Vol. 110, No. 1
Letters to the Journal
plasty in both eyes. Additionally, both eyes underwent extracapsular cataract extraction with intraocular lens implantation and filtering procedure that required later YAG capsulotomy in both eyes. The capsulotomy in the left eye was uneventful. In the right eye, however, there were also dispersed pigment deposits on the anterior surface of the intraocular lens that were thought to contribute to the patient's complaint of glare. A combined posterior capsulotomy and pigment lysis was therefore performed with the Q-switched, Nd:YAG laser (29.6 m] aimed at the posterior capsule and 16 m] directed at the pigmented deposits). One drop of apraclonidine 1 % was instilled to the patient's eye before and at the end of the procedure. One hour later intraocular pressure was 20 mm Hg. The patient was instructed to administer prednisolone acetate 1 % drops three times daily to the operated on eye in addition to his glaucoma medications. The following morning he complained of ocular pain and marked reduction of vision in the right eye. On examination visual acuity was 20/300 and intraocular pressure was 60 mm Hg. He was treated with systemic hyperosmotic agents plus topical timolol and additional apraclonidine. Intraocular pressure remained in the mid 30s for the next 24 hours and then decreased to the low teens with recovery of 20/40 visual acuity on the third day after the procedure. No progression of visual field loss occurred, and one year later visual acuity was 20/25 and intraocular pressure was 13 mm Hg. The absence of an early postlaser pressure increase does not preclude a markedly increased intraocular pressure 24 to 48 hours later, even when apraclonidine is used at the time of the operation. We now recommend that patients with severe glaucomatous damage be seen not only early after these procedures, but also 24 hours later. Whether the high intraocular pressure measured after 24 hours represents a late pressure increase or a persistent rise that was attenuated by the apraclonidine cannot be determined. The marked increase in intraocular pressure observed in our patient may be related to the "extended procedure" that was actually a combination of posterior capsulotomy and pigment lysis from the anterior surface of the intraocular lens. Released pigment particles could have reached and obstructed the trabecular meshwork. Additionally, the shock waves created by aiming the beam at the pigment deposits on the anterior lens surface may also have caused damage to the trabeculum more
95
than in a typical posterior capsulotomy. where the intraocular lens serves as a barrier.
References 1. Stark, W. J., Worthen, D., Holladay, J. T., and Murray, G.: Neodymium:YAG lasers. An FDA report. Ophthalmology 92:209,1985. 2. Slomovic, A. R., and Parrish, R. K.: Acute elevations of intraocular pressure following Nd:YAG laser posterior capsulotomy. Ophthalmology 92:973, 1985. 3. Pollack, 1. P., Brown, R. H., Crandall, A. S., Robin, A. 1., Stewart, R. H., and White, G. 1.: Prevention of the rise in intraocular pressure following neodymium- YAG posterior capsulotomy using topicall % apraclonidine. Arch. Ophthalmol. 106:754, 1988.
The Onset of Malignant Glaucoma After Prophylactic Laser Iridotomy A. Robinson, M.D., M. Prialnic, M.D., D. Deutsch, M.D., and H. Savir, M.D.
Department of Ophthalmology, Golda Medical Center, Hasharon Hospital, and Sackler School of Medicine, Tel-Aviv University.
Inquiries to H. Savir, M.D., Hasharon Hospital, PetahTiqva, P.O. Box 121, Israel. A 43-year-old woman had bilateral glaucoma, since the age of 16 years, which progressed to absolute glaucoma in the right eye, and chronic closed-angle glaucoma in the left eye. Corrected visual acuity in the left eye was 20/30. The intraocular pressure was less than 20 mm Hg while using topical pilocarpine 4% every eight hours, timolol 0.5% every 12 hours, and acetazolamide (250 mg once daily). The central anterior chamber was deep and gonioscopy showed a slit-like open angle. The visual field was normal. Three months earlier the patient had undergone laser iridotomy in the left eye because of an intraocular pressure of 28 mm Hg and a closable angle. The intraocular pressure remained slightly increased (21 to 24 mm Hg) and the angle was closable, though the coloboma of the iris was patent. She was admitted to the ophthalmology department because of a sudden onset of pain and
96
AMERICAN JOURNAL OF OPHTHALMOLOGY
blurred vision in the left eye. Visual acuity was 20/100; the intraocular pressure was 38 mm Hg with mild conjunctival injection and a clear cornea. The anterior chamber was shallow; the pupil was 2 mm in diameter and not responsive to light. A patent iridotomy, incipient cataract, and normal fundus with cup/disk ratio of 0.6 were observed. Gonioscopy disclosed a completely closed angle. The patient was treated initially with hyperosmotic agents and topical pilocarpine 4%. After three days of unsuccessful medical treatment trabeculectomy was performed. Postoperatively the intraocular pressure rose to 45 mm Hg with a flat anterior chamber. Malignant glaucoma was diagnosed and intensive treatment with cycloplegics and mannitol was given. The anterior chamber did not reform and air was injected into the anterior chamber. This was followed two days later by pars plana vitrectomy with Healon injection to the anterior chamber. Despite transient improvement the pressure again rose with recurrent shallowing of the anterior chamber. Deep vitrectomy to aspirate the aqueous from the vitreous resulted in maintenance of normal intraocular pressure and a moderately deep anterior chamber. Two weeks later the intraocular pressure rose suddenly to 50 mm Hg, and a shallow anterior chamber was noted. Pars plana vitrectomy and lensectomy were successfully performed. Five months postoperatively the best-corrected visual acuity was 20/40. Slit-lamp examination of the left eye showed a clear cornea, deep anterior chamber, and intraocular pressure of 15 mm Hg without medical treatment. On reassessing the development of our patient's illness we think it is possible that the course of malignant glaucoma began after the prophylactic laser iridotomy that she had undergone three months previously. This could explain the lack of response to conventional treatment (pilocarpine and acetazolamide) that she received on admission. The administration of a cycloplegic at this stage might have prevented the progression of the malignant glaucoma and the ensuing surgical intervention.
Amantadine and Corneal Deposits F. T. Fraunfelder, M.D., and S. Martha Meyer, B.S. National Registry of Drug-Induced Ocular Side Effects. This study was supported in part by a grant from Research to Prevent Blindness, Inc., New York.
July, 1990
Inquiries to F. T. Fraunfelder, M.D., Department of Ophthalmology, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Rd., Portland OR 972013098. '
Amantadine hydrochloride (Symmetrel) is used in the management of Parkinson's disease, tardive dyskinesia, and the prophylaxis of influenza A2 (Asian) virus infections. Ocular side effects are rare; however, blurred vision, sudden loss of vision, colored lilliputian visual hallucinations, oculogyric crises, and mydriasis have been reported.l" These side effects appear to be dose-related and are reversible." The National Registry of Drug-Induced Ocular Side Effects has received nine case reports of corneal lesions associated with the use of oral amantadine hydrochloride. The corneal pattern seen in the affected patients was diffuse, white punctate subepithelial opacities, more prominent inferonasally, occasionally associated with a superficial punctate keratitis, corneal epithelial edema, and markedly reduced visual acuity. The dosage of amantadine was between 200 and 400 mg per day. The interval between therapy initiation and onset of the corneal reaction was one to two weeks. After discontinuation of drug use, the keratopathy disappeared in all patients usually in a few weeks; however, a six-week recovery period was necessary in one patient. Oral amantadine hydrochloride was reinstituted in two patients, and the corneal deposits recurred. A cause-and-effect relationship is highly likely, since the corneal deposits resolved upon removal of the drug, and recurred in both patients in whom it was reinstituted. The superficial corneal deposits, associated edema and superficial punctate keratitis suggest the presence of the drug in the tear film. A 10-JLI tear sample would contain 1.5 ng of amantadine hydrochloride, which is ten times lower than the assay limit of 20 ng (personal communication, E. I. DuPont DeNemours & Co., Newark, Delaware). Amantadine hydrochloride has, however, been found in other secreted fluids, such as saliva" and nasal mucus'> As with other oral agents, such as vitamin A,6 which are secreted from various glands, including the lacrimal glands, amantadine hydrochloride may be secreted in the tear film thereby causing corneal deposits and corneal irritation. There is a growing list of drugs" which are probably secreted by the lacrimal gland into the tear film. These drugs can cause corneal, conjunctival, or eyelid irritation, punctal occlusion, or corneal deposits based on the degree of toxicity of the offending drug. Amantadine hy-
Letters to the Journal
plasty in both eyes. Additionally, both eyes underwent extracapsular cataract extraction with intraocular lens implantation and filtering procedure that required later YAG capsulotomy in both eyes. The capsulotomy in the left eye was uneventful. In the right eye, however, there were also dispersed pigment deposits on the anterior surface of the intraocular lens that were thought to contribute to the patient's complaint of glare. A combined posterior capsulotomy and pigment lysis was therefore performed with the Q-switched, Nd:YAG laser (29.6 m] aimed at the posterior capsule and 16 m] directed at the pigmented deposits). One drop of apraclonidine 1 % was instilled to the patient's eye before and at the end of the procedure. One hour later intraocular pressure was 20 mm Hg. The patient was instructed to administer prednisolone acetate 1 % drops three times daily to the operated on eye in addition to his glaucoma medications. The following morning he complained of ocular pain and marked reduction of vision in the right eye. On examination visual acuity was 20/300 and intraocular pressure was 60 mm Hg. He was treated with systemic hyperosmotic agents plus topical timolol and additional apraclonidine. Intraocular pressure remained in the mid 30s for the next 24 hours and then decreased to the low teens with recovery of 20/40 visual acuity on the third day after the procedure. No progression of visual field loss occurred, and one year later visual acuity was 20/25 and intraocular pressure was 13 mm Hg. The absence of an early postlaser pressure increase does not preclude a markedly increased intraocular pressure 24 to 48 hours later, even when apraclonidine is used at the time of the operation. We now recommend that patients with severe glaucomatous damage be seen not only early after these procedures, but also 24 hours later. Whether the high intraocular pressure measured after 24 hours represents a late pressure increase or a persistent rise that was attenuated by the apraclonidine cannot be determined. The marked increase in intraocular pressure observed in our patient may be related to the "extended procedure" that was actually a combination of posterior capsulotomy and pigment lysis from the anterior surface of the intraocular lens. Released pigment particles could have reached and obstructed the trabecular meshwork. Additionally, the shock waves created by aiming the beam at the pigment deposits on the anterior lens surface may also have caused damage to the trabeculum more
95
than in a typical posterior capsulotomy. where the intraocular lens serves as a barrier.
References 1. Stark, W. J., Worthen, D., Holladay, J. T., and Murray, G.: Neodymium:YAG lasers. An FDA report. Ophthalmology 92:209,1985. 2. Slomovic, A. R., and Parrish, R. K.: Acute elevations of intraocular pressure following Nd:YAG laser posterior capsulotomy. Ophthalmology 92:973, 1985. 3. Pollack, 1. P., Brown, R. H., Crandall, A. S., Robin, A. 1., Stewart, R. H., and White, G. 1.: Prevention of the rise in intraocular pressure following neodymium- YAG posterior capsulotomy using topicall % apraclonidine. Arch. Ophthalmol. 106:754, 1988.
The Onset of Malignant Glaucoma After Prophylactic Laser Iridotomy A. Robinson, M.D., M. Prialnic, M.D., D. Deutsch, M.D., and H. Savir, M.D.
Department of Ophthalmology, Golda Medical Center, Hasharon Hospital, and Sackler School of Medicine, Tel-Aviv University.
Inquiries to H. Savir, M.D., Hasharon Hospital, PetahTiqva, P.O. Box 121, Israel. A 43-year-old woman had bilateral glaucoma, since the age of 16 years, which progressed to absolute glaucoma in the right eye, and chronic closed-angle glaucoma in the left eye. Corrected visual acuity in the left eye was 20/30. The intraocular pressure was less than 20 mm Hg while using topical pilocarpine 4% every eight hours, timolol 0.5% every 12 hours, and acetazolamide (250 mg once daily). The central anterior chamber was deep and gonioscopy showed a slit-like open angle. The visual field was normal. Three months earlier the patient had undergone laser iridotomy in the left eye because of an intraocular pressure of 28 mm Hg and a closable angle. The intraocular pressure remained slightly increased (21 to 24 mm Hg) and the angle was closable, though the coloboma of the iris was patent. She was admitted to the ophthalmology department because of a sudden onset of pain and
96
AMERICAN JOURNAL OF OPHTHALMOLOGY
blurred vision in the left eye. Visual acuity was 20/100; the intraocular pressure was 38 mm Hg with mild conjunctival injection and a clear cornea. The anterior chamber was shallow; the pupil was 2 mm in diameter and not responsive to light. A patent iridotomy, incipient cataract, and normal fundus with cup/disk ratio of 0.6 were observed. Gonioscopy disclosed a completely closed angle. The patient was treated initially with hyperosmotic agents and topical pilocarpine 4%. After three days of unsuccessful medical treatment trabeculectomy was performed. Postoperatively the intraocular pressure rose to 45 mm Hg with a flat anterior chamber. Malignant glaucoma was diagnosed and intensive treatment with cycloplegics and mannitol was given. The anterior chamber did not reform and air was injected into the anterior chamber. This was followed two days later by pars plana vitrectomy with Healon injection to the anterior chamber. Despite transient improvement the pressure again rose with recurrent shallowing of the anterior chamber. Deep vitrectomy to aspirate the aqueous from the vitreous resulted in maintenance of normal intraocular pressure and a moderately deep anterior chamber. Two weeks later the intraocular pressure rose suddenly to 50 mm Hg, and a shallow anterior chamber was noted. Pars plana vitrectomy and lensectomy were successfully performed. Five months postoperatively the best-corrected visual acuity was 20/40. Slit-lamp examination of the left eye showed a clear cornea, deep anterior chamber, and intraocular pressure of 15 mm Hg without medical treatment. On reassessing the development of our patient's illness we think it is possible that the course of malignant glaucoma began after the prophylactic laser iridotomy that she had undergone three months previously. This could explain the lack of response to conventional treatment (pilocarpine and acetazolamide) that she received on admission. The administration of a cycloplegic at this stage might have prevented the progression of the malignant glaucoma and the ensuing surgical intervention.
Amantadine and Corneal Deposits F. T. Fraunfelder, M.D., and S. Martha Meyer, B.S. National Registry of Drug-Induced Ocular Side Effects. This study was supported in part by a grant from Research to Prevent Blindness, Inc., New York.
July, 1990
Inquiries to F. T. Fraunfelder, M.D., Department of Ophthalmology, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Rd., Portland OR 972013098. '
Amantadine hydrochloride (Symmetrel) is used in the management of Parkinson's disease, tardive dyskinesia, and the prophylaxis of influenza A2 (Asian) virus infections. Ocular side effects are rare; however, blurred vision, sudden loss of vision, colored lilliputian visual hallucinations, oculogyric crises, and mydriasis have been reported.l" These side effects appear to be dose-related and are reversible." The National Registry of Drug-Induced Ocular Side Effects has received nine case reports of corneal lesions associated with the use of oral amantadine hydrochloride. The corneal pattern seen in the affected patients was diffuse, white punctate subepithelial opacities, more prominent inferonasally, occasionally associated with a superficial punctate keratitis, corneal epithelial edema, and markedly reduced visual acuity. The dosage of amantadine was between 200 and 400 mg per day. The interval between therapy initiation and onset of the corneal reaction was one to two weeks. After discontinuation of drug use, the keratopathy disappeared in all patients usually in a few weeks; however, a six-week recovery period was necessary in one patient. Oral amantadine hydrochloride was reinstituted in two patients, and the corneal deposits recurred. A cause-and-effect relationship is highly likely, since the corneal deposits resolved upon removal of the drug, and recurred in both patients in whom it was reinstituted. The superficial corneal deposits, associated edema and superficial punctate keratitis suggest the presence of the drug in the tear film. A 10-JLI tear sample would contain 1.5 ng of amantadine hydrochloride, which is ten times lower than the assay limit of 20 ng (personal communication, E. I. DuPont DeNemours & Co., Newark, Delaware). Amantadine hydrochloride has, however, been found in other secreted fluids, such as saliva" and nasal mucus'> As with other oral agents, such as vitamin A,6 which are secreted from various glands, including the lacrimal glands, amantadine hydrochloride may be secreted in the tear film thereby causing corneal deposits and corneal irritation. There is a growing list of drugs" which are probably secreted by the lacrimal gland into the tear film. These drugs can cause corneal, conjunctival, or eyelid irritation, punctal occlusion, or corneal deposits based on the degree of toxicity of the offending drug. Amantadine hy-
