- Email: [email protected]
Presumed activation of herpetic keratouveitis after argon laser peripheral iridotomy
In 1997, the United States Congress passed the Food and Drug Administration Modernization Act, which extended the Prescription Drug User Fee Act of 1992. This continued the program of sponsors paying a user fee, which the Food and Drug Administration uses to employ additional reviewers to accelerate drug review. Although the impact of the Prescription Drug User Fee Act and the Food and Drug Administration Modernization Act on resources in the ophthalmology division of the Food and Drug Administration is not clear, during this interval, the Ophthalmology Division (part of the Division of Anti-Inflammatory, Analgesic and Ophthalmic Drugs) continued its rapid rate of new drug application review. A pharmaceutical firm at the end of a multiyear development process submits a new drug application, in which the preclinical, clinical, and chemical investigations are documented, and a request is made for marketing of a new drug. Upon receipt, the Food and Drug Administration rapidly determines the completeness of the application and, within 45 days, advises the pharmaceutical firm if the application will be formally filed. Once filed, the Food and Drug Administration then reviews the application from various aspects (e.g., preclinical safety studies, chemical stability and purity of the product, and clinical efficacy and safety). During this review process, the Food and Drug Administration may contact the firm for clarification on certain issues. The continued rapid review of new ophthalmic drugs by the Food and Drug Administration means that clinicians will have rapid access to these new agents for general use. REFERENCE
1. Novack GD. Review times for ophthalmic new drug applications (NDAs) at the United States Food and Drug Administration (FDA). Am J Ophthalmol. 1998;126:122–126.
Presumed Activation of Herpetic Keratouveitis After Argon Laser Peripheral Iridotomy Bruce D. Gaynor, MD, Robert L. Stamper, MD, and Emmett T. Cunningham, Jr, MD, PhD, MPH PURPOSE:
To describe presumed activation of herpetic keratouveitis after argon laser peripheral iridotomy.
Accepted for publication May 17, 2000. From the Francis I. Proctor Foundation (B.D.G., E.T.C.) and the Department of Ophthalmology (B.D.G., R.L.S., E.T.C.), University of California, San Francisco, San Francisco, California. Inquiries to Emmett T. Cunningham, Jr., MD, PhD, MPH, The Pearl & Samuel J. Kimura Ocular Immunology Laboratory, The Francis I. Proctor Foundation, University of California Medical Center, San Francisco, CA 94143-0944; fax: (415) 476-0527; e-mail: emmett@itsa. ucsf.edu
VOL. 130, NO. 5
METHOD:
Case report. A 68-year-old man developed chronic, unilateral, anterior uveitis associated with decreased corneal sensation, focal keratitis, and increased intraocular pressure after argon laser peripheral iridotomy. Treatment with oral acyclovir and discontinuation of topical latanoprost resulted in prompt and continued control of both the intraocular inflammation and pressure. CONCLUSION: Herpetic keratouveitis may occur after argon laser iridotomy, and it should be considered when postoperative inflammation persists despite appropriate use of topical corticosteroids, particularly in patients with a history of herpetic eye disease. (Am J Ophthalmol 2000;130:665– 667. © 2000 by Elsevier Science Inc. All rights reserved.) RESULTS:
I
NFECTION WITH HERPES VIRUS IS ONE OF THE MOST
common causes of keratouveitis. Clues to the diagnosis include the presence of decreased corneal sensation, increased intraocular pressure, localized iris atrophy, and focal keratitis. We report a case of presumed herpetic keratouveitis that followed the application of argon laser peripheral iridotomy and that may have been exacerbated by the prolonged use of latanoprost for intraocular pressure control. A 68-year-old Iraqi-born American man underwent a prophylactic peripheral argon laser iridotomy in his left eye for what were believed to be occludable iridocorneal angles. The left eye subsequently developed a chronic, anterior uveitis with increased intraocular pressure as high as 40 mm Hg. Over the ensuing 2 years, the inflammation was intermittently controlled with topical prednisolone acetate (1%), but the uveitis flared and the intraocular pressure rose each time the corticosteroids were tapered. Ocular history was notable only for trachoma as a child. Medications at the time of referral included prednisolone acetate (1%), six times daily, latanoprost (0.005%), at bedtime, brimonidine tartrate (0.2%), twice daily, and betaxolol (0.25%), twice daily, all in the left eye, as well as oral methazolamide (50 mg), twice daily. Examination revealed a best-corrected visual acuity of RE: 20/20⫺2, LE: 20/50. Intraocular pressure was RE: 16 mm Hg, LE: 40 mm Hg. Corneal sensation was markedly decreased inferotemporally in the left eye. Slit-lamp examination revealed mild subconjunctival scarring in both eyes consistent with prior trachoma. Examination of the right eye was otherwise unremarkable. Examination of the left anterior segment disclosed a localized area of corneal thickening inferotemporally with overlying epithelial microcysts and bullae, and underlying keratic precipitates (Figure 1). No evidence of anterior chamber inflammation existed. Fundus examination with a dilated pupil revealed a cup-to-disk ratio of 0.6 bilaterally with full neuroretinal rims. The patient was found to have presumed herpetic keratouveitis and was placed on acyclovir (800 mg), five
BRIEF REPORTS
665
FIGURE 1. Edema of the left inferotemporal cornea obscuring iris detail (Top; arrowheads). High magnification slit-lamp examination of this area using retroillumination (Bottom) reveals a large epithelial bulla with an underlying keratic precipitate (arrowhead) and surrounding epithelial microcysts. Corneal sensation was decreased in this area, and intraocular pressure was increased, consistent with the diagnosis of herpetic keratouveitis.
times daily, and the latanoprost was discontinued. Within 6 weeks, the inflammation in the left eye was well controlled on fluoromethalone (0.1%), twice daily, and the intraocular pressure had dropped to 19 mm Hg on betaxolol (0.25%), dorzolamide hydrochloride (2%), and brimonidine tartrate (0.2%), each twice daily. The intraocular inflammation and pressure of the patient have remained controlled for 11 months of follow-up. The respective roles of argon laser peripheral iridotomy and of latanoprost in the initial activation and subsequent persistence of the episode of herpetic keratouveitis of our 666
AMERICAN JOURNAL
patient remain presumptive. Of note, however, studies in humans1,2 and experimental animals3,4 suggest that both ultraviolet light1,3 and excimer laser2,4 can promote herpes virus reactivation. Moreover, clinical5 and experimental evidence6 suggests that application of topical latanoprost can increase the severity and the number of recurrences of herpetic keratitis. We, therefore, recommend that the diagnosis of herpetic keratouveitis be considered in patients with persistent anterior chamber inflammation after laser peripheral iridotomy, particularly when a history of herpetic eye disease exists. OF
OPHTHALMOLOGY
NOVEMBER 2000
REFERENCES
1. Perna JJ, Mannix ML, Rooney JF, Notkins AL, Straus SE. Reactivation of latent herpes simplex virus infection by ultraviolet light: a human model. J Am Acad Dermatol 1987;17:473– 478. 2. Pepose JS, Laycock KA, Miller JK, et al. Reactivation of latent herpes simplex virus by excimer laser photokeratectomy. Am J Ophthalmol 1992;114:45–50. 3. Laycock KA, Lee SF, Brady RH, Pepose JS. Characterization of a murine model of recurrent herpes simplex viral keratitis induced by ultraviolet B radiation. Invest Ophthalmol Vis Sci 1991;32:2741–2746. 4. Dhaliwal DK, Barnhorst DAJ, Romanowski E, Rehkopf PG, Gordon YJ. Efficient reactivation of latent herpes simplex virus type 1 infection by excimer laser keratectomy in the experimental rabbit ocular model. Am J Ophthalmol 1998; 125:488 – 492. 5. Wand M, Gilbert CM, Liesegang TJ. Latanoprost and herpes simplex keratitis. Am J Ophthalmol 1999;127:602– 604. 6. Kaufman HE, Varnell ED, Thompson HW. Latanoprost increases the severity and recurrence of herpetic keratitis in the rabbit. Am J Ophthalmol 1999;127:531–536.
Unusual Corneal Deposit After the Topical Use of Cyclosporine as Eyedrops Shu Kachi, Koji Hirano, Yoshiko Takesue, and Masanori Miura PURPOSE:
To report a patient who developed bilateral corneal opacities 5 days after the beginning topical cyclosporine. METHODS: Case report. A 45-year-old woman with graftversus-host disease presented with bilateral corneal deposits. She had been treated with topical physiological saline solution, sodium hyaluronate, ofloxacin, fluorometholone, and oxybuprocaine. Cyclosporine eyedrops were added for persistent corneal epithelial defect bilaterally. Five days after cyclosporine, she complained of visual loss and dense corneal opacities were detected that covered the pupil bilaterally. RESULTS: Deposits were also observed on the punctal plugs, and infrared spectroscopy and X-ray analysis showed that these deposits had properties of cyclosporine. CONCLUSION: Topical cyclosporine, alone or in combination with other eyedrops, may cause severe corneal deposits in patients with disturbance of the corneal Accepted for publication Jun 14, 2000. From the Department of Ophthalmology (S.K., K.H.), Nagoya University School of Medicine, Nagoya, Japan, the Department of Ophthalmology (Y.T.), Fukuoka University Chikushi Hospital, and the Medical Institute of Bioregulation, Kyushu University (M.M.), Fukuoka, Japan. Inquiries to Shu Kachi, MD, Department of Ophthalmology, Nagoya University School of Medicine, Tsuruma-cho 65, Showa-ku, Nagoya 466-8550, Japan; fax: 81-52-744-2278; e-mail: [email protected] Supported by a Grant-in-aid Scientific Research from the Ministry of Education, Japan (Hirano K: (C)11671732).
VOL. 130, NO. 5
epithelial barrier and decreased tear clearance. (Am J Ophthalmol 2000;130:667– 669. © 2000 by Elsevier Science Inc. All rights reserved.)
C
YCLOSPORINE EYEDROPS ARE USED AFTER KERATO-
plasty in high-risk cases to prevent graft rejection. Topical cyclosporine is also used to treat severe vernal keratoconjunctivitis,1 keratoconjunctivitis sicca,2 and various immune-related corneal disorders. Despite the severe side effects after systemic use of cyclosporine, topical cyclosporine can generally be used without serious adverse effects. We present a patient who developed bilateral white corneal deposits 5 days after beginning cyclosporine eyedrops. A 45-year-old woman was followed by a neighboring ophthalmologist because of dry eye syndrome caused by graft-versus-host disease after bone marrow transplantation for acute myelogenous leukemia. After transplantation, she was treated with systemic cyclosporine, and by topical physiological saline solution, 0.1% sodium hyaluronate, 0.3% ofloxacin, and 0.1% fluorometholone for dry eye syndrome. She was also treated with 0.4% oxybuprocaine for the relief of severe ocular pain. As the bilateral corneal epithelial defect persisted even after the application of punctal plugs, 2% cyclosporine distilled in olive oil was added as eyedrops 3 times a day bilaterally. Five days later, she complained of severe visual loss in association with bilateral corneal opacities and was referred to the Nagoya University Hospital (Nagoya, Japan) for analysis of the corneal deposits. On her initial examination, her visual acuity was hand motion bilaterally and the Schirmer test was RE: 2 mm and LE: 1 mm. Bilateral, dense, snow white corneal opacities formed a “niveau” about 4 mm below the upper limbus and covered the entire pupil. The opacities became gradually lighter toward the lower limbus (Figure 1). The opacities were associated with corneal neovascularization developing from the limbus and small epithelial defects in the central part of the cornea. As the patient did not agree to keratectomy, infrared spectroscopy and X-ray analysis were conducted on the deposits on the punctal plugs. The spectroscopic pattern of the deposits showed a pattern similar to that of cyclosporine (Figure 2A). Additionally, the deposits were found by X-ray analysis to be made up of carbon, oxygen, sodium sulfate, and chloride, whereas the control cyclosporine contained carbon and oxygen (Figure 2B). She is now followed at the Chikushi Hospital using therapeutic soft contact lenses and eyedrops of physiological saline solution. After 12 months, no improvement in the corneal findings has been noted. Unfortunately, we could not conduct an analysis on the corneal deposits. The history of the patient whose deposits appeared immediately after the topical use of cyclosporine and the results of the deposits on the punctal plugs strongly
BRIEF REPORTS
667
1. Novack GD. Review times for ophthalmic new drug applications (NDAs) at the United States Food and Drug Administration (FDA). Am J Ophthalmol. 1998;126:122–126.
Presumed Activation of Herpetic Keratouveitis After Argon Laser Peripheral Iridotomy Bruce D. Gaynor, MD, Robert L. Stamper, MD, and Emmett T. Cunningham, Jr, MD, PhD, MPH PURPOSE:
To describe presumed activation of herpetic keratouveitis after argon laser peripheral iridotomy.
Accepted for publication May 17, 2000. From the Francis I. Proctor Foundation (B.D.G., E.T.C.) and the Department of Ophthalmology (B.D.G., R.L.S., E.T.C.), University of California, San Francisco, San Francisco, California. Inquiries to Emmett T. Cunningham, Jr., MD, PhD, MPH, The Pearl & Samuel J. Kimura Ocular Immunology Laboratory, The Francis I. Proctor Foundation, University of California Medical Center, San Francisco, CA 94143-0944; fax: (415) 476-0527; e-mail: emmett@itsa. ucsf.edu
VOL. 130, NO. 5
METHOD:
Case report. A 68-year-old man developed chronic, unilateral, anterior uveitis associated with decreased corneal sensation, focal keratitis, and increased intraocular pressure after argon laser peripheral iridotomy. Treatment with oral acyclovir and discontinuation of topical latanoprost resulted in prompt and continued control of both the intraocular inflammation and pressure. CONCLUSION: Herpetic keratouveitis may occur after argon laser iridotomy, and it should be considered when postoperative inflammation persists despite appropriate use of topical corticosteroids, particularly in patients with a history of herpetic eye disease. (Am J Ophthalmol 2000;130:665– 667. © 2000 by Elsevier Science Inc. All rights reserved.) RESULTS:
I
NFECTION WITH HERPES VIRUS IS ONE OF THE MOST
common causes of keratouveitis. Clues to the diagnosis include the presence of decreased corneal sensation, increased intraocular pressure, localized iris atrophy, and focal keratitis. We report a case of presumed herpetic keratouveitis that followed the application of argon laser peripheral iridotomy and that may have been exacerbated by the prolonged use of latanoprost for intraocular pressure control. A 68-year-old Iraqi-born American man underwent a prophylactic peripheral argon laser iridotomy in his left eye for what were believed to be occludable iridocorneal angles. The left eye subsequently developed a chronic, anterior uveitis with increased intraocular pressure as high as 40 mm Hg. Over the ensuing 2 years, the inflammation was intermittently controlled with topical prednisolone acetate (1%), but the uveitis flared and the intraocular pressure rose each time the corticosteroids were tapered. Ocular history was notable only for trachoma as a child. Medications at the time of referral included prednisolone acetate (1%), six times daily, latanoprost (0.005%), at bedtime, brimonidine tartrate (0.2%), twice daily, and betaxolol (0.25%), twice daily, all in the left eye, as well as oral methazolamide (50 mg), twice daily. Examination revealed a best-corrected visual acuity of RE: 20/20⫺2, LE: 20/50. Intraocular pressure was RE: 16 mm Hg, LE: 40 mm Hg. Corneal sensation was markedly decreased inferotemporally in the left eye. Slit-lamp examination revealed mild subconjunctival scarring in both eyes consistent with prior trachoma. Examination of the right eye was otherwise unremarkable. Examination of the left anterior segment disclosed a localized area of corneal thickening inferotemporally with overlying epithelial microcysts and bullae, and underlying keratic precipitates (Figure 1). No evidence of anterior chamber inflammation existed. Fundus examination with a dilated pupil revealed a cup-to-disk ratio of 0.6 bilaterally with full neuroretinal rims. The patient was found to have presumed herpetic keratouveitis and was placed on acyclovir (800 mg), five
BRIEF REPORTS
665
FIGURE 1. Edema of the left inferotemporal cornea obscuring iris detail (Top; arrowheads). High magnification slit-lamp examination of this area using retroillumination (Bottom) reveals a large epithelial bulla with an underlying keratic precipitate (arrowhead) and surrounding epithelial microcysts. Corneal sensation was decreased in this area, and intraocular pressure was increased, consistent with the diagnosis of herpetic keratouveitis.
times daily, and the latanoprost was discontinued. Within 6 weeks, the inflammation in the left eye was well controlled on fluoromethalone (0.1%), twice daily, and the intraocular pressure had dropped to 19 mm Hg on betaxolol (0.25%), dorzolamide hydrochloride (2%), and brimonidine tartrate (0.2%), each twice daily. The intraocular inflammation and pressure of the patient have remained controlled for 11 months of follow-up. The respective roles of argon laser peripheral iridotomy and of latanoprost in the initial activation and subsequent persistence of the episode of herpetic keratouveitis of our 666
AMERICAN JOURNAL
patient remain presumptive. Of note, however, studies in humans1,2 and experimental animals3,4 suggest that both ultraviolet light1,3 and excimer laser2,4 can promote herpes virus reactivation. Moreover, clinical5 and experimental evidence6 suggests that application of topical latanoprost can increase the severity and the number of recurrences of herpetic keratitis. We, therefore, recommend that the diagnosis of herpetic keratouveitis be considered in patients with persistent anterior chamber inflammation after laser peripheral iridotomy, particularly when a history of herpetic eye disease exists. OF
OPHTHALMOLOGY
NOVEMBER 2000
REFERENCES
1. Perna JJ, Mannix ML, Rooney JF, Notkins AL, Straus SE. Reactivation of latent herpes simplex virus infection by ultraviolet light: a human model. J Am Acad Dermatol 1987;17:473– 478. 2. Pepose JS, Laycock KA, Miller JK, et al. Reactivation of latent herpes simplex virus by excimer laser photokeratectomy. Am J Ophthalmol 1992;114:45–50. 3. Laycock KA, Lee SF, Brady RH, Pepose JS. Characterization of a murine model of recurrent herpes simplex viral keratitis induced by ultraviolet B radiation. Invest Ophthalmol Vis Sci 1991;32:2741–2746. 4. Dhaliwal DK, Barnhorst DAJ, Romanowski E, Rehkopf PG, Gordon YJ. Efficient reactivation of latent herpes simplex virus type 1 infection by excimer laser keratectomy in the experimental rabbit ocular model. Am J Ophthalmol 1998; 125:488 – 492. 5. Wand M, Gilbert CM, Liesegang TJ. Latanoprost and herpes simplex keratitis. Am J Ophthalmol 1999;127:602– 604. 6. Kaufman HE, Varnell ED, Thompson HW. Latanoprost increases the severity and recurrence of herpetic keratitis in the rabbit. Am J Ophthalmol 1999;127:531–536.
Unusual Corneal Deposit After the Topical Use of Cyclosporine as Eyedrops Shu Kachi, Koji Hirano, Yoshiko Takesue, and Masanori Miura PURPOSE:
To report a patient who developed bilateral corneal opacities 5 days after the beginning topical cyclosporine. METHODS: Case report. A 45-year-old woman with graftversus-host disease presented with bilateral corneal deposits. She had been treated with topical physiological saline solution, sodium hyaluronate, ofloxacin, fluorometholone, and oxybuprocaine. Cyclosporine eyedrops were added for persistent corneal epithelial defect bilaterally. Five days after cyclosporine, she complained of visual loss and dense corneal opacities were detected that covered the pupil bilaterally. RESULTS: Deposits were also observed on the punctal plugs, and infrared spectroscopy and X-ray analysis showed that these deposits had properties of cyclosporine. CONCLUSION: Topical cyclosporine, alone or in combination with other eyedrops, may cause severe corneal deposits in patients with disturbance of the corneal Accepted for publication Jun 14, 2000. From the Department of Ophthalmology (S.K., K.H.), Nagoya University School of Medicine, Nagoya, Japan, the Department of Ophthalmology (Y.T.), Fukuoka University Chikushi Hospital, and the Medical Institute of Bioregulation, Kyushu University (M.M.), Fukuoka, Japan. Inquiries to Shu Kachi, MD, Department of Ophthalmology, Nagoya University School of Medicine, Tsuruma-cho 65, Showa-ku, Nagoya 466-8550, Japan; fax: 81-52-744-2278; e-mail: [email protected] Supported by a Grant-in-aid Scientific Research from the Ministry of Education, Japan (Hirano K: (C)11671732).
VOL. 130, NO. 5
epithelial barrier and decreased tear clearance. (Am J Ophthalmol 2000;130:667– 669. © 2000 by Elsevier Science Inc. All rights reserved.)
C
YCLOSPORINE EYEDROPS ARE USED AFTER KERATO-
plasty in high-risk cases to prevent graft rejection. Topical cyclosporine is also used to treat severe vernal keratoconjunctivitis,1 keratoconjunctivitis sicca,2 and various immune-related corneal disorders. Despite the severe side effects after systemic use of cyclosporine, topical cyclosporine can generally be used without serious adverse effects. We present a patient who developed bilateral white corneal deposits 5 days after beginning cyclosporine eyedrops. A 45-year-old woman was followed by a neighboring ophthalmologist because of dry eye syndrome caused by graft-versus-host disease after bone marrow transplantation for acute myelogenous leukemia. After transplantation, she was treated with systemic cyclosporine, and by topical physiological saline solution, 0.1% sodium hyaluronate, 0.3% ofloxacin, and 0.1% fluorometholone for dry eye syndrome. She was also treated with 0.4% oxybuprocaine for the relief of severe ocular pain. As the bilateral corneal epithelial defect persisted even after the application of punctal plugs, 2% cyclosporine distilled in olive oil was added as eyedrops 3 times a day bilaterally. Five days later, she complained of severe visual loss in association with bilateral corneal opacities and was referred to the Nagoya University Hospital (Nagoya, Japan) for analysis of the corneal deposits. On her initial examination, her visual acuity was hand motion bilaterally and the Schirmer test was RE: 2 mm and LE: 1 mm. Bilateral, dense, snow white corneal opacities formed a “niveau” about 4 mm below the upper limbus and covered the entire pupil. The opacities became gradually lighter toward the lower limbus (Figure 1). The opacities were associated with corneal neovascularization developing from the limbus and small epithelial defects in the central part of the cornea. As the patient did not agree to keratectomy, infrared spectroscopy and X-ray analysis were conducted on the deposits on the punctal plugs. The spectroscopic pattern of the deposits showed a pattern similar to that of cyclosporine (Figure 2A). Additionally, the deposits were found by X-ray analysis to be made up of carbon, oxygen, sodium sulfate, and chloride, whereas the control cyclosporine contained carbon and oxygen (Figure 2B). She is now followed at the Chikushi Hospital using therapeutic soft contact lenses and eyedrops of physiological saline solution. After 12 months, no improvement in the corneal findings has been noted. Unfortunately, we could not conduct an analysis on the corneal deposits. The history of the patient whose deposits appeared immediately after the topical use of cyclosporine and the results of the deposits on the punctal plugs strongly
BRIEF REPORTS
667