Ocular complications and loss of vision due to herpes zoster ophthalmicus in patients with HIV infection and a comparison with HIV-negative patients

Abstract

The aim of the work is to describe the occurrence of ocular complications and loss of vision due to herpes zoster ophthalmicus (HZO) in HIV-positive patients who received early antiviral therapy for HZO. This is a post hoc analysis of prospectively collected data. Twenty-four HIV-positive patients with HZO were included in this report; male to female ratio was 3.8:1; mean age was 33.5 (±14.9) years. The visual outcome was good, with 14/24 patients having 6/6 vision; severe vision loss (≤6/60) occurred in only 2/24. There was no statistical difference in the visual outcome between the HIV-positive and -negative patients (P = 0.69), although severe vision loss was more likely in HIV-infected patients. The ocular complications of HZO in HIV-infected patients were: reduced corneal sensation (17/24), corneal epithelial lesions (14/24), uveitis (12/24), elevated intraocular pressure (10/24) and extra-ocular muscle palsy (3/24). The severity of rash was similar in the two groups but multidermatomal rash occurred only in HIV-infected patients (4/24). There was no difference in the occurrence of ocular complications of HZO between HIV-positive and HIV-negative patients. HZO associated ocular complications and visual loss is low in HIV-infected patients if treated with HZO antiviral therapy and was comparable with HIV-negative patients. Early institution of HZO antiviral therapy is recommended to reduce ocular complication and vision loss.

Keywords

varicella zoster virus herpes zoster ophthalmicus HIV infection AIDS vision loss ocular complications

Introduction

Herpes zoster ophthalmicus (HZO) occurs secondary to infection from varicella zoster virus, which is a member of the herpes virus family. Upon initial infection varicella causes chicken pox. Shingles or HZO occurs when the latent organism is re-activated from its dormancy in the Gasserian ganglion. Increasing age, immunosuppressive therapy, HIV infection, trauma and debilitating diseases like tuberculosis increase risk for re-activation.^1,2 HZO is recognized as a potential marker of HIV infection, especially when it occurs in otherwise healthy young individuals.^3,4

There are considerable variations in the occurrence of ocular complications and visual loss in HZO. Immunocompetence and early administration of antiviral therapy for HZO are associated with better outcomes.^5–11 HZO in the presence of HIV infection is more severe, with greater tendency for recurrences, involvement of multiple dermatomes and disseminated rash. Ocular complications and subsequent loss of vision also occurs at a greater frequency in the presence of HIV infection with reported rates of occurrence ranging from 50 to 78%,^2,12 while in immunocompetent patients they are reported to occur in 14–28%.^5,6 Bayu and Alemayehu reported on 100 consecutive patients with HZO. Ninety-five percent were HIV-positive. Severe loss of vision occurred in 70% of those patients.¹¹ These findings are in agreement with other smaller reports from the African continent where the use of antiviral therapy for HZO is limited due to poor availability and economic reasons.^12–16 The occurrence of ocular complications was significantly less, with good visual outcome when all patients received intensive antiviral therapy, as seen in a report by Margolis et al.⁷ The aim of this report is to describe the ocular complications and occurrence of loss of vision due to HZO in HIV-positive patients who received early antiviral therapy for HZO. The differences in the occurrence of the various ocular complications and visual loss in HIV-positive and HIV-negative patients were also evaluated.

Method

This is a post hoc analysis of a prospective, longitudinal, non-comparative study which was aimed at evaluating factors which predict visual outcome in HZO.¹⁷ Sixty-four patients fulfilling the inclusion criteria were included for analysis in the primary study. Of these, 24 tested positive for HIV infection and their data were reviewed.

The inclusion criteria were the presence of the typical zoster rash in the distribution of the ophthalmic division of the trigeminal nerve with or without ocular involvement, and patients presenting within 72 hours of onset of the rash. Exclusion criteria included presence of pre-existent uveitis, glaucoma, corneal and retinal disease. In addition, patients not compliant with the treatment and patients not available for follow-up were excluded.

Following a detailed history, all patients underwent general physical, dermatological and ocular examination. Rash severity and its dermatomal distribution were evaluated. The presence of Hutchinson sign indicated by the presence of the zoster rash along the side and tip of the nose was specifically noted.

At presentation and subsequent follow-up at 1, 2 and 4-week intervals and then at three and six months, best corrected visual acuity, corneal sensation, detailed slit-lamp examination to detect anterior segment involvement and fundoscopy to detect posterior segment complications of HZO was done in all patients. Distance visual acuity was measured with illuminated Snellen chart at 6 m distance, with the patient wearing their spectacle correction. If visual acuity was <6/6, then automated refraction was done and vision was recorded with appropriate correction. Corneal sensation was checked with a wisp of cotton first in the unaffected eye followed by the affected eye. Corneal sensation was recorded as normal or reduced in comparison to the unaffected eye. The presence of ocular complication was documented at each visit. All patients with evidence of any ocular involvement underwent intraocular pressure measurement by applanation tonometry at every follow-up visit.

All patients underwent laboratory testing which included haemoglobin, blood sugar, serum creatinine and enzyme-linked immunosorbent assay for HIV (after pretest counselling, if the patients HIV status was not known). All patients were administered oral acyclovir in the dose of 800 mg five times daily for 7–10 days and topical acyclovir 3% ointment five times daily. Topical broad spectrum antibiotics, cycloplegics and lubricating eye ointments were prescribed when indicated. Topical steroids with or without systemic steroids were given for uveitis depending on the severity of inflammation. Topical antiglaucoma medications were prescribed when indicated and included timolol maleate (0.5%, twice daily), dorzolamide (2%, twice daily) and brimonidine (0.2%, twice daily) either singly or in combination.

Snellen acuity was converted into decimal equivalent for the purposes of statistical analysis. In addition, the following categories of visual loss were distinguished: Group 1 with no visual loss, Group 2 with mild loss (visual acuity [VA]: 6/9 to ≥6/18), Group 3 with moderate visual loss (VA: 6/24 to 6/36) and Group 4 with severe visual loss (VA ≤6/60) as per the classification recommended by the International Council of Ophthalmology for grading visual loss in clinical research.¹⁸

The occurrence of each ocular complication was recorded as present or absent for the purposes of statistical analysis. All acute corneal epithelial lesions were grouped together and corneal stromal lesions were grouped together for analysis as the incidence of each specific lesion was too low to be subjected to statistical analysis individually. Chronic epithelial lesions were seen in only two patients and this complication was not subjected to statistical analysis. Postherpetic neuralgia (PHN) was defined as any persistent herpetic pain persisting one month after the resolution of the rash.

Descriptive statistics were computed first, with mean (SD) computed for continuous variables and percentage counts for categorical variables. Chi square test for categorical variable and Student's t-test for continuous variables were done to test Statistical independence. P < 0.05 was considered to be statistically significant. All statistical tests were done using SPSS version 10.

Results

Of the 64 patients who were included for the initial analysis 24/64 (37.5%) were positive for HIV infection. At the time of occurrence of HZO only 6/24 (25%) were known to be HIV-positive and of these only 4(16.6%) were on antiretroviral therapy (ART). The remaining 18/24 (75%) were diagnosed with HIV infection after the onset of HZO. The CD4 count in most of the patients was not known and was not tested for as part of the study protocol, due to cost constraints.

There was a male preponderance in the HIV-positive patients, with the male to female ratio of 3.8:1 (19 men and 5 women). The age range of the patients was 6–63 years with a mean (+ SD) of 33.45(+ 14.9) years. There was a statistically significant difference in the mean ages of HIV-positive patients with HZO and HIV negative-patients with HZO (50.0[+ 16.7]) (P < 0.001).

The occurrence of the various ocular complications of HZO in the HIV-positive patients is enumerated in Table 1. Loss of corneal sensation was the commonest ocular complication followed by corneal epithelial lesions and uveitis. Elevated intraocular pressure was detected in 10/12 patients with uveitis. None of the patients had posterior segment complications of HZO like retinitis. Two patients had oculomotor nerve palsy and one had abducens nerve palsy, which resolved completely over a period of 1–3 months.

Table 1

Occurrence of ocular complications of herpes zoster ophthalmicus in HIV-positive patients

Ocular complications	N = 24 (%)
Loss of corneal sensation	17/24 (70.8)
Corneal epithelial lesions	14/24 (58.3)
Corneal stromal lesions	4/24 (16)
Hutchinson sign positive	12/24 (50)
Uveitis	12/24 (50)
Secondary glaucoma	10/24 (41.6)
Extraocular muscle paralysis	3/24 (12.5)
Post herpetic neuralgia	10/24 (41.6)
Severe rash	6/24 (25)

Table 2

Comparing the occurrence of various systemic factors and ocular complications of herpes zoster ophthalmicus in HIV-positive patients with HIV-negative patients

Systemic factors		HIV +ve	HIV –ve	P value
Age	Mean (±SD)	33.2 (±14.6) years	50.0 (±16.7) years	<0.001
Gender	Male	19	18	0.01
	Female	5	22
Ocular complications
Loss of corneal sensation	Present	17	25	0.33
	Absent	7	15
Conjunctival involvement	Present	23	31	0.41
	Absent	1	9
Corneal epithelial lesions	Present	14	25	0.80
	Absent	10	15
Corneal stromal lesions	Present	4	12	0.35
	Absent	20	28
Uveitis	Present	12	18	0.30
	Absent	12	22
Hutchinson sign	Present	12	17	0.40
	Absent	12	23
Severe rash	Present	6	9	0.30
	Absent	18	31
Postherpetic neuralgia	Present	10	23	0.65
	Absent	14	17
Visual outcome	Mean (±SD)	0.77 (±0.39)	0.82 (±0.35)	0.69

Chi square test was done when the independent variables were categorical and Student's t-test was done for quantitative variables like age and visual acuity

There was no statistically significant difference in the occurrence of the various ocular complications due to HZO between HIV-positive and HIV-negative patients (Table 2). Though there was no statistically significant difference between the two groups in the occurrence of severe rash, multi-dermatomal involvement occurred in 4/24 patients with HIV infection and none in the HIV-negative group.

The visual outcome was good in most patients with 14/24 having 6/6 vision or better; mild loss of vision was seen in 7/24 with acuity in the range of 6/9 to 6/12; moderate loss of vision (6/18 to 6/36) in 1/24 due to stromal keratitis; severe loss of vision with vision worse than 6/36 in 2/24, due to severe uveitis and glaucoma in one and severe uveitis leading to phthisis bulbi in the other. There was no statistically significant difference in the visual outcome between the HIV-positive and HIV-negative patients (P = 0.69). However the incidence of severe visual loss was higher in HIV-positive patients when compared with HIV-negative patients (2/24 HIV-positive versus 1/40 HIV-negative). The patient who developed phthisis bulbi due to uveitis was not compliant with steroid therapy.

Discussion

HZO occurs due to an age-related decrease in cell-mediated immunity to primary varicella infection in the elderly population. With the HIV epidemic it is commonly noted in younger patients, with occurrences of HZO young individuals previously thought to be healthy. This scenario should raise the suspicion of HIV infection. In our study there was a statistically significant difference in the mean age of HIV-positive and HIV-negative patients. However HZO is not an AIDS-defining illness with HZO occurring in the setting of immunodysregulation rather than immunosuppression.¹⁹ In the ART era, HZO often occurs during immune recovery and is considered one of the immune reconstitution inflammatory syndromes.^20,21

In this study, occurrences of ocular complications of HZO and associated loss of vision in HIV-positive patients were comparable to their occurrence in HIV-negative patients. This could be attributed to the administration of antiviral therapy for HZO in the early phase of the disease. Margolis et al. reported very good visual outcome in HIV patients with HZO, with all 35 of their patients maintaining normal visual acuity.⁶ This is in contrast to the reports from resource-constrained settings, with non-availability of antiviral therapy for HZO, where the visual outcomes were poor. In a report on 100 patients by Bayu and Alemayhu¹¹, visual acuity <6/120 occurred in 40% of the patients, with another 40% having final visual acuity in the range of 6/60 to 6/120 20/200 to 20/400. However a recent report by van Dyk and Meyer¹⁹, most patients had good ocular outcomes and all these patients received antiviral therapy for HZO. Even in immunocompetent patients the outcomes are better in those treated with antiviral therapy for HZO than those who did not receive treatment.^9,10,22 The differences in outcome in different regions of the world can be attributed to the use and efficacy of antiviral therapy for HZO.

The occurrence of PHN in 10/24(41.6%) in our study was unusually high but all patients responded well to treatment. Rash severity was greater in HIV patients with multidermatomal involvement occurring only in the HIV-positive patients in this series; however, this difference was not statistically significant. Recurrence of HZO occurred only in HIV positive patients and these variations in HZO rash are well documented in the literature. Extraocular muscle paralysis also occurred only in HIV-positive patients which resolved completely.

Based on the findings of this study and a review of the literature, we conclude HZO associated ocular complications and visual loss are infrequent in HIV-positive patients treated with HZO antiviral therapy and were comparable with HIV-negative patients. The outcomes in HIV positive and HIV negative patients are comparable. All apparently young heathly individuals with HZO should be evaluated for HIV seropositivity. Antiviral therapy for HZO should be instituted as early as possible in all patients to reduce ocular complications and loss of vision.

Funding sources: None.

Guarantor: SN.

Contributorship: SN was involved in the conception of the study, did the statistical analysis, researched data, contributed to the discussion and wrote the manuscript. MJ researched data helped with the statistical analysis and reviewed/edited the manuscript. JS was involved in the conception of the study, contributed to the discussion and reviewed/edited the manuscript.

Footnotes

Acknowledgements

None.

Conflict of interest: None.

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