Vol. 113, No. 3
Letters to The Journal
therapy before culture results was as follows: fortified tobramycin 15 m g / m l and cefazolin 33.3 mg/ml, one drop of each in the right eye every 30 minutes around the clock, and homatropine, one drop twice a day in the right eye. In 24 hours, cultures of the ulcer and the contact-lens case grew Pseudomonas aeruginosa sensitive to gentamicin, mezlocillin, and ciprofloxacin. The right cornea showed a 360-degree ring infiltrate together with deep Descemet's folds and diffuse central deep corneal haze. Less than 24 hours later a descemetocele was visible. Corneal transplantation was performed promptly on the same day. An 11-mm donor button was sutured into an 11-mm recipient bed. Trephination of the perforated cornea was done with cyanoacrylate adhesive and sodium hyaluronate. 2 On the first postoperative day, uncorrected right visual acuity was hand movements at 1 m. The anterior chamber showed a microscopic hyphema, but no evidence of recurrence of the infection was evident. Tobramycin and ceftazidime eyedrops were administered hourly around the clock. Forty-eight hours postoperatively, prednisolone sodium acetate eyedrops were added four times a day to the right eye. The patient was discharged on the fifth postop erative day and was followed up on an outpa tient basis. Six months after surgery (Figure), the patient had a clear graft and was not taking medications. Best-corrected visual acuity with spectacles was 20/30 + 2 . Pseudomonas corneal ulcers have previously been documented in neutropenic patients in fected with HIV.1 The rapidly progressive course in this patient with required prompt
337
surgical intervention, which enabled the resto ration of vision. This case illustrates the risk of contact-lens wear in the patient positive for HIV with mini mal symptoms and signs of the disease. This patient wore a gas-permeable, daily-wear lens. This mode of lens wear has relatively low risk for contracting corneal ulcers. 3 Even though it is difficult to speculate on the possible inci dence of corneal ulcers in this group of pa tients, it is clear from the cases described in the literature that a patient infected with HIV who contracts a Pseudomonas corneal ulcer will probably have a fulminant course, and will be at extremely high risk of losing the involved eye.
References 1. Nanda, M., Pflugfelder, S. C, and Holland, S.: Fulminant pseudomonal keratitis and scleritis in hu man immunodeficiency virus-infected patients. Arch. Ophthalmol. 109:503, 1991. 2. MacRae, S., Herman, C , Stulting, R. D., Lippman, R., Whipple, D., Wilkinson, C. P., Scott, C, Smith, R. E., and Phillips, D.: Corneal ulcer and adverse reaction rate in premarket contact lens stud ies. Am. J. Ophthalmol. 111:457, 1991. 3. Maguen, E., Nesburn, A. B., and Macy, J. I.: Combined use of sodium hyaluronate and tissue adhesive in penetrating keratoplasty of corneal per forations. Ophthalmic Surg. 15:55, 1984.
Crystalline Keratopathy and Epikeratophakia Steven B. Brooks, M.D., Leslie Bruce-Lyle, M.D., Narsing A. Rao, M.D., and Kenneth W. Wright, M.D. Department of Ophthalmology, University of South ern California School of Medicine and Doheny Eye Institute (S.B.B., L.B.-L., N.A.R., K.W.W.); and Divi sion of Ophthalmology, Childrens Hospital of Los Angeles (K.W.W.).
Figure (Maguen, Salz, and Nesburn). Penetrating keratoplasty six months postoperatively.
Inquiries to Kenneth W. Wright, M.D., Division of Ophthalmology, Childrens Hospital of Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027. Infectious crystalline keratopathy was first described by Gorovoy and associates 1 in 1983.
338
AMERICAN JOURNAL OF OPHTHALMOLOGY
They reported the development of unusual crystalline-appearing, needle-like stromal opac ities in a corneal graft six months after surgery. Since then, other cases of one small series have been reported in the literature. 2,3 Most cases have occurred in grafts after penetrating keratoplasty and, in almost all instances, the pa tients have been treated with topical corticosteroids on a long-term basis. In the majority of patients in whom positive cultures were ob tained, Streptococcus viridans was found, al though other bacteria and even fungi and calci um have been implicated. 34 We encountered infectious crystalline keratopathy in a young child one month after epikeratophakia for the treatment of unilateral aphakia. Of particular note in this case is that the patient had not been treated with topical corticosteroids before the development of this lesion. On July 24, 1990, a 28-month-old boy under went lensectomy and anterior vitrectomy for unilateral posterior lenticonus and mild, persis tent, primary hyperplastic vitreous. After re peated failures at contact-lens use, he under went epikeratophakia on April 15, 1991. The graft was +18.00 diopters, 8.5 mm lenticular, and lathed from lyophilized donor tissue. The procedure was uncomplicated and, postoperatively, the patient was treated with bacitracin ointment and full-time pressure patching; topi cal corticosteroids were not used. Although the graft remained clear, it failed to re-epithelialize fully, leaving a small, persistent epithelial de fect. A bandage contact lens was applied on May 13, 1991, and treatment with sodium sulfacetamide, 10% drops four times a day, was started. Four days later, a diffuse stromal haze, without focal infiltrate, was present in the graft. The central epithelial defect remained. The bandage contact lens was removed, and cul tures were taken. Three days later, the status of the graft was unchanged and, while the patient was under chloral hydrate sedation, several sutures were removed because of associated vascular growth. A single-suture lateral tarsorrhaphy was performed in an attempt to promote epithelial healing. Culture results on the mate rial obtained three days previously showed light growth of alpha-hemolytic Streptococcus organisms, but this was considered a contami nant. Because of the difficulty in examining the patient in the clinic, on May 28 he was exam ined under general anesthesia, and the graft was removed. Material from the graft-host in
March, 1992
terface was submitted for cultures for bacteria and fungi. The removed lenticula was fixed in 4% formaldehyde solution and processed for histopathologic examination. Subconjunctival injections of gentamicin and cefuroxime were given at the conclusion of the operation, and treatment with topical fortified cefazolin and gentamicin was begun. Cultures of the graft-host interface were posi tive for S. viridans and aerobic diphtheroids. Histopathologic examinations of the lenticula disclosed corneal stroma without nuclei. There were numerous foci of gram-positive cocci se questered between anterior stromal lamellae (Figure). Although occasional acute and chron ic inflammatory cells were present in the deeper portions of the tissue, the clusters of bacteria were free from any associated inflammatory infiltrate. The histopathologic diagnosis of crystalline keratopathy in the epikeratophakia graft was made. The topical treatment was changed to fortified vancomycin, which cov ered both S. viridans and aerobic diphtheroids. After ten days of antibiotic treatment, and after four cultures were reported as negative, treat ment with dexamethasone 0.1% was instituted to reduce corneal stromal scarring and corneal vascularization. The cornea slowly re-epithelialized and by two months was relatively clear with a good red reflex and only a faint stromal haze.
TZ~" Figure (Brooks and associates). Photomicrograph of corneal stroma from the removed epikeratophakia graft. Numerous gram-positive cocci are present within the lamellae of the cornea stroma, but there is an absence of cellular infiltration (Gram stain, x 630).
Letters to The Journal
Vol. 113, No. 3
The pathogenesis of infectious crystalline keratopathy is unclear. Long-term use of topi cal corticosteroids has been thought to play an important role by causing sufficient local immunosuppression to allow intracorneal growth of bacteria with essentially no host inflammato ry response. 1,3 The role of bacterial factors has also been considered important, both in terms of limiting the inflammatory or immune stimu lus and decreasing the effectiveness of antibiot ic treatment. The production of a biofilm mate rial (for example, dextran) by the bacteria may limit their immunogenicity as well as drug penetrability. 6 Of interest in our case was the absence of any treatment with corticosteroids. Since our pa tient was immunocompetent, we concluded that in epikeratophakia, at least when lyophilized tissue is used, topical corticosteroids are not necessary for the development of crystal line lesions. We speculated that the lyophilized graft, being a devitalized tissue, provides the initial environment in which bacteria can mul tiply, free of a host response. This environ ment, together with various factors related to the bacteria themselves (for example, dextran production), may then allow the development of diffuse stromal opacity.
References 1. Gorovoy, M. S., Stern, G. A., Hood, I., and Allen, C : Intrastromal noninflammatory bacterial colonization of a corneal graft. Arch. Ophthalmol. 101:1749, 1983. 2. Reiss, G. R., Campbell, R. J., and Bourne, W. M.: Infectious crystalline keratopathy. Surv. Ophthalmol. 31:69, 1986. 3. Nanda, M., Soong, H. K., Krenz, M. P., and Green, W. R.: Intracorneal bacterial colonization in a crystalline pattern. Graefes Arch. Clin. Exp. Oph thalmol. 224:251, 1986. 4. Zabel, R. W., Mintsioulis, G., MacDonald, I., and Tuft, S.: Infectious crystalline keratopathy. Can. ]. Ophthalmol. 23:311, 1988. 5. Ormerod, L. D., and Meisler, D. M.: Bacterial factors in the pathogenesis of infectious crystalline keratopathy. ARVO abstracts. Supplement to Invest. Ophthalmol. Vis. Sci. Philadelphia, J. B. Lippincott, 1991, p. 1166.
339
Unilateral Corneal Vesicles Secondary to Dipivefrin Therapy D e n i s e Satterfield, M.D., Mark J. M a n n i s , M.D., and A. Tyrone Glover, M.D. Department of Ophthalmology, University of Cali fornia, Davis. Inquiries to Mark }. Mannis, M.D., 1603 Alhambra Blvd., Sacramento, CA 95816. Ocular and systemic side effects secondary to dipivefrin hydrochloride therapy are reported ly rare. We encountered an unusual case of unilateral corneal vesicles believed to be secon dary to dipivefrin therapy. A 41-year-old man was referred to our insti tution because of recent onset of monocular diplopia and blurring in the left eye, most marked in the late afternoon and evening. Mixed mechanism glaucoma had been diag nosed two years previously. The patient had been treated during this period with pilocarpine gel in both eyes. Three months previously, dipivefrin 0.1% therapy had been started in the left eye only. However, because of visual symp toms, the patient discontinued it just before being examined by us. On ocular examination, visual acuity was 20/20 in both eyes. Multiple, fine, intraepithelial vesicles in the paracentral cornea of the left eye were seen (Figure). The stroma and endothelium were normal. These lesions in the left eye appeared to be similar to the vesicles seen in Meesman's corneal dystrophy. The right cor nea was normal, as were results of the rest of the ocular examination. The vesicles and symp toms of blurring and monocular diplopia re solved two months after the discontinuation of the dipivefrin. Dipivefrin hydrochloride ophthalmic solu tion, USP 0.1%, has been marketed since 1980. Side effects of the drug include red eye, head ache, ocular pain, dilated pupil and blurred vision, blepharoconjunctivitis, follicular con junctivitis, papillary conjunctivitis, and rarely, corneal toxicity.1"3 Allergan Pharmaceuticals has received a few reports of corneal toxicity, including one of corneal edema, one of dendritic keratitis, four cases of punctate keratitis, and one case of epitheliopathy (written communication, Arlene Gwon, M.D., Allergan Pharmaceuticals, Octo ber 1990). There is one case report in the
Letters to The Journal
therapy before culture results was as follows: fortified tobramycin 15 m g / m l and cefazolin 33.3 mg/ml, one drop of each in the right eye every 30 minutes around the clock, and homatropine, one drop twice a day in the right eye. In 24 hours, cultures of the ulcer and the contact-lens case grew Pseudomonas aeruginosa sensitive to gentamicin, mezlocillin, and ciprofloxacin. The right cornea showed a 360-degree ring infiltrate together with deep Descemet's folds and diffuse central deep corneal haze. Less than 24 hours later a descemetocele was visible. Corneal transplantation was performed promptly on the same day. An 11-mm donor button was sutured into an 11-mm recipient bed. Trephination of the perforated cornea was done with cyanoacrylate adhesive and sodium hyaluronate. 2 On the first postoperative day, uncorrected right visual acuity was hand movements at 1 m. The anterior chamber showed a microscopic hyphema, but no evidence of recurrence of the infection was evident. Tobramycin and ceftazidime eyedrops were administered hourly around the clock. Forty-eight hours postoperatively, prednisolone sodium acetate eyedrops were added four times a day to the right eye. The patient was discharged on the fifth postop erative day and was followed up on an outpa tient basis. Six months after surgery (Figure), the patient had a clear graft and was not taking medications. Best-corrected visual acuity with spectacles was 20/30 + 2 . Pseudomonas corneal ulcers have previously been documented in neutropenic patients in fected with HIV.1 The rapidly progressive course in this patient with required prompt
337
surgical intervention, which enabled the resto ration of vision. This case illustrates the risk of contact-lens wear in the patient positive for HIV with mini mal symptoms and signs of the disease. This patient wore a gas-permeable, daily-wear lens. This mode of lens wear has relatively low risk for contracting corneal ulcers. 3 Even though it is difficult to speculate on the possible inci dence of corneal ulcers in this group of pa tients, it is clear from the cases described in the literature that a patient infected with HIV who contracts a Pseudomonas corneal ulcer will probably have a fulminant course, and will be at extremely high risk of losing the involved eye.
References 1. Nanda, M., Pflugfelder, S. C, and Holland, S.: Fulminant pseudomonal keratitis and scleritis in hu man immunodeficiency virus-infected patients. Arch. Ophthalmol. 109:503, 1991. 2. MacRae, S., Herman, C , Stulting, R. D., Lippman, R., Whipple, D., Wilkinson, C. P., Scott, C, Smith, R. E., and Phillips, D.: Corneal ulcer and adverse reaction rate in premarket contact lens stud ies. Am. J. Ophthalmol. 111:457, 1991. 3. Maguen, E., Nesburn, A. B., and Macy, J. I.: Combined use of sodium hyaluronate and tissue adhesive in penetrating keratoplasty of corneal per forations. Ophthalmic Surg. 15:55, 1984.
Crystalline Keratopathy and Epikeratophakia Steven B. Brooks, M.D., Leslie Bruce-Lyle, M.D., Narsing A. Rao, M.D., and Kenneth W. Wright, M.D. Department of Ophthalmology, University of South ern California School of Medicine and Doheny Eye Institute (S.B.B., L.B.-L., N.A.R., K.W.W.); and Divi sion of Ophthalmology, Childrens Hospital of Los Angeles (K.W.W.).
Figure (Maguen, Salz, and Nesburn). Penetrating keratoplasty six months postoperatively.
Inquiries to Kenneth W. Wright, M.D., Division of Ophthalmology, Childrens Hospital of Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027. Infectious crystalline keratopathy was first described by Gorovoy and associates 1 in 1983.
338
AMERICAN JOURNAL OF OPHTHALMOLOGY
They reported the development of unusual crystalline-appearing, needle-like stromal opac ities in a corneal graft six months after surgery. Since then, other cases of one small series have been reported in the literature. 2,3 Most cases have occurred in grafts after penetrating keratoplasty and, in almost all instances, the pa tients have been treated with topical corticosteroids on a long-term basis. In the majority of patients in whom positive cultures were ob tained, Streptococcus viridans was found, al though other bacteria and even fungi and calci um have been implicated. 34 We encountered infectious crystalline keratopathy in a young child one month after epikeratophakia for the treatment of unilateral aphakia. Of particular note in this case is that the patient had not been treated with topical corticosteroids before the development of this lesion. On July 24, 1990, a 28-month-old boy under went lensectomy and anterior vitrectomy for unilateral posterior lenticonus and mild, persis tent, primary hyperplastic vitreous. After re peated failures at contact-lens use, he under went epikeratophakia on April 15, 1991. The graft was +18.00 diopters, 8.5 mm lenticular, and lathed from lyophilized donor tissue. The procedure was uncomplicated and, postoperatively, the patient was treated with bacitracin ointment and full-time pressure patching; topi cal corticosteroids were not used. Although the graft remained clear, it failed to re-epithelialize fully, leaving a small, persistent epithelial de fect. A bandage contact lens was applied on May 13, 1991, and treatment with sodium sulfacetamide, 10% drops four times a day, was started. Four days later, a diffuse stromal haze, without focal infiltrate, was present in the graft. The central epithelial defect remained. The bandage contact lens was removed, and cul tures were taken. Three days later, the status of the graft was unchanged and, while the patient was under chloral hydrate sedation, several sutures were removed because of associated vascular growth. A single-suture lateral tarsorrhaphy was performed in an attempt to promote epithelial healing. Culture results on the mate rial obtained three days previously showed light growth of alpha-hemolytic Streptococcus organisms, but this was considered a contami nant. Because of the difficulty in examining the patient in the clinic, on May 28 he was exam ined under general anesthesia, and the graft was removed. Material from the graft-host in
March, 1992
terface was submitted for cultures for bacteria and fungi. The removed lenticula was fixed in 4% formaldehyde solution and processed for histopathologic examination. Subconjunctival injections of gentamicin and cefuroxime were given at the conclusion of the operation, and treatment with topical fortified cefazolin and gentamicin was begun. Cultures of the graft-host interface were posi tive for S. viridans and aerobic diphtheroids. Histopathologic examinations of the lenticula disclosed corneal stroma without nuclei. There were numerous foci of gram-positive cocci se questered between anterior stromal lamellae (Figure). Although occasional acute and chron ic inflammatory cells were present in the deeper portions of the tissue, the clusters of bacteria were free from any associated inflammatory infiltrate. The histopathologic diagnosis of crystalline keratopathy in the epikeratophakia graft was made. The topical treatment was changed to fortified vancomycin, which cov ered both S. viridans and aerobic diphtheroids. After ten days of antibiotic treatment, and after four cultures were reported as negative, treat ment with dexamethasone 0.1% was instituted to reduce corneal stromal scarring and corneal vascularization. The cornea slowly re-epithelialized and by two months was relatively clear with a good red reflex and only a faint stromal haze.
TZ~" Figure (Brooks and associates). Photomicrograph of corneal stroma from the removed epikeratophakia graft. Numerous gram-positive cocci are present within the lamellae of the cornea stroma, but there is an absence of cellular infiltration (Gram stain, x 630).
Letters to The Journal
Vol. 113, No. 3
The pathogenesis of infectious crystalline keratopathy is unclear. Long-term use of topi cal corticosteroids has been thought to play an important role by causing sufficient local immunosuppression to allow intracorneal growth of bacteria with essentially no host inflammato ry response. 1,3 The role of bacterial factors has also been considered important, both in terms of limiting the inflammatory or immune stimu lus and decreasing the effectiveness of antibiot ic treatment. The production of a biofilm mate rial (for example, dextran) by the bacteria may limit their immunogenicity as well as drug penetrability. 6 Of interest in our case was the absence of any treatment with corticosteroids. Since our pa tient was immunocompetent, we concluded that in epikeratophakia, at least when lyophilized tissue is used, topical corticosteroids are not necessary for the development of crystal line lesions. We speculated that the lyophilized graft, being a devitalized tissue, provides the initial environment in which bacteria can mul tiply, free of a host response. This environ ment, together with various factors related to the bacteria themselves (for example, dextran production), may then allow the development of diffuse stromal opacity.
References 1. Gorovoy, M. S., Stern, G. A., Hood, I., and Allen, C : Intrastromal noninflammatory bacterial colonization of a corneal graft. Arch. Ophthalmol. 101:1749, 1983. 2. Reiss, G. R., Campbell, R. J., and Bourne, W. M.: Infectious crystalline keratopathy. Surv. Ophthalmol. 31:69, 1986. 3. Nanda, M., Soong, H. K., Krenz, M. P., and Green, W. R.: Intracorneal bacterial colonization in a crystalline pattern. Graefes Arch. Clin. Exp. Oph thalmol. 224:251, 1986. 4. Zabel, R. W., Mintsioulis, G., MacDonald, I., and Tuft, S.: Infectious crystalline keratopathy. Can. ]. Ophthalmol. 23:311, 1988. 5. Ormerod, L. D., and Meisler, D. M.: Bacterial factors in the pathogenesis of infectious crystalline keratopathy. ARVO abstracts. Supplement to Invest. Ophthalmol. Vis. Sci. Philadelphia, J. B. Lippincott, 1991, p. 1166.
339
Unilateral Corneal Vesicles Secondary to Dipivefrin Therapy D e n i s e Satterfield, M.D., Mark J. M a n n i s , M.D., and A. Tyrone Glover, M.D. Department of Ophthalmology, University of Cali fornia, Davis. Inquiries to Mark }. Mannis, M.D., 1603 Alhambra Blvd., Sacramento, CA 95816. Ocular and systemic side effects secondary to dipivefrin hydrochloride therapy are reported ly rare. We encountered an unusual case of unilateral corneal vesicles believed to be secon dary to dipivefrin therapy. A 41-year-old man was referred to our insti tution because of recent onset of monocular diplopia and blurring in the left eye, most marked in the late afternoon and evening. Mixed mechanism glaucoma had been diag nosed two years previously. The patient had been treated during this period with pilocarpine gel in both eyes. Three months previously, dipivefrin 0.1% therapy had been started in the left eye only. However, because of visual symp toms, the patient discontinued it just before being examined by us. On ocular examination, visual acuity was 20/20 in both eyes. Multiple, fine, intraepithelial vesicles in the paracentral cornea of the left eye were seen (Figure). The stroma and endothelium were normal. These lesions in the left eye appeared to be similar to the vesicles seen in Meesman's corneal dystrophy. The right cor nea was normal, as were results of the rest of the ocular examination. The vesicles and symp toms of blurring and monocular diplopia re solved two months after the discontinuation of the dipivefrin. Dipivefrin hydrochloride ophthalmic solu tion, USP 0.1%, has been marketed since 1980. Side effects of the drug include red eye, head ache, ocular pain, dilated pupil and blurred vision, blepharoconjunctivitis, follicular con junctivitis, papillary conjunctivitis, and rarely, corneal toxicity.1"3 Allergan Pharmaceuticals has received a few reports of corneal toxicity, including one of corneal edema, one of dendritic keratitis, four cases of punctate keratitis, and one case of epitheliopathy (written communication, Arlene Gwon, M.D., Allergan Pharmaceuticals, Octo ber 1990). There is one case report in the
