Recurrent Herpes Simplex Keratitis Research Articles

Long-term Follow-up Results after Prophylactic Antiviral Administration in Patients with Herpes Simplex Keratitis

Purpose: We analyzed the effectiveness of prophylactic oral antivirals in preventing herpes simplex keratitis (HSK) and the clinical manifestations of recurrence.Methods: A retrospective analysis was conducted on 30 eyes of 30 patients diagnosed with HSK who received prophylactic oral antiviral agents for > 6 months. We analyzed the initial and recurrent clinical features of HSK, the recurrence rate, and the relationship between recurrence and the duration of oral antivirals.Results: The mean age of the patients was 64.5 ± 14.0 years, and the mean follow-up duration was 72.4 ± 40.3 months. Of the 30 eyes, 21 (70%) experienced HSK recurrence. The initial clinical features of recurrent cases included herpetic epithelial keratitis (14.3%), stromal keratitis (47.6%), and endotheliitis (38.1%). Notably, no significant associations were observed between the initial clinical features of HSK or the duration of oral antivirals and HSK recurrence. However, male patients exhibited a significantly higher recurrence rate. Epithelial keratitis (47.6%) was the most common HSK type observed during recurrence.Conclusions: A recurrence rate of 70% was observed in patients who received prophylactic oral antiviral treatment for > 6 months. Herpetic epithelial keratitis was the most common clinical phenotype after recurrence. Notably, long-term clinical monitoring could assist in predicting and preventing recurrence.

A supramolecular gel with unique rheological properties for treating corneal virus infection

Herpes simplex keratitis (HSK) caused by herpes simplex virus-1 infection of the cornea has taken a significant toll on the visual health of people worldwide. Anti-viral hydrogels are preferred in the treatment of HSK due to enhanced topical drug retention and reduced side effects, however, current polymer-based gelling systems usually generate clumpy or uneven gel layers on ocular surface, and are easily cleared by eyelid blinking. This study proposes a supramolecular gel co-assembled by all-small-molecule building blocks including ganciclovir and 2′-deoxyguanosine in the presence of potassium ions. The developed gel performs fascinating rheological and texture properties including high viscoelastic, good spread ability, and deformation recovery behavior, enabling the formation of a uniform and thin gel layer on ocular surface to resist the clearance by eyelid blinking and tear washing. The gel shows similar ocular convenience, but much longer drug retention in ocular tissues and higher therapeutic efficacy compared to the clinical ganciclovir gel on the primary and recurrent mouse HSK models, rabbit HSK models, and also efficiently inhibited the HSV-1 replication in ex vivo human corneal tissues. The results suggest that this all-small-molecule supramolecular gel could be a promising drug formulation for treating HSK. Data and materials availabilityThe main data supporting the results in this study are available within the paper and its Supplementary Information. The associated raw data and analyzed datasets are too large to be readily shared publicly, but they are available from the corresponding author on reasonable request.

Corneal epithelial scarring secondary to recurrent herpes simplex keratitis

Corneal epithelial scarring secondary to recurrent herpes simplex keratitis

Role of tear exosomes in the spread of herpes simplex virus type 1 in recurrent herpes simplex keratitis.

Herpes simplex keratitis (HSK) is the most common but serious infectious keratitis with high recurrence. It is predominantly caused by herpes simplex virus type 1 (HSV-1). The spread mechanism of HSV-1 in HSK is not entirely clear. Multiple publications indicate that exosomes participate in the intercellular communication process during viral infections. However, there is rare evidence that HSV-1 spreads in HSK by exosomal pathway. This study aims to investigate the relationship between the spread of HSV-1 and tear exosomes in recurrent HSK. Tear fluids collected from total 59 participants were included in this study. Tear exosomes were isolated by ultracentrifugation, then identified by silver staining and western blot. The size was determined by dynamic light scattering (DLS). The viral biomarkers were identified by western blot. The cellular uptake of exosomes was studied using labelled exosomes. Tear exosomes were indeed enriched in tear fluids. Collected exosomes own normal diameters consistent with related reports. The exosomal biomarkers existed in tear exosomes. Labelled exosomes were successfully taken up by human corneal epithelial cells (HCEC) in large numbers in a short time. After cellular uptake, HSK biomarkers were detectable by western blot in infected cells. Tear exosomes should be the latent sites of HSV-1 in recurrent HSK and might be involved in the spread of HSV-1. Besides, this study verifies HSV-1 genes can be indeed transferred between cells by exosomal pathway, providing new inspiration for the clinical intervention and treatment as well as the drug discovery of recurrent HSK.

Nectin-1 and Non-muscle Myosin Heavy Chain-IIB: Major Mediators of Herpes Simplex Virus-1 Entry Into Corneal Nerves.

Herpes Simplex Virus 1 (HSV-1) invades corneal nerves upon its infection of the cornea and then establishes latency in the trigeminal ganglion (TG). The latent virus in TG is often reactivated and travels back to the cornea, causing recurrent herpes simplex keratitis (HSK). The entry of HSV-1 into the corneal nerve is considered the initial step of infection resulting in HSV-1 latency and HSK recurrence. Several gD and gB receptors have been identified, including nectin-1, herpes virus entry medium (HVEM) and 3-O-sulfated heparan sulfate (3-OS-HS) as gD receptors, and non-muscle myosin heavy chain IIA (NMHC-IIA), NMHC-IIB and myelin-associated glycoprotein (MAG) as gB receptors. However, which receptors contribute to the entry of HSV-1 into corneal nerves are yet to be determined. This study observed that receptors nectin-1, HVEM, 3-OS-HS, NMHC-IIA, and NMHC-IIB, not MAG, were expressed in healthy corneal nerves. Further, we cultured TG neurons extracted from mice in vitro to screen for functional gD/gB receptors. Both in vitro siRNA knockdown and in vivo antibody blocking of either nectin-1 or NMHC-IIB reduced the entry and the replication of HSV-1 as shown by qPCR analysis and immunofluorescence measure, respectively. Also, we observed that the re-localization and the upregulation expression of NMHC-IIB after HSV-1 exposure were inhibited when gD receptor nectin-1 was knocked down. These data suggest that nectin-1 was the main gD receptor and NMHC-IIB was the main gB receptor in mediating HSV-1 entry and hold promise as therapeutic targets for resolving HSV-1 latency and HSK recurrence.

Activation of the STAT5 Signaling Pathway by Yiqi Jiedu Formula Induces Regulatory T Cell-Mediated Alleviation of Corneal Immunopathological Damage in Mice With Recurrent Herpes Simplex Keratitis.

This study aimed to investigate the effect of Yiqi Jiedu (YQJD) formula on the repair of corneal lesions in mice with recurrent herpes simplex virus keratitis (HSK). Sixty female BALB/c mice were randomly divided into three groups: a normal control group (Naive), a recurrence model group (Re), and a YQJD group. After inducing recurrence by ultraviolet irradiation, the ocular surfaces of different groups of mice were observed using a slit lamp and photographed, and ocular surface scores were calculated. The abundance of CD4+CD25+Foxp3+ regulatory T (Treg) cells was determined by flow cytometry in peripheral blood and spleen cells. The CD4+Foxp3+ Tregs were assessed by immunofluorescence in the cornea. The levels of the cytokines IL-10 and TGF-β in serum and splenocyte culture supernatants were detected by enzyme-linked immunosorbent assay. Furthermore, the activation status of the STAT5 signaling pathway was examined by protein blotting, and the effect of YQJD on Treg cells through inhibition of the STAT5 pathway was observed in vitro. YQJD alleviated corneal inflammation by enhancing the STAT5 signaling pathway, thereby promoting the differentiation of CD4+CD25+Foxp3+ Treg cells, increasing the levels of anti-inflammatory cytokines such as IL-10 and TGF-β, and maintaining immune tolerance. YQJD increased the proportion of CD4+Foxp3+ Treg cells; also, in the cornea, YQJD inhibited the aggregation of macrophages and CD4+ cells and reduced the proportion of Th17 cells and other pro-inflammatory cells. Moreover, YQJD promoted the secretion of IL-4 to protect the cornea, leading to the mitigation of corneal immunopathological damage. YQJD reduced corneal lesions in recurrent HSK mice by stimulating Treg cells, inducing immune tolerance, and inhibiting corneal immunopathological responses via modulation of the STAT5 signaling pathway.

Outcome of Lamellar Graft Patching for the Treatment of Noninfectious Corneal Perforations.

The aims of this study were to evaluate the clinical outcome of lamellar graft patching used for treating noninfectious corneal perforations and to determine the clinical factors affecting tectonic integrity. This retrospective study includes a total of 71 eyes of 67 patients who underwent lamellar graft patching for the treatment of corneal perforations due to persistent epithelial defects secondary to limbal stem cell deficiency (LSCD, 21 eyes; 29.6%), peripheral ulcerative keratitis (17 eyes; 23.9%), neurotrophic keratitis due to herpes simplex keratitis (HSK, 14 eyes; 19.7%), and other causes (19 eyes; 26.8%). We evaluated the tectonic integrity of the globe, visual outcomes, and postoperative complications. Tectonic integrity was achieved in 53 eyes (74.6%). The survival proportions of eyes that achieved clear grafts were 77.8% and 65.2% at 12 and 24 months, respectively. Graft failure was observed in 19 eyes (26.8%). The survival rate of tectonic integrity and eyes that finally achieved a clear graft was significantly worse in eyes with LSCD compared with those without ( P < 0.001). The logarithm of minimal angle resolution improved significantly from 1.79 ± 0.98 to 1.22 ± 0.87 at 12 months and 1.08 ± 0.81 at 24 months. Postoperative complications included cataract formation (32 eyes, 45.1%), intraocular pressure rise (23 eyes, 32.4%), recurrent perforations (15 eyes, 21.1%), infectious keratitis (14 eyes, 19.7%), recurrence of herpes simplex keratitis (7 eyes, 9.9%), and traumatic graft dehiscence (1 eye, 1.4%). Lamellar graft patching is an effective and safe surgical treatment for noninfectious corneal perforations; however, careful attention to severe complications is necessary, especially in eyes with LSCD.

Outcomes of Patients with Herpes Simplex Keratitis Before and After the Implementation of a New Treatment Guideline in Sydney, Australia.

Outcomes of Patients with Herpes Simplex Keratitis Before and After the Implementation of a New Treatment Guideline in Sydney, Australia.

Impact of Adherence (Compliance) to Oral Acyclovir Prophylaxis in the Recurrence of Herpetic Keratitis: Long-Term Results From a Pediatric Cohort.

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. 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. 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. 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.

Adverse Events of Intense Pulsed Light Combined With Meibomian Gland Expression Versus Meibomian Gland Expression in the Treatment of Meibomian Gland Dysfunction.

To analyze the occurrence and causes of adverse events (AEs) in intense pulsed light (IPL) combined with meibomian gland expression (MGX) and MGX treatment alone for meibomian gland dysfunction (MGD). A retrospective study was conducted on MGD patients treated in Wuhan Aier Hankou Eye Hospital from February 2018 to October 2019 to compare the AEs between IPL-MGX and MGX groups. Relevant AEs that occurred during the treatment and within 1 month after the patients' last treatment were recorded and the causes of the AEs were analyzed. A total of 2,282 patients received IPL-MGX and 1,407 received MGX treatment. No serious AEs occurred in both groups. There were 74 AEs in the IPL-MGX group, with an incidence of 3.24%, including 14 significant AEs (2 cases of epidemic keratoconjunctivitis, 1 recurrent herpes simplex keratitis (HSK), 9 new onsets of floaters, 1 recurrent glaucomatocyclitic crises, and 1 recurrent iridocyclitis). There were 27 AEs in the MGX group with a rate of 1.92%, including 4 significant AEs (2 cases of keratoconjunctivitis epidemic, 2 new cases of floaters). Compared with the IPL-MGX group, the incidence of AEs in the MGX group was lower (P = 0.017). Both IPL-MGX and MGX treatment are safe therapies with low risk for AEs. IPL treatment is not recommended for young children (age 10 or less) as well as patients with anterior uveitis or glaucomatocyclitic crises. The previous history of HSK and eyes with high myopia are advised to exercise caution in IPL treatment. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

IL28B Genetic Variations in Patients with Recurrent Herpes Simplex Keratitis.

Background and objectives: Recurrent herpes simplex keratitis (HSK) is the most common cause of corneal blindness in the developed world. A relationship between host gene polymorphisms and the recurrence of herpes simplex virus (HSV) infection has previously been proposed. Thus, the aim of this study was to investigate a potential association between the IL28B host genotype and recurrent HSK. Materials and Methods: Eighty patients older than 18 years of age of both genders with a history of recurrent herpes simplex labialis (HSL) were considered for inclusion. Seventy-five of these patients were found to be seropositive for HSV-1 and were subsequently enrolled in the study. Twenty-four of the enrolled patients also had a history of recurrent HSK associated with severe corneal scarring and visual acuity deterioration. Total DNA was isolated from whole blood samples. A single-nucleotide polymorphism (SNP) rs12979860 near the IL28B gene on chromosome 19 was genotyped. Results: A significant association was observed between recurrent HSK and two SNPs of the IL28B genotype (CCrs12979860 and CTrs12979860, p < 0.01). The variation CCrs12979860 showed a significantly greater association with HSK (16 out of 26 patients) compared with CTrs12979860 (8 out of 34 patients). Conclusion: Seropositive individuals with a history of recurrent HSK are likely to have the CC IL28B genotype. This genotype may be related to incomplete control of the infection and more frequent periodical viral shedding along the first nerve branch of the trigeminal ganglion, which clinically manifests as recurrent herpes keratitis. The clinical manifestation of recurrent HSV-1 infection seems to be influenced by polymorphism of the IL28B genotype.

Clinical translation of recommendations from randomized trials for management of herpes simplex virus keratitis.

To standardize initial anti-viral therapy for herpes simplex keratitis (HSK). To determine prescribing trends for the management of HSK and compare the trends to available clinical trial evidence. Retrospective review of patients at the Sydney Eye Hospital, Australia. Three hundred and one eyes of 296 patients prescribed anti-virals for HSK aged 18 years and above, from 1 January 2012 to 31 December 2013. Patients were identified from viral swab results, pharmacy records and International Classification of Diseases 10 (ICD-10) coding data. Initial anti-viral therapy. Anti-viral therapy was given for therapeutic and prophylactic indications at presentation in 256 (85%) and 45 (15%) eyes, respectively. Overall, anti-virals prescribed included valaciclovir 500-1000 mg 1-3 times daily, aciclovir 200-400 mg 1-5 times daily, topical aciclovir 2-5 times daily and topical trifluorothymidine two hourly or as needed daily or combined oral and topical anti-virals. Indication and dose of prescribed anti-virals aligned with clinical evidence in 125 of 141 eyes (89%) with epithelial HSK, 2 of 22 eyes (9%) with stromal without ulceration HSK, 6 of 18 (28%) eyes with endothelial HSK and 31 of 45 (69%) eyes with HSK prophylaxis. Overall, 164 eyes (54%) received 'evidence-based' anti-viral therapy. Prescribing patterns for anti-viral therapy to treat and prevent recurrence of HSK were diverse. Local guidelines are needed to standardize the indications and dose of initial anti-viral therapy for HSK. Implementation of these guidelines will likely improve patient care and rationalize the use of health resources.

Immunization with dendritic cell-based DNA vaccine pRSC-NLDC145.gD-IL21 protects mice against herpes simplex virus keratitis.

The aim of this study is to investigate the effects of constructed dendritic cell (DC)-based DNA vaccine (pRSC-NLDC145.gD-IL21) carried by chitosan nanoparticle in preventing primary or recurrent herpes simplex virus keratitis (HSK) in mice. The expression of constructed plasmid 'pRSC-NLDC145.gD-IL21' was verified by western blot and immunofluorescence. Plasmids that were embedded in chitosan were inoculated to test its therapeutic effect against primary or recurrent HSK in mice. Humoral and cellular immune response, clinical scores of herpes keratitis and inflammatory infiltration were measured. The expressed glycoprotein D (gD) of pRSC-NLDC145.gD-IL21 DNA/chitosan nanoparticle vaccine could effectively target corneal DCs and significantly alleviate the symptoms of both primary and recurrent HSK mice via eliciting strong humoral and cellular immune response. Our data suggested that DC-based DNA vaccine could be a better choice for HSK treatment in the future.

Analysis of cause of recurrent herpes simplex keratitis after vitrectomy

Objective To analyze the related factors about the recurrence of herpes simplex keratitis (HSK) after vitrectomy. Methods The data of 108 eyes of 108 patients with HSK from Mar. 2013 to Jul. 2016 were collected and analyzed retrospectively. Herpes simplex keratitis was recurred in some patients after operation. The preoperative, intraoperative and postoperative factors related with recurrence of HSK were compared and analyed between the recurrent cases and no recurrent cases. Results In 108 eyes, 36 (33.3%) eyes were found recurrent HSK after vitrectomy. The size of vitrectomy cutter head, intraoperative observation system, intraocular tamponade, postoperative capsular membrane integrity were not relative with recurrence of HSK. And the age, diabetes, preoperative HSK recurrence times, operative time, surgical methods, corneal epithelial curettage, postoperative high intraocular pressure, corneal lesions and influenza were relative with recurrence of HSK. Conclusion The factors affected the function of corneal epithelial cells and the local or systemic immune are related with the postoperative recurrence of HSK. Key words: Vitrectomy; Simplex keratitis, herpes; Cause, recurrence

Recurrent herpetic keratitis despite antiviral prophylaxis: A virological and pharmacological study

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 (ACVR) 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 ACVR virus and identification may aid in adapting treatment. Incomplete 24-h drug coverage may also explain some cases of failure of prophylaxis.

Oral antivirals for preventing recurrent herpes simplex keratitis in people with corneal grafts.

Ocular herpes is a viral infection of the eye caused by the herpes simplex virus (HSV), a double-stranded DNA virus. Corneal scarring caused by herpes simplex keratitis (HSK) is the leading infectious cause of penetrating corneal graft in high-income countries. Acyclovir is an antiviral drug known to have a protective effect against recurrences in herpetic eye disease. While there are some studies which have evaluated the effects of intervention with oral antiviral in preventing such recurrences in people with corneal grafts, a systematic review of all comparative clinical trials has not been previously undertaken. To assess the efficacy of oral antivirals such as acyclovir in any dosage when taken for six months or more, in preventing recurrence of herpetic keratitis in people having corneal graft surgery for herpetic keratitis. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2016), Embase (January 1980 to June 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 1 June 2016. We handsearched conference proceedings and contacted authors of the included studies and researchers active in the field. We included randomised controlled trials (RCTs). People enrolled in these trials had corneal grafts for HSK. The intervention was oral antivirals for six months or more following the corneal graft surgery, and this was compared to no treatment or placebo. Two review authors independently assessed trial quality and extracted data. We contacted trial investigators for any clarification or missing information. We graded the certainty of the evidence using GRADE. We included three trials, involving 126 participants, comparing the use of oral acyclovir to no treatment or placebo. Two studies were conducted in single centres in Turkey and the USA, and one was multi-centred in the Netherlands. In general, the studies were poorly reported and it was difficult to judge the extent to which bias had been avoided.Oral acyclovir may reduce the risk of recurrence of herpetic keratitis (risk ratio (RR) 0.29, 95% confidence interval (CI) 0.13 to 0.64, 126 people, low-certainty evidence). Based on data from the included trials, this corresponds to approximately 23 fewer cases of HSK recurrence (95% CI 29 fewer cases to 12 fewer cases) per 100 corneal graft operations if oral acyclovir is used.Oral acyclovir may reduce the risk of graft failure (RR 0.40, 95% CI 0.16 to 0.97, 126 people, low-certainty evidence). Based on data from the included trials, this corresponds to approximately 13 fewer cases of graft failure (95% CI 18 fewer cases to 1 fewer cases) per 100 corneal graft operations if oral acyclovir is used.None of the studies reported any serious side effects of the antivirals necessitating stoppage or change. None of the trials reported outcomes over the long term (more than two years) or any data on quality of life. Compared to placebo or to no treatment, oral antiviral (acyclovir) may reduce the risk of recurrence of herpetic keratitis in the first 12 months in eyes that have undergone corneal graft surgery.

Long-Term Outcomes of Deep Anterior Lamellar Keratoplasty Treating Posterior Stroma-Implicated Herpetic Corneal Opacities.

To evaluate the long-term outcomes of deep anterior lamellar keratoplasty for the management of deep stromal corneal opacities after herpes simplex keratitis (HSK) infection. Case records of patients who underwent deep anterior lamellar keratoplasty between January 2006 and June 2012 to treat HSK-related deep stromal corneal scars were retrospectively analyzed. The cases were divided into folds-on, folds-off, and no-folds groups based on the presence of stromal folds intraoperatively. The main outcome measures were best-corrected visual acuity, endothelial cell density, and complications. A total of 89 patients (89 eyes; 54 men and 35 women; 47.1 ± 12.9 years old) were included. Based on intraoperative events, 48 eyes had no stromal folds, 27 eyes had folds that were centrally peeled off, and 14 eyes had folds that could not be peeled. The average follow-up period was 50.4 ± 12.7 months. The mean best-corrected visual acuity improved from 1.63 ± 60.52 logMAR preoperatively to 0.44 ± 0.31 logMAR at the last visit (P < 0.001). Mean postoperative endothelial cell density was 1738 ± 573 cells per square millimeter. Eight eyes experienced HSK recurrence, 3 eyes had an episode of stromal rejection, and 3 eyes developed corneal endothelial decompensation. Cases in the folds-off group had a significantly higher rate of Descemet membrane microperforations compared with the other groups. Deep anterior lamellar keratoplasty is a viable alternative for the management of HSK-related deep stromal opacity. Although posterior corneal folds can be relieved intraoperatively in some of these cases, folds near Descemet membrane should be left in situ because of the high risk of Descemet membrane perforation.

Management and Prevention of Herpes Zoster Ocular Disease.

Herpes zoster (HZ) is caused by reactivation of latent varicella zoster virus (VZV) in people who have had chicken pox, usually resulting in a painful, unilateral, dermatomal, vesicular rash. Herpes zoster ophthalmicus occurs when the first division of cranial nerve V is involved. HZ is common, with approximately 1 million new cases per year in the United States, and occurs in 1 in 3 persons. Although the rate of HZ increases with age, over half of all cases occur under the age of 60 years. Complications of herpes zoster ophthalmicus include eye disease, postherpetic neuralgia (PHN), and strokes. VZV has also been found in temporal arteritis biopsies. There is growing evidence that HZ is followed by chronic active VZV infection contributing to these complications. In view of this, and the efficacy of suppressive antiviral treatment in reducing recurrent herpes simplex keratitis, a randomized controlled trial of suppressive valacyclovir to reduce new or worsening anterior segment disease and/or PHN is needed. The zoster vaccine (ZV) is safe and effective in reducing the burden of illness, severity of PHN, and incidence of HZ. It is Centers for Disease Control and Prevention recommended for persons aged 60 years and above without impaired cellular immunity, and Food and Drug Administration approved for those aged 50 and older. It is most effective in preventing HZ in recipients in their 50s. Because of underusage of the ZV, it has not impacted the epidemiology of the disease. Barriers to its use include cost, variable reimbursement, frozen storage, and lack of a strong recommendation by doctors.

Clinical efficacy of oral ganciclovir for prophylaxis and treatment of recurrent herpes simplex keratitis.

Background:Herpes simplex keratitis (HSK) caused by herpes simplex virus 1 (HSV-1), which has high recurrent rate and incidence of severe vision loss, is the leading cause of infectious blindness in the world. The aim was to explore the clinical efficacy of oral ganciclovir (GCV) in the prevention of recurrent HSK.Methods:A multicenter, prospective, randomized, single-blind, and controlled clinical trial was conducted from April 2010 to June 2013. One hundred seventy-three patients (173 eyes involved) who were diagnosed as recurrent HSK definitely, including stromal keratitis and corneal endotheliitis, were divided into three groups randomly: negative control (placebo) group was topically administered with 0.15% GCV ophthalmic gel, 4 times per day and 0.1% fluorometholone eye drops, 3 times per day until resolution of HSK; positive control acyclovir (ACV) group was topically adopted the same ophthalmic gel and eye drops and additionally received oral ACV 400 mg 5 times a day for 10 weeks and followed by 400 mg 2 times per day for 6 months; test GCV group was topically adopted the same treatment as negative control group and additionally received oral GCV 1000 mg 3 times per day for 8 weeks. The symptoms and signs were evaluated before and after the therapy 1st week, 2nd week and then followed up every 2 weeks until recovery. Furthermore, we followed up recurrence of HSK for every 3 months after recovery and then assessed the cure time, recurrent rate and adverse reactions.Results:One hundred and seventy-three patients were followed up 7–48 months (mean 32.1 ± 12.3 months), but 34 patients were failed to follow-up. The cure time was 12.1 ± 4.3, 11.9 ± 4.0 weeks in negative control (placebo) group and positive control ACV group respectively (P = 0.991), which was longer than that in test GCV group (8.6 ± 2.8 weeks) and there was a significant difference between test GCV group and negative control (placebo) group or positive control ACV group (P = 0.000). Furthermore, the recurrent rate was higher in negative control (placebo) group (47.3%) than that in positive control group ACV (26.7%) and test GCV group (17.2%), and there was a great significant difference among the three groups (P = 0.007), but there was no significant difference between positive control ACV group and test GCV group (P = 0.358). In addition, there was no obvious adverse reaction expect neutropenia (only one patient in test GCV group).Conclusion:Short-term oral GCV could cure recurrent HSK and endotheliitis, shorten the course, reduce recurrent rate of HSK and have confirmed safety.

Immunological aspects of acute and recurrent herpes simplex keratitis.

Herpes simplex keratitis (HSK) belongs to the major causes of visual morbidity worldwide and available methods of treatment remain unsatisfactory. Primary infection occurs usually early in life and is often asymptomatic. Chronic visual impairment and visual loss are caused by corneal scaring, thinning, and vascularization connected with recurrent HSV infections. The pathogenesis of herpetic keratitis is complex and is still not fully understood. According to the current knowledge, corneal scarring and vascularization are the result of chronic inflammatory reaction against HSV antigens. In this review we discuss the role of innate and adaptive immunities in acute and recurrent HSV ocular infection and present the potential future targets for novel therapeutical options based on immune interventions.