Like other members of the alphaherpesvirus subfamily, the VZV (also termed the human herpesvirus type 3) is an enveloped virus that has double-stranded DNA, a short reproductive cycle, the potential to cause major host cell destruction during active replication, and the ability to establish lifelong latency in sensory neural ganglia.⁷ Several different genotypes vary geographically.⁷

The initial virus spread is believed to occur during childhood through the respiratory tract, where viral particle replication begins in the nasopharynx. Viremia then progresses from the nasopharynx to the skin through lymphatic spread leading to the development of varicella (chickenpox), which is characterized by an initial generalized rash, after which a latent infection develops in sensory neurons in the dorsal root ganglia.⁷ T cell-mediated immune mechanisms keep the VZV in check within these sensory ganglia as evidenced by the fact that once the T cell-specific immunity is below a certain level, a person is at risk for VZV reactivation.⁷,⁸

Although the virulence of the specific strain that primarily infects an individual may have a pathogenetic impact, local host factors play the predominant role.⁸ Established predisposing factors include old age, immunosuppression, pregnancy, and HIV infection. Certain malignancies, and lymphoproliferative disorders can compromise virus-specific cellular immunity causing a reactivation and replication of the latent virus that spreads through sensory neurons causing zoster (shingles) and zoster-associated pain (ZAP).⁷,¹¹

Herpes zoster not only develops in individuals who have already contracted the virus through community-acquired infections (wild-type varicella) but also can occur through varicella vaccination in childhood (vaccine-type VZV).⁸ Herpes zoster ophthalmicus (HZO) occurs when VZV reactivation occurs in the ophthalmic division of the trigeminal nerve (V1).⁹ Once reactivation occurs, the virus can move down the neurons and satellite cells along sensory axons to the skin. Virus spread results in viremia and triggers a local inflammatory immune response in the sensory nerves and the skin.⁸,⁹ Therefore, the pathophysiology of acute and long-term complications of adnexal as well as ocular HZO may not solely be attributable to viremia, but immune mechanisms and tissue inflammation play a role as well.⁸ Reactivation of the virus occurs repeatedly throughout the patient’s life, but some of these reactivations may be subclinical, which helps to boost the immune response to VZV.⁹

The mean age of onset of chickenpox is around 4.5 years (range, 4-13 years), but the incidence has sharply declined due to routine vaccination.¹² Following a brief (24-hour) period of prodromal symptoms, the rash rapidly develops
and quickly evolves. Although ocular involvement is seen in only 4% of chickenpox patients,¹³ in those with ophthalmic symptoms, eyelid manifestations predominate and are seen in 62.5% of cases.¹⁴ The eyelid lesions usually appear on or near the lid margin and are morphologically similar to the typical varicella vesicles elsewhere in the body.¹⁴ They may be observed in various stages of evolution (vesicle, papule, or scab) surrounded by a distinct red base. But in contrast to the rash elsewhere in the body, the eyelid lesions are usually isolated rather than grouped.¹⁴ Eyelid lesions heal without sequelae within 2 weeks.¹,⁷,¹² Other ocular manifestations are rare but punctal and canalicular stenosis, dacryocystitis, conjunctivitis, disciform keratitis, iridocyclitis, panuveitis, glaucoma, cataract, chorioretinitis, neuroretinitis, optic neuritis, optic atrophy, and internal ophthalmoplegia also have been reported.¹²,¹³,¹⁴,¹⁵,¹⁶,¹⁷ Although the disease is mild and self-limiting in most cases, it can have devastating consequences in immunocompromised hosts or during pregnancy.⁷,¹²

Out of the one million newly diagnosed cases of herpes zoster estimated to occur annually in the United States, HZO constitutes 10% to 20%,⁹,¹⁸,¹⁹,²⁰ and for the past 2 decades, the incidence of HZO has been rising at an alarming rate (3.6% per year).²⁰ The cause of this trend is unknown, but it is hypothesized that mass varicella vaccinations in children may have reduced the exposure to wild-type varicella in the general population.²⁰ Other alternative explanations include a rise in the number of patients with immunocompromised conditions, an improvement in health-seeking behavior, and an increasingly aging population.⁸,²⁰ HZO is indiscriminate of gender and has no seasonal preference, although the incidence and severity rise with increasing age, especially in patients older than 60 years. Age is a predictor of the severity of acute pain that accompanies HZO. More importantly, postherpetic neuralgia (PHN) is estimated to develop in 36.6% and 47.5% of patients older than 60 and 70 years, respectively.⁸,²¹ A notable exception to this rule is in patients with an HIV infection where the age of onset of HZO is usually less than 50 years, although other factors causing immunosuppression could also be associated with a younger age of onset.²²

The clinical manifestations of HZO are divided into three phases: a preeruptive phase, an acute eruptive phase, and a chronic or relapsing phase. The preeruptive phase is characterized by neuropathic pain, which is often described by patients as burning, tingling, or shooting in nature. The pain initially is mild, then gradually rises in crescendo, and usually follows the distribution of the ophthalmic division of the trigeminal nerve (V1). The pain may or may not be accompanied by viral prodromal symptoms.⁹

Following the preeruptive phase, the rash begins to appear.⁸ The skin eruptions associated with acute HZO can be highly variable in severity and extent; however, the frontal nerve, which innervates the scalp, the forehead, and the upper eyelid, is almost invariably affected in all patients.²³ It is also the site where the most severe skin lesions are observed, while skin lesions at the nasociliary dermatome are seen less frequently, in 60% of patients.²³ The two terminal branches of the nasociliary nerve, the external nasal and the infratrochlear nerves, may be involved either alone or together.²³ Hutchinson sign is the acronym given to papulovesicular lesions on the side and top of the nose due to involvement of the external nasal nerve.⁸,¹⁰,²³ Clinically, the acute skin rash varies from a few scattered maculovesicular skin lesions (Figure 68.1) to severe confluent, hemorrhagic bullous eruptions,²³ and new skin lesions continue to appear for 3 to 5 days. The rash of HZO evolves through the same stages as the disease elsewhere in the body, with erythema, macules, papules, and vesicles, which subsequently pustulate and crust (Figure 68.2).⁸ Periorbital edema and ptosis are commonly observed, and in some patients, both eyelids are severely edematous to the extent that the palpebral fissure can hardly be opened for ocular inspection.²⁴ Other adnexal manifestations include punctal and canalicular stenosis or even dacryocystitis.²⁵,²⁶