| OCR Text |
Show Journal of hleuro- Ophthalmology 15( i): 209- 211, 1995. © 1995 Lippincott- Raven Publishers, Philadelphia Recovery from Ocular Ischemic Syndrome After Treatment with Verapamil Jacqueline M. S. W i n t e r k o r n , Ph. D., M . D . , and Richard L. Beckman, M . D . Vasospasm has been implicated as a cause of amaurosis fugax, which can be controlled by administration of the calcium channel blockers nifedipine or verapamil. However/ vasospasm has not previously been thought to be involved in chronic ocular ischemia. We report a patient with ocular ischemic syndrome, which may have had vasospasm as a contributing cause, since the patient also developed amaurosis fugax despite daily aspirin therapy. An 80- year- old man with chronic open- angle glaucoma developed chronic ocular ischemia characterized by progressively decreased visual acuity, pain, rubeosis, and hypotony, as well as transient visual dimming. Medical evaluation revealed no evidence of carotid stenosis, thromboembolism, or vasculitis as the cause of ocular ischemia. When the calcium channel blocker verapamil was administered, the episodes of transient visual dimming ceased immediately. In addition, soon thereafter, visual acuity improved, the rubeosis partially regressed, and the hypotony reversed. This case indicates that the calcium channel blocker verapamil may be effective in treating cases of ocular ischemic syndrome, when vasospasm is a contributing cause. Ocular ischemic syndrome is a condition in which hypoperfusion of the globe leads to acute and chronic defects in ocular tissues. Decreasing vision is usually accompanied by ocular pain. Other signs of ischemia in the eye include corneal clouding, uveitis, and anterior and posterior segment neovascularization. Intraocular pressure frequently is low, reflecting insufficient perfusion of the ciliary body. The most common causes of ocular ischemic syndrome include stenosis, thromboembolism, and vasculitis of the carotid artery or its branch to the eye, the ophthalmic artery. Vasospasm, which underlies some cases of amaurosis fugax or transient visual loss ( 1- 3), has not previously been implicated as a contributing cause of chronic ocular ischemic syndrome. We describe a patient with a history of chronic open- angle glaucoma, in whom ocular ischemic syndrome was diagnosed when he developed progressive visual loss and ocular pain and was found to have rubeosis and hypotony. The patient experienced superimposed episodes of transient visual dimming. The absence of a fixed vascular lesion and the recurrence of amaurosis fugax suggested a vasospastic component ( 1,2), and the calcium channel blocker verapamil was started. Not only did the episodes of transient visual dimming cease, but soon thereafter the visual acuity improved, the rubeosis partially regressed, and the intraocular pressure returned to elevated levels. These signs indicated successful medical treatment of ocular ischemic syndrome. Manuscript, received February 15, 1995. From the Departments of Ophthalmology and Neurology & Neuroscience, Cornell University Medical Center, New York, New York 11030, U. S. A. Address correspondence and reprint requests to Dr. J, M. S. Winterkorn, Neuro- Ophthalmology, 900 Northern Boulevard, Great Neck, NY 11201, U. S. A. CASE REPORT An 80- year- old man with mild hypertension had undergone four surgical procedures for pseudoex-foliative glaucoma in the left eye. Four years prior to this evaluation, combined cataract extraction 209 210 /. M. S. WINTERKORN AND R. L. BECKMAN and trabeculectomy were performed on his left eye. The trabeculectomy failed, and the intraocular pressure remained elevated. Two years later, the patient underwent a second trabeculectomy in his left eye at another site, which also failed. A few months later, a revision of the trabeculectomy was attempted, using peribulbar injections of 5- fluoro-uracil ( 5FU). This procedure also failed to lower intraocular pressure. Finally, a year later, the patient received an erbium- YAG laser sclerostomy, but subsequently still required pressure- lowering medication, including systemic Diamox and topical pilocarpine and Timoptic. The intraocular pressure in the left eye remained between 22 and 25. Eight months following his last surgical procedure for glaucoma, the patient reported an episode of amaurosis fugax in the left eye with visual loss lasting 10 min. Medical evaluation, including carotid duplex scanning and echocardiography, revealed no structural abnormality in the heart or carotid vasculature, and the patient was treated with daily aspirin 325 mg. A month later, the patient complained of decreasing vision and an ache in his left eye. Visual acuity in the left eye, which had been 20/ 25, was now 20/ 100. Slit- lamp examination of the left anterior chamber revealed mild iritis. Iris neovascularization was evident, continuing into the anterior chamber angle, but without angle closure. Retinal neovascularization was not seen on funduscopy or demonstrated on fluorescein angiography, although the fluorescein angiogram of the left eye did demonstrate delayed filling in the arterial phase. The right eye continued to have a normal examination with 20/ 20 visual acuity, full visual field, unremarkable slit- lamp examination, and intraocular pressure of 12 mm Hg without medication. In the left eye, intraocular pressure was down to 17 mm Hg. Further medical workup did not reveal a cause for the left ocular ischemic syndrome. Blood tests were normal, including those for hypercoagulability ( complete blood count, Westergren sedimentation rate, blood chemistries, anti- nuclear antibody, anti- cardiolipin antibody, protein C, protein S, factor VIII, anti- phosphotidylcholine and - serine). Neither carotid stenosis nor significant plaque were demonstrated on magnetic resonance imaging or magnetic resonance angiography. Bilateral temporal artery biopsies were negative. The iritis did not resolve with topical steroid therapy, and the intraocular pressure progressively fell despite decreasing glaucoma medication, until it stabilized at 12 mm Hg after all medications for glaucoma had been discontinued. The patient continued to take 350 mg of aspirin daily, and diltiazem for hypertension. His condition did not improve over the next four months: examination of the left eye continued to show visual acuity of 20/ 100, rubeosis, and intraocular pressure decreased to 12 mm Hg off all glaucoma medication. The patient then reported several episodes of amaurosis fugax in the left eye, consisting of darkening of his vision over ~ 3 min to total visual blackout and followed by resolution to baseline. No visual disturbance occurred in the right eye. In a patient with neither carotid stenosis nor an embolic source, these recurrent episodes of amaurosis fugax despite daily aspirin therapy suggested the diagnosis of vasospasm in the circulation of the anterior visual pathways ( 1). After discussion with the patient's internist, the calcium channel blocker verapamil, previously demonstrated to be clinically beneficial in patients with amaurosis fugax of vasospastic etiology ( 2), was substituted for diltiazem. Verapamil was prescribed in slow- release form 120 mg twice daily. No significant change was seen in blood pressure control on periodic office measurements or on an ambulatory 24- h monitoring. No further episodes of amaurosis fugax occurred, and the pain in the left eye resolved. On examination two weeks later, the patient reported improved vision in his left eye, and examination recorded visual acuity of 20/ 50 + OS. Examinations during the succeeding weeks found regression of the rubeosis. The intraocular pressure rose again to the low 20s and required reinstitution of antiglaucoma therapy. The patient's improved condition has been stable now for two years. DISCUSSION This case provides support for the hypothesis that vasospasm in the ocular circulation contributes to visual loss and that calcium channel blockers may be effective in treating ocular conditions caused by vasospasm. Prior reports ( 1,2) have indicated that vasospasm may precipitate amaurosis fugax in some patients. Patients with amaurosis fugax whose medical evaluation did not demonstrate an embolic source and whose attacks did not resolve with antiplatelet or anticoagulating agents experienced cessation of amaurotic attacks immediately upon treatment with a therapeutic dose of nifedipine or verapamil. Furthermore, when the medication was discontinued, the symptom recurred until the medication was restarted. The patient described here, like the patients previously reported with vasospastic amaurosis fugax, had no further attacks of transient visual loss after starting therapy with verapamil. In addi- / Nemo- Ophthalmol, Vol. 15, No. 4, 1995 OCULAR ISCHEMIC SYNDROME AND VASOSPASM 111 tion, soon after starting verapamil, this patient experienced reversal or relief of chronic symptoms and signs of ocular ischemia, including improvement in visual acuity, resolution of iritis, regression of rubeosis, and elevation of intraocular pressure by 10 mm Hg, all suggesting increased ocular perfusion. In this patient, the calcium channel blocker verapamil was apparently successful at reversing ocular ischemia, even though another calcium channel blocker prescribed for treatment of hypertension, diltiazem, had not proven protective. This observation is consistent with the pharmacology of calcium channel blockers ( 3), a widely diverse family of agents differing in therapeutic mechanism and efficacy at different sites of action. The effects of calcium channel blockers have been ascribed to their capacity to reduce toxic levels of intracellular calcium, stabilize membranes, and increase perfusion by vasodilating and to their interaction with intracellular messengers, cyclic nucleotides, and neurotransmitters. At least two types and four subtypes of biochemically unique calcium channels have been identified in several tissues, acting differently to pump calcium out of cells in the event of tissue destruction. Calcium channel blockers differ in their ability to recognize and to modulate these distinct calcium channels in various tissues. But while the presence of extracellular calcium and its influx into cells during anoxia are critical in producing neuronal damage, that influx in vitro does not seem to take place through dedicated calcium channels, but rather through a sodium- calcium ion exchanger, in part explaining why calcium channel blockers have not provided effective protection against glaucoma and ischemic optic neuropathies. In addition, they also differ importantly in the degree to which they influence other neurotransmitter systems, for example, by alpha stimulation, beta blocking, and postsynaptic modulation ( 3- 6). Such differences may underlie the contrary and controversial results obtained using different calcium channel blockers in studies attempting to improve ocular blood flow in chronic open- angle glaucoma and low- tension glaucoma ( 7,8). Whereas nifedipine and verapamil have been reported to decrease intraocular pressure, leading to stabilization or improvement of visual field in chronic open- angle glaucoma ( 9), trials with other calcium channel blockers have been inconclusive. So far, diltiazem has not proven effective in treating ocular conditions. Therefore, possible reasons for the superior response of this patient's ocular problems to verapamil compared with diltiazem, while at the same time achieving comparable blood pressure control, include the greater influence of verapamil on ocular circulation and the relative cardioselectivity of diltiazem, the effect of verapamil on both alpha- 1 and alpha- 2 adrenergic receptors, and the greater potency of verapamil, resulting in its acting as a stronger vasodilator at much lower doses than diltiazem. This case suggests that vasospasm may play a role in ocular conditions caused by ischemia and that calcium channel blockers may provide effective therapy for such conditions. The clinical success of calcium channel blockers in the treatment of diseases involving ocular ischemia will depend upon the wise or fortunate choice among agents to be tested in clinical trials, This choice should be based upon understanding of biochemical interaction with a variety of receptors in ocular structures, some of which have yet to be defined. Acknowledgment: The authors appreciate the technical assistance of Deborah Siegel Humanitzki. REFERENCES 1. Winterkorn JMS, Teman AJ. Recurrent attacks of amaurosis fugax treated with calcium channel blocker. Ann Neurol 1991; 30: 423- 5. 2. Winterkorn JMS, Kupersmith M, Wirtschafter JD, Forman S. Treatment of vasospastic amaurosis fugax with calcium channel blockers. N Engl J Med 1993; 329: 396- 8. 3. Gilman AG, Rail TW, Nies AS, Taylor P. Goodman and Git-man's The Pharmacological Basis of Therapeutics. Eimsford, NY: Pergamon Press, 1993. 4. Braunwald E. Mechanism of action of calcium- channel-blocking agents. N Engl } Med 1982; 307: 1618- 27. 5. Skarby TVC, Hogestatt ED. Differential effects of calcium channel antagonists and BayK 8644 on contractile responses to exogenous noradrenaline and adrenergic nerve stimulation in the rabbit ear artery. Br / Pharmacol 1990; 101 ( 4): 961- 7. 6. Pednnelli R, Saivetti S. Heterogeneous interference of nicardipine, verapamil, and diltiazem with forearm responsiveness to adrenergic stimulation in hypertensive patients. Am Heart } 1991; 122: 342- 51. 7. Schumer RA, Podos SM, The nerve of glaucoma! Arch Ophthalmol 1994; 112: 37- 44. 8. Netland PA, Chaturvedi N, Dreyer EB. Calcium channel blockers in the management of low- tension and open- angle glaucoma. Am ] Ophthalmol 1993; 155: 608- 16. 9. Gaspar AX, Flammer J, Hendrickson P, Influence of nifedipine on the visual fields of patients with optic- nerve- head diseases. Eur J Ophthalmol 1992; 4( l): 24- 8. / Neuro- Ophthalmol, Vol. 15, No. 4, 1995 |
