we add a cephalosporin for gram-positive coverage but avoid vancomycin unless clinical and laboratory sensitivity results support its use. We no longer use antifungals unless there is more definitive clinical evidence of fungal keratitis. With this approach we hope to reduce toxicity during the treatment of corneal ulcers. REFERENCES
1. Bullard SR, O'Day DM. Pseudomembranous conjunctivitis
2. 3. 4. 5.
6.
following topical gentamicin therapy. Arch Ophthalmol 1997;115:1591-2. Barron B. Corneal toxicity from acidic vancomycin solution [letter]. Arch Ophthalmo/1993;111:18. Stem GA, Killingsworth DW. Complications of topical antimicrobial agents. lnt Ophthalmol Clin 1989;29:137-42. Wilson PM II. Adverse external ocular effects of topical ophthalmic medications. Surv Ophthalmoll979;24:57-88. McNab AA. Lacrimal canalicular obstruction associated with topical ocular medication. Aust N Z J Ophthalmol 1998;26:219-23. O'Brien TP, Maguire MG, Fink NE, Alfonso E, McDonnell P. Efficacy of ofloxacin vs cefazolin and tobramycin in the therapy for bacterial keratitis. Report from the Bacterial Keratitis Study Research Group. Arch Ophthalmol 1995; 113:1257-65.
Key words: canalicular stenosis, corneal ulcer, antibiotics, topical administration
CAN J OPHTHALMOL-VOL. 35, NO.6, 2000
335