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Background and Objectives : Herpes simplex keratitis (HSK) is the leading infectious cause of corneal damage and associated loss of visual acuity. Because of its frequent recurrence, it represents a major health problem; thus, timely and accurate diagnosis is the key to successful treatment. To enable this, we aimed to determine HSK patients' demographic and clinical features. Materials and Methods : This prospective study included 55 patients diagnosed with HSK between March 2019 and August 2022 at the Department of Ophthalmology, Clinical Hospital Rijeka. Results : We found that HSK is most prevalent in the elderly, with 72.73% of patients older than 60. The most common HSK types were dendritic (HSK-D; 43.64%) and stromal with epithelial ulceration (HSK-SEU 23.64%). HSK recurrences occurred in 65.45% of patients, with most having two to five recurrences (55.56%). Visual acuity at presentation (65.5%) and after treatment (50.9%) was mostly in the 20/50 range. The longest period until the disease symptoms were resolved was in the group with stromal HSK without epithelial ulceration (HSK-SnEU), for which symptoms lasted more than 11 weeks in 87.5% of patients. The overall incidence of HSK-related complications was high (85.45%), with 76.4% of patients having corneal scarring. The average time from symptom to treatment was 15.78 days. Interestingly, we observed a strong seasonality in the incidence of HSK, which was most prevalent in the colder months, with 63.6% of cases occurring between October and March. Conclusions : To the best of our knowledge, this is the first prospective study in Croatia, and one of the few in Europe, to describe the demographic and clinical features of HSK patients. We found that HSK is most common in the elderly population, with its dendritic form as a clinical presentation. We have shown that HSK is prone to recurrence and secondary complications, with a worryingly long time between symptom and treatment, indicating the need for diagnostic testing in routine practice.

Objective: To describe the demographics and clinical profile of Herpes Simplex Virus (HSV) Keratitis in patients presenting to a multi-tier ophthalmology hospital network in South India., Methods: We have reviewed the medical records of all patients having a clinical diagnosis of any form of HSV keratitis, seen between May 2012 and August 2020 across the L V Prasad Eye Institute network. All the further analyses of the groups were performed using the keywords used for making the diagnosis of HSV keratitis and the data were collected from the electronic medical record system., Results: There were a total of 8308 (N = 8897 eyes) patients. Male: female ratio was 5368 (64.61%):2940 (35.39%). Unilateral involvement was in 7719 (92.91%) patients. The most common age group affected was between the third to fifth decades of life with 1544 (18.58%). 3708 (1.68%) eyes had mild visual impairment (< 20/70) while the rest of them had moderate to severe visual impairment as observed mainly (p ≤ 0.01) in Necrotizing stromal keratitis. 7314 (82.21%) eyes had normal intraocular pressure (10-21 mm Hg) while raised most commonly in keratouveitis (P ≤ 0.01). Epithelial Keratitis, Immune Stromal Keratitis, Endotheliitis, Neurotrophic keratopathy and Keratouveitis were observed in 1875 (17.22%) eyes, 5430 (61.03%) eyes, in 129(1.45%) eyes, 1188 (13.35%) eyes, 148 (1.66%) eyes and 256 (2.88%) eyes respectively., Conclusion: Based on our institute-based data, the most common type of HSV keratitis is Immune stromal keratitis followed by epithelial keratitis. Although not representative of the general population, this data provide useful insights related to HSV keratitis from India., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: The objective of this study is to evaluate the clinical features of pediatric herpes simplex virus keratitis, its recurrence rates, and its effects on visual acuity., Methods: In this retrospective case series, records of pediatric patients (0-16 years) who presented with herpes simplex virus keratitis between January 2012 and September 2021 were evaluated. Data including age, gender, additional systemic diseases, the number of recurrences, recurrence time, treatment protocol, follow-up period, and presence of amblyopia were reviewed., Results: Twenty-four patients (16 females and 8 males) with a mean age of 6.6 ± 4 (1.1-15) years were included in the study. The mean follow-up time was 21 ± 19.9 (7-94) months. Four patients (16.6%) had bilateral keratitis. Including all 4 patients with bilateral involvement, a total of 10 (41.6%) patients had additional systemic diseases that cause immunodeficiency. After prophylactic antiviral treatment for at least 6 months (except for isolated epithelial keratitis), recurrence was detected in 5 (22.7%) patients, who were all immunodeficient. Among immunodeficient individuals, the recurrence rate was found to be 50%. Keratitis recurrence was significantly associated with immunodeficiency ( P = 0.03). However, type of keratitis ( P = 0.42), gender ( P = 0.47), and bilaterality ( P = 0.54) were not related with recurrence. 66.7% of the patients younger than 10 years developed amblyopia during follow-up., Conclusions: In childhood, the most frequent corneal manifestation of herpes simplex virus is stromal keratitis that mostly progresses with corneal scarring, residual astigmatism, and amblyopia. The recurrence rate increases in the presence of immunosuppression. Close follow-up, rapid diagnosis, and treatment are critical for battling against amblyopia and achieving good visual prognosis., Competing Interests: Conflict of Interest: None, (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate the rates of Herpes Simplex Virus types 1 (HSV-1) and 2 (HSV-2) in ocular specimens., Methods: Retrospective case series of all patients with a positive laboratory evaluation for ocular HSV performed at the Auckland District Health Board, Auckland, New Zealand between 1 January 2006 and 31 December 2017 were included in the study., Results: A total of 423 specimens were positive for HSV-1 (99.3%, n = 419) or HSV-2 (0.7%; n = 4). The majority of positive tests were identified through DNA amplification (n = 352; 83%) testing while the remainder were obtained by viral culture (n = 71; 17%). Ocular disease caused by HSV-2 in this study included acute retinal necrosis (n = 2), keratitis (n = 1), and blepharitis (n = 1)., Conclusions: HSV type 2 is a rare cause of ocular and peri-ocular infection but may cause severe, vision threatening disease.

Although past research has shown an association between obesity and herpes simplex virus infection, the relationship between body mass index (BMI) and herpetic stromal keratitis (HSK) recurrence has never been investigated. In this study, we included HSK patients who received oral valacyclovir as prophylactic treatment between January 2016 and January 2021. Recurrence, possible risk factors, and the time to recurrence were recorded during follow-ups. Among the 56 patients included in this study, recurrence was reported in 21 (37.5%) patients. The age at disease onset and mean follow-up time were not significantly different in the recurrence and non-recurrence groups. However, in the Cox regression analysis, BMI ≥ 24 kg/m 2 was noted as the variable having significant correlation with recurrence ( p = 0.01 in univariate analysis and p = 0.001 in multivariate analysis). In conclusion, overweight and obesity were revealed as risk factors for HSK recurrence in patients receiving long-term antiviral prophylaxis. Further studies are needed to determine the appropriate acyclovir concentrations in the blood or aqueous humour in order to achieve desirable prophylactic effects, especially in the overweight and obese patients.

Introduction: The manifestations of herpes simplex virus keratitis range from epithelial keratitis to vision-threatening stromal keratitis. There are limited studies done on our part regarding stromal keratitis. The aim of the study was to find out the prevalence of stromal keratitis among herpes simples keratitis patients in a tertiary eye hospital., Methods: This descriptive cross-sectional study was conducted among patients who presented with herpes simplex virus keratitis in a tertiary eye hospital between 1 January 2020 to 28 February 2022. Ethical clearance was taken from Ethical Review Board (Reference number: 1/2079/80). Data was collected from hospital records which was reviewed and visual acuity at presentation and at one-month follow-up, clinical details on examination were recorded and, diagnosis of the stage of disease given in the case record was noted. Convenience sampling was used. Point estimate and 95% Confidence Interval were calculated., Results: Among 112 Herpes simplex keratitis patients, the prevalence of stromal keratitis was 38 (33.93%) (25.16-42.70, 95% Confidence Interval)., Conclusions: The prevalence of stromal keratitis among patients of herpes simplex keratitis was similar to studies conducted in similar settings., Keywords: herpes simplex keratitis; keratitis; prevalence.

Purpose: We aimed to review available data on the incidence of herpes simplex virus (HSV) keratitis and other HSV ocular disease and to estimate the global burden of HSV ocular disease., Methods: We searched Medline and Embase databases to October 2020 for studies reporting on the incidence of HSV ocular disease. Study quality was evaluated using a four-point checklist. Pooled estimates were applied to 2016 population data to estimate global HSV ocular disease burden. Numbers with uniocular vision impairment (any visual acuity <6/12) were estimated by applying published risks to case numbers., Results: Fourteen studies had incidence data; seven met our quality criteria. In 2016, an estimated 1.7 (95% confidence interval, 95% CI 1.0-3.0) million people had HSV keratitis, based on a pooled incidence of 24.0 (95% CI 14.0-41.0; N = 2; I 2  = 97.7%) per 100,000 person-years. The majority had epithelial keratitis (pooled incidence 16.1 per 100,000; 95% CI 11.6-22.3; N = 3; I 2  = 92.6%). Available studies were few and limited to the USA and Europe. Data were even more limited for HSV uveitis and retinitis, although these conditions may collectively contribute a further >0.1 million cases. Based on global incidence, some 230,000 people may have newly acquired uniocular vision impairment associated with HSV keratitis in 2016., Conclusion: Over 1.8 million people may have herpetic eye disease annually. Preventing HSV infection could therefore have an important impact on eye health. Herpetic eye disease burden is likely to have been underestimated, as many settings outside of the USA and Europe have higher HSV-1 prevalence and poorer access to treatment.

A retrospective chart review examined adult patients with herpes simplex (HSV) and zoster (HZO) keratitis at a single institution. Patients who suffered a poor outcome (defined as visually significant corneal scarring, neurotrophic keratitis, secondary glaucoma, or requiring corneal surgery) were identified and each outcome type was analyzed in relation to age, sex, diabetes mellitus, immunosuppression, and a prior history of ≥2 ocular procedures.Advanced age, diabetes mellitus, and a prior history of ≥2 ocular procedures may be risk factors for poor outcomes in HSV, but not HZO, keratitis. In HSV, older age and DM were specifically associated with visually significant corneal scarring, while older age and male sex were associated with secondary glaucoma. Future prospective studies are warranted to determine the ideal management (including prophylaxis) in patients with these characteristics.

Anti-glaucoma agents-induced corneal toxicity may be misdiagnosed as herpetic simplex keratitis (HSK). In our study, nineteen glaucoma patients were presumed to have HSK before referral. Corneal lesions were classified into (I) linear pseudodendritic lesions formed by elevated opacified cells, (II) linear pseudodendritic lesions formed by grouped superficial punctate keratitis (SPK), (III) satellite full-thickness epithelial defects, (IV) satellite lesions formed by elevated opacified cells, and (V) geographic lesions formed by grouped SPK. We observed thirty-one events, with 15 in the lower and 16 in the central corneas. There were 21 (67.7%) type II, five (16.1%) type V, two (6.5%) of each for types III and IV, and one (3.2%) type I events. Among linear lesions (types I and II), 17 (77.3%) had horizontal and 5 (22.7%) had curvilinear orientations. Exposure duration to the last-added anti-glaucoma agent was three days to 14.5 years. About half of the events (16/31, 51.6%) used prostaglandin analogues, and 30/31 (96.8%) applied benzalkonium chloride (BAK)-containing agents. All lesions resolved within two months after decreasing offending medications or enhancing protection of ocular surface. In conclusion, anti-glaucoma agents-induced pseudodendritic keratitis presents majorly in central-lower cornea as horizontally linear lesions, and BAK-containing agents are observed in the most events., (© 2021. The Author(s).)

Purpose: To evaluate the long-term role of adherence to oral acyclovir prophylaxis in reducing the risk for recurrent herpes simplex virus keratitis (HSK) in children., Methods: A retrospective cohort study was performed including all pediatric patients 16 years or younger) with their first HSK diagnosis and treatment at our center. Children were started on a standardized oral acyclovir prophylactic regimen after the acute phase. Adherence to prophylaxis was assessed monthly through parent interviews. The possible association between any recurrence (not only the first) and exposure to acyclovir prophylaxis was evaluated using random-effects multivariate logistic regression., Results: A total of 20 eyes of 17 patients (8 boys and 9 girls) were included. The mean follow-up time was 3.5 years. Adherence to acyclovir prophylaxis was registered in 100% of patients with no recurrences and in 36.4% of patients with 1 or more recurrences (P = 0.035). All other tested variables (time of follow-up, sex, age, infectious diseases, underlying hematological diseases, eye, and HSK type) did not differ between the 2 groups. The multivariate model confirmed the lower risk for recurrence in patients who were compliant to therapy (adjusted odds ratio 0.04, 95% confidence intervals 0.00-0.42, P = 0.008). No adverse effects were recorded during follow-up., Conclusions: Oral acyclovir prophylaxis is a safe and an effective medical treatment for recurrent HSK and its long-term efficacy is associated with compliance to the therapy., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To assess prevalence, clinical manifestations, required keratoplasties, follow-up, and outcome in patients with Herpes Simplex Virus Keratitis (HSK) attending a University Tertiary Referral Center., Design: Retrospective (12 years), descriptive, observational study., Methods: A total of 817 eyes with clinical diagnosis of HSK from 779 patients were classified by the type of presentation. We gathered data on the visual acuity, refraction, IOP, and required surgical procedures., Results: Stromal involvement including scars represented the most common diagnosis in our department and the main indication of penetrating keratoplasty (PKP). Epithelial keratitis (16%) presented with the best visual acuity at the first visit. Necrotizing keratitis represented 17% of the patients, 78% of whom required PKP; this group also had the worst visual acuity at first examination and was the main indication for emergency PKP. Among all eyes, 288 (35%) required PKP. A total of 230 (28%) PKPs were elective procedures and 58 (7%) PKPs were performed as emergency procedures. Two patients with quiet endothelial decompensations after recurrent HSV endotheliitis were treated with DMEK and had good visual outcomes without HSV recurrence at last follow-up., Conclusions: HSK is a prevalent disease with severe consequences when not treated appropriately and on time. Even when making an accurate diagnosis, the disease can be extremely aggressive, with all the implications it brings to the patients and health system. Elective PKP had better outcomes in terms of visual acuity and clear graft percentage compared to emergency PKP., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Purpose: To report anti-viral therapy and outcomes for patients with herpes simplex keratitis (HSK) in a quaternary centre in Sydney, Australia., Methods: A retrospective case review of patients who received anti-viral medications for any form of HSK was conducted. Cases were identified from pathology results, pharmacy records and hospital coding data from 2012 to 2013. Clinical details including initial anti-viral treatment and outcome were collated from the medical records. Outcome was determined from when initial anti-viral treatment was stopped or changed, and classified as either clinically resolved, partially resolved or worsened for therapeutic indication; or as either success or failure for prophylaxis., Results: Anti-viral therapy was given for therapeutic and prophylactic indications at presentation in 252 (85%) and 44 patients (15%), respectively. Topical aciclovir five times daily and valaciclovir in doses ranging from 500 mg to 1 g, one to three times daily were the preferred anti-viral therapies. One hundred and fourteen patients (n = 114/296, 38.5%) also received topical corticosteroids. An outcome was determined for 210/296 (71%) patients. For therapeutic indication, half of the patients (90/174) partially resolved within 8 days, with best outcomes achieved for endothelial HSK (8/11, 73%) and keratouveitis (21/36, 58%). Adverse events, observed in 20% (35/174) of patients, included corneal perforation (n = 8) and secondary bacterial keratitis (n = 6). Prophylaxis with antiviral therapy was successful in two-thirds of patients after 6 months., Conclusions: Clinical and visual outcomes varied with the type of HSK and prescribed therapies. Diverse initial anti-viral therapies were identified; standardising them may improve outcomes., (© 2021 The Authors Ophthalmic & Physiological Optics © 2021 The College of Optometrists.)

Purpose: To describe the demographic features and clinical characteristics of patients with herpes keratitis (HK) and limbal stem cell deficiency (LSCD) and identify possible factors associated with development of LSCD after HK., Methods: In this retrospective case-series study, records of patients with a clinical diagnosis of HK seen at Massachusetts Eye and Ear over a 5-year period were reviewed for evidence of LSCD. Patient demographics, medical history, treatment, and best-corrected visual acuities (BCVAs) were recorded., Results: We identified 626 patients with HK. Fifty-seven had been diagnosed with LSCD (9.3%). Thirteen percent of patients with herpes zoster keratitis (N= 25) and 7% of patients with herpes simplex keratitis (N= 32) had LSCD (P = 0.01). Keratitis caused by herpes zoster virus [odds ratios (OR), 1.77; 95% confidence interval (CI), 0.97-3.19; P = 0.01], stromal involvement (OR, 2.28; 95% CI, 1.27-4.18; P = 0.02), and the use of topical antihypertensives (OR, 2.28; 95% CI, 1.27-4.18; P = 0.02) were found to be associated with a higher likelihood of developing LSCD. The final logarithm of the minimum angle of resolution (LogMAR) BCVA was significantly lower in patients with LSCD compared with those without LSCD with a mean BCVA of 1.34 ± 1.52 LogMar (∼20/200) as compared to 0.18 ± 0.54 LogMar (∼20/30 ± 20/60) in those patients without LSCD (P = 0.005)., Conclusions: Our data suggest that HK may be a risk factor for development of LSCD. Patients with HK should be monitored for the development of LSCD to reduce the risk of chronic ocular surface morbidity., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Herpes Simplex Virus (HSV) is the most common virus that causes eye disease. Although around 60% of the world's population are seropositive for HSV antigens, fortunately, it is estimated that only 1% of seropositive individuals develop eye disease. The most common ocular manifestation of HSV is keratitis, while uveitis and retinal necrosis occur in a small number of cases. HSV keratitis is a debilitating disease, for several reasons: pain , photophobia, and vision loss in acute disease, latency of the virus which leads to infection reactivation from various triggers, scarring, and neovascularisation, leading to permanent vision loss with poor visual rehabilitation prospects. The Herpetic Eye Disease Study (HEDS) was a landmark series of randomised controlled trials in the 1990s that set the benchmark for evidence-based treatment guidelines for anterior eye herpetic disease. Since this time, there has been a change in the distribution of seroprevalence of herpes in the community, a simplified diagnostic classification, advances in treatment options, an emergence of new and a better understanding of risk factors, and discoveries in science that show promise for vaccine and novel future treatments. However, many of the principles of the HEDS study remain rightly entrenched in clinical practice. In this article, the HEDS study is revisited 20 years on through the lens of published literature, to determine current best practise and look towards the future.

Herpes simplex keratitis, caused primarily by human herpes simplex virus type 1 (HSV-1), remains the most common infectious cause of unilateral blindness and vision impairment in the industrialized world. Major advances in the care of HSV keratitis have been driven in large part by the landmark Herpetic Eye Disease Study randomized clinical trials, which were among the first in ophthalmology to reflect emerging trial conventions, including multicenter subject enrollment, double-masking, placebo controls, and a priori sample size determinations. The results of these trials now form much of the evidence basis for the management of this disease. However, management patterns in clinical practice often deviate from evidence-based care. These perceived quality gaps have given rise to the evolving field of implementation science, which is concerned with the methods of promoting the application of evidence-based medicine within routine care. To overcome variations in the quality and consistency of care for HSV keratitis, a range of clinical- and technology-based innovations are proposed. The most pressing needs include the following: a rational and tractable disease classification scheme that provides an immediate link between the anatomical localization of disease (corneal epithelial, stromal, or endothelial) and the appropriate treatment, and the actualization of an electronic medical record system capable of providing evidence-based treatment algorithms at relevant points of care. The latter would also input data to population-wide disease registries to identify implementation-rich targets for quality improvement, education, and research. These innovations may allow us to reduce the human and economic burdens of this highly morbid, and often blinding, disease.

Aims: To determine herpes simplex virus (HSV) DNA positivity in corneal scraping samples obtained from patients with microbial keratitis whose findings were not specific for HSV keratitis and to evaluate these particular cases with respect to clinical features and antiviral treatment results., Methods: Records of patients with microbial keratitis treated in a tertiary eye care hospital within the 3-year period were evaluated retrospectively. Real-time polymerase chain reaction (PCR) was used to identify HSV DNA. Smear slides were evaluated by light microscopy. Patients with typical presentations and histories of HSV keratitis were excluded., Results: Two hundred and seventy-six eyes of 276 patients were included in the study. HSV-1 DNA was detected in 25 eyes (9%). In these 25 eyes, the initial diagnosis was fungal or bacterial keratitis. The mean symptom duration was 20 ± 14 days (2-60 days). The risk factors were ocular surgery (20%), blepharitis (16%), trauma (8%) and contact lens wear (4%); however, the majority of patients did not have any specific cause for keratitis (52%). Clinical features were variable and not typical for any particular etiology. Culture and microscopic examinations revealed bacteria and/or fungi in 6 patients in addition to herpes infection. Antiviral treatment was successful in 72% of patients., Conclusion: Herpetic corneal infections can present without typical dendritic or geographic ulcers and may be masked by other infections. Real-time PCR is a useful method for rapid and definitive diagnosis. HSV infection should be considered for microbial keratitis without specific risk factors, with negative culture results and poor response to antimicrobial agents.

Purpose: To determine the presence of herpes simplex virus and varicella zoster virus (HSV 1 and 2, VZV) in the cornea of normal subjects by multiplex real time quantitative (qPCR) assay and evaluate its utility in the diagnosis of viral keratitis., Methods: Corneal epithelial cells from 33 eyes of 22 patients undergoing photorefractive keratectomy surgery (controls) and 50 corneal scrapings from 50 patients with suspected HSV keratitis were analyzed for the presence of HSV1 by conventional PCR and for presence of HSV1 and 2 and/or VZV by multiplex real-time PCR. Corneal scrapings of patients were also tested for HSV1 antigen by immunofluorescence assay (IFA). The results were compared and clinical records reviewed., Results: HSV1 and VZV DNA were detected in 8/33 controls (mean-14.3 ± 7.96, range: 3-29.1 copies/mL) and 2/33 controls (mean-10.7 ± 10.9, range 3-18.5 copies/ml) respectively. HSV2 was not detected in any of the controls. Copy numbers above the mean + 1SD of controls were considered significant for viral load in patient samples. Significantly higher number of corneal scrapings (39/50, 78%) from patients were positive for HSV1 (1.2 × 10 6 copies/mL ± 3.7 × 10 6 copies/mL) by real time qPCR compared to IFA (11/48, 23%, P value 0.0001) and conventional PCR (20/50, 40%, P value 0.0002). Double infection with HSV-1 (1.5 × 10 7 copies/ml) and HSV-2 (3.57 × 10 4 copies/ml) in one case and VZV infection (1.03 × 10 2 copies/ml) in another was also detected by the multiplex real-time PCR., Conclusion: Multiplex real-time PCR reliably detects HSV1 and 2 and VZV DNA and is ideal for the diagnosis of HSV and VZV keratitis in an ocular microbiology laboratory., Competing Interests: None

Purpose : To analyze the pattern of uveitis at two tertiary hospitals in South Africa which has a high prevalence of HIV, TB and syphilis. Methods : Data of 198 patients were obtained retrospectively between August 2014 and August 2016, including patient demographics, clinical examination, special investigations and final diagnosis. Results : Infectious uveitis was the most common aetiological category (47%), followed by idiopathic (34.8%) and non-infectious (18.2%). Syphilis was the most common identifiable cause (16.2%). Other important causes were toxoplasmosis, herpes viruses, tuberculosis and HLA-B27. HIV positive patients, who constituted 40% of the study population, were more likely to present with a posterior or panuveitis (relative risk 1.50, 95% CI 1.19-1.89) and more likely to have an infectious cause compared to HIV negative patients (relative risk 2.47, 95% CI 1.82-3.35). Conclusions : This study emphasizes the importance of HIV testing and investigations for infectious causes of uveitis, especially syphilis, in this population.

Purpose: To describe the clinical manifestations of herpes simplex keratitis (HSK) in a tertiary referral center in South Korea and to determine whether ascorbic acid treatment prevents recurrence of herpetic epithelial keratitis., Methods: This retrospective cohort study included all consecutive patients with herpetic keratitis referred to our center from January 2010 to January 2015. Clinical features, ocular complications, and recurrences were recorded., Results: In total, 149 eyes of the 133 patients (72 male and 61 female) were followed for an average of 24.6 ± 13.2 months. Sixteen (12.0%) patients had bilateral HSK. The most frequent HSK subtype was epithelial keratitis (49.7%), which was followed by stromal keratitis (23.5%). Epithelial keratitis was the most likely subtype to recur. Complications occurred in 122 (81.9%) eyes. The most common complication was corneal opacity. Recurrences were observed in 48 (32.2%) eyes. The recurrence rates were lower in the prophylactic oral antiviral agent group (16 / 48 eyes, 33.3% vs. 49 / 101 eyes, 48.5%) and the ascorbic acid treatment group (13 / 48 eyes, 27.1% vs. 81 / 101 eyes, 70.3%) compared with the groups without medications. Univariate logistic regression analysis revealed that both factors significantly reduced the risk of recurrence (acyclovir: odds ratio, 0.25; 95% confidence intervals, 0.12 to 0.51; ascorbic acid: odds ratio, 0.51; 95% confidence intervals, 0.20 to 0.91)., Conclusions: This retrospective study described the clinical findings of HSK in a tertiary referral center in South Korea. Prophylactic oral antiviral agent treatment and oral ascorbic acid administration may lower the risk of recurrence., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2018 The Korean Ophthalmological Society.)

Purpose: To evaluate the incidence, related perioperative factors, clinical characteristics, and possible etiologies of epithelial keratitis after cataract surgery., Methods: A retrospective chart review of 666 eyes in 666 patients who underwent cataract surgery was performed to evaluate the incidence of epithelial keratitis and related factors in the postoperative period., Results: Postoperative epithelial keratitis developed in 15 eyes. Eleven of the 15 eyes were diagnosed with herpes simplex keratitis (HSK); 10 of the 11 eyes were diagnosed by polymerase chain reaction, and the remaining 1 eye by clinical diagnosis. All patients diagnosed with HSK had no previous clinical history of the infection before undergoing cataract surgery. Initially, the diagnosis of all 15 eyes was toxic keratitis, but the final diagnosis of 11 of the initial 15 was found to be epithelial herpes keratitis. The incision location was shown to be related to the occurrence of HSK in our study (P < 0.05)., Conclusions: HSK epithelial keratitis after cataract surgery is a relatively uncommon complication and can be misdiagnosed in its early disease course because of its relative rarity. This study explores the possibility that the temporal corneal penetrating incisional approach used in routine cataract surgery interrupts the corneal nerves and subsequently can trigger reactivation of HSK.

Purpose: To evaluate the association between diabetes mellitus (DM) and presence and severity of Herpes simplex eye disease (HSED)., Methods: We conducted two sub-studies. We included the patients seen on the Cornea Service of the Wills Eye Hospital from January 2008 to August 2012. Study 1 included 541 patients with HSED and 3226 controls. Study 2 involved 40 diabetic and 120 non-diabetic ocular surface HSED patients. Severity of ocular surface HSED was graded as mild, moderate, or severe, based on best-corrected visual acuity (BCVA). Patients were excluded if they had fewer than two office visits or had non-Herpes simplex-related vision-threatening conditions. Diabetes was graded as: diet group (DM controlled with diet), oral group (DM controlled with oral medications), and insulin group (DM control required insulin)., Results: Five of 541 (0.93%) HSED patients had type 1 DM, similar to 19/3246 (0.59%) controls (p = 0.375); 48 of 541 (8.88%) HSED patients had type 2 DM, similar to 287/3246 (8.84%) controls (p = 0.981). Using multinomial logistic regression analyses, the probability/risk of being in the severe ocular surface HSED group as opposed to the mild ocular surface HSED group were not statistically significantly different between DM patients and those without DM (p = 0.120; OR, 1.900; 95% CI, 0.846-4.266)., Conclusions: There may not be a positive association between type 2 DM and HSED.

Recurrent herpes simplex keratitis (HSK) is a leading infectious cause of blindness in industrialized countries. Antiviral prophylaxis (AVP) may fail to prevent recurrence of HSK due to viral resistance, inadequate dosing, or poor patient compliance. In this prospective multicenter study, we enrolled immunocompetent patients with recurrent HSK despite AVP. Ocular samples were tested by PCR for herpes simplex virus 1 (HSV-1). HSV-1 drug resistance was assessed with a genotypic assay based on UL23 and UL30 gene sequencing. After curative full dose valacyclovir (VACV) treatment was started, peak and trough acyclovir (ACV) plasma concentrations were measured, and patient compliance to AVP was assessed with a questionnaire. The study sample was comprised of 43 patients. Six (14%) patients were positive for HSV-1 using PCR, of whom 5 (83%) harbored genotypically ACV-resistant (ACV R ) virus, due to mutations in UL23 (n = 4) or UL30 (n = 1). Disease duration was statistically significantly longer in patients with viral resistance compared to other HSK patients [35.5 ± 23.4 years (range, 6.8-68.4 years) versus 11.1 ± 12.3 years (range, 0.8-56.3 year) respectively; Mann-Whitney p = 0.01)]. While patients were treated with full dose VACV, trough ACV plasma concentrations were below the threshold for ACV sensitivity in 9.5% of cases, and compliance was poor in 5.3% of cases. To summarize, HSV-1 resistance to ACV seems to be a significant cause of failure of prophylaxis in patients with HSK and is associated with longer disease duration. Most PCR-positive samples contained genotypically ACV R virus and identification may aid in adapting treatment. Incomplete 24-h drug coverage may also explain some cases of failure of prophylaxis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: To determine whether human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS), diabetes mellitus, and atopic disease are associated with herpes simplex virus (HSV) eye disease and to examine the characteristics of patients with HIV infection and HSV eye disease., Design: Retrospective case-control study., Methods: A hospital-based control group was matched to outpatient visits from June 1, 2010, through May 31, 2014, at Montefiore Medical Center (Bronx, NY). Inclusion criteria were a diagnosis of HSV eye disease during the study period and residency in the Bronx. Associations evaluated included age, sex, HIV/AIDS, diabetes mellitus, and atopic disease., Results: HSV eye disease was confirmed in 70 patients, who were compared with 280 controls. Patients with ocular HSV had a greater prevalence of HIV/AIDS compared with controls (8.6% and 2.9%, respectively). Using multivariate analysis to control for age and sex, atopic dermatitis [odds ratio (OR) 3.08, 95% confidence interval (CI), 0.84-11.20] and diabetes with chronic complications (OR 2.25, 95% CI, 0.91-5.61) approached significance, whereas HIV/AIDS (OR 3.37, 95% CI, 1.09-10.40), an age less than 45 years (OR 2.89, 95% CI, 1.54-5.41), and male sex (OR 1.85, 95% CI, 1.07-3.18) were significant. In patients with HIV infection and HSV eye disease, 3 of 6 (50%) had confirmed AIDS at the time of ocular HSV diagnosis., Conclusions: Patients with HIV infection have more than a 3-fold increased risk of developing ocular HSV.

Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) are highly prevalent viruses capable of establishing lifelong infection. Genital herpes in women of childbearing age represents a major risk for mother-to-child transmission (MTCT) of HSV infection, with primary and first-episode genital HSV infections posing the highest risk. The advent of antiviral therapy with parenteral acyclovir has led to significant improvement in neonatal HSV disease mortality. Further studies are needed to improve the clinician's ability to identify infants at increased risk for HSV infection and prevent MTCT, and to develop novel antiviral agents with increased efficacy in infants with HSV infection., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To identify the demographic and clinical associations of patients presenting with herpetic keratitis in New Zealand compared with presentations of presumed microbial keratitis., Methods: A prospective, 6-month, observational case series of presumed microbial keratitis (including marginal keratitis), specifically identifying all cases of herpes simplex and varicella zoster keratitis attending an emergency eye clinic was conducted. Main outcome measures included demographics, presenting signs and symptoms, and medical, ocular, and drug history., Results: A total of 140 cases of herpetic keratitis were identified, which comprised 125 cases of herpes simplex virus (89%) and 15 cases of varicella zoster virus (11%). Herpes simplex keratitis was associated with a history of keratitis (n = 58, phi = 0.24, P < 0.0001), Maori ethnicity (n = 27, phi = 0.26, P < 0.0001), respiratory disease (n = 18, phi = 0.14, P = 0.009), corticosteroid use (n = 23, phi = 0.22, P < 0.0001), and cardiovascular disease (CVD) (n = 10, phi = 0.11, P = 0.03). Inverse association was observed between herpes simplex keratitis and ocular surface disease (n = 8, phi = -0.16, P < 0.002) and Asian ethnicity (n = 4, phi = -0.11, P = 0.04). Varicella zoster keratitis was associated with CVD (n = 3, phi = 0.15, P = 0.03)., Conclusions: Patients with asthma, CVD, on long-term corticosteroid inhalers or creams, or of Maori ethnicity need particular assessment to investigate herpes simplex as a possible cause of keratitis. Clinicians prescribing inhaled corticosteroids or topical corticosteroid creams should be aware of possible association with herpes simplex keratitis.

Unlabelled: Acquired immune deficiency syndrome (AIDS) is associated with a wide spectrum of systemic and ocular infectious diseases. Little information is known about Herpes Simplex Virus type 1 (HSV-1) keratoconjunctivitis in association with AIDS. Because HSV-1 is becoming, day by day, a common eye disease (nearly 100% patients of over 60 years old harbor HSV in their trigeminal ganglia at autopsy), this article discussing a worldwide public health problem., Aim: The purpose of this paper is to compare the incidence and clinical aspects of HSV-1 Keratitis in HIV/ AIDS patients compared with the general population who develops HSV- 1 Keratitis., Method: The study is retrospective and comparative. Each patient was examined thoroughly at the biomicroscope ocular slit after corneal staining with fluorescein or rose bengal. Visual acuity, intraocular pressure and corneal sensitivity were also examined., Results: From 170 patients with HIV and ocular anterior segment disorders, 47 patients had viral etiology. 58 patients had keratitis; 14 of them were HSV-1 keratitis., Conclusion: Doctors should be aware of the existence of the ocular damage in HIV/ AIDS and emphasize the importance of regular ophthalmologic examination of patients with HIV/ AIDS as HSV infection is common nowadays among the general population.

Purpose: To calculate the incidence and prevalence of herpes simplex virus (HSV) eye disease in a large, well-defined population in Northern California, USA, and to determine the recurrence rate following an initial episode of disease in this cohort., Methods: A retrospective, observational, cohort study using population-based data and medical record review. The patient database of a large, regional health maintenance organization (Northern California Kaiser Permanente) was searched, and the study population consisted of 1,042,351 people over a 1-year study period from 1 July 1998 through 30 June 1999. Only ocular HSV cases with definitive clinical or laboratory confirmed diagnoses were included. Active and inactive cases were included, however only active cases were used in incidence and prevalence calculations. Bilateral disease was counted as one case. Newly diagnosed cases were followed for recurrence from initial presentation through 31 December 2002., Results: After chart review of 322 possible cases, 71 new cases and 59 previously diagnosed active cases of ocular HSV were confirmed. This resulted in an incidence rate of 6.8 new cases/100,000 person-years (95% confidence interval, CI, 5.3-8.6). Incidence increased with age, and rates were highest in people over 75 years of age (p < 0.001). The recurrence rate in new cases was 18% for the 3-year follow-up time, and was equal to 5% per year (95% CI 3-9%)., Conclusion: The incidence and prevalence of ocular herpes simplex in this study was lower than previously reported. Incidence increased with age, and there were significantly higher rates in the older population.

Purpose: The aim of this study was to describe clinical manifestations of herpetic ocular infection caused by herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV) in a referral center in Northern Italy., Methods: This retrospective study included 241 patients with herpetic ocular infection referred to the tertiary-care Ocular Immunology and Uveitis Service, at the San Raffaele Scientific Institute in Milan, from January 2006 to August 2013. The main clinical parameters evaluated were etiology, clinical features, ocular complications, and recurrences of the infection., Results: Two hundred forty-one patients (144 female and 97 male) were followed for a mean time of 24.9 ± 18.2 months (range, 12-72). One hundred eighty-nine (78.4%) patients had HSV, 45 (18.7%) had VZV, and 7 (2.9%) had CMV infection. In the HSV and VZV groups, the most frequent manifestation was keratitis (41.3% and 31.1%, respectively), followed by anterior uveitis (33.3% and 28.9%, respectively). The most common CMV presentation was retinitis (71.4%). The main complications observed were glaucoma (38.1% in HSV group, 40% in the VZV group, and 28.6% in the CMV group) and cataract (27.5% in HSV group, 26.7% in VZV group, and 28.6% in CMV group), whereas retinal detachment frequently occurred in patients with retinitis (50%, 42.9%, and 40% among HSV, VZV, and CMV patients, respectively). Recurrences were observed in 65.1%, 51.1%, and 28.6% of patients with HSV, VZV, and CMV, respectively., Conclusions: Manifestations of herpetic ocular disease in our patients are comparable with other published series. However, the rate of ocular complications and recurrences during follow-up were higher compared with other series.

Importance: Immune dysregulation in patients with atopy has been hypothesized to increase susceptibility to viral infections. Herpetic eye disease (due to herpes simplex and herpes zoster) is a significant cause of visual impairment, and data on an association between this sight-threatening disease and atopy are limited., Objective: To assess the association between atopy and herpetic eye disease, including herpes simplex virus (HSV) ocular disease and herpes zoster ophthalmicus (HZO)., Design, Setting, and Participants: Retrospective, population-based case-control study from January 1, 2006, through December 31, 2007, at Kaiser Permanente Hawaii, a multispecialty managed care organization serving approximately 15% of the general Hawaiian population. Participants were 217,061 patients enrolled in the Kaiser Permanente Hawaii health plan during the study period., Main Outcomes and Measures: Clinical diagnosis of HSV ocular disease or HZO during the study period determined by an initial search of the electronic medical record of Kaiser Permanente Hawaii and then confirmed through individual medical record review by a uveitis and cornea fellowship-trained ophthalmologist. Atopic disease status was determined based on International Classification of Diseases, Ninth Revision codes for patients with HSV ocular disease or HZO and 2 control groups, each randomly selected at a 4:1 ratio of controls to cases., Results: One hundred fourteen patients with HSV ocular disease and 137 patients with HZO were identified. Using the age- and sex-matched controls, patients who had atopy had a 2.6-fold (95% CI, 1.6-4.2; P < .001) higher odds of having HSV ocular disease compared with patients who did not have atopy. Similarly, patients with atopy had a 1.8-fold (95% CI, 1.2-2.8; P = .01) increased odds of having HZO. Patients with 2 or more atopic conditions had an 8.9-fold (95% CI, 3.5-22.6; P < .001) higher odds of having HSV ocular disease and a 2.9-fold (95% CI, 1.1-7.7; P = .04) higher odds of having HZO., Conclusions: AND RELEVANCE The association between atopy and herpetic eye disease may be explained by various factors, including immunologic dysfunction in patients with atopy. Clinically, these results could help support the diagnosis of herpetic eye disease in these patients.

Purpose: Long-term acyclovir (ACV) prophylaxis, recommended to prevent recurrent herpes simplex virus type 1 (HSV-1) ocular disorders, may pose a risk for ACV-refractory disease due to ACV resistance. We determined the effect of ACV prophylaxis on the prevalence of corneal ACV-resistant (ACV(R)) HSV-1 and clinical consequences thereof in patients with recurrent HSV-1 keratitis (rHK)., Methods: Frequencies of ACV(R) viruses were determined in 169 corneal HSV-1 isolates from 78 rHK patients with a history of stromal disease. The isolates' ACV susceptibility profiles were correlated with clinical parameters to identify risk factors predisposing to ACV(R) rHK., Results: Corneal HSV-1 isolates with >28% ACV(R) viruses were defined as ACV(R) isolates. Forty-four isolates (26%) were ACV-resistant. Multivariate analyses identified long-term ACV prophylaxis (≥12 months) (odds ratio [OR] 3.42; 95% confidence interval [CI], 1.32-8.87) and recurrence duration of ≥45 days (OR 2.23; 95% CI, 1.02-4.87), indicative of ACV-refractory disease, as independent risk factors for ACV(R) isolates. Moreover, a corneal ACV(R) isolate was a risk factor for ACV-refractory disease (OR 2.28; 95% CI, 1.06-4.89)., Conclusions: The data suggest that long-term ACV prophylaxis predisposes to ACV-refractory disease due to the emergence of corneal ACV(R) HSV-1. ACV-susceptibility testing is warranted during follow-up of rHK patients.

Objective: To further define the spectrum of clinical disease and treatment among patients with herpes zoster ophthalmicus (HZO) and ocular herpes simplex viral (HSV) infection presenting at a large city hospital for the underserved in the United States., Methods: Retrospective review of medical records of 64 patients (40 HZO and 24 ocular HSV infection) presenting to the Bellevue Hospital Emergency Department for the management of herpetic eye disease for which an ophthalmologic consultation was obtained from January 1, 2006, to December 31, 2011., Results: The mean age of patients with HZO was 51 ± 15 years (n=40) versus 33 ± 16 years for patients with ocular HSV infection (n=24; P<0.0001). Overall, 73% of patients with HZO were aged <60 years (n=29 of 40), of whom, 90% (26 of 29) were immunocompetent. The most common decade of onset of HZO was 50 to 59 years (11 of 40, 28%). Four patients with HZO were immunocompromised (n=4 of 40; 10%), with 3 aged <60 years attributable to human immunodeficiency virus (n=3 of 29, 10%). The study included 12 patients eligible to receive the herpes zoster vaccine. None of these patients had a history of vaccination. Of the 24 patients with ocular HSV infection, corneal stromal disease was present in 7 patients and infectious epithelial keratitis in 10 patients. No patients were treated with long-term oral antiviral prophylaxis., Conclusions: Acute HZO was seen more commonly than ocular HSV infection. Patients with HZO were significantly older than those with ocular HSV infection. Available prevention modalities, such as the vaccine against herpes zoster and long-term oral antiviral therapy to reduce ocular HSV infection recurrence, were underused.

Herpes simplex virus (HSV) infection of the corneal stroma is the most prominent cause of scar formation impairing visual acuity and HSV keratitis is the leading cause of corneal opacity throughout the world. Suriname lacked test systems for microbial causes of ocular disease, therefore a polymerase chain reaction-based Herpes virus assay was introduced, enabling prompt recognition, and timely treatment, preventing progressive eye damage. The incidence and epidemiology of Herpes simplex virus type 1 (HSV-1), type 2 (HSV-2), and varicella zoster virus (VZV) in ocular disease in Suriname was assessed. In a cross-sectional prospective study, ocular swabs were collected from 91 patients with a presumptive α-Herpes virus ocular infection attending the Academic Hospital between November 2008 and August 2010 and were tested by a PCR-based α-Herpes virus assay. Alpha-Herpes virus ophthalmic infections were caused predominantly by HSV-1 with a prevalence of 31%. The prevalences of VZV, HSV-2, and a mixed HSV-1/HSV-2 infection were 4%, 3%, and 2%, respectively. The first reported annual incidence of herpetic induced ocular disease in Suriname was estimated at 11.4 per 100,000 person-years (95% CI, 4.8-18.1). No clear age, ethnic or gender dependent difference in incidence was observed. The information obtained on α-Herpes virus positive ocular infections and the distribution of subtypes provided the first insight in the South American situation of α-Herpes virus induced ocular disease., (Copyright © 2012 Wiley Periodicals, Inc.)

Aims: To report long term visual outcomes, complications and graft survival of patients undergoing deep anterior lamellar keratoplasty (DALK) to treat corneal scarring secondary to herpes simplex virus (HSV) keratitis., Methods: Retrospective, non-comparative case series. 18 patients who underwent DALK for HSV keratitis related corneal scarring between January 2004 and February 2007 were included. DALK was performed by Anwar's big bubble technique. Data collected for analysis included preoperative characteristics, intraoperative complications and postoperative acuity, complications and subsequent operations., Results: Mean best corrected distance visual acuity (LogMAR) improved from 1.51 ± 0.90 preoperatively to 0.82 ± 0.85 at the last follow-up (p=0.05). 27% of patients with more than 4 years follow-up had a best corrected distance visual acuity of 6/12 or better and 64% were 6/24 or better. Six patients (33%) experienced a recurrence of HSV keratitis and 9 (50%) experienced an episode of graft rejection. There were five cases (28%) of graft failure, four of whom had had a previous episode of graft rejection. Logistic regression did not find an association with graft rejection, HSV recurrence, any other observed postoperative host corneal vascularisation and any postoperative complication. The majority of patients underwent a second operation with 50% requiring cataract surgery., Conclusions: DALK for the treatment of HSV related corneal scarring is associated with a high percentage of postoperative complications. DALK in this context is also associated with a large percentage of secondary operations. Patients should be aware of this when giving informed consent for DALK to treat HSV related corneal scars.

Herpes simplex virus (HSV) is associated with a variety of ocular diseases, including epithelial and stromal keratitis. HSV can cause stromal opacification and is believed to be the leading cause of infectious blindness in the developed world. An improved understanding of the global burden of HSV keratitis, including the incidence of severe vision loss, could have a significant effect on prevention and treatment and place it in perspective among causes of corneal ulceration. We found that the global incidence of HSV keratitis is roughly 1.5 million, including 40,000 new cases of severe monocular visual impairment or blindness each year. We also discuss relevant epidemiologic issues regarding HSV epithelial and stromal disease., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Herpes simplex virus is a frequent cause of keratitis. Clinical forms are usually classified as epithelial, stromal, endothelial, or neurotrophic. Management depends on the respective degrees of these various components, with some patients presenting with compound forms. In the acute phase of the disease, the therapeutic strategy is based primarily on antiviral drugs, which can be given topically or systemically, according to the level of corneal involvement (superficial or deep), its severity, and practical constraints with respect to the patient's lifestyle. Other measures may be utilized according to the type of keratitis (debridement and mydriatic eye drops in epithelial keratitis, steroids in stromal and endothelial diseases). On a longer term basis, management aims to limit the frequency of recurrences, especially if the patient is subjected to a triggering factor for viral reactivation. Preventive treatment is also based on antiviral drugs, mostly oral, with dosage that must be adapted to the patient's individual history. Other treatments may also help to reduce the frequency of recurrences, in particular topical cyclosporine, but further studies are required to better delineate such indications., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Background: Ocular complications of herpes zoster ophthalmicus (HZO) may lead to substantial visual disability, severe post-herpetic neuralgia and rarely fatal cerebral complications., Aim: To identify the pattern of ocular manifestation in herpes zoster ophthalmicus., Materials and Methods: A cross-sectional descriptive study was under taken including the clinically diagnosed cases of HZO. All of them underwent a complete ophthalmological evaluation., Results: Sixty-eight cases of HZO were examined, of which 37 (54.4 %) were male and 31 (45.6%) female. The mean age was 48.7 ± 18.5 years. Most of the patients (64.7 %) were above the age of 40 years. 77.94 % of the patients had some form of ocular involvement. Pain (77.9 %) was the commonest ocular complaint. In young patients less than 35 years, HIV was the most common risk factor (19.3 %).Visual status was good in the majority (73.5 %) of patients at presentation. Lid and adnexal findings (45.8 %) were most common ocular involvement followed by conjunctivitis (41.1 %). Corneal complication was seen in 38.2 % of cases, uveitis in 19.1 % and post-herpetic neuralgia (PHN) and secondary glaucoma each in 5.8 %., Conclusion: Eyelid and ocular adnexal involvement is most commonly found in patients with herpes zoster ophthalmicus followed by corneal complication and uveitis. There needs to be awareness of ocular involvement, which can be sight threatening, among the HZO patients and other medical departments and an increased emphasis on regular ophthalmic examination., (© NEPjOPH.)

Objectives: To provide an estimate of the incidence of herpes simplex virus (HSV) eye disease in a community-based cohort, and to investigate the effect of prophylactic oral antiviral therapy on HSV recurrences and outcomes., Methods: All Olmsted County, Minnesota, residents diagnosed with ocular HSV from 1976 through 2007 were retrospectively reviewed. The frequency of recurrences and adverse outcomes, such as vision loss or need for surgery, were compared between untreated patients and those treated prophylactically with oral antiviral medication., Results: Three hundred ninety-four patients with ocular HSV were identified, yielding an annual incidence of 11.8 per 100,000 people (95% confidence interval [CI], 10.6-13.0). No trends in incidence or adverse outcomes were identified during the 32-year period. Oral antiviral therapy was prescribed in 175 patients. Patients were 9.4 times more likely (95% CI, 5.0-17.9) to have a recurrence of epithelial keratitis, 8.4 times more likely (95% CI, 5.2-13.7) to have a recurrence of stromal keratitis, and 34.5 times more likely (95% CI, 10.8-111.1) to have a recurrence of blepharitis or conjunctivitis if not being treated prophylactically at the time of the recurrence. Twenty patients experienced adverse outcomes, and 17 (85%) were not being treated with oral antiviral medications immediately preceding the adverse event., Conclusions: Oral antiviral prophylaxis was associated with a decreased risk of recurrence of epithelial keratitis, stromal keratitis, conjunctivitis, and blepharitis due to HSV. Patients with adverse outcomes due to ocular HSV were usually not being treated with oral antiviral prophylaxis.

Background: Blindness studies have shown that keratitis complicated by the use of traditional eye medications is a major factor of childhood blindness in developing countries. Most cases of such keratitis were presumably due to nutritional causes or bacterial infection. The patterns of outcome that are seen in hospitals may be different., Objective: To determine the clinical types of keratitis seen in children at a tertiary hospital and compare with other reports., Method: A retrospective analysis was conducted using the records of children who presented with keratitis to the eye unit of the University College Hospital, Ibadan, Nigeria, over a three-year period from January 2003 to December 2005. Information obtained were the demographic data, the etiological type of keratitis and visual outcome of management., Result: Ninety-five patients with keratitis seen during this three-year period were children. Of these, 47 (49.5%) patients had presumed herpes simplex keratitis; 78.9% of children with herpes simplex keratitis presented with combined epithelial and stromal disease; 21 (22.1%) had keratitis that was associated with a recent measles infection and protein calorie malnutrition. Fifteen (15.8%) had keratitis associated with phlyctenular keratoconjunctivitis, eight (8.4%) patients had bacterial/fungal keratitis, while four (4.2%) had vernal ulcers. Both the right and left eyes were affected in 47.6% and 52.4% of cases, respectively. Bilateral keratitis occurred in eight of the children with measles, and six patients with herpes simplex keratitis. Fifty-nine eyes had visual acuity recorded after the keratitis healed. Of these, the visual outcome was very poor in six (20.0%) eyes with herpes simplex keratitis and eight (100%) eyes with bacterial/fungal keratitis. All eyes with suppurative keratitis associated with measles developed dense corneal scars or were perforated., Conclusion: Herpes simplex keratitis was the leading cause of keratitis in children seen at this tertiary hospital, and clinical presentations do not differ from those reported in other populations. Very poor visual outcome was associated with all types of keratitis except those with herpes keratitis. Blindness studies may underrepresent the burden of herpes simplex keratitis in the location of this study.

Aim: To determine the incidence, methods of diagnosis, treatment strategies and outcomes for acute retinal necrosis (ARN) in the UK., Methods: A 12-month active case ascertainment study was carried out between March 2001 and March 2002 to record cases of ARN presenting to ophthalmologists via the British Ophthalmological Surveillance Unit (BOSU) reporting system. Questionnaires were sent to the reporting consultants, requesting data on patient characteristics, presentation, clinical findings, investigations and treatment. Diagnosis was made using the American Uveitis Society diagnostic criteria. Further questionnaires were sent at 2 weeks and 6 months to assess outcome and therapies., Results: 74 cases of ARN were reported by 58 consultants between March 2001 and March 2002. Questionnaires were returned for 49 cases (66.2%), of which 18 (36.7%) were excluded. Of the 31 cases included, 22 (71.0%) were male and 9 (29.0%) were female. The age range was 13 to 85 years (mean 54.3 years). 28 cases (90.3%) were unilateral, with 3 patients (9.7%) presenting with bilateral ARN. An aqueous or vitreous biopsy was performed in only 18 patients, with one patient having both. Herpes viral DNA analysis was performed on all 19 biopsies, with identification of the viral DNA in 16; results from 3 biopsies were not documented. Varicella zoster virus (VZV) was the commonest cause identified in 10 patients (56%). Of the 31 subjects, 27 (87.1%) were treated for ARN with systemic antiviral treatment: with intravenous antiviral in 23 cases (85.2%) and oral antiviral in 4 cases (14.8%). 21 of these patients went on to receive oral antiviral maintenance therapy. In addition to antiviral treatment, systemic steroids were given to 16 subjects (51.6%). Surgical intervention for retinal detachment was performed on 5 patients., Conclusions: During the 12-month study period, 31 cases of ARN met the diagnostic criteria set by the American Uveitis Society. The incidence in the UK based on this study is approximately 1 case per 1.6 to 2.0 million population per year. We have ascertained that the management of ARN throughout the UK is variable, suggesting that national guidelines would be of benefit.

Background: Herpes simplex virus (HSV) is the leading cause of infectious corneal blindness in the developed world. Eighty percent of the general population develop asymptomatic viral latency in the trigeminal ganglion following orofacial inoculation, but only 0.2% of all such orofacial inoculations are followed by recurrent corneal reactivation. Recurrences still threaten graft survival following penetrating keratoplasty, so that advance identification of patients at increased risk would be helpful in aftercare following penetrating keratoplasty. The HLA B27 phenotype is associated with increased susceptibility to genital HSV. However, no such association has been reported for herpetic eye disease., Methods: The HLA phenotypes of 129 patients who underwent penetrating keratoplasties for herpetic corneal scars were available for retrospective analysis. Four of these patients were positive for HLA-B27. The 125 HLA-B27-negative patients served as controls. The mean follow-up was 2.2 years. We compared the frequencies of herpetic recurrence and graft failure in the two groups using the Kaplan-Meier method and applied log-rank statistics., Results: After the average period of follow-up, 75% (three patients) of the HLA B27-positive patients experienced either graft failure or at least one reversible recurrence of the herpetic eye disease, as against only 25% of controls. This difference was highly statistically significant (p<0.01)., Conclusion: This retrospective analysis suggests that the HLA B27 phenotype promotes recurrence of herpetic eye disease following penetrating keratoplasty. HLA B27-positive patients should be closely monitored, and the indications for prophylactic antiviral therapy should be viewed liberally in this group.

Purpose: To compare the incidence of herpes simplex virus (HSV) epithelial recurrence and graft survival after penetrating keratoplasty (PK) in patients with and without self-reported atopy., Design: Retrospective cohort comparative study., Setting: Cornea Service, Wills Eye Hospital., Study Population: Patients who presented with previously diagnosed ocular HSV between March 2003 and March 2004 and who underwent primary PK for ocular HSV at the Cornea Service. From the 58 patients invited, 49 patients (50 eyes) were included. Nine patients were ineligible in accordance with the exclusion criteria: no active classic HSV episode before PK, immunosuppression, less than one year of follow-up, previous history of PK before presentation at the Service. Eligible patients filled out a questionnaire regarding their history of atopic disease, considering: presence of allergic rhinitis, asthma, or atopic dermatitis. Ocular history was obtained through chart review. main outcome measures: Incidence of epithelial HSV recurrences and corneal graft survival in both groups., Results: Each group (atopic and nonatopic) included 25 eyes. The atopic patients had a mean incidence of 0.07 episode/eye year (SD +/- 0.9) compared with 0.12/eye year (standard deviation [SD] +/- 0.21) in the nonatopics (P = .002). At 10 years of follow-up, the survival rate in the atopics was of 92% and in the nonatopics was of 79% (P = .88)., Conclusions: Nonatopics had significantly more epithelial recurrences after PK compared to atopics; however, both groups presented low incidences of recurrences and high graft survival rates.

Purpose: To determine whether atopy is associated with herpes simplex virus (HSV) ocular disease., Design: Retrospective, population-based, case-control study., Setting: Large, regional health maintenance organization (Northern California Kaiser Permanente)., Study Population: 1,042,351 people over a one-year period., Observation Procedures: Electronic database search for HSV ocular disease and subsequent chart review determined study eligibility. Two age-matched control groups (one population-based and one clinic-based) were randomly chosen. Medical record review determined the presence of atopy. Severe atopic disease was defined by diagnostic code or illness requiring an emergency room visit, hospitalization, or treatment with a systemic corticosteroid., Main Outcome Measures: Presence of HSV eye disease, presence of atopy, and characterization of atopy severity., Results: HSV eye disease was found in 172 patients. HSV cases had a greater prevalence of atopy (34%, 58/172) than the clinic-based (25%, 43/172) or the population-based controls (21%, 36/172, odds ratio (OR) 1.5, 95% confidence interval (CI) 0.9 to 2.6 and OR 1.9, 95%, CI 1.1 to 3.3, respectively). The association of HSV ocular disease with severe atopy was even greater, with a history of severe atopic disease in 13% (22/172) of patients with HSV ocular disease as compared with 6% (11/172) of patients in the clinic control group and 3% (5/172) of patients in the population control group (OR 2.0, 95% CI 0.7 to 5.9 and OR 4.8, 95% CI 1.6 to 19.2, respectively)., Conclusions: Patients with HSV ocular disease are more likely to have a history of atopic disease, especially severe atopic disease, than age-matched controls.

Purpose: To review the changing epidemiology of herpes simplex virus infection, emerging patterns of herpetic ocular disease, and the challenges and promise of herpes simplex virus vaccine therapy., Design: Perspective., Methods: Literature review., Results: An epidemic increase in genital herpes simplex type 2 infection is reflected in a 30% increase in HSV-2 antibodies in the United States since 1976. Approximately one in four people in the United States over age 30 is infected with HSV-2. Primary acquisition of herpes simplex type 1 is becoming progressively delayed in many industrialized countries, in contrast to developing nations where the virus is acquired early in life and is ubiquitous. Changes in sexual behavior among young adults have been associated with a recent increase in genital HSV-1 infection, resulting from oral-genital rather than genital-genital contact. Clinical trials of HSV vaccines using selected herpes simplex virus type 2 proteins mixed in adjuvant have shown limited efficacy in seronegative women, but not in men., Conclusions: The recent epidemic of genital herpes simplex type 2 infection is likely to result in an increase in neonatal ocular herpes and in delayed cases of acute retinal necrosis syndrome. The increase in genital HSV-1 may lead to industry production of vaccines that contain components of both HSV-1 and HSV-2 targeted toward limiting genital disease and transmission. As newer herpes simplex vaccines become available, ophthalmologists must be vigilant that a boost in immunity against HSV does not have a paradoxical effect in exacerbating break-through cases that develop immune-mediated herpes simplex stromal keratitis.

Purpose: To study the incidence of herpetic eye disease (HED) of the ocular surface in diabetics., Design: Observational historical cohort study., Setting: A district of the largest health maintenance organization in Israel (the Central District of Clalit Health Services)., Participants: We reviewed the electronic medical records of all patients older than 50 years (159634 patients) in the district, and of these, 22382 (14.0%) patients had diabetes mellitus., Methods: All filled prescriptions for acyclovir eye ointment between January 1, 2001 and December 31, 2003 (1483 tubes) and all hemoglobin A1c laboratory tests during 2003 (41910 tests) were documented. An ocular surface HED event was defined when a patient consumed at least 1 tube of topical acyclovir per month, whereas no acyclovir use was documented 3 months before and 3 months after that event., Main Outcome Measures: Incidence of ocular surface HED events in diabetics compared with nondiabetics adjusted for age and gender., Results: After age and gender adjustment, significantly more diabetics had ocular surface HED (5.21 per thousand) compared with nondiabetics (4.27 per thousand; P<0.0001). Stratification by age revealed a significantly higher prevalence of HED in diabetics, aged 60 to 79 years. Recurrent herpetic events occurred during the study period in 25.2% of HED-affected diabetics, and in 16.6% of HED-affected nondiabetics (P = 0.05). Diabetics with poor glycemic control (mean annual hemoglobin A1c > 9%) consumed significantly more ocular acyclovir (P = 0.01). Multivariate analysis revealed this effect to be independent of age, gender, place of birth, or place of residency., Conclusions: Ocular surface HED is significantly more common among patients with diabetes mellitus. Poor glycemic control correlates with increased consumption of ocular acyclovir in diabetic patients.

Background/aim: There are few clinical series in the literature of infective keratitis in the elderly, even though this age group constitutes a significant proportion of those affected by this condition. The authors aimed to determine the incidence and risk factors for infective keratitis in those over 60 years, the causative organisms, antibiotic susceptibilities, visual and tectonic outcome, and surgical intervention rate., Methods: A retrospective review of all patients aged 60 years and over admitted to the Sydney Eye Hospital with a diagnosis of infective keratitis, between September 1998 and December 2002., Results: 190 patients were identified with a mean age of 75.5 (SD 9.6) years (range 60-101). Local risk factors were found in 93.7%, and systemic risk factors in 27.9%. Organisms were cultured in 62.8%, and 7.9% had positive herpes simplex virus (HSV) polymerase chain reaction (PCR). Perforation or severe thinning occurred in 36% overall, but in 80% with positive HSV PCR. Acute surgical intervention was required in 43.7%, with acute penetrating keratoplasty performed in 17.9%, and 8.9% required evisceration. Mean presenting visual acuity was 1.82 (SD 1.24), equivalent to 6/300, excluding 26.3% with vision of light perception (LP) or worse. Mean final visual acuity was 1.24 (SD 1.16), equivalent to 6/100, excluding 19.5% with vision of LP or worse (p<0.0005)., Conclusions: The elderly represent a distinct clinical group in the context of microbial keratitis. Predisposing factors are very common, they present with poor vision, have a high complication and surgical intervention rate, and a poor visual outcome compared to younger patients. The microbiological spectrum is similar to younger age groups, except that HSV is more common and may increase the risk of severe corneal thinning and perforation. Most bacterial isolates remain sensitive to currently available antibiotic preparations.