Get to Know HZO
Gain a comprehensive understanding of the various treatment options to effectively manage this condition.
By Aaron Bronner, OD

Release Date: May 15, 2021
Expiration Date: May 15, 2024
Estimated Time to Complete Activity: 2 hours

Jointly provided by Postgraduate Institute for Medicine (PIM) and Review Education Group

Educational Objectives: After completing this activity, the participant should be better able to:

  • Understand the current standard of care for herpes zoster ophthalmicus.
  • Understand the importance of early detection to initiate timely treatment.
  • Determine when to use different treatment modalities.
  • Prescribe topical steroids/antivirals appropriately.
  • Recognize the role of oral antivirals in herpes zoster ophthalmicus treatment.

Target Audience: This activity is intended for optometrists engaged in routine eye care and primary care of ocular disease.

Accreditation Statement: In support of improving patient care, this activity has been planned and implemented by the Postgraduate Institute for Medicine and Review Education Group. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education, the Accreditation Council for Pharmacy Education, and the American Nurses Credentialing Center, to provide continuing education for the healthcare team. Postgraduate Institute for Medicine is accredited by COPE to provide continuing education to optometrists.

Reviewed by: Salus University, Elkins Park, PA

Faculty/Editorial Board: Aaron Bronner, OD, Pacific Cataract and Laser Institute, Kennewick, WA.

Credit Statement: This course is COPE approved for 2 hours of CE credit. Activity #121689 and course ID 72518-SD. Check with your local state licensing board to see if this counts toward your CE requirement for relicensure.

Disclosure Statements: 

Author: Dr. Bronner has no financial interests to disclose.

Managers and Editorial Staff: The PIM planners and managers have nothing to disclose. The Review Education Group planners, managers and editorial staff have nothing to disclose.

Determining the right avenue of treatment for herpes zoster ophthalmicus (HZO), which occurs when the varicella-zoster virus (VZV) is reactivated in the ophthalmic section of the trigeminal nerve, can be a challenge. While antiviral use during the acute, infectious stage is common, treatment in later, post-infectious stages can vary. With the potential for chronic and recurrent disease, it can be difficult for clinicians to identify the right management approach.

The purpose of this article is to review what we do know about HZO, including its clinical manifestations. We will also delve into its treatment and where these concepts diverge from its cousins herpes simplex virus (HSV) 1 and 2, with which HZO is sometimes mistakenly blended in our education.

A severe episode of HZO affecting the nasociliary branch of the fifth cranial nerve. The patient has profound ocular involvement and already has a total corneal epithelial defect. The severity increases the likelihood of complex and chronic ocular involvement.
Fig. 1. A severe episode of HZO affecting the nasociliary branch of the fifth cranial nerve. The patient has profound ocular involvement and already has a total corneal epithelial defect. The severity increases the likelihood of complex and chronic ocular involvement. Photo used with permission of Brian Johnson, OD. Click image to enlarge.

Clinical Manifestations 

While shingles lesions occur most commonly on the trunk and abdomen—which is where the disease gets its name—the most frequently involved cranial nerve is the trigeminal nerve (CN V). When the ophthalmic branch of the CN V is affected, the condition may affect the ocular structures, at which point it may be described as HZO, an entity accounting for 10% to 20% of all cases of zoster.1,2

The cornea is among the most frequently involved ocular tissues in HZO. Keratitis occurs in up to 65% of HZO cases and has varied manifestations.3,4 In seeking to distinguish this from its cousin HSV keratitis, it's useful to point out that while HSV corneal disease may vacillate from one manifestation to the next without any particular chronology, HZO seems to follow a sequential chronology with some manifestations possible in the first few days and weeks after the initial infection and others only manifesting months to years following the episode.1,5

Infectious epithelial keratitis. As with HSV, true infection of the corneal epithelium sets the stage for other corneal manifestations, and with VZV this initial infection begins as focal patches of coarse vesicular epithelial keratitis. There are often multiple lesions scattered across the cornea. Within one to three days’ time, these lesions either regress or coalesce to form pseudodendrites.1,5 Despite similar names and gross appearance, pseudodendrites, which appear in 50% to 75% of cases of HZO corneal disease, are readily distinguished from the HSV dendritic equivalents primarily though lack of ulceration and secondarily through lack of terminal end-bulbs.3,4,6,7 Because of the absence of ulceration in either forms of varicella zoster ophthalmicus (VZO) epithelial keratitis, neither pseudodendrites nor their vesicular precursors stain with fluorescein, though staining with rose bengal is reported variably.3-5,7    

Stromal/endothelial keratitis. In general, it’s thought that HZO stromal keratitis represents an inflammatory manifestation of the disease rather than a true infection, though there is some controversy surrounding this. A form of deep keratitis follows the infectious episode in around 40% to 50% of cases.3,4 The early form of this with HZO, known as nummular corneal infiltrates, occurs immediately below the previous pseudodendrite within the anterior corneal stroma and follows the infectious episode by a period of seven to 14 days.5-7 More rarely, an acute form of endotheliitis may also develop within this same timeframe and may cause significant corneal edema and subsequent disruption to vision. Depending on the severity of the attack, this endotheliitis could result in corneal decompensation and the need for endothelial transplantation.3,5 Both nummular and endothelial keratitis are frequently paired with anterior uveitis.5 While stromal disease typically follows infectious epitheliopathy, it may occur without history of a previous epithelial episode in 10% of patients.7

Pseudodendrite seen with HZO. This occurred two weeks after the beginning of a shingles rash involving the brow of this patient. Note that the lesion is not ulcerated and only stains with rose bengal in a patchy manner.
Fig. 2. Pseudodendrite seen with HZO. This occurred two weeks after the beginning of a shingles rash involving the brow of this patient. Note that the lesion is not ulcerated and only stains with rose bengal in a patchy manner. Click image to enlarge.

Corneal mucous plaques. A late corneal manifestation of HZO is mucous plaque keratitis (MPK). The incidence varies but is estimated at 4% to 13% and typically develops one to three months after an infectious episode, though occasionally its appearance may be delayed by years.5,8,9 The lesions of MPK are coarse, grayish filamentous elevations weakly adherent to epithelium, and may be linear or dendriform in appearance.8 As these are actually mucous deposits and not epithelial ulcerations, they stain negatively with fluorescein but vigorously with rose bengal. 

Some sources report the lesions as having a predilection for prior foci of epithelial or stromal disease, and others report them as freely migratory.4,5,8 Patients will be symptomatic with red, irritated eyes as a result of the mechanical shearing forces on the corneal epithelium. Culture and cytology show no viral activity.10,11 As these are not infectious, steroids may be considered. Their efficacy, however, is variable from study to study.4,7,9 The lesions can be manually removed, leaving behind intact epithelium, but tend to recur. The development of MPK may be linked to more serious ocular events, but their own presence is transitory, with a natural history characterized by gradual resolution leaving behind a mild underlying stromal haze.11,12  

Marginal keratitis. Sclerokeratitis and serpiginous keratitis are uncommon, late manifestations of HZO, occurring one to four months after the infectious episode.5 These are each presumed to be inflammatory responses secondary to a stromal inflammation or limbal vasculitis. Serpiginous keratitis manifests as a peripheral arcuate-shaped area of corneal ulceration and infiltration. It is often paired with localized corneal edema. As the condition progresses, thinning and vascularization take place, which may ultimately lead to perforation. The lesions have been described as similar to a Mooren’s-type ulceration. Sclerokeratitis results as an inflammatory spillover from a preceding episode of HZO-linked scleritis. It may be seen following cases of HZO scleritis when corticosteroid therapy has been too rapidly tapered. It also may cause stromal thinning and guttering of the peripheral cornea.4,5,7

Natural History of HZO

Varicella-zoster virus is a member of the alpha herpesviradae family of human herpes viruses, which includes HSV 1 and 2, cytomegalovirus (CMV) and Epstein Barr virus (EBV). Like all families, the viruses that make up this group share many core similarities; in the case of alpha herpesviradae, the ability to create latency, the inability of body to fully clear the virus once initial infection has occurred and periodic reactivation are shared. 

VZV causes disease during one of two states: the primary infection, known as varicella (or, more commonly, chickenpox) and secondly, an endogenous reactivation of latent VZV in the form of herpes zoster or shingles. Primary infection occurs as a result of direct contact with or via respiratory droplets from an infected individual. It manifests as chickenpox, the widely recognized itchy vesicular rash that spreads across the body.5 Though ocular involvement here is unusual, lid and conjunctival vessels as well as dendriform corneal lesions are all occasionally encountered.9

Upon either vaccination or resolution of a varicella infection, the virus (the wild type or the attenuated vaccine type, depending on the source of exposure) is transported to a dorsal root ganglion of sensory nerves where, in combination with host cellular immunity, it establishes latency. About 10% to 30% of infected individuals will have latency broken and the virus will migrate from one of the ganglion reservoirs, typically resulting in the classic shingles vesicular rash respecting a dermatome.1,5 The switch from latency to active disease seems to require some stress to host cell-mediated immunity, and the disease’s increasing rate with advancing age may be tied directly to the immunosenescence, explaining the elevated risk with age.1,2,5,43

Disciform keratitis/corneal immune rings. These two forms of late stromal keratitis, which can occur within HZO, typically manifest months after the infectious episode. Though often discussed part and parcel with each other, they probably result from quite different immunologic scenarios.5,10,13 The etiology of disciform keratitis is debatable and not completely defined as infectious or inflammatory, but the target is most likely the endothelium and would probably be more accurately described as disciform endotheliitis. Clinically, disciform disease is characterized by a suddenly developing circular form of corneal edema with an intact epithelium and no clearly definable infiltrate, which may have underlying keratic precipitates.5,9,10   

Less common than disciform keratitis are corneal ring infiltrates.5,13 Ring infiltrates are most often described in Acanthamoeba keratitis as one of the late stromal manifestations of that disease, but they may also be part of the clinical presentation of other sources of microbial keratitis as well as with both HSV and HZO keratitis. With viral forms, corneal rings are most typically thought to be composed of antigen-antibody complexes. When fronts of antigen migrating outward from the nidus of involvement meet a front of antibody migrating in from the limbus, the result is precipitate of an Ab-Ag complex.11-13 Unlike microbial rings, which are generally ulcerated and apical, classic viral rings are usually not ulcerated, and their location varies.

It’s important to note that the clinical appearance of many forms of HSV and HZO anterior segment disease are indistinguishable. Therefore, it is important to establish a prior history of HZO in these cases, the timing from which will aid in the diagnosis.

Interstitial keratitis. The development of significant corneal haze, vascularization and lipid deposition may follow any of the intense preceding forms for HZO keratitis. Corneal neovascularization following or as part of herpetic eye disease seems to be mediated by T-cells and, as with other forms of deep HZO keratitis, may be purely inflammatory or may be caused by a latent viral infection within the corneal stroma and may perpetuate for years.5

Neurotrophic disease. Neurotrophy of the cornea is a relatively common manifestation of HZO, with an estimated 20% to 45% of patients exhibiting signs of neurotrophic disease within the first year after infection, and with risk increasing following more severe episodes of HZO.5,7,9 The clinical manifestation of corneal hypoesthesia is neurotrophic keratitis (NK), which may be mild or very severe. Classification of hypoesthesia can be performed with an esthesiometer or, as in our clinic, dental floss or cotton wisps. 

The clinical picture of HZO neurotrophic disease is similar to that seen with herpes simplex, but is reported as being more severe.5,7 Severe cases manifest as oval, “boggy” ulcerations most commonly found in the central of paracentral inferior cornea. Without successful treatment, these ulcerations may develop scarring, secondary superinfection or progressive melting, thinning and perforation.7,9,10

Mucous plaque keratitis with HZO. This patient had a shingles episode four months prior to being referred in for eye pain. The patient did not feel the eye was involved with the initial episode. Note that these lesions, unlike the pseudodendrite in Figure 2, stain vigorously with rose bengal.
Fig. 3. Mucous plaque keratitis with HZO. This patient had a shingles episode four months prior to being referred in for eye pain. The patient did not feel the eye was involved with the initial episode. Note that these lesions, unlike the pseudodendrite in Figure 2, stain vigorously with rose bengal. Click image to enlarge.

Zoster-associated uveitis. This is the second-most common manifestation of HZO, developing in up to 40% of patients.5,9 A history of HZO increases the risk for development of uveitis by 13 times compared with the patients with shingles alone.14 And though keratouveitis may develop twice as frequently as uveitis alone, HZO remains an important cause of isolated uveitis, particularly in an elderly population, where it may account for a high percentage of isolated uveitis cases.14-16 When seen as an association with HZO keratitis, the uveitis follows the timeline for keratitis described above. As an isolated finding, however, it can lag behind the acute HZO episode, in some cases by years.16

When seen in combination with keratitis, as a keratouveitis or endotheliitis plus uveitis, the diagnosis is generally straightforward. In the case of delayed manifestation, its clinical diagnosis is more difficult. Any unilateral uveitis in a patient over the age of 60 should prompt questioning for a recent or remote history of HZO or periocular shingles rash, among whom it accounts for a high percentage of uveitis cases. Helpful ophthalmic clues may be sectoral iris atrophy and subsequently mild corectopia, and poor direct pupillary response (with intact consensual response on fellow eye), diffusely distributed, medium-sized keratitis precipitates and ocular hypertension, though studies vary on their incidence with HZO uveitis. Ocular hypertension is also associated with a more chronic course of disease.16,17  

Rarely, HZO can result in severe panuveitis: acute retinal necrosis (ARN) or progressive outer retinal necrosis (PORN). Each of these entities can progress to severe vision loss.18 Among other sources of vision loss, untreated cases of ARN or PORN will go on to have profound vision loss from rhegmatogenous retinal detachment in up to 75% of cases, which highlights the importance of dilating uveitis patients to make sure there is no posterior involvement.17,18

Treatment Approaches

Efforts to manage HZO can be broken down into prevention of disease, treatment of active infection, treatment of post-infectious inflammatory events and treatment of corneal neurotrophy. 

A double corneal ring occurring four months following a shingles episode in a 42-year-old patient. The lesion does not stain with fluorescein or rose bengal. This issue resolved with treatment and the patient has had one further flare of HZO but has been quiet for three years.
Fig. 4. A double corneal ring occurring four months following a shingles episode in a 42-year-old patient. The lesion does not stain with fluorescein or rose bengal. This issue resolved with treatment and the patient has had one further flare of HZO but has been quiet for three years. Click image to enlarge.

Vaccination. Prevention of varicella zoster in its two forms has been accomplished with two related vaccinations. The first, Varivax (Merck), is given to infants to reduce primary infection, with good results. This vaccine has seen significant success and has reduced the incidence of varicella in at-risk populations by 70%.5,19,20  

However, there are possible consequences of this vaccination program, primarily the unknown impact on the epidemiology of the shingles. It’s speculated by some that widespread vaccination may actually increase the rate of herpes zoster at least over the short term.19 Theoretically, people who have latent, wild-type VZV infection will see a reduction in their normal environmental exposures to VZV as a wider percentage of children are vaccinated. This then results in a reduction in immune boosting to the virus that accompanies these exposures and may manifest as increasing rates of shingles and at younger ages.5,9,20,21

While the jury is out on the role of Varivax in increasing the prevalence of shingles in an at-risk population, two things are not in debate: (1) the average age of patients developing shingles is decreasing and (2) the incidence of shingles is going up.22-24 Detractors of Varivax point this out as a cause-and-effect relationship while supporters note these trends may have preceded widespread use of Varivax and can also be seen in countries without varicella vaccination programs.22-24

For patients at risk for shingles, Zostavax (Merck) or Shingrix (GlaxoSmithKline) should be used to reduce risk. Zostavax is a smaller dose of the same attenuated virus used in Varivax. This vaccine reduces the development of shingles by around 50%, and lowers the chances of developing severe disease and the potential for post-herpetic neuralgia as well.25-27 Zostavax’s effectiveness, however, seems to vary with patient age. Those between 60 and 69 saw a reduction in disease of 60%, but only 40% when dosed beyond the age of 70. Further, as a live virus, there is the slight risk of inducing zoster with the vaccine. Though the CDC recommended this vaccine for all people over the age of 60, its use has lagged way behind that of Varivax, with only 31% of eligible adults receiving the vaccine.27

The more recently developed Shingrix vaccine substitutes the live attenuated virus of Varivax and Zostavax for a viral subunit. Though efficacy of Shringrix seems superior to Zostavax with 91% efficacy even beyond the age of 70—and, theoretically, using a viral subunit reduces potential for causing a reactivation—it is a two-dose schedule and, perhaps partially as a result of this, has failed to gain wide penetrance into the at-risk population.26,27

Thus far, it seems logical that shingles vaccines are perhaps best suited for patients with elevated risk of shingles but not an immediate history of it. That said, recent history of shingles does not contraindicate a booster, which may still be beneficial to the patient; in fact, the CDC recommends Zostavax in all people over the age of 60 regardless of previous episodes.25 

Exactly how beneficial a vaccine may be after a previous episode probably relates to patient-specific factors such as immune status and the timing of vaccination relative to the episode. One author makes the case that the immune boost following an episode of shingles lasts for around three years, so recommending the vaccine three years after a flare seems reasonable.28 Further, neither vaccine has a permanent effect and each can be repeated five years after a previous dose.

The lack of high utilization of these vaccines should be a concern within optometry and, though we generally play little role in recommending vaccinations, strongly advocating for shingles vaccination to our patients is within our purview. Keeping in mind that up to 20% of all shingles cases may involve ocular structures and each case carries the potential for debilitating, chronic or recurrent pathology to the eye, it stands to reason that as providers on the forefront of the nation’s eye care, we should be actively taking a role in recommending our patients get this vaccine. Currently, the American Academy of Ophthalmology recommends that all patients 50 and older receive one or the other vaccine.27

Iritis in HZO. The iritis in this eye developed about two months after the episode of MPK seen in Figure 3. The patient had modest AC reaction, sectoral iris atrophy and a distorted, poorly reactive pupil (this photo is in a non-dilated eye). Two years later, the patient is still unable to come off of steroids without a flare-up of their disease.
Fig. 5. Iritis in HZO. The iritis in this eye developed about two months after the episode of MPK seen in Figure 3. The patient had modest AC reaction, sectoral iris atrophy and a distorted, poorly reactive pupil (this photo is in a non-dilated eye). Two years later, the patient is still unable to come off of steroids without a flare-up of their disease. Click image to enlarge.

Antivirals. In the late 1970s, acyclovir was developed as a highly selective, minimally toxic antiviral nucleoside analog effective in the treatment of both HSV 1 and 2 as well as VZV. The mechanism of acyclovir is to block guanosine base pairing, thereby halting DNA synthesis.29 Acyclovir’s selectivity and subsequent safety is derived from it being phosphorylated into its active form by viral thymidine kinase, and thus it only blocks DNA synthesis in virally infected cells. Acyclovir’s disadvantage is its poor bioavailability; possibly only 10% is absorbed following an 800mg dose, the standard dose for VZV treatment.30 

From acyclovir, the prodrug valacyclovir, which shows improved bioavailability compared with its parent drug, was developed.29,30 Penciclovir, a later-developed antiviral drug, had even poorer bioavailability than acyclovir and possibly a weaker mechanism of action, but from penciclovir the prodrug famciclovir was developed, which shows a 77% bioavailability.29,30 Ganciclovir is a related guanosine analog that has greater potential for toxicity than the other antivirals when dosed systemically and so remains a secondary option in all cases except the treatment of cytomegalovirus.30,31 

Though these groups of medications are found to be effective in both HSV and VZV, the inhibitory concentration (IC50) of acyclovir is 3µg/mL for VZV and somewhere between 0.5µl/ml and 2µl/ml for HSV 1 and 2.30 Due to this greater concentration demand for VZV, all antivirals used in its treatment are dosed at higher levels than HSV-based disease. For example, the standard dose of acyclovir or valacyclovir for HSV is half that used for HZO (400mg five times per day for acyclovir or 500mg TID with valacyclovir for HSV keratitis) compared with that used in HZO (800mg five times per day with acyclovir/1000mg TID with valacyclovir).

The use of these medications in the treatment of HZO is established based on research with acyclovir in the 1980s, which showed benefit in reducing the duration of viral shedding and symptoms, limiting the severity of disease and reduction in late manifestations of the disease, and later studies showing a reduction in PHN.32,33 Finally, although there is good rationale to expect guanosine analogs to be useful for VZO, the actual effectiveness of their use has been called into question. A large retrospective review found no evidence of reduction in severity of the acute episode or in the reduction of complications of the disease in patients treated with oral acyclovir (800mg five times per day) vs. those who were not treated.34

Theoretically, it’s possible to expect that suppression dosing, found effective for HSV via the HEDS study, may also be helpful in cases of VZV, though it might be anticipated to be needed at higher dosages than those given with HSV.35 However, no general consensus or recommendation on this matter exists and community practice is divided.36 In the literature, I identified a couple of small reviews that support the use of low-dose chronic acyclovir. Both of these studies suggest that, in select populations the use of prophylactic therapy may result in substantial reduction of recurrence, but both studies are too limited in design to broadly apply.22,37 The ongoing Zoster Eye Disease Study seeks to clarify some uncertainty with the use of prophylactic antivirals but, to date, no information has been published and enrollment has been significantly below expectation.38 

At this time, despite the lack of good data on the topic, over half of the cornea specialists polled in one review use long-term suppression therapy for chronic or recurrent HZO.36

This is the patient from Figure 1. After years of dealing with unremitting zoster-related inflammation, iritis and neurotrophy, the patient’s cornea opacified and vascularized, and the pupil became irregular and non-responsive. His case illustrates the potentially catastrophic impact of HZO on the visual system.
Fig. 6. This is the patient from Figure 1. After years of dealing with unremitting zoster-related inflammation, iritis and neurotrophy, the patient’s cornea opacified and vascularized, and the pupil became irregular and non-responsive. His case illustrates the potentially catastrophic impact of HZO on the visual system. Photo used with permission of Brian Johnson, OD. Click image to enlarge.

Topical antivirals. Topical acyclovir may have some effect on the corneal infectious manifestations of VZV; however, the topical form of this drug is not available in the United States.5,29 Trifluridine, an older antiviral, is effective in the treatment of infectious ocular HSV, but is not effective against HZO and so should not be used.5 Therefore, until recently there were no available products to be used topically against HZO. This may have changed with the release of Zirgan (ganciclovir 0.15% gel, Bausch + Lomb). A small case series suggests that the use of topical ganciclovir may have shortened the duration of the disease.39 While this study does not provide extremely strong evidence of effect, we know that ganciclovir does have efficacy against VZV, which makes its topical use a reasonable adjunct in some cases of HZO, particularly during the actively infectious stage manifesting with pseudodendrites.30

Corticosteroids. The use of corticosteroids in cases of corneal HZO is an area of debate and is even more controversial than in HSV, where at least in stromal and endothelial disease it is felt to be a required component of treatment as determined by the HEDS study.40 In McGill’s article from 1987 on the uncertain mechanisms of both simplex and varicella zoster etiologies of stromal keratitis, the suggestion is made that injudicious treatment with corticosteroids may prolong episodes and promote recurrence.6  This advice is echoed in Holland’s Cornea; Dr. Lee acknowledges the effectiveness of corticosteroids to treat these manifestations on one hand, but on the other recommends they should be avoided, when possible, given the potential for extending the duration of disease beyond its normal course.

Despite the mini controversy surrounding their use, these recommendations against their use do not appear to be explicitly followed in clinical practice. The most widely used treatment modality for HZO is a combination of topical corticosteroids and oral antivirals, according to one review on practice patterns among cornea specialists.36 At our clinic, we treat cases of HZO with steroids when reduction in vision is likely to occur in their absence, which would be cases of significant stromal/interstitial disease, corneal endothelial disease and uveitis but generally not epithelial disease. The dosage of steroid varies on a case-by-case basis, but generally we will seek to use the lowest dose of steroid that allows total elimination of clinical inflammation.

Treatment of neurotrophic disease. NK may be one of the most troublesome and recalcitrant forms of zoster-related keratitis to manage. While ulcers and epithelial disturbances associated with neurotrophy can wax and wane over the disease course, unless the underlying level of corneal hypoesthesia remits, the problems will recur. Treatment varies and can include lubrication, punctal occlusion with either plugs or cauterization, bandage contact lenses—often used chronically—amniotic membrane, autologous serum eye drops, scleral contact lenses, Oxervate (cenegermin, Dompé), tarsorrhaphy and conjunctival/Gunderson flaps.41,42

While conservative therapy is helpful in mild and acute manifestations, long-term management of NK in unremitting recurrent cases should use long-term solutions, either a scleral contact lens, a conjunctival flap (where the visual potential is limited), a partial or full tarsorrhaphy or perhaps Oxervate. When considering Oxervate for long-term management of NK, it’s important to recognize that it has not been shown to increase corneal sensitivity, the underlying mechanism of NK, but only to speed the healing of the ulcer itself.42 Our clinic has used the medication in recalcitrant cases of NK to good effect with positive responses in both the acute phase (healing the ulcer) and the chronic phase (preventing re-ulceration).  


Herpes zoster is a systemic infectious disease with a moderately high predilection for the ocular and periocular tissue. When the trigeminal nerve is affected, ophthalmic findings frequently manifest. These manifestations are extremely variable, though they seem to follow a predictable timeline. Early-stage findings such as epitheliopathy may resolve and give way to mid-stage findings such as nummular keratitis. These in turn may become disciform keratitis, or in more serious cases serpiginous disease. Within the eye, iritis and panuveitis may develop. Essentially, any unusual unilateral red eye in a patient with a history of ipsilateral shingles in the preceding six months should have HZO on the differential.

Though use of antivirals in the acute, infectious stage is widespread, treatment approaches in the later, post-infectious stages are more varied. The potential for chronic and recurrent disease are particularly troublesome and can leave the clinician stumbling along a poorly defined treatment algorithm. Further, for one reason or another, shingles is becoming more common and occurring at a younger age. 

This highlights perhaps the most important thing optometrists can be doing in the management of HZO—start helping to prevent the disease. As a profession, we need to be vocal with our patients in promoting the use of one of the two available shingles vaccines. An ounce of prevention is worth a pound of cure after all, particularly when the “pound of cure” is not well defined or even particularly effective, as is the case with much of our management options with HZO once the disease has taken hold.

Dr. Bronner is an attending optometrist at Pacific Cataract and Laser Institute in Kennewick, WA. He has no financial interests to disclose.

1. Liesegang TJ. Herpes Zoster Ophthalmicus: Natural History, Risk Factors, Clinical Presentation and Morbidity. Ophthalmology. 2008;115:S3-S12.

2. Borkar DS, Tham VM, Esterberg E, et al. Incidence of herpes zoster ophthalmicus: results from the pacific ocular inflammation study. Ophthalmology. 2013;120(3):451-6.

3. Kaufman SC. Anterior segment complications of herpes zoster ophthalmicus. Ophthalmology. 2008;115:S24-32.

4. Cobo LM. Corneal complications of herpes zoster ophthalmicus. Cornea. 1988;7(1):50-6.

5. Barry Lee W, Liesegang TJ. Herpes Zoster Keratitis. In: Krachmer JH, Mannis MJ, Holland EJ eds. Cornea. 4th ed. St Louis: Mosby; 2004:1075-90.

6. McGill J. The enigma of herpes stromal disease. Br J Ophthalmol. 1987;71(2):118-25.

7. Liesegang TJ. Corneal complications from herpes zoster ophthalmicus. Ophthalmology. 1985;92(3):316-24.

8. Marsh RJ, Cooper M. Ophthalmic zoster: mucous plaque keratitis. Br J Ophthalmol. 1987;71(10):725-8.

9. Rapuano C, Luchs JI, Kim T. Corneal Infections, Inflammations, and Surface Disorders. In: Anterior Segment; The Requisites in Ophthalmology. Mosby; 2000:115-8.

10. Holland EJ, Brilakis HS, Schwartz GS. Herpes Simplex Keratitis. In: Krachmer JH, Mannis MJ, Holland EJ, eds. Cornea. 2nd ed. St. Louis: Mosby; 2004:1043-74.

11. Mondion BJ, Rabin BS, Kessler E, et al. Corneal rings with gram negative bacteria. Arch Opthalmol. 1977;95(12):2222-5.

12. Sery TW, Pinkes AH, Nagy RM. Immune corneal rings: I. Evaluation of reaction to equine albumin. Invest Ophthalmol. 1962;1:672-85.

13. Sery TW, Pinkes AH, Nagy RM. Immune corneal rings: III. Mechanism of local corneal ring formation. Invest Ophthalmol. 1962;1:762-72.

14. Wang TJ, Hu CC, Lin HC. Increased risk of anterior uveitis following herpes zoster: a nationwide population-based study.  Arch Ophthalmol. 2012;130(4):451-5.

15. Chatzistefanou K, Markomichelakis NN, Christen W, et al. Characteristics of uveitis presenting for the first time in the elderly. Ophthalmology. 1998;105(2):347-52.

16. Tugal-Tutkum I, Cimino L, Aydin Akova Y. Review for the disease of the year: varicella zoster virus-induced anterior uveitis. Ocul Immunol Inflamm. 2018;26(2):171-7.

17. Jap A, Chee SP. Viral anterior uveitis. Curr Opin Ophthalmol. 2011;22(6):483-8.

18. Duker JS, Blumenkranz MS. Diagnosis and management of the acute retinal necrosis syndrome. Surv Ophthalmol. 1991;35(5):327-43.

19. Brisson M, Edmunds WJ, Gay NJ, et al. Modelling the impact of immunization on the epidemiology of varicella zoster virus. Epidemiol Infection. 2000;125(3):651-69.

20. Seward JF, Watson BM, Peterson CL, et al. Varicella disease after introduction of varicella vaccine in the United States. JAMA. 2002;287(5):606-11.

21. Quirk M. Varicella vaccination reduces risk of herpes zoster. Lancet Infect Dis. 2002;2(8):454.

22. Miserocchi E, Fogliato G, Bianchi I, et al. Clinical features of ocular herpetic infection in an Italian referral center. Cornea. 2014;33(6):565-70.

23. Davies EC, Pavan-Langston D, Chodosh J. Herpes zoster ophthalmicus: declining age at presentation. Br J Ophthalmol. 2016;100(3):312-4.

24. Jeng B. Herpes zoster eye disease: new ways to combat an old foe. Ophthalmology. 2018;125(11):1671-4.

25. Centers for Disease Control and Prevention. Shingles vaccination: what you need to know: 

26. Gelb LD. Preventing herpes zoster through vaccination. Ophthalmology. 2008;115:S35-8.

27. AOA Policy Statement: Recommendations for Herpes Zoster Vaccine for Patients 50 Years of Age and Older. Ophthalmology. 2018;125(11):1813-6.

28. Cohen J. Herpes zoster. New Engl J Med. 2013;369(18):1766-7.

29. De Clercq ED, Field HJ. Antiviral prodrugs – the development of successful prodrug strategies for antiviral chemotherapy. Br J Pharmacol. 2006;147(1):1-11.

30. Gnann JW. Antiviral therapy of varicella-zoster virus infections. In: Arvin A, et al Eds. Human Herpesviruses: Biology Therapy and Immunoprophylaxis. Cambridge University Press; 2007.

31. Koyano S, Suzutani T, Yoshida I, et al. Analysis of phosphorylation pathways of antiherpesvirus nucleosides by varicella-zoster virus specific enzymes. Antimicrob Agents Chemother. 1996;40(4):920-3.

32. Cobo LM, Foulks GN, Liesegang T, et al. Oral acyclovir in the treatment of acute herpes zoster ophthalmicus. Ophthalmology. 1986;93(6):763-70.

33. Hoang-Xuan T, Buchi ER, Herbort CP, et al. Oral acyclovir for herpes zoster ophthalmicus. Ophthalmology. 1992;99(7):1062-71.

34. Aylward GW, Claoue CM, Marsh RJ, et al. Influence of oral acyclovir on ocular complications of herpes zoster ophthalmicus. Eye. 1994;8:70-4.

35. Acyclovir for the prevention of herpes simplex virus eye disease. Herpetic Eye Disease Study Group. N Engl J Med. 1998;339(5):300-6.

36. Sy A, McLeod SD, Cohen EJ, et al. Practice patterns and opinions in the management of recurrent or chronic herpes zoster ophthalmicus. Cornea. 2012;31(7):786-90.

37. Seok JK, Kim K, Rok Do Y, et al. Low-dose acyclovir is effective for prevention of herpes zoster in myeloma patients treated with bortezomib: a report from the Korean Multiple Myeloma Working Party (KMMWP) Retrospective Study. Jpn J Clin Oncol. 2011;41(3):353-7.

38. Cohen E, Jeng BH, Troxel AB, et al. Enrollment in The Zoster Eye Disease Study. Cornea. 2020;39(12):1480-4.

39. Aggarwal S, Cavalcanti BM, Pavan-Langston DP. Treatment of pseudodendrites in herpes zoster ophthalmicus with topical ganciclovir 0.15% gel. Cornea. 2014;33(2):109-13.

40. Wilhelmus KR, Gee L, Hauck WW, et al. Herpetic Eye Disease Study. A controlled trial of topical corticosteroids for herpes simplex stromal keratitis. Ophthalmology. 1994;101(12):1883-95.

41. Dua HS, Gomes J, King AJ, et al. The amniotic membrane in ophthalmology. Surv Ophthalmol. 2004;49(1):51-77.

42. Bonini S, Lambiase A, Rama P, et al. Phase II randomized, double-masked vehicle-controlled trial of recombinant human nerve growth factor for neurotrophic keratitis. Ophthalmology. 2018;125(9):1332-43.

43. Miller AE. Selective decline in cellular immune response to varicella-zoster in the elderly. Neurology. 1980;30(6):582-7.