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Review

Varicella-Zoster Virus Infection and Varicella-Zoster Virus Vaccine-Related Ocular Complications

1
Ophthalmology Department of the Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of Shenzhen, Shenzhen 518172, China
2
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, China
*
Author to whom correspondence should be addressed.
Vaccines 2025, 13(8), 782; https://doi.org/10.3390/vaccines13080782
Submission received: 11 June 2025 / Revised: 16 July 2025 / Accepted: 22 July 2025 / Published: 23 July 2025
(This article belongs to the Special Issue Varicella and Zoster Vaccination)

Abstract

The varicella-zoster virus is a human herpesvirus that causes varicella as the primary infection and HZ as the reactivation of a latent infection. Ten to twenty percent of cases of herpes zoster ophthalmicus (HZO) involve the ophthalmic branch of the fifth cranial nerve. Any area of the eye may be affected by the condition. HZ has a lifetime risk of more than 30%. Complications from herpes zoster can significantly lower quality of life. The goal of HZ vaccinations is to stop HZ activation and PHN formation. Despite the uncommon possibility of side effects such as eye problems, the majority of vaccines on the market now are safe. The purpose of this review is to discuss VZV infection and analyze and summarize the ocular complications following VZV vaccination.

1. Introduction

Varicella-zoster virus (VZV) is a neurotropic human herpesvirus and a double-stranded DNA virus that can cause two distinct diseases: varicella (chickenpox) and herpes zoster (shingles), a vesicular dermatomal rash brought on by the latent virus reactivating. Varicella zoster virus-specific T cell-mediated immunity is largely in charge of regulating viral reactivation and causing herpes zoster. Months to years after the initial infection resolves, VZV establishes latency in peripheral ganglia neurons. Endogenous (subclinical) reactivation and exogenous re-exposure to VZV periodically increase immunity, and VZV-specific memory T cells, which have a mixed central and effector nature, are crucial for preserving VZV latency [1]. A latent virus can nevertheless replicate and produce recurring clinical illness [2]. Declining T cell immunity, not humoral immunity, is primarily responsible for the rise in VZV reactivation seen with aging [3]. Regardless of varicella incidence, herpes zoster is a rare, year-round condition with no seasonal predominance. There is no proof that HZ is caused by an external VZV infection, meaning that it can be contracted by coming into contact with an HZ or varicella carrier. Instead, variables affecting the virus–host relationship—most notably the host’s VZV-CMI, which preserves VZV latency—determine the prevalence of HZ. Even in nations where varicella vaccination has all but eradicated the disease, a number of epidemiologic studies have demonstrated that the age-specific incidence of HZ has risen in the previous seven decades [4,5,6,7].
HZ has a lifetime risk of more than 30%. The incidence rate of HZ in people aged 50 and older varies from 5.23 to 10.9/1000 person-years [8] and from 3 to 5/1000 person-years globally [9]. As people age, the frequency and severity of HZ rise. Nearly half of older adults with HZ experience problems [9], and 50% of those who live to age 85 will acquire HZ [9,10,11]. Herpes zoster and its aftereffects can cause irreparable loss of independence and significantly lower quality of life [12]. Postherpetic neuralgia (PHN), the most common disabling consequence of HZ, is characterized by neuropathic pain and dysesthesia that persists for weeks, months, or even years after the rash has healed [13,14,15,16]. The frequency of PHN rises significantly with age [13,17]. The development of vaccinations to protect older adults from HZ is prompted by the rising incidence of HZ and its crippling consequences as people age. The FDA has approved a number of vaccines to prevent VZV. A live attenuated virus called Varivax is used to prevent varicella in children [18]. In 2006, the FDA authorized Zostavax, a live attenuated Oka strain virus, for the secondary prevention of zoster. However, because of the risk of zoster reactivation in immunocompromised persons and its gradual decline in immunogenicity, its usage has been restricted [19]. The FDA authorized Shingrix, a recombinant subunit zoster vaccine, in 2017, for the prevention of zoster in immunocompetent people 50 years of age and older. Clinicians should be aware of the possibility of post-vaccination VZV infection or reactivation, even if it seems to be uncommon. A pertinent overview of VZV infection and ocular problems linked to VZV vaccination is hence the goal of this work.

2. VZV Infection and Common Related Ocular Complications

2.1. VZV Infection

Primary VZV infection results in varicella, which is typified by a widespread itchy rash that quickly develops from macules to papules to vesicular lesions and finally crusts. VZV creates a permanent delay in the sensory and autonomic ganglia during the initial infection [20,21]. HZ, a localized illness of the skin, nerve, and sensory ganglia, is caused by VZV replication after reactivation from latency. Herpes zoster typically only affects the dermatome innervated by a single dorsal root or cranial nerve ganglion, resulting in unilateral radicular discomfort and a vesicular rash [22]. The clustering of the lesions indicates intraneural transmission to the skin. Regardless of varicella incidence, herpes zoster is a rare, year-round condition with no seasonal predominance.

2.2. Common Ocular Complications Associated with VZV Infection

Ocular problems can occasionally be linked to primary VZV infection in children. In 12–25% of cases, a moderate acute anterior uveitis may develop, resulting in discomfort, perilimbal injection, swelling of the lids, irritation, photophobia, and reduced visual acuity [23]. Furthermore, there have been documented instances of acute retinal necrosis (ARN) complicating a primary VZV infection [24].
Herpes zoster ophthalmicus (HZO) is the involvement of the ophthalmic branch of the trigeminal nerve, and it represents 10–20% of HZ cases [25]. The disease can impact any part of the eye, including the conjunctiva, cornea, trabecular meshwork, and uvea, which are frequently the sites of immune-mediated injury as well as direct viral invasion. Due to the paralysis of the orbicular muscle, the virus can cause lagophthalmos, which is the inability to close the eyelids completely, as well as hyperemia, edema, skin rashes, ptosis, and impaired palpebral motility [26,27,28]. Conjunctivitis was the most prevalent manifestation at the conjunctival level. Corneal surface epithelial keratitis [26,28], pseudodendrites [27,28,29], anterior stromal infiltrates [26,28], late corneal mucous plaque keratitis (MPK) [30], disciform keratitis [26,28], endothelitis with possible endothelial cell loss [31], neurotrophic keratitis due to sensory nerve involvement with corneal hypoesthesia or anesthesia [29,32,33], or exposure keratitis, if linked to an eyelid defect [26], are among the ocular structures most commonly affected by HZO. Scleritis and episcleritis [27,34,35], cataracts [29], anterior uveitis [27,28,32,36], and iris degeneration with sectoral atrophy [27,28] are further signs of HZO. High intraocular pressure during HZO is frequently observed and may be associated with subsequent glaucoma [27,29,37] and trabeculitis [28]. An uncommon side effect of HZO is optic neuritis [32]. VZV is also the most common cause of ARN, as was previously indicated.
According to reports, 6.6–10% of patients experience a reduction in visual acuity as a result of HZO due to possible ocular problems [27,34,38].

3. Varicella-Zoster Virus Vaccines and Associated Ocular Complications

3.1. Varicella-Zoster Virus Vaccines

The FDA has approved a number of vaccines to prevent VZV. A live attenuated virus called Varivax (Merck, Whitehouse Station, NJ, USA) is used to prevent varicella in children [18]. Since the varicella immunization program was put into place in 1995, there has been a notable decline in both the incidence of varicella and hospitalizations attributable to the disease [39]. Rarely, keratitis or anterior uveitis have been reported in the days after vaccination. It is unclear to determine whether the ocular issues in the majority of these cases were caused by the live attenuated virus that was injected or by the wild-type virus’s pre-existing latency, notwithstanding the temporal link [40,41].
For the secondary prevention of zoster, Zostavax (Merck, Whitehouse Station, New Jersey) is a live attenuated Oka strain virus that was approved by FDA in 2006. The live attenuated virus is the same in both Zostavax and Varivax, but Zostavax has a larger dosage. Zostavax decreased the “burden of illness due to HZ” by 61.1%; decreased the “incidence of clinically significant PHN” by 66.5%; and decreased the “incidence of HZ” by 51.3% [42]. Furthermore, Zostavax markedly decreased the adverse impact of HZ on quality of life and capacity to perform activities of daily living. Additionally, Zostavax significantly reduced the negative effects of HZ on quality of life and ability to carry out daily tasks [43].
However, after receiving the Zostavax vaccine, some individuals with a history of HZO may experience ocular, dermatological, or widespread recurrence, according to some studies [27,35,44]. However, because of the risk of zoster reactivation in immunocompromised persons and its gradual decline in immunogenicity, its usage has been restricted. In many nations today, the recombinant zoster vaccine Shingrix has largely replaced Zostavax. Shingrix is a subunit vaccination that includes the AS01B adjuvant system together with the VZV glycoprotein E antigen. For individuals aged 50 and over, Shingrix is a new, highly effective, and well-tolerated vaccine alternative that reduces the incidence of HZ (more than 90% decrease in risk of HZ) and postherpetic neuralgia. According to US and Canadian guidelines, it is recommended above a live attenuated HZ vaccination in immunocompetent persons and is not contraindicated in immunocompromised subjects [45]. One rare but dangerous possible ocular side effect of recombinant zoster immunization is uveitis recurrence. There have been numerous reports of uveitis reactivation after Shingrix. It is quite uncommon for HZO to develop after Shingrix.

3.2. Ocular Adverse Events Following VZV Vaccination

Although they have many advantages, vaccines can potentially have negative effects. Among these problems, uveitis and ocular inflammation are rather common [46]. We have summarized and compared all the cases in Table 1 and Table 2.
According to previously published reports, 20 cases comprising 24 patients with VZV-associated ocular complications have been described [47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66]. The average age of patients after Varivax was 17.2 years (range, 5–42 years), and the average age of patients after Herpes Zoster Vaccines was 69.1 years (range, 50–89 years), with a male-to-female ratio of 7:5; 45.8% patients presented systemic symptoms, and 79.1% of patients experienced varying degrees of decline in visual acuity, with the onset of symptoms varying from 24 h to 3 years. In total, 79.2% of patients had underlying medical conditions. Corticosteroids and/or antiviral medications were used to treat every case. Except for one patient who died from the primary disease [59], one patient with significant visual decline [62], and one patient who developed secondary neovascularization [63], the remaining patients recovered well.
Only 54.2% of the cases underwent VZV DNA testing, and the results showed that three of these patients tested positive for the Oka strain of the VZV vaccine [52,55], pointing to a possible connection between ARN and vaccination strain infection. And five of these patients had wild-type VZV, suggesting that VZV reactivation rather than vaccination reactivation may have been the cause of the majority of ARN cases. Additionally, the majority of patients had cirrhosis, diabetes, and inflammatory gastrointestinal disorders, which are systemic metabolic conditions that may have contributed to the development of ARN following VZV immunization.
After receiving the VZV vaccine, patients who develop uveitis frequently experience serious systemic illness, indicating that those who have serious underlying illnesses or conditions affecting their immune systems may be more vulnerable to negative reactions to the VZV vaccine. Potential vulnerability to attenuated VZV vaccinations could be the cause of this.
Previous history of HZO is identified by other studies as a risk factor for a potential recurrence after vaccination [50,53,54]. Among our cases, 8 involved recurrence or worsening of pre-existing conditions following vaccination. But according to a study based on the Health-Claim Database [67], patients who received Zostavax did not have a higher risk of anterior segment complications than those who were initially diagnosed with HZ. It was also noted that the reactivation of the virus and HZ after Zostavax vaccination is extremely uncommon. Therefore, despite these possible hazards, the vaccine is regarded as safe [68], problems are uncommon [69], and a history of HZO does not actually preclude vaccination [25,35,50,53,70,71]. According to Shingrix’s post-licensure surveillance, there were few complaints of uveitis and a reporting rate of 0.6/100,000 for inflammatory eye disorders [72]. Potential immune-mediated disorders occurred at a similar rate for both vaccine recipients and controls at all time points, according to the results of two sizable randomized placebo-controlled phase 3 studies of the Shingrix [73]. Similarly, when compared to controls, individuals who already had potential immune-mediated disorders did not show a higher risk of developing a new immune-mediated process or experiencing an exacerbation of their pre-existing condition following immunization.
Table 1. Patients with complications after Varivax.
Table 1. Patients with complications after Varivax.
StudyDiagnosisVaccine NameVaccine TypeAgeGenderSignsSymptomsLab TestsMedical HistoryInterval Post-Vaccination ^TreatmentOutcome
Esmaeli-Gutstein et al. [47]Anterior and intermediate uveitis (left eye)varicella vaccineLive attenuated16Fgeneralized vesicular rash on her face and trunkphotophobia, blurred vision, and redness in the left eyenonenone1 week after vaccinationpo acyclovir, topical corticosteroidsresolved completely
Naseri et al. [48]Herpes zoster virus sclerokeratitis and anterior uveitis (left eye)varicella vaccineLive attenuated9Mrash in left facered left eyewild-type VZV DNA (+)mild childhood asthma and mild eczema3 years after vaccinationpo acyclovir/topical corticosteroidsfaint anterior stromal scar
Fine et al. [49]Bilateral APMPPEvaricella vaccineLive attenuated11Msevere headaches and tinnitusblurry vision and photopsiasVZV Ab (+)none10 days after vaccinationpo acyclovir/oral corticosteroidspartially resolved
Gonzales et al. [52]Bilateral ARNvaricella vaccineLive attenuated20Mnonered eyes and blurry visionOka strain VZV DNA (+)immunosuppressant for an inflammatory gastroenteropathy1 month after vaccinationio foscarnet, antiviral drugs, pars plana vitrectomyundisclosed
Hayat et al. [66]Bilateral ARNvaricella vaccineLive attenuated42Mgeneralized vesicular rash, malaise, arthralgia, and body achesblurred visionOka strain VZV DNA (+)previously undiagnosed human immunodeficiency virus infection4 weeks after vaccinationio /iv foscarnet, antiviral drugsvisual acuity improved
Andrade et al. [65]Uveitisvaricella vaccineLive attenuated5Mvesicular cutaneous lesionshyperemiaVZV DNA (+)steroid-dependent nephrotic syndrome14 days after vaccinationiv/po antiviral drugs, steroids, topical corticosteroidclinically stable
^ Time between last vaccination and initial ocular symptom/sign.
Table 2. Patients with complications after Herpes Zoster Vaccines.
Table 2. Patients with complications after Herpes Zoster Vaccines.
StudyDiagnosisVaccine NameVaccine TypeAgeGenderSignsSymptomsLab TestsMedical HistoryInterval Post-Vaccination ^TreatmentOutcome
Khalifa et al. [50]Exacerbation of Zoster Interstitial KeratitisZOSTAVAXLive attenuated50Fnonevision loss, extensive epithelial edema, and diffuse stromal haze involving the lower two-thirds of the left corneanoneZoster Interstitial Keratitis35 days after vaccinationoral valacyclovir, topical corticosteroidundisclosed
Charkoudian et al. [51]ARN (left eye)ZOSTAVAXLive attenuated77Fnonesevere vision lossVZV DNA (+)diabetes mellitus with secondary end-stage renal disease6 days after vaccinationpo/iv antiviral drugs, vitrectomyundisclosed
Bilateral ARNZOSTAVAXLive attenuated80Mrash and feversevere vision lossVZV DNA (+)hypertension and renal transplantation2 months after vaccinationpo/iv antiviral drugs, io foscarnet, bilateral vitrectomyundisclosed
Sham et al. [53]Exacerbation of anterior uveitis (right eye)ZOSTAVAXLive attenuated86Mnonevision loss and worsened corneal edemanonemedical history of HZO with anterior uveitis3 weeks after vaccinationpo valacyclovir, topical corticosteroidsreturn to his baseline condition
Hwang et al. [54]Reactivation of Herpes Zoster KeratitisZOSTAVAXLive attenuated63Mnoneredness, pruritus, photophobia, and painnonenon-Hodgkin lymphoma and right-sided HZO2 weeks after vaccinationoral valacyclovir, topical corticosteroidpunctate
epithelial keratopathy and a mild subepithelial haze
Heath et al. [55]ARN (left eye)ZOSTAVAXLive attenuated78FnonefloatersOka strain VZV DNA (+)noteworthy for rheumatoid arthritis, latent autoimmune diabetes of adulthood and osteoporosis6 weeks after vaccinationpo valaciclovir, topical corticosteroids, pars plana vitrectomyA pigmented scar
Jastrzebski et al. [56]ARNZOSTAVAXLive attenuated67Fnonecentral corneal staining, corneal perforationnonerecurrent
unilateral herpes zoster keratouveitis
2 weeks after vaccinationoral famciclovir/ penetrating keratoplastyresidual pigmented keratic precipitates on the corneal endothelium and punctate epithelial erosions
Ali et al. [57]ARN and contralateral cutaneous eruptionZOSTAVAXLive attenuated63Mvaricella skin eruption
on the right side of his face
insidious deterioration in visionVZV DNA (+)none3 months after vaccinationio foscarnet, po antiviral drugs, po steroidsnone
Lehmann et al. [58]Reactivation of Herpes Zoster Stromal KeratitisSHINGRIXRecombinant zoster vaccine89Mnonediffuse stromal edema, anterior stromal granular infiltrate, and keratic precipitatesnoneherpes-zoster-associated stromal keratitis3 weeks after the first dosetopical corticosteroidresolved
Weinlander et al. [59]ARN (left eye)ZOSTAVAXLive attenuated64Mnonefloaters and cloudy visionWild-type VZV DNA (+)metabolic syndrome and impaired glucose tolerance16 months after vaccinationpo valacyclovir, po/topical corticosteroidsstable region of chorioretinal atrophy
ARN (left eye)ZOSTAVAXLive attenuated62Mnonefloaters and blurred visionWild-type VZV DNA (+)end-stage liver disease and diabetes mellitus type 27 months after vaccinationpo valacyclovir, topical corticosteroidsdied from complications of his cirrhosis
Heydari-Kamjani et al. [60]Bilateral uveitis sarcoidosisSHINGRIXRecombinant zoster vaccine53Fheadachesleft eye redness, photophobia, and eye painnonemild persistent asthma4 days after vaccinationtopical corticosteroidnone
Chen R.I. et al. [61]ARN (left eye)SHINGRIXRecombinant zoster vaccine65Fsystemic vesicular rash and hypoxic respiratory failureworsening floaters and blurred visionwild-type VZV DNA (+)immunomodulator for multiple myeloma6 weeks after vaccinationio foscarnet, iv/po antiviral drugsfree of active retinitis
Menghini et al. [62]ARN with obliterative angiopathy (left eye)ZOSTAVAXLive attenuated76Mnoneblurry vision, slight pain, and rednesswild-type VZV DNA (+)insulin-dependent diabetes mellitus, chronic lymphocytic leukemia2 days after vaccinationio foscarnet, iv/po/iv antiviral drugs, iv/po steroidsleft eye visual acuity dropped to perception only
Richards et al. [63]Recurrent bilateral multifocal choroiditisSHINGRIXRecombinant zoster vaccine57Farm swelling at the injection site, chills, malaise, subjective fever, and tinnitusacute decrease in vision in the right eye (OD) and new metamorphopsia in the left eyenoneimmunosuppressant for multifocal choroiditis24 h after the first dosepo steroids and continued methotrexateintravitreal bevacizumab for a secondary choroidal neovascular membrane
Recurrent bilateral anterior and mild intermediate uveitisSHINGRIXRecombinant zoster vaccine69Mheadacheblurred visionnoneidiopathic recurrent bilateral anterior and mild intermediate uveitis1 month after the second dosepo valacyclovir/topical corticosteroidsnone
Recurrent anterior uveitis (left eye)SHINGRIXRecombinant zoster vaccine70Fnonemildly decreased visionnonerecurrent unilateral anterior uveitis and corneal neovascularization2 weeks after the first doseoral valacyclovir, topical corticosteroidreturn to quiescence
R. T. Liu et al. [64]Reactivation of herpes zoster keratitisSHINGRIXRecombinant zoster vaccine75Fnonedecreased visual, corneal foldsnoneHZO keratitisTwo and a half weeksoral valacyclovir, topical corticosteroidcompletely resolved
^ Time between last vaccination and initial ocular symptom/sign.
The underlying mechanism of ocular complications following varicella-zoster vaccination remains unclear. There are different views on different vaccines. There are two possible explanations for the activation of ocular complications after vaccination with live attenuated vaccine: one possibility is that some patients may have immunosuppression, leading to vaccine strain virus infection; the second possibility is that vaccine strain viruses are rarely detected in patients who develop varicella rash after vaccination, and these viruses are more likely to represent the reactivation of varicella [42].
Theoretically, Shingrix cannot cause iatrogenic infection because it is a subunit vaccine rather than an attenuated live virus. It contains the AS01B adjuvant-formulated VZV glycoprotein-E. There could be two possible pathways, as opposed to the direct infection from attenuated but still active live attenuated vaccinations that cause uveitis: (1) Several in vitro investigations, including those involving monophosphorylate lipid A (MPL), have shown that the adjuvant AS01B can cause uveitis. (2) The manufacturing of the Shingrix vaccine, which uses Chinese hamster ovary (CHO) cells, may include trace levels of host cell proteins (HCPs) in the finished vaccine, which could cause autoimmune reactions [64]. In the existing case reports, due to limitations in detection methods, only some patients underwent genotyping, and no patients who received the subunit herpes zoster vaccine were found to have the Oka strain positive genotype. This suggests that the possible cause of ocular complications in patients after receiving the recombinant subunit vaccine may be immune modulation phenomena leading to the reactivation of dormant VZV [60].
The latest article proposes a new hypothesis suggesting that the injection site of vaccination may be related to ocular complications following vaccination [74]. There may be a potential correlation between the pathophysiological mechanisms of upper limb vaccination and post-vaccination ocular complications. Proximal viral infections—those closer to the head—can allow the virus to directly reach the retina through the central retinal artery, which is a branch of the ophthalmic artery that originates from the internal carotid artery. It suggests that retinitis requires proximal viremia after vaccination closer to the head, allowing the virus to reach the trigeminal ganglion or superior cervical ganglion. Vaccination in the thigh would reduce the likelihood of the virus reaching its target ganglia. In many countries, Varivax is given to young children by injection into the thigh rather than the arm. Young children who were given Varivax by injection into the leg did not have any ocular complications. In the currently reported cases, except for one 5-year-old child, all other cases were older than 9 years. For this 5-year-old child, the injection site was clearly documented as the right upper limb. There were no cases of ocular complications in children under the age of 9 years, even though many million doses of Varivax have been given to young children under the age of 9 years, often in the leg.

4. Conclusions

All things considered, more research is necessary to fully understand the connection between the VZV vaccine and ocular problems. Half of adults who reach the age of 85 will suffer from HZ, and one-third of adults will develop it throughout their lives. HZ has a significant negative influence on older people, despite the fact that it is rarely fatal. It causes persistent neuropathic pain, diminished physical and social functioning, emotional discomfort, decreased productivity, medical expenses, and irreversible loss of independence. The most economical methods of reducing disease incidence have been found to be preventative vaccines against concurrent conditions. Although ocular side effects after VZV vaccine are possible, they are quite uncommon, and immunization is advised.

Author Contributions

Formal Analysis, H.L. (Huihui Li); Investigation, H.L. (Huihui Li) and J.Y.; Resources, H.L. (Huihui Li) and J.Y.; Data Curation, H.L. (Huihui Li) and H.L. (Hailan Liao); Writing—Original Draft Preparation, J.Y. and Y.J.; Writing—Review and Editing, Y.J.; Supervision, Y.J.; Project Administration, Y.J. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Data Availability Statement

Data are available on request.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Ouwendijk, W.J.; Laing, K.J.; Verjans, G.M.; Koelle, D.M. T-cell immunity to human alphaherpesviruses. Curr. Opin. Virol. 2013, 3, 452–460. [Google Scholar] [CrossRef] [PubMed]
  2. Steiner, I.; Kennedy, P.G.; Pachner, A.R. The neurotropic herpes viruses: Herpes simplex and varicella-zoster. Lancet Neurol. 2007, 6, 1015–1028. [Google Scholar] [CrossRef] [PubMed]
  3. Levin, M.J. Immune senescence and vaccines to prevent herpes zoster in older persons. Curr. Opin. Immunol. 2012, 24, 494–500. [Google Scholar] [CrossRef] [PubMed]
  4. Harpaz, R. Do varicella vaccination programs change the epidemiology of herpes zoster? A comprehensive review, with focus on the United States. Expert Rev. Vaccines 2019, 18, 793–811. [Google Scholar] [CrossRef] [PubMed]
  5. Harpaz, R.; Leung, J.W. The Epidemiology of Herpes Zoster in the United States During the Era of Varicella and Herpes Zoster Vaccines: Changing Patterns Among Older Adults. Clin. Infect. Dis. 2019, 69, 341–344. [Google Scholar] [CrossRef] [PubMed]
  6. Wolfson, L.J.; Daniels, V.J.; Altland, A.; Black, W.; Huang, W.; Ou, W. The Impact of Varicella Vaccination on the Incidence of Varicella and Herpes Zoster in the United States: Updated Evidence From Observational Databases, 1991–2016. Clin. Infect. Dis. 2020, 70, 995–1002. [Google Scholar] [CrossRef] [PubMed]
  7. Thompson, R.R.; Kong, C.L.; Porco, T.C.; Kim, E.; Ebert, C.D.; Acharya, N.R. Herpes Zoster and Postherpetic Neuralgia: Changing Incidence Rates From 1994 to 2018 in the United States. Clin. Infect. Dis. 2021, 73, e3210–e3217. [Google Scholar] [CrossRef] [PubMed]
  8. van Oorschot, D.; Vroling, H.; Bunge, E.; Briquet, B.; Diaz-Decaro, J.; Curran, D.; Yawn, B. A systematic literature review of herpes zoster incidence worldwide. Hum. Vaccines Immunother. 2021, 17, 1714–1732. [Google Scholar] [CrossRef] [PubMed]
  9. Kawai, K.; Gebremeskel, B.G.; Acosta, C.J. Systematic review of incidence and complications of herpes zoster: Towards a global perspective. BMJ Open 2014, 4, e004833. [Google Scholar] [CrossRef] [PubMed]
  10. Hope-Simpson, R.E. The nature of herpes zoster: A long-term study and a new hypothesis. Proc. R. Soc. Med. 1965, 58, 9–20. [Google Scholar] [CrossRef] [PubMed]
  11. Yawn, B.P.; Gilden, D. The global epidemiology of herpes zoster. Neurology 2013, 81, 928–930. [Google Scholar] [CrossRef] [PubMed]
  12. Drolet, M.; Brisson, M.; Schmader, K.E.; Levin, M.J.; Johnson, R.; Oxman, M.N.; Patrick, D.; Blanchette, C.; Mansi, J.A. The impact of herpes zoster and postherpetic neuralgia on health-related quality of life: A prospective study. CMAJ Can. Med. Assoc. J. 2010, 182, 1731–1736. [Google Scholar] [CrossRef] [PubMed]
  13. Kost, R.G.; Straus, S.E. Postherpetic neuralgia—Pathogenesis; treatment, and prevention. N. Engl. J. Med. 1996, 335, 32–42. [Google Scholar] [CrossRef] [PubMed]
  14. Cohen, J.I. Clinical practice: Herpes zoster. N. Engl. J. Med. 2013, 369, 255–263. [Google Scholar] [CrossRef] [PubMed]
  15. Johnson, R.W.; Rice, A.S. Clinical practice. Postherpetic neuralgia. N. Engl. J. Med. 2014, 371, 1526–1533. [Google Scholar] [CrossRef] [PubMed]
  16. Forbes, H.J.; Thomas, S.L.; Smeeth, L.; Clayton, T.; Farmer, R.; Bhaskaran, K.; Langan, S.M. A systematic review and meta-analysis of risk factors for postherpetic neuralgia. Pain 2016, 157, 30–54. [Google Scholar] [CrossRef] [PubMed]
  17. Dworkin, R.H.; Portenoy, R.K. Pain and its persistence in herpes zoster. Pain 1996, 67, 241–251. [Google Scholar] [CrossRef] [PubMed]
  18. White, C.J.; Kuter, B.J.; Hildebrand, C.S.; Isganitis, K.L.; Matthews, H.; Miller, W.J.; Provost, P.J.; Ellis, R.W.; Gerety, R.J.; Calandra, G.B. Varicella vaccine (VARIVAX) in healthy children and adolescents: Results from clinical trials, 1987 to 1989. Pediatrics 1991, 87, 604–610. [Google Scholar] [PubMed]
  19. Bharucha, T.; Ming, D.; Breuer, J. A critical appraisal of ‘Shingrix’, a novel herpes zoster subunit vaccine (HZ/Su or GSK1437173A) for varicella zoster virus. Hum. Vaccines Immunother. 2017, 13, 1789–1797. [Google Scholar] [CrossRef] [PubMed]
  20. Lal, H.; Cunningham, A.L.; Godeaux, O.; Chlibek, R.; Diez-Domingo, J.; Hwang, S.-J.; Levin, M.J.; McElhaney, J.E.; Poder, A.; Puig-Barberà, J.; et al. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N. Engl. J. Med. 2015, 372, 2087–2096. [Google Scholar] [CrossRef] [PubMed]
  21. Cunningham, A.L.; Lal, H.; Kovac, M.; Chlibek, R.; Hwang, S.-J.; Díez-Domingo, J.; Godeaux, O.; Levin, M.J.; McElhaney, J.E.; Puig-Barberà, J.; et al. Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older. N. Engl. J. Med. 2016, 375, 1019–1032. [Google Scholar] [CrossRef] [PubMed]
  22. Gnann, J.W., Jr.; Whitley, R.J. Clinical practice. Herpes zoster. N. Engl. J. Med. 2002, 347, 340–346. [Google Scholar] [CrossRef] [PubMed]
  23. Johnston, N.R. Red eye in chickenpox: Varicella-related acute anterior uveitis in a child. BMJ Case Rep. 2010, 2010, bcr0120102678. [Google Scholar] [CrossRef] [PubMed]
  24. Gargouri, S.; Khochtali, S.; Zina, S.; Khairallah, M.; Zone-Abid, I.; Kaibi, I.; Ben Yahia, S.; Feki, J.; Khairallah, M. Ocular involvement associated with varicella in adults. J. Ophthalmic Inflamm. Infect. 2016, 6, 47. [Google Scholar] [CrossRef] [PubMed]
  25. Liesegang, T.J. Herpes zoster ophthalmicus natural history, risk factors, clinical presentation, and morbidity. Ophthalmology 2008, 115, S3–S12. [Google Scholar] [CrossRef] [PubMed]
  26. Kaufman, S.C. Anterior segment complications of herpes zoster ophthalmicus. Ophthalmology 2008, 115, S24–S32. [Google Scholar] [CrossRef] [PubMed]
  27. Tugal-Tutkun, I.; Cimino, L.; Akova, Y.A. Review for Disease of the Year: Varicella Zoster Virus-Induced Anterior Uveitis. Ocul. Immunol. Inflamm. 2018, 26, 171–177. [Google Scholar] [CrossRef] [PubMed]
  28. Vrcek, I.; Choudhury, E.; Durairaj, V. Herpes Zoster Ophthalmicus: A Review for the Internist. Am. J. Med. 2017, 130, 21–26. [Google Scholar] [CrossRef] [PubMed]
  29. Ghaznawi, N.; Virdi, A.; Dayan, A.; Hammersmith, K.M.; Rapuano, C.J.; Laibson, P.R.; Cohen, E.J. Herpes zoster ophthalmicus: Comparison of disease in patients 60 years and older versus younger than 60 years. Ophthalmology 2011, 118, 2242–2250. [Google Scholar] [CrossRef] [PubMed]
  30. Marsh, R.J. Herpes zoster keratitis. Trans. Ophthalmol. Soc. UK 1973, 93, 181–192. [Google Scholar] [PubMed]
  31. Reijo, A.; Antti, V.; Jukka, M. Endothelial cell loss in herpes zoster keratouveitis. Br. J. Ophthalmol. 1983, 67, 751–754. [Google Scholar] [CrossRef] [PubMed]
  32. Kahloun, R.; Attia, S.; Jelliti, B.; Attia, A.Z.; Khochtali, S.; Ben Yahia, S.; Zaouali, S.; Khairallah, M. Ocular involvement and visual outcome of herpes zoster ophthalmicus: Review of 45 patients from Tunisia, North Africa. J. Ophthalmic Inflamm. Infect. 2014, 4, 25. [Google Scholar] [CrossRef] [PubMed]
  33. Cobo, M.; Foulks, G.N.; Liesegang, T.; Lass, J.; Sutphin, J.; Wilhelmus, K.; Jones, D.B. Observations on the natural history of herpes zoster ophthalmicus. Curr. Eye Res. 1987, 6, 195–199. [Google Scholar] [CrossRef] [PubMed]
  34. Yawn, B.P.; Wollan, P.C.; Sauver, J.L.S.; Butterfield, L.C. Herpes zoster eye complications: Rates and trends. Mayo Clin. Proc. 2013, 88, 562–570. [Google Scholar] [CrossRef] [PubMed]
  35. Tran, K.D.; Falcone, M.M.; Choi, D.S.; Goldhardt, R.; Karp, C.L.; Davis, J.L.; Galor, A. Epidemiology of Herpes Zoster Ophthalmicus: Recurrence and Chronicity. Ophthalmology 2016, 123, 1469–1475. [Google Scholar] [CrossRef] [PubMed]
  36. Kido, S.; Sugita, S.; Horie, S.; Miyanaga, M.; Miyata, K.; Shimizu, N.; Morio, T.; Mochizuki, M. Association of varicella zoster virus load in the aqueous humor with clinical manifestations of anterior uveitis in herpes zoster ophthalmicus and zoster sine herpete. Br. J. Ophthalmol. 2008, 92, 505–508. [Google Scholar] [CrossRef] [PubMed]
  37. Thean, J.H.; Hall, A.J.; Stawell, R.J. Uveitis in Herpes zoster ophthalmicus. Clin. Exp. Ophthalmol. 2001, 29, 406–410. [Google Scholar] [CrossRef] [PubMed]
  38. Szeto, S.K.; Sugita, S.; Horie, S.; Miyanaga, M.; Miyata, K.; Shimizu, N.; Morio, T.; Mochizuki, M. Prevalence of Ocular Manifestations and Visual Outcomes in Patients With Herpes Zoster Ophthalmicus. Cornea 2017, 36, 338–342. [Google Scholar] [CrossRef] [PubMed]
  39. Lopez, A.S.; Zhang, J.; Marin, M. Epidemiology of Varicella During the 2-Dose Varicella Vaccination Program-United States, 2005–2014. MMWR Morb. Mortal. Wkly. Rep. 2016, 65, 902–905. [Google Scholar] [CrossRef] [PubMed]
  40. Centers for Disease Control and Prevention. Prevention of varicella: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb. Mortal. Wkly. Rep. 1996, 45, 1–36. [Google Scholar]
  41. Krall, P.; Kubal, A. Herpes zoster stromal keratitis after varicella vaccine booster in a pediatric patient. Cornea 2014, 33, 988–989. [Google Scholar] [CrossRef] [PubMed]
  42. Oxman, M.N.; Levin, M.; Johnson, G.; Schmader, K.; Straus, S.; Gelb, L.; Arbeit, R.; Simberkoff, M.; Gershon, A.; Davis, L.; et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N. Engl. J. Med. 2005, 352, 2271–2284. [Google Scholar] [CrossRef] [PubMed]
  43. Schmader, K.E.; Johnson, G.R.; Saddier, P.; Ciarleglio, M.; Wang, W.W.B.; Zhang, J.H.; Chan, I.S.F.; Yeh, S.-S.; Levin, M.J.; Harbecke, R.M.; et al. Effect of a zoster vaccine on herpes zoster-related interference with functional status and health-related quality-of-life measures in older adults. J. Am. Geriatr. Soc. 2010, 58, 1634–1641. [Google Scholar] [CrossRef] [PubMed]
  44. Galea, S.A.; Sweet, A.; Beninger, P.; Steinberg, S.P.; LaRussa, P.S.; Gershon, A.A.; Sharrar, R.G. The safety profile of varicella vaccine: A 10-year review. J. Infect. Dis. 2008, 197 (Suppl. S2), S165–S169. [Google Scholar] [CrossRef] [PubMed]
  45. Syed, Y.Y. Recombinant Zoster Vaccine (Shingrix®): A Review in Herpes Zoster. Drugs Aging 2018, 35, 1031–1040. [Google Scholar] [CrossRef] [PubMed]
  46. Agarwal, M.; Majumder, P.D.; Babu, K.; Konana, V.K.; Goyal, M.; Touhami, S.; Stanescu-Segall, D.; Bodaghi, B. Drug-induced uveitis: A review. Indian J. Ophthalmol. 2020, 68, 1799–1807. [Google Scholar] [CrossRef] [PubMed]
  47. Esmaeli-Gutstein, B.; Winkelman, J.Z. Uveitis associated with varicella virus vaccine. Am. J. Ophthalmol. 1999, 127, 733–734. [Google Scholar] [CrossRef] [PubMed]
  48. Naseri, A.; Good, W.V.; Cunningham, E.T. Herpes zoster virus sclerokeratitis and anterior uveitis in a child following varicella vaccination. Am. J. Ophthalmol. 2003, 135, 415–417. [Google Scholar] [CrossRef] [PubMed]
  49. Fine, H.F.; Kim, E.; Flynn, T.E.; Gomes, N.L.; Chang, S. Acute posterior multifocal placoid pigment epitheliopathy following varicella vaccination. Br. J. Ophthalmol. 2010, 94, 282–283, 363. [Google Scholar] [CrossRef] [PubMed]
  50. Khalifa, Y.M.; Jacoby, R.M.; Margolis, T.P. Exacerbation of zoster interstitial keratitis after zoster vaccination in an adult. Arch. Ophthalmol. 2010, 128, 1079–1080. [Google Scholar] [CrossRef] [PubMed]
  51. Charkoudian, L.D.; Kaiser, G.M.; Steinmetz, R.L.; Srivastava, S.K. Acute retinal necrosis after herpes zoster vaccination. Arch. Ophthalmol. 2011, 129, 1495–1497. [Google Scholar] [CrossRef] [PubMed]
  52. Gonzales, J.A.; Levison, A.L.; Stewart, J.M.; Acharya, N.R.; Margolis, T.P. Retinal necrosis following varicella-zoster vaccination. Arch. Ophthalmol. 2012, 130, 1355–1356. [Google Scholar] [CrossRef] [PubMed]
  53. Sham, C.W.; Levinson, R.D. Uveitis exacerbation after varicella-zoster vaccination in an adult. Arch. Ophthalmol. 2012, 130, 793–794. [Google Scholar] [CrossRef] [PubMed]
  54. Hwang, C.W., Jr.; Steigleman, W.A.; Saucedo-Sanchez, E.; Tuli, S.S. Reactivation of herpes zoster keratitis in an adult after varicella zoster vaccination. Cornea 2013, 32, 508–509. [Google Scholar] [CrossRef] [PubMed]
  55. Heath, G.; Depledge, D.P.; Brown, J.R.; Hale, A.D.; Tutil, H.; Williams, R.; Breuer, J. Acute Retinal Necrosis Caused by the Zoster Vaccine Virus. Clin. Infect. Dis. 2017, 65, 2122–2125. [Google Scholar] [CrossRef] [PubMed]
  56. Jastrzebski, A.; Brownstein, S.; Ziai, S.; Saleh, S.; Lam, K.; Jackson, W.B. Reactivation of Herpes Zoster Keratitis With Corneal Perforation After Zoster Vaccination. Cornea 2017, 36, 740–742. [Google Scholar] [CrossRef] [PubMed]
  57. Ali, A.; Kirschenbaum, M.D.; Sharma, S.; Wandel, T.L. Acute retinal necrosis and Contralateral cutaneous eruption after the shingles vaccine. Retin. Cases Brief Rep. 2021, 15, 43–44. [Google Scholar] [CrossRef] [PubMed]
  58. Lehmann, A.; Matoba, A. Reactivation of Herpes Zoster Stromal Keratitis After HZ/su Adjuvanted Herpes Zoster Subunit Vaccine. Ophthalmology 2018, 125, 1682. [Google Scholar] [CrossRef] [PubMed]
  59. Weinlander, E.J.; Wang, A.L.; Jaru-Ampornpan, P.; Altaweel, M.M.; Nork, T.M. Two cases of acute retinal necrosis due to varicella zoster despite prior shingles vaccination. Retin. Cases Brief Rep. 2019, 13, 241–243. [Google Scholar] [CrossRef] [PubMed]
  60. Heydari-Kamjani, M.; Vante, I.; Uppal, P.; Beckler, M.D.; Kesselman, M.M. Uveitis Sarcoidosis Presumably Initiated After Administration of Shingrix Vaccine. Cureus 2019, 11, e4920. [Google Scholar] [CrossRef] [PubMed]
  61. Chen, R.I.; Deaner, J.D.; Srivastava, S.K.; Lowder, C.Y. Acute retinal necrosis following recombinant subunit varicella-zoster virus vaccine. Am. J. Ophthalmol. Case Rep. 2020, 20, 100962. [Google Scholar] [CrossRef] [PubMed]
  62. Menghini, M.; Raja, V.; Raiter, J.; Balaratnasingam, C.; Constable, I.J. Acute retinal necrosis associated with herpes zoster vaccination. Retin. Cases Brief Rep. 2021, 15, 166–168. [Google Scholar] [CrossRef] [PubMed]
  63. Richards, P.J.; Wingelaar, M.J.; Armbrust, K.R.; Kopplin, L.J. Uveitis reactivation following recombinant zoster vaccination. Am. J. Ophthalmol. Case Rep. 2021, 23, 101115. [Google Scholar] [CrossRef] [PubMed]
  64. Lu, T.J.; Ta, C.N. Reactivation of Herpes Zoster Keratitis Following Shingrix Vaccine. Case Rep. Ophthalmol. 2022, 13, 104–108. [Google Scholar] [CrossRef] [PubMed]
  65. Andrade, C.; Cordeiro, M.d.A.; Baptista, R.B.; Nunes, B.S.; Garcia, A.M.; Silva, T.M.; Pinto, M.V. Post-varicella vaccination uveitis in a child with nephrotic syndrome receiving immunosuppressive treatment: A case report. Front. Pediatr. 2025, 13, 1567164. [Google Scholar] [CrossRef] [PubMed]
  66. Hayat, U.; Afroz, S. Generalized Rash and Bilateral Retinal Necrosis in an Adult Healthcare Worker after Post-Exposure Herpes Zoster Vaccination: A Rare Case Report. Kans. J. Med. 2020, 13, 324–325. [Google Scholar] [CrossRef] [PubMed]
  67. Liu, R.T.; Yeung, S.N.; Carleton, B.; Etminan, M. Risk of Anterior Segment Complications Associated With the Live Herpes Zoster Vaccine: Evidence From a Health-Claim Database. Cornea 2018, 37, 952–956. [Google Scholar] [CrossRef] [PubMed]
  68. Willis, E.D.; Woodward, M.; Brown, E.; Popmihajlov, Z.; Saddier, P.; Annunziato, P.W.; Halsey, N.A.; Gershon, A.A. Herpes zoster vaccine live: A 10 year review of post-marketing safety experience. Vaccine 2017, 35, 7231–7239. [Google Scholar] [CrossRef] [PubMed]
  69. Simberkoff, M.S.; Arbeit, R.D.; Johnson, G.R.; Oxman, M.N.; Boardman, K.D.; Williams, H.M.; Levin, M.J.; Schmader, K.E.; Gelb, L.D.; Keay, S.; et al. Safety of herpes zoster vaccine in the shingles prevention study: A randomized trial. Ann. Intern. Med. 2010, 152, 545–554. [Google Scholar] [CrossRef] [PubMed]
  70. Cheetham, T.C.; Marcy, S.M.; Tseng, H.-F.; Sy, L.S.; Liu, I.-L.A.; Bixler, F.; Baxter, R.; Donahue, J.G.; Naleway, A.L.; Jacobsen, S.J. Risk of Herpes Zoster and Disseminated Varicella Zoster in Patients Taking Immunosuppressant Drugs at the Time of Zoster Vaccination. Mayo Clin. Proc. 2015, 90, 865–873. [Google Scholar] [CrossRef] [PubMed]
  71. Tseng, H.F.; Lewin, B.; Hales, C.M.; Sy, L.S.; Harpaz, R.; Bialek, S.; Luo, Y.; Jacobsen, S.J.; Reddy, K.; Huang, P.-Y.; et al. Zoster Vaccine and the Risk of Postherpetic Neuralgia in Patients Who Developed Herpes Zoster Despite Having Received the Zoster Vaccine. J. Infect. Dis. 2015, 212, 1222–1231. [Google Scholar] [CrossRef] [PubMed]
  72. Tavares-Da-Silva, F.; Co, M.M.; Dessart, C.; Hervé, C.; López-Fauqued, M.; Mahaux, O.; Van Holle, L.; Stegmann, J.-U. Review of the initial post-marketing safety surveillance for the recombinant zoster vaccine. Vaccine 2020, 38, 3489–3500. [Google Scholar] [CrossRef] [PubMed]
  73. López-Fauqued, M.; Campora, L.; Delannois, F.; El Idrissi, M.; Oostvogels, L.; De Looze, F.J.; Diez-Domingo, J.; Heineman, T.C.; Lal, H.; McElhaney, J.E.; et al. Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials. Vaccine 2019, 37, 2482–2493. [Google Scholar] [CrossRef] [PubMed]
  74. Kennedy, P.G.E.; Grose, C. Insights into pathologic mechanisms occurring during serious adverse events following live zoster vaccination. J. Virol. 2025, 99, e0181624. [Google Scholar] [CrossRef] [PubMed]
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MDPI and ACS Style

Yu, J.; Li, H.; Ji, Y.; Liao, H. Varicella-Zoster Virus Infection and Varicella-Zoster Virus Vaccine-Related Ocular Complications. Vaccines 2025, 13, 782. https://doi.org/10.3390/vaccines13080782

AMA Style

Yu J, Li H, Ji Y, Liao H. Varicella-Zoster Virus Infection and Varicella-Zoster Virus Vaccine-Related Ocular Complications. Vaccines. 2025; 13(8):782. https://doi.org/10.3390/vaccines13080782

Chicago/Turabian Style

Yu, Jing, Huihui Li, Yuying Ji, and Hailan Liao. 2025. "Varicella-Zoster Virus Infection and Varicella-Zoster Virus Vaccine-Related Ocular Complications" Vaccines 13, no. 8: 782. https://doi.org/10.3390/vaccines13080782

APA Style

Yu, J., Li, H., Ji, Y., & Liao, H. (2025). Varicella-Zoster Virus Infection and Varicella-Zoster Virus Vaccine-Related Ocular Complications. Vaccines, 13(8), 782. https://doi.org/10.3390/vaccines13080782

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