Increasing hospitalisation of patients with herpes zoster ophthalmicus-an interdisciplinary retrospective analysis.

BACKGROUND: The occurrence of herpes zoster is rising globally. Future trends will be influenced by changes in population demographics and the growing number of patients at risk. Overall this poses a challenge for healthcare systems. METHODS: In our interdisciplinary, single-centre retrospective analysis, we aimed to assess the burden of the disease within the Department of Dermatology and the Eye Centre from the Medical Centre, University of Freiburg from 2009-2022. We obtained data from 3034 cases coded using the ICD-10 B02.x. Patients were characterised by sex, age, year of treatment, and type of treatment (inpatient vs. outpatient). RESULTS: Overall we observed a 200% increase in the number of herpes zoster patients over the 13-year period. Upon closer analysis, this was mainly due to a rise in inpatient treatment for herpes zoster ophthalmicus. CONCLUSIONS: If the incidence of herpes zoster ophthalmicus continues to increase at the current rate the number of hospitalisations of zoster ophthalmicus would double by 2040, assuming guideline-appropriate treatment. Overall, the results show a growing need for inpatient ophthalmological care.

Characteristics of Prescreened Patients Who Did Not Participate in the Zoster Eye Disease Study.

PURPOSE: The Zoster Eye Disease Study (ZEDS) is a multicenter randomized clinical trial (RCT) funded by the National Eye Institute aiming to determine the efficacy of suppressive valacyclovir treatment in herpes zoster ophthalmicus (HZO) that enrolled fewer participants than planned (527/780, 67.6%). Understanding reasons for nonparticipation of likely eligible prescreened patients provides insights into patient populations that are not represented by ZEDS and barriers in clinical trials. METHODS: In this retrospective cohort study, HZO adults likely eligible for ZEDS with a history of a typical rash and a medical record within the past year of an episode of epithelial or stromal keratitis or iritis were prescreened at activated Participating Clinical Centers from 2017 to 2022 using a standard prescreening log. De-identified data including demographic information, reasons for exclusion because of ineligibility, and patient refusal were retrospectively entered into REDCap and analyzed. RESULTS: Prescreening logs with reasons for nonconsent (1244/1706, 72.9%) were included in the data set. Patients were excluded from the study (915/1244, 73.6%) because they did not meet all inclusion criteria (619/915, 67.7%) or met an exclusion criterion (296/915, 32.3%). Among the 12 exclusion criteria for the ZEDS study, immunocompromise (76/296, 25.7%) and renal insufficiency (50/296, 16.9%) were most frequently reported. Patient refusal to participate (327/1,244, 26.3%) was common. CONCLUSION: The most common reasons for ineligibility were immunocompromise and renal insufficiency. There may be benefits to long-term antiviral use in these populations not captured in ZEDS. A quarter (26.3%) of prescreened patients refused participation, showing the substantial impact of patient preferences on trial participation.

Long-term risk of herpes zoster following COVID-19: A retrospective cohort study of 2 442 686 patients.

The long-term risk of herpes zoster (HZ) after recovery from a SARS-CoV-2 infection is unclear. This retrospective cohort study assessed the risk of HZ in patients following a COVID-19 diagnosis. This retrospective, propensity score-matched cohort study was based on the multi-institutional research network TriNetX. The risk of incident HZ in patients with COVID-19 was compared with that of those not infected with SARS-CoV-2 during a 1-year follow-up period. Hazard ratios (HRs) and 95% confidence intervals (CIs) of HZ and its subtypes were calculated. This study identified 1 221 343 patients with and without COVID-19 diagnoses with matched baseline characteristics. During the 1-year follow-up period, patients with COVID-19 had a higher risk of HZ compared with those without COVID-19 (HR: 1.59; 95% CI: 1.49-1.69). In addition, compared with the control group patients, those with COVID-19 had a higher risk of HZ ophthalmicus (HR: 1.31; 95% CI: 1.01-1.71), disseminated zoster (HR: 2.80; 95% CI: 1.37-5.74), zoster with other complications (HR: 1.46; 95% CI: 1.18-1.79), and zoster without complications (HR: 1.66; 95% CI: 1.55-1.77). Kaplan-Meier curve analysis (log-rank p < 0.05) results indicated that the risk of HZ remained significantly higher in patients with COVID-19 compared with those without COVID-19. Finally, the higher risk of HZ in the COVID-19 cohort compared with that in the non-COVID-19 cohort remained consistent across subgroup analyses regardless of vaccine status, age, or sex. The risk of HZ within a 12-month follow-up period was significantly higher in patients who had recovered from COVID-19 compared with that in the control group. This result highlights the importance of carefully monitoring HZ in this population and suggests the potential benefit of the HZ vaccine for patients with COVID-19.

Pediatric herpes zoster ophthalmicus: a systematic review.

PURPOSE: While typically affecting older adults and immunocompromised individuals, herpes zoster ophthalmicus (HZO) has been reported with varying manifestations and complications in children. In this review, we evaluate reported cases of pediatric HZO in the literature and discuss the epidemiology, risk factors, clinical presentation, treatment and outcomes. METHODS: A literature search on PubMed, Scopus, and Web of Science databases was performed using the terms "pediatric herpes zoster ophthalmicus" and "herpes zoster ophthalmicus children." Publications that were not specific to HZO or pediatric populations were excluded, as were publications that were not available to review or not published in the English language. RESULTS: Fifty-seven reports describing 130 cases of HZO or HZO-related complications were reviewed. Major risk factors for pediatric HZO included intrauterine exposure to varicella or primary varicella infection at a young age; HZO also occurred in patients who had received varicella vaccination. Both healthy and immunocompromised children were affected, with the majority of affected children being immunocompetent. The diagnosis of HZO is primarily clinical. Children appear to have good vision recovery and resolution of symptoms if they are treated promptly and if they adhere to treatment regimens, except for irreversible vision loss related to uncommon complications such as optic neuritis. CONCLUSION: HZO occurs in both healthy and immunocompromised children. Recognizing this treatable condition is essential for reducing ocular and systemic morbidity. Long-term follow-up and assessments of the impact on health in adulthood are lacking. More systematic study is needed to determine the incidence of HZO in children and appropriate diagnostic and treatment protocols for the care of pediatric patients with HZO.

Aseptic meningitis after amenamevir treatment for herpes zoster ophthalmicus with oculomotor nerve palsy in a patient taking immunosuppressant.

A 79-year-old woman presented with vomiting after being prescribed amenamevir by her primary care physician. She had a medical history of rheumatoid arthritis and was administered prednisolone and methotrexate. She was finally diagnosed with herpes zoster ophthalmicus and aseptic meningitis, and intravenous antiviral therapy was initiated. However, the patient developed oculomotor nerve palsy on the 11th day of hospitalization. In this case, there was a time lag between the administration of antiviral drugs and clinical improvement. Our case suggests the necessity of selecting antivirals, especially in high-risk cases of CNS complications, to avoid the low intracerebral transferability of antiviral drugs, including amenamevir.

Spontaneous Extrusion of a Conjunctivolith Containing Herpes Virus Confirmed by Electron Microscopy and Energy Dispersive Spectroscopy.

: This report describes the spontaneous extrusion from between the eyelids of a presumed conjunctivolith in a patient with resolving severe herpes zoster ophthalmicus. A 57-year-old man presented for ophthalmologic assessment and management due to severe left herpes zoster ophthalmicus. At one subsequent ophthalmologic assessment, a conjunctivolith spontaneously egressed the lateral commissure of the OS when the lateral fornix was inspected. The conjunctivolith was retrieved from the floor of the consulting room. Electron microscopic analysis and energy dispersive spectroscopy was undertaken to determine its composition. Scanning electron microscopy showed that the conjunctivolith was composed of carbon, calcium, and oxygen. Transmission electron microscopy diagnosed Herpes virus within the conjunctivolith. Conjunctivoliths, or possible lacrimal gland stones, are a very rare phenomenon, and their etiology is currently unclear. In this case, there was likely to have been an association between herpes zoster ophthalmicus and the conjunctivolith.

Herpes Zoster Ophthalmicus With Dacryoadenitis Complicated by Recurrent Orbital Inflammation.

Herpes zoster ophthalmicus represents a zoster infection in the first division of the trigeminal nerve and has potentially serious complications involving the ocular and orbital structures. Herpes zoster ophthalmicus occurs in approximately 10% to 20% of individuals with herpes zoster and can lead to significant morbidity, particularly in patients with multiple comorbidities. The authors present a case of herpes zoster ophthalmicus along with dacryoadenitis in a patient with uncontrolled diabetes and rheumatoid arthritis who was misdiagnosed, had delayed treatment, and experienced recurrence with orbital symptoms during follow up. Prompt recognition, initiation of therapy and careful monitoring and follow up are important for treating herpes zoster ophthalmicus and preventing recurrence and long-term sequelae.

Impact of the use of anti-glaucoma medications on the risk of herpetic keratitis recurrence.

PURPOSE: Numerous case reports have associated anti-glaucoma medications with recurrence of herpes simplex virus (HSV) and herpes zoster virus (HZV) keratitis. The aim of our study was to determine whether different anti-glaucoma agents are associated with recurrence of herpetic keratitis. METHODS: This was a retrospective cohort study using health databases from a Canadian province from January 2001 to December 2012. A new cohort of users on topical prostaglandins (PGs), beta blockers (BBs), alpha-2 agonists (AAs) and carbonic anhydrase inhibitors (CAIs) was created. The date of the third anti-glaucoma drug dispensation within 90 days was deemed the index date of the case. Herpetic keratitis events, as defined by an ICD-9/10 code for HSV or HZV keratitis, or the dispensation of an anti-viral medication by either an ophthalmologist or an optometrist, were examined prior to and following the index date. Risk ratios (RRs) were computed to compare the risk of HSV/HZV keratitis among the PG, BB, AA, and CAI groups individually and collectively while adjusting for age and sex. RESULTS: Among 19,986 users of glaucoma medications identified, there were 684 cases of HSV/HZV keratitis. There was no increased risk of HSV/HZV keratitis recurrence for any of the four glaucoma medications classes individually or collectively when adjusted for age and sex. There was also no increased risk for redeveloping either HSV keratitis only or HZV keratitis only amongst all anti-glaucoma users. CONCLUSION: There is no association between the use of topical ocular hypotensive therapies and HSV/HZV keratitis recurrence. Further studies are needed to confirm these findings.

Dermatomal Granulomatous Dermatitis and Vasculitis Following Herpes Zoster Ophthalmicus.

Cutaneous granulomatous dermatoses are uncommon sequelae of herpes zoster (HZ) infection that have been documented in the literature, with granulomatous vasculitis described in rare cases. Here, we report a patient with HZ ophthalmicus who developed edematous plaques with central scarring in a V1 dermatomal distribution with histopathological changes of a granulomatous dermatitis including features of granulomatous vasculitis. J Drugs Dermatol. 2022;21(10):1127-1128. oi:10.36849/JDD.6749.

Neuro-Ophthalmological Complications of the COVID-19 Vaccines: A Systematic Review.

BACKGROUND: A worldwide mass vaccination campaign against the coronavirus disease 2019 (COVID-19) pandemic is currently underway. Although the safety data of the clinical trials did not report specific concerns regarding neuro-ophthalmological adverse events, they involved a limited number of individuals and were conducted over a relatively short time. The aim of the current review is to summarize the available postmarketing data regarding the occurrence of neuro-ophthalmological and other ocular complications of the COVID-19 vaccines. EVIDENCE ACQUISITION: Electronic searches for published literature were conducted using Ovid MEDLINE, Embase, Web of Science, Google Scholar, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov. The search strategy incorporated controlled vocabulary and free-text synonyms for the concepts of COVID, vaccines, and visual and neuro-ophthalmologic diseases and symptoms. RESULTS: A total of 14 case reports and 2 case series have been selected for inclusion in the final report, reporting 76 cases of post-COVID-vaccination adverse events. The most common adverse event was optic neuritis (n = 61), followed by uveitis (n = 3), herpes zoster ophthalmicus (n = 2), acute macular neuroretinopathy (n = 2), optic disc edema as an atypical presentation of Guillain-Barré syndrome (n = 1), (arteritic anterior ischemic optic neuropathy; n = 1), abducens nerve palsy (n = 1), oculomotor nerve palsy (n = 1), Tolosa-Hunt syndrome (n = 1), central serous retinopathy (n = 1), acute zonal occult outer retinopathy (n = 1), and bilateral choroiditis (n = 1). Most cases were treated with high-dose steroids and had a favorable clinical outcome. CONCLUSION: Since the implementation of the COVID-19 vaccination campaign in the past year, several post-COVID-vaccination neuro-ophthalmological complications have been described. However, considering the number of individuals that have been exposed to the vaccines, the risk seems very low, and the clinical outcome in most cases is favorable. Therefore, on a population level, the benefits of the vaccines far outweigh the risk of neuro-ophthalmological complications.

A Case Report of Herpes Zoster Ophthalmicus and Meningitis After COVID-19 Vaccination.

There are several reports that herpes zoster characterized by reactivation of varicella zoster virus (VZV) following coronavirus disease 2019 (COVID-19) vaccines can occur. Herein, we report VZV meningitis, herpes zoster ophthalmicus (HZO), and late neurotrophic keratitis after receiving a second dose of messenger RNA (mRNA) COVID-19 vaccine. A 74-year-old man developed a vesicular skin rash on the forehead, scalp, nose, and left upper eyelid with a severe headache. Five days earlier, he received a second dose of the BNT162b2 mRNA vaccine on his left arm. Ocular examination revealed conjunctival hyperemia and pseudodendrite in the peripheral cornea. VZV was detected in the cerebrospinal fluid using polymerase chain reaction. The patient was diagnosed with HZO and meningitis. The patient was treated with intravenous acyclovir and topical acyclovir ointment and levofloxacin 1.5% eye drops. One month later, he developed a central epithelial defect with a rolled margin, typical of a neurotrophic ulcer. Treatment with a therapeutic contact lens and a combination of topical recombinant human epithelial growth factor and ofloxacin ointment was initiated. At six months after vaccination, the slit-lamp examination findings were stable with a mild corneal superficial stromal haze.

Herpes Zoster Opthalmicus-Related Ophthalmoplegia: Anatomical, Pathogenetic, and Therapeutic Perspectives.

OBJECTIVE: To investigate the anatomical, pathogenetic, and pharmacological characteristics of herpes zoster ophthalmicus (HZO)- related ophthalmoplegia. METHODS: Case report-based systematic review was performed. RESULTS: This study included 96 patients (54 [56.25%] women and 42 [43.75%] men [P = 0.221]). The mean age at presentation was 64.32 ± 17.48 years. All the patients included in the study had HZO- related ophthalmoplegia, with rash presenting as initial symptom in 87 (90.62%) cases, and diplopia in 9 (9.38%) cases. Thirty-seven (38.54%) patients achieved complete recovery, whereas 59 (61.46%) patients had permanent ophthalmoplegia. Females recovered in 26/54 cases and males in 11/42 cases (P = 0.028). Recovery rates after peroral versus intravenous antivirals (15/38 versus 19/46) and > 10 days versus ≤10 days antiviral treatment (22/54 versus 12/30) did not significantly differ ( P = 0.865 and P = 0.947, respectively). immunocompetent patients treated with corticosteroids had significantly better recovery rates compared to immunodeficient counterparts (17/34 [50.00%] and 5/22 [22.73%], respectively [ P = 0.041]). CONCLUSIONS: The outcome of HZO-related ophthalmoplegia is associated with gender, immune status, corticosteroid use, and time of antiviral treatment initiation.

Initial outcomes of mitomycin intravascular chemoembolization (MICE) for corneal neovascularization.

PURPOSE: To report on the preliminary outcomes of mitomycin C (MMC) intravascular chemoembolization (MICE) for corneal neovascularization (NV). METHODS: This is a retrospective case series of three consecutive eyes that underwent MICE for progressive corneal NV with sight threatening lipid keratopathy. A 1.0 cc syringe was partially filled with MMC (0.4 mg/mL) and attached to a 33-gauge needle used to cannulate the vessels. The MMC (0.01-0.05 ml) was injected with enough retrograde hydrostatic force to fill efferent and afferent vessels. Follow-up ranged from 4 months to 1 year. RESULTS: Three eyes of three patients aged 59, 73 and 33 years were included. There were no intraoperative or postoperative complications associated with the MICE procedure. Patient 1 presented with progressive corneal NV and lipid keratopathy secondary to herpes zoster ophthalmicus (HZO) and a best-corrected spectacle visual acuity (BSCVA) of 20/100 Snellen. At one-year post-MICE, there was no recurrence (BSCVA was 20/20 Snellen). Patient 2 presented with idiopathic lipid keratopathy (BSCVA 20/50 Snellen). At four months post-MICE, there were no signs of recurrence (BSCVA 20/20 Snellen). Patient 3 presented with corneal NV and lipid keratopathy secondary to HZO (BSCVA 20/30 Snellen). At four months following two MICE treatments, resolution of the lipid keratopathy was noted (BSCVA 20/20 Snellen). CONCLUSIONS: Preliminary findings suggest that MICE may be an additional modality for treating progressive corneal NV with lipid keratopathy. Larger comparative studies with longer follow-up are warranted.

Effectiveness of the Recombinant Zoster Vaccine for Herpes Zoster Ophthalmicus in the United States.

PURPOSE: To examine the effectiveness of the recombinant zoster vaccine (RZV) for preventing herpes zoster ophthalmicus (HZO) in the general United States population. DESIGN: Retrospective, observational cohort study. PARTICIPANTS: Individuals enrolled in the OptumLabs Data Warehouse (OLDW; OptumLabs, Cambridge, MA) who were age eligible for herpes zoster (HZ) vaccination (≥50 years of age) from 2018 through 2019. The OLDW is a longitudinal, de-identified administrative claims and electronic health record database of patients in the United States with commercial insurance, Medicare Part D, or Medicare Advantage METHODS: Patients were required to have 365 days or more of continuous enrollment to be eligible. Those with a diagnosis code of HZ or an immunocompromising condition within 1 year before study inclusion were excluded. Vaccination with the RZV was ascertained by Current Procedural Terminology codes, and HZO was ascertained by International Classification of Diseases, Tenth Revision, codes. Cox proportional hazards regression models were used to estimate the hazard ratio of HZO associated with RZV, and inverse-probability weighting was used to control for confounding. Vaccine effectiveness was calculated from hazard ratios. MAIN OUTCOME MEASURES: Incidence of HZO in vaccinated versus unvaccinated person-times and vaccine effectiveness were assessed. RESULTS: From January 1, 2018, through December 31, 2019, a total of 4 842 579 individuals were included in this study. One hundred seventy-seven thousand two hundred eighty-nine (3.7%) received 2 valid doses of RZV. The incidence rate of HZO was 25.5 cases (95% confidence interval [CI], 17.4-35.8 cases) per 100 000 person-years in the vaccinated group compared with 76.7 cases (95% CI, 74.7-78.7 cases) in the unvaccinated group. The overall adjusted effectiveness of RZV against HZO was 89.1% (95% CI, 82.9%-93.0%). CONCLUSIONS: The effectiveness of RZV against HZO in individuals 50 years of age and older is high in a clinical setting. However, the low vaccination rate in this study highlights the public health need to increase HZV use. Ophthalmologists can play an important role in recommending vaccination to eligible patients.

ACUTE RETINAL NECROSIS: Difference in Outcome by Viral Type and Options for Antiviral Therapy.

PURPOSE: To investigate differences in outcomes of acute retinal necrosis with confirmed viral polymerase chain reaction between viral types and highlight different treatment options. METHODS: The study evaluated 22 eyes in 18 patients of polymerase chain reaction-positive acute retinal necrosis at the University of Pittsburgh Medical Center from 2007 to 2018. Outcome measures included final visual acuity, treatment paradigms, and retinal detachment rate. RESULTS: Eight eyes were polymerase chain reaction-positive for varicella zoster virus, two eyes for herpes simplex virus Type 1 (HSV-1), and 12 eyes for herpes simplex virus Type 2 (HSV-2). Final Snellen best-corrected visual acuity averaged 20/51 for varicella zoster virus, 20/25 for HSV-1, and 20/814 for HSV-2. Retinal detachment occurred in 2 (25%) of varicella zoster virus eyes and 8 (75%) of HSV-2 eyes. One eye with HSV-1 and three eyes with HSV-2 received cidofovir for treatment of refractory retinitis. CONCLUSION: Acute retinal necrosis secondary to HSV-2 tended to have persistent active retinitis with a higher rate of retinal detachment despite similar treatment protocols, suggesting that in some cases combination intravenous acyclovir and adjuvant intravitreal foscarnet injections are not sufficient. Despite the risk of renal toxicity, intravenous cidofovir may be a consideration in select patients.

Case Report: Acute Retinal Necrosis after Intravitreal Ranibizumab for Exudative Macular Degeneration.

SIGNIFICANCE: Acute retinal necrosis (ARN) may occur after intravitreal ranibizumab (IVR) treatment for patients with exudative age-related macular degeneration (AMD). Awareness of this unusual but devastating complication after IVR is needed. Early identification may help provide timely antiviral treatment and prevent irreversible visual loss. PURPOSE: This study aimed to report a case of ARN after IVR in a patient with exudative AMD. CASE REPORT: A 67-year-old male patient complained of blurred vision in his left eye for 1 month. The patient was diagnosed with exudative AMD after detailed ophthalmic clinical evaluations. He received IVR once in his left eye. Three days after IVR, he developed varicella-zoster virus-associated ARN, which was treated with systemic and intravitreal antiviral therapy. Because of progressive inflammation, the patient underwent 25G pars plana vitrectomy with silicone oil tamponade. Seven months later, the patient was administered intravitreal aflibercept once in his left eye. Three months after intravitreal aflibercept, he underwent removal of silicone oil, and retinal detachment occurred 2 weeks after the surgery because of low IOP, and the patient eventually discontinued treatment. CONCLUSIONS: This study reports the first case of varicella-zoster virus-associated ARN after IVR. Early ARN may be very difficult to distinguish from intraocular inflammation after IVR. Therefore, early detection of viral DNA in the intraocular fluid using polymerase chain reaction is recommended. Immediate antiviral treatment may be beneficial to prevent severe visual loss.

Development of Herpes Zoster Ophthalmicus in an Immunocompetent Pediatric Patient Following Facial Trauma.

Herpes zoster ophthalmicus (HZO) is a neuro-oculo-dermic infection caused by reactivation of latent varicella zoster virus in the dorsal root ganglia of the ophthalmic division of the trigeminal nerve. Although a rare diagnosis in an otherwise healthy, vaccinated pediatric patient, this entity may occur with increasing frequency among those with preceding trauma, particularly in the month prior to presentation. Herein, we highlight a case of HZO in a vaccinated, immunocompetent adolescent in the setting of recent facial trauma.

Short-Term Peripheral Nerve Stimulation Relieve Pain for Elder Herpes Zoster Ophthalmicus Patients: A Retrospective Study.

OBJECTIVE: Ophthalmic postherpetic neuralgia (PHN) is the final stage of herpes zoster (HZ) ophthalmicus and a severe refractory neuropathic pain, thus there is no curative treatment that could alleviate pain and reduce the incidence of ophthalmic PHN now. The purpose of this study is to evaluate therapeutic efficacy of short-term peripheral nerve stimulation (PNS) for elder patients with HZ ophthalmicus. MATERIALS AND METHODS: We performed a retrospective study from March 2015 to August 2019 in our pain department. All the HZ ophthalmicus patients underwent supraorbital nerve short-term PNS were included. The patients' data, including numeric rating scale (NRS), 36-Item short form health survey (SF-36), and analgesic consumptions, were retrospectively analyzed. Severe side effects also were recorded. RESULTS: A total of 68 patients were enrolled in this study. The NRS scores were significantly decreased at different time points after short-term PNS compared to baseline (p < 0.001). The SF-36 scores, including general health, social function, emotional role, mental health, bodily pain, physical functioning, physical role, and vitality, were significantly improved at different time points after treatment (p < 0.001). The average dosages of tramadol and pregabalin administered (mg/d) were both significantly reduced compared to baseline (p < 0.001). There was no bleeding, infection, pain increase, and other side effects after treatment. CONCLUSIONS: Short-term PNS is an effective and safe therapeutic alternative for elder patients with HZ ophthalmicus and could reduce the incidence of ophthalmic PHN.

Chronic and Recurrent Herpes Zoster Ophthalmicus.

Background and Objectives: This study sought to investigate the natural course, the chronicity and recurrence rate, and the risk factors of chronic and recurrent herpes zoster ophthalmicus (HZO). We also evaluated the effects of long-term treatment for HZO. Materials and Methods: Patients diagnosed and treated for HZO were included in the retrospective medical chart review. Multivariable-adjusted logistic and Cox regression models were used to show risk factors for chronic and recurrent HZO along with hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Among a total 130 of HZO patients, 31 patients (23.85%) had chronic disease and 19 patients (14.62%) had recurrent disease. The rate of chronic disease was higher in HZO with conjunctivitis, epithelial keratitis, and stromal keratitis. The recurrence rate increased in patients with chronic HZO (HR: 34.4, 95% CI: 3.6-324.6), epithelial keratitis (HR: 5.5, 95% CI: 1.3-30.0), stromal keratitis (HR: 18.8, 95% CI: 3.0-120.8), and increased intraocular pressure (IOP) (HR: 7.3, 95% CI: 1.6-33.2). Length of systemic antiviral therapy and anti-inflammatory eyedrop treatment were not associated with recurrent HZO (p = 0.847 and p = 0.660, respectively). The most common ocular manifestation for recurrent HZO was stromal keratitis. Conclusions: This study demonstrated a considerable frequency of chronic and recurrent HZO. Chronic HZO in the form of epithelial or stromal keratitis with increased IOP provoked a significant rise in the risk of recurrence.

Recurrent Herpes Zoster Ophthalmicus in a Patient With a Novel Toll-Like Receptor 3 Variant Linked to Compromised Activation Capacity in Fibroblasts.

BACKGROUND: Herpes zoster ophthalmicus occurs primarily in elderly or immunocompromised individuals after reactivation of varicella zoster virus (VZV). Recurrences of zoster ophthalmicus are uncommon because the reactivation efficiently boosts anti-VZV immunity. A 28-year-old female presented to our clinic with a history of multiple recurrences of zoster ophthalmicus. METHODS: Whole-exome sequencing (WES), analyses of VZV T-cell immunity, and pathogen recognition receptor function in primary antigen-presenting cells (APCs) and fibroblasts were performed. RESULTS: Normal VZV-specific T-cell immunity and antibody response were detected. Whole-exome sequencing identified a heterozygous nonsynonymous variant (c.2324C > T) in the Toll-like receptor 3 (TLR3) gene resulting in formation of a premature stop-codon. This alteration could potentially undermine TLR3 signaling in a dominant-negative fashion. Therefore, we investigated TLR3 signaling responses in APCs and fibroblasts from the patient. The APCs responded efficiently to stimulation with TLR3 ligands, whereas the responses from the fibroblasts were compromised. CONCLUSIONS: We report a novel TLR3 variant associated with recurrent zoster ophthalmicus. Toll-like receptor 3 responses that were unaffected in APCs but diminished in fibroblasts are in line with previous reports linking TLR3 deficiency with herpes simplex virus encephalitis. Mechanisms involving compromised viral sensing in infected cells may thus be central to the described immunodeficiency.