Corneal ulcer associated with deposits of norfloxacin

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  • suits are shown in the Table. Briefly, scattered T cells, B cells, and macrophages were found surrounding vessels in the recipient cornea1 button. Keratocyte and endothelial cell expression of vimentin was reduced in the cornea1 graft compared with the recipient cornea1 button. There was no subsequent notable development in this case.

    Inadvertently, the first surgeon did not remove the recipient cornea1 button. This uncommon intraoper- ative complication resulted in an unusual situation. A full-thickness keratoconic cornea1 button remained inside the anterior chamber of the recipient eye for 5 months. The recipient button epithelium was intact, and no anterior chamber epithelial ingrowth oc- curred. Cornea1 vascularization occurred in the recip ient button but not in the graft. Histology and immunochemistry did not disclose allograft rejection, but moderate inflammatory response was found with the vascularization process. We must emphasize that the first cornea1 graft survived this unusual condition. In fact, it was clear and thin, even if vimentin expression of the recipient button endothelium was stronger than that of the graft endothelium, and keratocyte density was decreased in the graft stroma.


    1. Purcell JJ. Expulsive hemorrhage. In: Brightbill FS. Cornea1 surgery: theory, technique, and tissue. St Louis: Mosby-Year Book, Inc, 1993:221-224.

    Cornea1 U leer Associated With Deposits of Norfloxacin Minako Konishi, MD, Masakazu Yamada, MD, and Yukihiko Mashima, MD

    PURPOSE: To report a case of cornea1 ulcer associated with deposits of norfloxacin. METHOD: Case report. A 40eyear-old man with right trigeminal and facial nerve palsies and de- creased tear secretion developed a cornea1 ulcer with white deposits in the right eye. The deposits were removed and analyzed by high-performance liquid chromatography. RESULTS: High-performance liquid chromatogra- phy results disclosed that the deposits on the cornea1 surface had the same retention time as norfloxacin. The patient discontinued norfloxacin ophthalmic solution and recovered successfully. CONCLUSION: Clinicians should be aware that frequent applications of topical norfloxacin in patients with decreased tear secretion may result in deposition of the drug on the cornea.

    F LUOROQUINOLONE OPHTHALMIC SOLUTIONS HAVE been widely used for the treatment of bacterial keratitis. Recently, there have been some reports of the deposition of topical ciprofloxacin (solution and ointment) on the cornea.le4 We encountered a patient who developed precipitates of norfloxacin, which has


  • FIGURE 1. White deposits are seen at the margin of cornea1 ulcer (arrows).

    I -3 1: Sample (10.55) 2: Norfloxacin (16.51)

    3: Lomefloxacin (24.86)

    FIGURE 2. The results of high-performance liquid chromatography analysis. The retention time of the peak of the cornea1 deposits (sample) was 18.55 minutes. The retention times of norfloxacin and lomefloxacin were 18.51 minutes and 24.86 minutes, respectively. The identical retention time of the cornea1 deposits and norfloxacin confirms that the deposits were norfloxacin.

    been used clinically in more than 10 countries, including the United States, European countries, and Japan, in the cornea1 ulcer.

    A 40.year-old man developed a cornea1 ulcer in the right eye. A local ophthalmologist initially treated the patient with frequent application of ophthalmic solutions consisting of norfloxacin, lomefloxacin hy- drochloride, hyaluronate sodium, and flavin adenine dinucleotide disodium. Because there was no im- provement, the patient was referred to our clinic. Kgeminal and facial nerve palsies that were caused by brain tumor surgery 6 years previously were present on the right side. Slit-lamp examination disclosed a horizontally oriented ulceration with white deposits in the center of the cornea of the right eye (Figure 1). A Schirmer test disclosed a decrease in basic tear secretion (right eye, 1 mm; left eye, 0 mm). Cornea1 sensation in the right eye was also decreased, as determined by Cachet-Bonnet anesthesiometer (right eye, 0 mm; left eye, 60 mm). Cultures were all negative.

    The deposits were easily removed from the cornea1 surface by scraping. The sample of the cornea1 deposits was analyzed by high-performance liquid

    Accepted for publication Aug 28, 1997. Department of Ophthalmology, Keio University School of Medicine. Inquiries to Masakazu Yamada, MD, Department of Ophthalmology,

    Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160, Japan; fax: 81-3-3359-8302; e-mail: yamadam@med.

    chromatography.5 The elution was performed using a 9OO:lOO (v/v) mixture of pH 2.4, 0.05 M potassium dihydrogen phosphate, and acetonitrile with an Inert- sil ODS-2 column (GL Science, Tokyo, Japan) at a rate of 1.0 ml/minute. The detector was set at a 280-nm wavelength. The retention time of the sam- ple taken from the cornea1 deposits was 18.55 min- utes, while those of norfloxacin and lomefloxacin were 18.51 minutes and 24.86 minutes, respectively (Figure 2). The retention time of the deposits and that of norfloxacin were identical, which confirmed that the deposit was norfloxacin.

    All previous eyedrops were discontinued and re- placed by ofloxacin ophthalmic solution, adminis- tered four times per day. The white deposits in the ulcer disappeared rapidly, and the ulcer was epitheli- alized in 10 days.

    Norfloxacin, as well as ciprofloxacin, has low solubility at neutral pH. Our patient had trigeminal and facial nerve palsies in the affected eye that resulted in decreased cornea1 sensation and incom- plete blinking. Frequent administration of topical norfloxacin in conjunction with cornea1 exposure and poor tear mixing attributable to incomplete blinking, and low reflex tearing attributable to de- creased cornea1 sensation, were potential contribut- ing factors. Norfloxacin deposition was thought to prevent reepithelialization of the defect because the ulcer was epithelialized soon after the discontinuation

    VOL. I 2s. No. 2 BRIEF REPORTS 259

  • of norfloxacin. Clinicians should be aware that fre- quent applications of topical norfloxacin in patients with a cornea1 defect accompanied by decreased tear secretion and poor tear mixing may result in drug deposition on the cornea.

    During the revision of this manuscript, a report of three other patients with cornea1 deposits of norfloxa- tin was published.6








    Leibowitz HM. Clinical evaluation of ciprofloxacin 0.3% ophthalmic solution for treatment of bacterial keratitis. Am J

    Ophthalmol 1991;112(4,suppl):34S-47s. Wilhelmus KR, Hyndiuk RA, Caldwell DR, et al. 0.3%

    ciprofloxacin ophthalmic ointment in the treatment of bacter- ial keratitis. Arch Ophthalmol 1993;111:1210-1218.

    Kanellopoulos AJ, Miller F, Wittpenn JR. Deposition of topical ciprofloxacin to prevent re-epithelialization of a cornea1 defect. Am J Ophthalmol 1994;117:258-259.

    Essepian JP, Rajpal R, OBrien TP. Tandem scanning confocal microscopic analysis of ciprofloxacin cornea1 deposits in vivo. Cornea 1995;14:402-407.

    Diamond JP, White L, Leeming JP, Hoh HB, Easty DL. Topical 0.3% ciprofloxacin, norfloxacin, and ofloxacin in treatment of bacterial keratitis: a new method for comparative

    evaluation of ocular drug penetration. Br J Ophthalmol 1995;79:606-609. Castillo A, Benitez Del Castillo JM, Toledano N, Sayagues 0,

    Garcia-Sanchez J. Deposits of topical norfloxacin in the treatment of bacterial keratitis. Cornea 1997;16:420-423.

    Bilateral Zonular Cataract Associated With the Mitochondrial Cytopathy of Pearson Syndrome Claus Cursiefen, MD, Michael Kikhle, MD, Wolfram Scheurlen, MD, and Gottfried 0. H. Naumann, MD

    PURPOSE: To report a child with the mitochondri- al cytopathy of Pearson syndrome and zonular cataract. METHOD: Case report. We describe a &year-old boy with Pearson syndrome. RESULTS: At age 3 years, the boy developed secondary strabismus caused by bilateral zonular cataract. Subsequently, he underwent successful bilateral cataract extraction with intraocular lens

    implantation. Postoperative visual acuity with best correction was RE, 20/25 and LE, 20/40. CONCLUSIONS: Children with Pearson syndrome should be examined ophthalmologically to rule out zonular cataract and possible amblyopia. Mito- chondrial cytopathies such as Pearson syndrome should be included in the differential diagnosis of congenital and early juvenile cataract.

    P EARSON BONE MARROW SYNDROME IS A MITOCHON- drial cytopathy that is characterized by sideroblas- tic anemia or pancytopenia and progressive liver and pancreas insufficiency. Growth retardation, kidney tubulopathy, and skin disorders are other reported clinical features. Pearson syndrome is believed to be a multiorgan disorder with phenotype and clinical course determined by the tissue distribution and relative proportions of abnormal mitochondrial DNA molecules. Vacuolized bone marrow precursor cells and the occurrence of distinct deletions in mitochon- drial DNA are diagnostic features.s3 Therapy is supportive, and the outcome of the disease is usually fatal.**

    Ocular manifestations of mitochondrial cytopath- ies, such as MELAS (myopathy, encephalopathy, lactacidemia, and strokelike episodes) syndrome and Kearns-Sayre syndrome (pigmentary retinopathy, ex- ternal ophthalmoplegia, cardiac conduction defects, and heart failure) are usually external ophthalmople- gia, ptosis, and retinopathy. Only one case of bilateral cornea1 opacities in a child with Pearson syndrome has been reported.4 Zonular cataract is a previously unreported feature of Pearson syndrome and, to our knowledge, only one report of