Chickenpox is a common childhood benign illness caused by the varicella zoster virus, which is a DNA virus of the herpes family. It causes an exanthematous vesicular rash, and can also be responsible for various benign ocular manifestations including eyelid and conjunctival vesicles, papillary conjunctivitis, and superficial punctate or dendritic keratitis. Other less common ocular complications include uveitis, chorioretinitis, cataracts, and glaucoma.1
Primary varicella infection can also cause neuroophthalmological complications such as optic neuritis, internal ophthalmoplegia, cranial nerve, and supranuclear palsy.2 Internal ophthalmoplegia is an uncommon complication of varicella infection. A total of 27 cases have been previously reported in the literature, with reports dating back to the 1930s.3 Only 2 cases of internal ophthalmoplegia associated with varicella infection have been reported in the past 14 years.4,5 We report a case of internal ophthalmoplegia following primary varicella infection in a 5-year-old boy.
A 5-year-old boy presented after his parents noticed redness of his right eye together with an enlarged pupil for the previous 2 days. He had developed chickenpox 1 week prior to developing eye signs. There was no history of trauma, but he was already under the care of the eye clinic for his moderate bilateral hypermetropia (+5.75 diopter sphere) and fully accommodative esotropia.
A vesicular rash involving mainly the forehead, periorbital areas (left more than right), and perioral areas was present. The right pupil was mydriatic in room lighting with a 4-mm anisocoria between the two eyes (Fig. 1). There was no direct or consensual light reflex and no response to accommodation in the right eye. The left pupil reacted normally with normal accommodation.
Figure 1. Photograph showing the distribution of the vesicular rash in the child’s periorbital areas together with right mydriasis.
His corrected visual acuity for distance was 0.00 crowded logarithm of the minimum angle of resolution (6/6) in both eyes, but his near visual acuity with reduced crowded logarithm of the minimum angle of resolution was 0.400 (6/15) in the right eye and 0.00 (6/6) in the left eye. A right acute anterior uveitis was also noted and treated with dexamethasone 0.1% drops four times a day. Posterior segment examination of both eyes was unremarkable. A diagnosis of right internal ophthalmoplegia secondary to varicella infection with likely involvement of the ciliary ganglion was made.
After 7 days, the right iritis resolved but the right pupil remained fixed and dilated. It was decided to try acyclovir oral suspension 400 mg four times a day for 10 days.
At 17 days from presentation, there was a mild improvement in mydriasis with anisocoria reduced to 3 mm in room lighting. There was an improved reaction to both light and accommodation of the right pupil. The boy was fitted with a photochromatic varifocal lens for the right eye with a +2.75 diopter sphere add for near. The varifocal lens was not well tolerated and subsequently changed to an executive bifocal. Six months from presentation, the internal ophthalmoplegia remained unchanged.
Internal ophthalmoplegia is a rare manifestation of varicella that usually follows the cutaneous manifestations by 1 to 2 weeks, although in a handful of cases it presented up to 3 months after skin eruption.1,4–6 In the study published by Jordan et al., 24 children were referred with ocular involvement after chickenpox.2 The most common findings were eyelid lesions, conjunctival pox, and conjunctivitis followed by uveitis and keratitis. None of these children had internal ophthalmoplegia.
In the previously reported cases of internal ophthalmoplegia after primary varicella, there appear to be some common features, as seen in Table 1. The condition tends to be uniocular. The majority of cases reported involve children younger than 8 years, with approximately a quarter of cases involving older patients. The oldest patient described was a 22-year-old Asian man.7 There appears to be a predilection for boys because 66% of cases involved males. This was also noted by Dubois et al.3
Table 1: The 27 Cases Reported in the Literature to Date
The pathophysiology of the condition is uncertain, but there are two possible mechanisms: either denervation of the ciliary ganglion or a lesion of the short ciliary nerves due to the viral infection in the form of a ganglionitis. Ross postulated a neural rather than muscular involvement when he noted a case where pupillary response to light directly and consensually started recovering before accommodation.10 This is reinforced by later reports in the literature of pilocarpine hypersensitivity in affected patients.1,3,4
The inflammatory reaction involved can contribute to paralysis of the iris sphincter muscle and result in mydriasis and signs of uveitis. It was previously thought that uveitis after primary varicella involved hematogenous spread because it was presumed that the virus directly invaded the internal ocular structures.8 However, an autoimmune response has to be considered because there is a lag between the appearance of the skin lesions and the ocular uveitis manifestations. This period of time corresponds with the appearance of detectable circulating antibodies, which happens to be almost a week from onset of the skin rash.9
Uveitis is a relatively common ocular manifestation of varicella infection.2 Half of the reported cases in the literature with an internal ophthalmoplegia secondary to varicella are documented to have a concurrent iritis or iridocyclitis (Table 1). In most cases, there was an effective response to a short course of topical steroid treatment. Only the case reported by Appel et al. had an accompanying vitritis and the patient responded well to topical steroids.9 A more recent report by de Castro et al.6 involved a child developing concurrent uveitis, interstitial keratitis, and internal ophthalmoplegia after primary varicella infection. Even here the uveitis resolved with topical steroids, but the patient still had a visually significant corneal scar 6 months from initial presentation.
In the majority of cases reported to have internal ophthalmoplegia, the anisocoria was permanent and partial recovery of pupillary reactions and accommodative power was possible (Table 1). Internal ophthalmoplegia did recover partially in a case reported by Ross10 and completely in a case reported by Caputo et al.11 In the case described by Ross, the child had a slightly dilated pupil and all reactions were normal 1 year from presentation. Accommodation was not the same as in the uninvolved eye but the child did not need a near lens for daily function.
Varicella is a common self-limiting condition and not routinely treated with antiviral medication. However, if treatment of chickenpox with systemic acyclovir is started 24 hours from the onset of the rash, it reduces the duration and severity of chickenpox in immunocompetent children.12 Whether acyclovir can reduce the serious complications of chickenpox is uncertain.12 There are no documented cases of treatment being given for internal ophthalmoplegia secondary to varicella, despite the likely irreversible anisocoria with reduced pupil reaction and accommodation. A decision in this case was made to try oral acyclovir in an attempt to reduce the severity of the long-term sequelae on the pupil.
In this case, the child did not receive the varicella vaccine because it is not routinely given in the United Kingdom. There are no documented cases of internal ophthalmoplegia after receiving the varicella vaccine.
Internal ophthalmoplegia associated with primary varicella infection is an atypical presentation and uncommon complication of the disease. It presents a diagnostic and therapeutic challenge to the clinician. To our knowledge, there are no documented cases in the literature that were given any oral antiviral medication. The patient in this case showed a potential mild response to oral acyclovir but, as reported in other cases, there can be spontaneous improvement. Acyclovir is a safe treatment to give to children. Clinicians should consider prescribing it when faced with such an uncommon complication of varicella and the child may show some improvement.
- Hodgkins PR, Luff AJ, Absolon MJ. Internal ophthalmoplegia: a complication of ocular varicella. Aust N Z J Ophthalmol. 1993;21:53–54. doi:10.1111/j.1442-9071.1993.tb00131.x [CrossRef]
- Jordan DR, Noel LP, Clarke WN. Ocular involvement in varicella. Clin Pediatr. 1984;23:434–436. doi:10.1177/000992288402300803 [CrossRef]
- Dubois HF, van Bijsterveld OP. Internal ophthalmoparesis: an uncommon complication of varicella, a common disease. Ophthalmologica (Basel). 1977;175:263–268. doi:10.1159/000308667 [CrossRef]
- Orssaud C, Roche O, El Dirani H, Dufier J. Delayed internal ophthalmoplegia and amblyopia following chickenpox. Eur J Pediatr. 2006;165:728–729. doi:10.1007/s00431-006-0155-7 [CrossRef]
- Heger T, Kolling GH, Dithmar S. Atypical tonic pupil as a complication of chickenpox infection. Ophthalmologe. 2003;100:330–333. doi:10.1007/s00347-002-0724-8 [CrossRef]
- de Castro LEF, Sarraf OA, Hawthorne KM, Solomon KD, Vroman DT. Ocular manifestations after primary varicella infection. Cornea. 2006;25:866–867. doi:10.1097/01.ico.0000224651.19837.6c [CrossRef]
- Laha PN, Srivastava JR. Unilateral ophthalmoplegia interna: a complication of chickenpox. J Indian Med Ass. 1955;24:334.
- Noel LP, Watson AG. Internal ophthalmoplegia following chicken pox. Can J Ophthalmol. 1976;11:267–269.
- Appel I, Frydman M, Savir H, Elian E. Uveitis and ophthalmoplegia complicating chickenpox. J Pediatr Ophthalmol. 1977;14:346–349.
- Ross JD. Ocular varicella with an unusual complication. Am J Ophthalmol. 1961;31:1307–1308.
- Caputo AR, Mickey KJ, Guo S. A Varicella-induced pupil abnormality. Pediatrics. 1992;89:685.
- Dunkle LM, Arvin AM, Whitley RJ, et al. A controlled trial of acyclovir for chickenpox in normal children. N Engl J Med. 1991;325:1539–1544. doi:10.1056/NEJM199111283252203 [CrossRef]
- Schlegel PG, von Wahlert J, Wissert J, Huenges R. Ophthalmoplegia interna after varicella. Monatsschr Kinderheilkd. 1992;140:396–397.
- Arcas J, Perez-Thoden M, Romero D, Lopez-Guajardo L, Alvarado M. Internal ophthalmoplegia: a rare complication of varicella. Rev Neurol. 1997;25:1066–1067.
The 27 Cases Reported in the Literature to Date
|1933||Babonnneix and Miget||3||F||10||OD||None||Unknown|
|1933||Babonnneix and Miget||3||M||7||OS||Unknown||Unknown|
|1947||Boulez & Chauvire||3||Unknown||Unknown||Unknown||Yes||Unknown|