Journal of Neuro-Ophthalmology, March 1992, Volume 12, Issue 1

Herpes zoster ophthalmicus. Anterior ischemic optic neuropathy and acyclovir.

A healthy 56-year-old man developed left-sided herpes zoster ophthalmicus, accompanied initially by ipsilateral anterior uveitis and increased intraocular pressure. Although he was treated in the subacute phase (5 days after skin eruption) with adequate oral doses of acyclovir for 10 days, the condition was later complicated by a left sectorial anterior ischemic optic neuropathy. The pathogenesis of this rare complication is discussed in this article.

IGurnal of Clillical Ncuro- ol'hthallllology 12( 1): 37- 40, 1992 Herpes Zoster Ophthalmiclis Anterior Ischemic Optic Neuropathy and Acyclovir F.- X. Borruat, M. D. and C. P. Herbort, M. D. ' i 1992 Raven Press, Ltd., New York A healthy 56- year- old man developed left- sided herpes zoster ophthalmicus, accompanied initially by ipsilateral anterior uveitis and increased intraocular pressure. Al­though he was treated in the subacute phase ( 5 days after skin eruption) with adequate oral doses of acyclovir for 10 days, the condition was later complicated by a left sectorial anterior ischemic optic neuropathy. The patho­genesis of this rare complication is discussed in this ar­ticle. Key Words: Acyclovir- Anterior ischemic optic neurop­athy- Herpes zoster ophthalmicus. From the Hopital Ophtalmique Jules Gonin, University Eye Clinic of Lausanne, Avenue de France 15, 1004 Lausanne, SWIt­zerland. Address correspondence and reprint requests to Dr. F.- X. Borruat, Hopital Ophtalmique Jules Gonm, Umverslty Eye Clinic of Lausanne, Avenue de France 15, 1004 Lausanne, SWIt­zerland. 37 Optic neuropathy is a rare, but severe, compli­cation of herpes zoster ophthalmicus ( HZO) ( 1,2). Papillitis ( 3- 5), retrobulbar neuritis ( 6- 12), optic at­rophy ( 13), and neuroretinitis ( 14,15), have been described. Most of the reported patients were iso­lated cases, but the approximate frequency of HZO- related optic neuropathies in six different studies is 1' 7c ( 6 in 579 cases) ( 9,11- 13,16,17). Both primary inflammatory damage to the nerve and secondary ischemic mechanisms have been cited as responsible for its pathogenesis ( 1,2,18). Systemic acyclovir ( ACV) is now a well­established treatment of HZO. It reduces the amount and severity of ocular complications when applied at adequate doses within 3 days of cutane­ous eruption ( 19,20). We report on a patient with typical HZO who was treated with oral ACV 5 days after onset and developed anterior ischemic optic neuropathy ( AION). To our knowledge, typ­ical sectorial AION secondary to HZO in an im­mune- competent patient has not been previously described. CASE REPORT An otherwise healthy 56- year- old man pre­sented with a 7- day history of left ocular pain. Five days before his initial visit, red skin lesions ap­peared around the left eyebrow. He reported hav­ing had an attack of right HZO a few years ago without complications. An examination revealed crusted skin lesions in the dermatome of the ophthalmic division of the left trigeminal nerve. Vision was 20/ 15 in both eyes. An examination of the right eye was unre­markable, but the left eye showed keratic precipi­tates, anterior uveitis ( 2 + cells) with intraocular pressure increased to 32 mmHg. Despite the pres­ence of vesicles for more than 3 days, oral ACV 5x 800 mg/ day for 10 days was started, and local treat- 38 F.- X. BORRUAT AND C. P. HERBORT ment included ACV ointment 5 x / day, scopol­amine 0.25% 3x/ day, and timolol 0.5% 2x / day. Twenty- seven days later ( 17 days after treatment cessation), the patient experienced a sudden and painless loss of vision in his left eye. Vision de­creased to 20/ 200, and the anterior segment was unremarkable, with a clear anterior chamber and intraocular pressure of 14 mmHg. A fundus exam­ination revealed prominent optic disc edema with capillary dilation and an inferior splinter hemor­rhage ( Fig. 1). Fluorescein angiography was per­formed and showed early temporal superior hy­pofluorescence ( Fig. 2, between arrows) with late diffuse staining, compatible with a sectorial AION. Goldmann perimetry ( Fig. 3) showed an absolute visual field loss corresponding to the sector of disc ischemia. Ocular motility was normal. An exami­nation of the right eye was unremarkable with a visual acuity of 20/ 15. An extensive medical and neurologic examina­tion failed to reveal any abnormality. The patient, a nonsmoker, showed no evidence of cardiovascu­lar disorder. Arterial blood pressure was 125/ 80 mmHg. A cerebral computed tomography ( CT) scan was normal. Neck and transcranial Doppler studies failed to show any arterial stenosis, and flow in the ophthalmic artery was normal on both sides. Blood examination showed erythrocyte sed­imentation rate, 7 mrn/ h; hemoglobin, 156 gIl; he­matocrit, 46%; platelets, 275 g/ I; leukocytes, 10.1 G. 1. Left optic nerve swelling with capillary dilation and splinter hemorrhage. FIG. 2. Fluorescein angiography intermediate phase, left eye: hypofluorescent superior optic disc ( between arrows), diffuse staining of the remaining optic disc, more pronounced temporally. gil ( neutrophils 72%, lymphocytes 23%, mono­cytes 5%); negative human immunodeficiency vi­rus ( HIV); glucose, 5.23 mmol/ l; total plasma pro­teins 74 gIl. Cerebrospinal fluid contained slightly raised protein ( 635 mgll; normal: < 410 mg/ l), which is a frequent finding in HZO ( 3,18). Oral prednisone was started at 1 mglkg/ day and then tapered over 1 month. There was gradual re­sorption of the disc edema with temporal superior sectorial optic nerve atrophy. Visual acuity did not improve, and the visual field loss remained un­changed. FIG. 3. Goldmann perimetry, left eye: absolute loss in the nasal inferior Visual field. HERPES ZOSTER OPHTHALMICUS 39 DISCUSSION Herpes zoster ophthalmicus is caused by the re­activation of the varicella- zoster virus ( VZV), which has remained latent in the Gasserian gan­glion since the patient's primary infection. The re­activation of V2V is associated with a depression of the cellular- mediated immunity ( 21). Such an immunological depression is more common in el­derly patients, as assessed by the lymphocyte­transformation test or by the skin test reactivity ( 21,22). Recurrences of H20 are frequent in immu­nocompromised hosts, but can surface in other­wise healthy patients. Hope- Simpson reported the frequency of a second attack of herpes zoster to be as common in patients with a previous episode of zoster as first attacks were in the general popula­tion ( 9 recurrences in 192 patients with previous zoster; 192 cases of zoster in 3,500 patients ( 23)). Optic neuropathies are rare complications of HZO, probably occurring in less than 1% of all HZO cases ( 9,11- 13,16,17). Whether anterior or posterior, the evolution and prognosis of VZV­induced optic neuropathies is unpredictable. Some patients have good visual recovery, and others ex­perience poor or no visual improvement with or without treatment, depending on the severity and the type of tissue injury- ischemic or demyelinat­ing ( 24). A sudden, painless visual loss occurred 32 days after the onset of H20 in our patient despite a lO- day course of ACV at an adequate dosage but started late ( 5 days after skin eruption). The clinical presentation as well as the results of fluorescein angiography were typical of AION, possibly caused by either a thrombosis or an arteritis in­volving the short posterior ciliary arteries. Ipsilateral cerebral ischemia is a well- recognized complication of H20 ( 25) and was found to appear at an average of 31 days following the onset of H20 in a review of 36 patients ( 26). Pathology data on lethal cases of H20 complicated by contralat­eral hemiplegia revealed segmental granuloma­tous angiitis ( 27,28). In these patients, V2V anti­gens were found within the media of ipsilateral cerebral vessels innervated by the trigeminal nerve, suggesting an immunological process in­volving the formation of tissular immune com­plexes. Recent ocular pathology studies of H20 are lacking because of the generally good prognosis that has developed with the advent of acyclovir treatment ( 19). In 1968, Naumann et al. reported on pathology data from 21 eyes of H20 patients ( 29). These eyes were enucleated 7 days to 8 years after the onset of HZO because of pain, phthisis bulbi, or corneal ulceration. Posterior ciliary peri­neural and intraneural as well as vascular and peri­vascular lymphocytic infiltration was a prominent feature ( 18 of 21 cases) and was frequently found to be segmental. It is interesting that the eye of a 71- year- old woman, enucleated 5 weeks after the onset of H20, showed a posterior ciliary granulo­matous arteritis and a granulomatous choroiditis, features indeed very similar to H20- related cere­bral vasculitis. The fact that perineural and peri­vascular inflammation was less pronounced in the early enucleated eye ( 7 days after H20 onset) than in 3 eyes enucleated later ( 5, 6, and 12 weeks after H20 onset) suggests that immunological pro­cesses are involved in the pathogenesis of H20. These pathological reports support the idea that AION in our case could be due to segmental pos­terior ciliary granulomatous arteritis. Reactivation of viral replication occurring at the end of ACV therapy is mostly unlikely in our patient, as this is the case only in severely immunocompromised pa­tients, thus favoring the hypothesis of an immune­induced arteritis. Acyclovir is an antiviral drug that is helpful in the acute phase of viral dissemination when direct viral invasion and replication occur ( 19). However, ACV is probably unable to influence secondary im­munological processes. Treatment of H20 with a high dose of oral ACV ( 5 x 600- 800 mg/ day for at least 7 days) when given within 3 days of the cu­taneous eruption drastically reduces the rate of se­vere ocular complications ( 19,20). Such treatment does not block the antibody titer rise against vari­cella- zoster virus ( 30). We recently showed that when given late, ACV does not reduce the rate of H20- related ocular complications ( 31). For our pa­tient, delayed ACV therapy did not prevent a sec­ondary complication, as AION appeared 32 days after the onset of H20, the same average time at which other cerebral complications were noted to appear ( 26). Acyclovir has only been recently introduced, and we are aware of only two other reports of H20- related optic neuropathies treated with ACV, both in HIV- positive patients ( 32,33). These patients had extensive ocular involvement ( uveitis, vitritis, retinitis, and optic neuropathy) probably as a result of massive viral invasion. Optic nerve involvement occurred in the acute infectious phase in both patients and was ascribed to direct viral involvement. There was a favorable outcome in one case with ACV therapy alone ( 33). In conclusion, because the type of late compli­cation of H20 as seen in our patient is thought to I Clrn Neuro- ophthalmol. Vol. 12. No. 1. 1992 40 F.- X. BORRUAT AND C. P. 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