Anterior segment complications of HZO were common in our patients, as a majority had keratoconjunctivitis and/or iritis. The association of anterior segment HZO with HZON is well characterized by previous studies (4–8,10–14,16,17). Herpes zoster ophthalmicus intermediate and posterior segment complications other than the optic neuropathy were not observed in our series, although vitiris (7,17) choroidal involvement (9), acute retinal necrosis (ARN) (27,28), and progressive outer retinal necrosis (PORN) (24,29) previously have been described. Also, it has been reported that retrobulbar optic neuropathy may precede development of ARN (27,28) and PORN (24,29) in immunocompromised individuals.
The close temporal relationship of optic neuropathy after the development of cutaneous zoster provided the basis for diagnosing HZON. Although ophthalmic manifestations of herpes zoster may be delayed by up to 6 months or more (19,20,30), our case series used a relatively narrow timeframe of 1 month between trigeminal rash and onset of optic neuropathy to confirm attribution of the optic neuropathy to VZV (3–18). The mean time from rash to HZON in our series was 14.1 days (range: 6–30 days).
In addition to a clear temporal association between the cutaneous zoster and optic neuropathy, ancillary testing may be used in diagnosing HZON, particularly in excluding other potential causes. Brain MRI is helpful in excluding demyelinative optic results. Erythrocyte sedimentation rate and CRP may be useful in excluding giant cell arteritis. Levels of these nonspecific inflammatory markers previously have been reported as normal in HZON (3,5,11,13,14). Excluding other infectious causes of optic neuropathy may require additional serum and CSF studies (7,13,14,16,17). CSF analysis in HZON may show a mild lymphocytic pleocytosis (5,9,12,14), although this was not observed in 1 patient in our series. Varicella zoster virus PCR of CSF was normal in our patients and in a previous report (9) and, thus, did not aid in the diagnosis of HZON. High levels of VZV antibody in CSF were reported in 1 case of HZON (9) and elevated serum VZV antibody titers also have been reported (9,12,16,17). Thus, there may be a role for CSF and/or serum antibody studies in diagnosing HZON.
While the precise pathophysiologic mechanism of HZON is unknown, it seems that it is likely multifactorial given the diversity of HZON presentation (18). Gündüz and Özdemir (5) first proposed a unifying 3-component mechanism attributing optic nerve involvement to direct viral invasion of the optic nerve (via trans-synaptic [31–33] and hematogenous routes ), extension of local inflammation from adjacent meningeal and brain tissue (35,36) and/or generalized ocular ischemia (37). Perineuritis, a common pathologic finding in HZO, also could play a role in vision loss in HZON (35).
Although treatment regiments of our patients were diverse, all received systemic antiviral therapy in addition to topical and/or systemic corticosteroids. In all our patients, treatment with systemic antiviral agents (acyclovir, valacyclovir, and famciclovir) was started before the onset of HZON due to cutaneous and/or ophthalmic disease manifestations. However, HZON may progress despite aggressive systemic antiviral therapy. Previous reports and our study have yet to define the role for systemic corticosteroids in treatment of HZON. Based on the previously reported cases which satisfy our study's inclusion criteria (Table 2), corticosteroids seem to improve the visual outcome. Of the prior reports, 9 of 12 patients (75%) receiving systemic corticosteroids showed improved final acuity (3,4,6,7,9,11–14,16,18), whereas 3 of 5 patients (60%) who did not receive corticosteroids showed improved final visual acuity (5,8,10,15,17). In contrast, in our patient cohort, only 1 of the 4 patients treated with corticosteroids showed visual acuity improvement, whereas both eyes that did not receive systemic corticosteroids had the best final acuity (20/25 and 20/50).
Conclusions regarding treatment of HZON based on our case series are subject to several limitations. Treatment regimens were diverse due to patient management by different clinicians. In addition, involvement of different providers at different institutions introduced a selection bias. Different medical comorbidities also may have affected treatment outcomes. Finally, the retrospective nature of our study and relatively small number of patients also limit our conclusions.
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