Persistent pupillary dilation in herpes simplex uveitis Debra A. Goldstein,* MD; Andrew A. Mis,† MD; Frederick S. Oh,* MD; Jean G. Deschenes,‡ MD ABSTRACT • RÉSUMÉ Objective: To report the association between herpes simplex virus (HSV) and iris atrophy with pupillary dilation. Design: Retrospective case series. Participants: Patients with a clinical diagnosis of HSV keratouveitis seen between November 1993 and April 1994 in a single university uveitis clinic. There were 6 women and 7 men, aged 17 to 69 years (mean age 44.4 years). Methods: Patient information was collected, including history and medications used, and a complete ophthalmologic evaluation was performed, with careful documentation of iris detail and pupillary size. Results: Thirteen of 13 patients demonstrated some degree of iris atrophy; 9 of 13 had pupillary dilation on the affected side despite not being on dilating drops. Conclusions: Iris atrophy and pupillary dilation in a patient with unexplained anterior uveitis suggests the diagnosis of HSV keratouveitis. Objet : Compte rendu de l’association entre le virus herpès simplex (HSV) et l’atrophie de l’iris avec dilatation de la pupille. Nature : Rétrospective d’une série de cas. Participants : Les patients ayant un diagnostic de kérato-uvéite HSV examinés entre novembre 1993 et avril 1994 dans une clinique universitaire d’uvéite. Il y avait 6 femmes et 7 hommes, de 17 à 69 ans (âge moyen, 44,4 ans). Méthodes : Recueil de l’information sur les patients, y compris l’histoire et les médicaments utilisés, et évaluation ophtalmologique complète, avec documentation minutieuse et détaillée de l’iris et de la taille de la pupille. Résultats : Les 13 patients ont tous montré un certain degré d’atrophie de l’iris; 9 avaient une dilatation de la pupille du côté affecté, sans avoir reçu de gouttes de dilatation. Conclusions : L’atrophie de l’iris et la dilatation de la pupille chez un patient avec uvéite antérieure inexpliquée suggère un diagnostic de kérato-uvéite HSV.
H
erpetic uveitis may be difficult to diagnose in the absence of corneal scarring or a history of herpes.1–4 A number of clues may suggest the diagnosis, including iris pigment epithelial atrophy.1,2,5 Most forms of acute anterior uveitis result in transient pupillary miosis.6 We have noted, however, the frequent occurrence of pupillary dilation in patients with herpes simplex virus (HSV) uveitis. We present a series of patients with a clinical diagnosis of HSV keratouveitis and persistent pupillary dilation, and suggest that this may be a helpful clinical sign suggesting the diagnosis of herpetic uveitis.
Patients were excluded if there was a history of ocular surgery, greater than 2 clock-hours of posterior synechia, or use of miotics or mydriatics in either eye within the preceding 2 months. Patients with a history of herpetic zoster were excluded. Patients who met inclusion criteria were asked to return for slit-lamp examination, assessment of pupil size, bestcorrected visual acuity, intraocular pressure, and fundus examination. Iris atrophy was defined as focal if a sector of iris was involved, and diffuse if transillumination was observed throughout the iris.
Methods
Results
Patients with a diagnosis of keratouveitis were identified by reviewing the charts of one of the authors (Jean G. Deschenes) and were asked to return for follow-up. A diagnosis of HSV keratouveitis was based on the presence of uveitis in a patient with a definite history of herpetic eye disease or anterior stromal scarring in a dendritiform pattern consistent with previous herpetic keratitis.
Thirteen patients with HSV keratouveitis were examined between November 1993 and April 1994 (Table 1). There were 6 women and 7 men, aged 17–69 years (mean 44.4 years). Initial diagnosis of HSV uveitis was made, on average, 3 years prior to study examination (range 6 months–9 years). Clinical examination and treatment are described in Table 1.
From *the University of Illinois at Chicago Eye and Ear Infirmary, Chicago, Ill.; †the University of Manitoba, Misercordia Health Centre, Winnipeg, Man.; and ‡McGill University, Montreal, Que.
Correspondence to Debra Goldstein, MD, University of Illinois at Chicago, Eye and Ear Infirmary, 1905 West Taylor St., Chicago IL 60612-7243;
[email protected]
Presented in part at the Association for Research in Vision and Ophthalmology Annual Meeting in Fort Lauderdale, Fl., May 14, 1995
This article has been peer-reviewed. Cet article a été évalué par les pairs.
Originally received July 30, 2008. Revised Nov. 5, 2008 Accepted for publication Nov. 28, 2008 Published online Apr. 29, 2009
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Can J Ophthalmol 2009;44:314–6 doi:10.3129/i09-018
Pupillary dilation in herpes simplex uveitis—Goldstein et al. All patients demonstrated some degree of iris pigment epithelial atrophy. Nine had diffuse atrophy, 2 had focal superimposed upon diffuse atrophy, and 2 had focal atrophy. Nine had pupil dilation on the side of the HSV uveitis, with a mean difference in pupil size of 2.9 mm (range 1.5– 5 mm) (Fig. 1). Conclusions
Each of the 13 eyes with HSV keratouveitis developed iris atrophy. Iris atrophy is well described in herpes zoster ophthalmicus.5 There is also histological evidence of iris atrophy in both clinical and experimental HSV uveitis. Electron microscopic examination of iris from a patient with HSV uveitis and a fixed dilated pupil revealed destruction of iris muscle and pigment epithelium, and invasion of these tissues by viral particles.7 Light microscopic examination of iris from a patient with HSV keratouveitis revealed lymphocytes and plasma cells throughout the stroma, with iris sphincter necrosis and replacement by epithelioid cells.8 Another study of 24 eyes with HSV keratouveitis demonstrated diffuse infiltration of iris by lymphocytes and plasma cells.9 Focal infiltration was less frequent. Iris pigment epithelial necrosis was common.9 Almost 70% of eyes in this series developed pupillary dilation. This finding has not been well described previously in HSV. A case report of iris atrophy in a patient with HSV uveitis did not mention pupil size, although an accompanying photograph revealed pupillary dilation.10 Pupillary dilation has been better described in experimental uveitis; in 1 animal model of recurrent HSV uveitis, mydriasis was the earliest sign, often preceding iritis.11 The presentation of mydriasis before iritis raises the possibility that inflammation is not the sole cause of pupillary dilation. A neurologic or ischemic mechanism may also be involved, supported by the findings of peri- and intraneural invasion of long posterior ciliary nerves and vasculitis of accompanying blood vessels in HZV. Similar ischemia, however, has not been demonstrated histopathologically in HSV iris atrophy.
One series of patients with HSV keratouveitis described ischemic necrosis of the iris in 3 patients; however, all had also had cyclocryotherapy.12 Another animal model of HSV keratouveitis demonstrated early hypersensitivity to both mydriatics and miotics followed by late iridoplegia,13 possibly representing a viral effect on sympathetic and parasympathetic nervous systems. This implies an autonomic mechanism for pupil dilation and suggests the need for caution with dilators in HSV keratouveitis. Although this series is limited in that the diagnosis of herpetic uveitis was made solely on clinical grounds, with no laboratory confirmation, it does suggest that persistent pupil dilation in HSV uveitis may be a more frequent clinical finding than previously recognized. We suggest that unexplained pupillary dilation be added to the list of clinical clues suggesting a herpetic etiology in cases of anterior uveitis.
Fig. 1—Twenty-two-year-old man with a 3-year history of recurrent dendritic keratitis OS and a 2-year history of uveitis OS (A). Note the widely dilated pupil OS (B). The patient had been off dilating drops for 8 months at the time of this photograph.
Table 1—Patient characteristics and treatment parameters
Patient 1 2 3 4 5 6 7 8 9 10 11 12 13
Age
Sex
19 42 66 39 58 22 48 47 50 17 69 58 42
F F M M F M M F M M F M F
Involved Duration eye of uveitis OD OD OD OS OD OS OD OD OD OD OD OS OD
4y 1y 2y 3y 2y 2y 4y 9y 4y 2y 6 mo 4y 1y
Treatment
Dilators
A, FMT HA2% A, FMT Tropic1% A, P, B None A, Di None A, T, L, FMT None T, K None A, P, Ti None A, D None A, FMT HA2% A Tropic1% A, L, FMT None A, D None A, FMT A1%
Period dilators stopped prior to measurement
Iris atrophy
Pupil size OD/OS (mm)
7 mo 3 mo N/A N/A N/A N/A N/A N/A 5y 7 mo N/A N/A 2 mo
Marked diffuse Moderate focal Moderate diffuse Mild diffuse Moderate diffuse Marked diffuse Moderate focal Marked diffuse Moderate focal Mild diffuse Mild diffuse Mild diffuse Marked diffuse
6.5 / 2.5 4.0 / 2.0 9.0 / 7.0 4.0 / 7.0 6.0 / 4.0 2.5 / 7.5 3.0 / 3.5 6.0 / 2.0 3.0 / 3.0 4.5 / 3.0 3.0 / 3.0 2.5 / 2.5 6.0 / 3.0
Note: F, female; y, years; ACV, oral acyclovir; FMT, fluorometholone acetate; HA2%, homatropine 2%; mo, months; Tropic1%, tropicamide 1%; M, male; P, prednisolone acetate; B, betaxolol; N/A, not available; Di, diclofenac; T, trifluridine; L, levobunolol; K, ketorolac; Ti, timolol; D, dexamethasone; A1%, atropine 1%.
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Pupillary dilation in herpes simplex uveitis—Goldstein et al. The authors have no proprietary or commercial interest in any materials discussed in this article.
References 1. Gaynor BD, Margolis TP, Cunningham ET Jr. Advances in diagnosis and management of herpetic uveitis. Int Ophthalmol Clin 2000;40:85–109. 2. Van der Lelij A, Ooijman FM, Kijlstra A, Rothova A. Anterior uveitis with sectoral iris atrophy in the absence of keratitis: a distinct clinical entity among herpetic eye diseases. Ophthalmology 2000;107:1164–70. 3. Santos C. Herpes simplex uveitis. Bol Assoc Med P R 2004;96:77–83. 4. Thygeson P, Hogan MJ, Kimura SJ. Observations on uveitis associated with viral disease. Trans Am Ophthalmol Soc 1957;55:333–52. 5. Marsh RJ, Easty DL, Jones BR. Iritis and iris atrophy in herpes zoster ophthalmicus. Am J Ophthalmol 1974;78;255–61. 6. Goldstein DA, Mis AA, Deschênes JG, Burnier MN. Iris atrophy in herpes simplex uveitis. Invest Ophthalmol Vis Sci 1995;36:S150.
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7. Witmer R, Iwamoto T. Electron microscope observation of herpes-like particles in the iris. Arch Ophthalmol 1968;7:331–7. 8. Gupta K, Hoepner JA, Streeten BW. Pseudomelanoma of the iris in herpes simplex keratoiritis. Ophthalmology 1986;93:1524–7. 9. Teitelbaum CS, Streeten BW, Dawson CR. Histopathology of herpes simplex keratouveitis. Curr Eye Res 1987;6:189–94. 10. Chang TS, Brewer LV, Hooper PL. Primary herpes simplex iridocyclitis with iris atrophy. Arch Ophtalmol 1993;111:25–6. 11. Claoue C, Hill T, Blyth W, Easty D. Clinical findings after zosteriform spread of herpes simplex virus to the eye of the mouse. Curr Eye Res 1987;6:281–6. 12. Johns KJ, O’Day DM, Webb RA, Glick A. Anterior segment ischemia in chronic herpes simplex keratouveitis. Curr Eye Res 1991;10(Suppl):117–124. 13. Tokumatu T, Wilentz J. Iridoplegia and aqueous flare due to acute herpetic keratouveitis. Can J Ophthalmol 1975;10:193–200.
Keywords: herpes simplex, iridocyclitis, iris atrophy, pupil, mydriasis, dilation, uveitis
