[Recurrent herpetic erosion of the cornea: diagnosis, treatment and prevention of recurrences]. / gerpeticheskaya retsidiviruyushchaya eroziya rogovitsy: diagnostika, lechenie i preduprezhdenie retsidivov.

A group of patients was found to have a special form of recurrent corneal erosion caused by types I and II herpes virus. This form represents an independent form of ophthalmic herpes - herpetic recurrent erosion (HRE) of the cornea. The herpetic etiology of recurrent corneal erosion was confirmed by the immunofluorescence study of scraping from the conjunctiva, which revealed a high concentration of the herpes simplex virus antigen. Treatment of patients (171 patients, 182 eyes) with HRE included 2 consecutive stages: stage I - relief of acute symptoms of the disease with the help of conservative treatment (instillations of interferon inducers, autologous serum, corneal protectors, tear substitutes, use of therapeutic soft contact lenses); in some cases, phototherapeutic keratectomy was used in the absence of the effect of conservative therapy, as well as in the localization of the focus in the optical zone. Stage II involved anti-relapse therapy based on the use of a Russian-produced herpes vaccine in the intercurrent period. After vaccination, observation for 2 years or more showed that 81.3% of patients achieved clinical recovery (complete cessation of HRE recurrences), 15.8% had a decrease in the frequency and severity of relapses, while 2.9% of patients did not respond to the treatment.

[Chinese expert consensus on the diagnosis and treatment of herpes simplex keratitis (2023)].

As one of the common infectious corneal diseases, herpes simplex keratitis (HSK) has diverse clinical manifestations, is prone to recurrence, and can lead to blindness. In recent years, as new virus detection technologies, treatment drugs and surgical methods have emerged, there are more options for the diagnosis and treatment of HSK, but many problems still exist. In order to further standardize the clinical diagnosis and treatment of HSK and provide guidance and reference for clinical work, the Ocular Infection Group of Chinese Ophthalmologist Association has gathered relevant domestic experts, and reached this consensus on the diagnosis, treatment, and prevention of HSK through full discussion, on the basis of previous opinions, and in consideration of the latest research progress, relevant guidelines abroad and expert recommendations regarding the clinical care of patients with HSK.

In vivo CRISPR gene editing in patients with herpetic stromal keratitis.

In vivo CRISPR gene therapy holds large clinical potential, but the safety and efficacy remain largely unknown. Here, we injected a single dose of herpes simplex virus 1 (HSV-1)-targeting CRISPR formulation in the cornea of three patients with severe refractory herpetic stromal keratitis (HSK) during corneal transplantation. Our study is an investigator-initiated, open-label, single-arm, non-randomized interventional trial at a single center (NCT04560790). We found neither detectable CRISPR-induced off-target cleavages by GUIDE-seq nor systemic adverse events for 18 months on average in all three patients. The HSV-1 remained undetectable during the study. Our preliminary clinical results suggest that in vivo gene editing targeting the HSV-1 genome holds acceptable safety as a potential therapy for HSK.

IFN-λ Regulates Neutrophil Biology to Suppress Inflammation in Herpes Simplex Virus-1-Induced Corneal Immunopathology.

HSV-1 infection of the cornea causes a severe immunoinflammatory and vision-impairing condition called herpetic stromal keratitis (SK). The virus replication in corneal epithelium followed by neutrophil- and CD4+ T cell-mediated inflammation plays a dominant role in SK. Although previous studies demonstrate critical functions of type I IFNs (IFN-α/ß) in HSV-1 infection, the role of recently discovered IFN-λ (type III IFN), specifically at the corneal mucosa, is poorly defined. Our study using a mouse model of SK pathogenesis shows that HSV-1 infection induces a robust IFN-λ response compared with type I IFN production at the corneal mucosal surface. However, the normal progression of SK indicates that the endogenous IFN responses are insufficient to suppress HSV-1-induced corneal pathology. Therefore, we examined the therapeutic efficacy of exogenous rIFN-λ during SK progression. Our results show that rIFN-λ therapy suppressed inflammatory cell infiltration in the cornea and significantly reduced the SK pathologic condition. Early rIFN-λ treatment significantly reduced neutrophil and macrophage infiltration, and IL-6, IL-1ß, and CXCL-1 production in the cornea. Notably, the virucidal capacity of neutrophils and macrophages measured by reactive oxygen species generation was not affected. Similarly, ex vivo rIFN-λ treatment of HSV-1-stimulated bone marrow-derived neutrophils significantly promoted IFN-stimulated genes without affecting reactive oxygen species production. Collectively, our data demonstrate that exogenous topical rIFN-λ treatment during the development and progression of SK could represent a novel therapeutic approach to control HSV-1-induced inflammation and associated vision impairment.

Targeting herpes simplex virus with CRISPR-Cas9 cures herpetic stromal keratitis in mice.

Herpes simplex virus type 1 (HSV-1) is a leading cause of infectious blindness. Current treatments for HSV-1 do not eliminate the virus from the site of infection or latent reservoirs in the trigeminal ganglia. Here, we target HSV-1 genomes directly using mRNA-carrying lentiviral particles that simultaneously deliver SpCas9 mRNA and viral-gene-targeting guide RNAs (designated HSV-1-erasing lentiviral particles, termed HELP). We show that HELP efficiently blocks HSV-1 replication and the occurrence of herpetic stromal keratitis (HSK) in three different infection models. HELP was capable of eliminating the viral reservoir via retrograde transport from corneas to trigeminal ganglia. Additionally, HELP inhibited viral replication in human-derived corneas without causing off-target effects, as determined by whole-genome sequencing. These results support the potential clinical utility of HELP for treating refractory HSK.

[Therapeutic effect of acupoint injection as adjuvant treatment on dry eyes of convalescent herpes simplex keratitis].

OBJECTIVE: To evaluate the clinical effect of acupoint injection of houttuynia cordata as the accessory treatment on dry eyes of convalescent herpes simplex keratitis (HSK). METHODS: A total of 60 patients with dry eyes of convalescent HSK were randomized into an observation group and a control group, 30 cases in each one. In the control group, the artificial tears and anti-inflammatory drugs were combined in treatment. In the observation group, on the base of the treatment as the control group, the acupoint injection of houttuynia cordata at Neiqiuhou (Extra) was combined, 3 mL each time, once a day. After consecutive 3 injections, the injection was adjusted to be once every two days, consecutively for 3 times. The treatment for 6 times was as one course and one course of treatment was required. Separately, before treatment and in 7, 15 and 30 days after treatment, the changes of the scores of visual analogue scale (VAS), theresults of SchirmerⅠtest (SⅠT), the tear break-up time (BUT) and the score of corneal fluorescein staining (CFS) were observed and analyzed in the patients of the two groups. RESULTS: In 7, 15 and 30 days after treatment, VAS scores and CFS scores were all reduced as compared with those before treatment in the patients of the two groups (P<0.05), and the scores of VAS and CFS in the observation group were lower than those in the control group (P<0.05). In 7, 15 and 30 days after treatment, the values of SⅠT and BUT were all increased as compared with those before treatment in the patients of the two groups (P<0.05), and the values in the observation group were higher than the control group in 15 and 30 days after treatment (P<0.05). CONCLUSION: Acupoint injection of houttuynia cordata promotes corneal epithelial recovery, reduces the discomfort symptoms as well as increases tear secretion and the stability of tear film in dry eyes of convalescent herpes simplex keratitis.

Unique molecular signatures of antiviral memory CD8+ T cells associated with asymptomatic recurrent ocular herpes.

The nature of antiviral CD8+ T cells associated with protective and pathogenic herpes simplex virus type 1 (HSV-1) infections remains unclear. We compared the transcriptome, phenotype, and function of memory CD8+ T cells, sharing the same HSV-1 epitope-specificities, from infected HLA-A*0201 positive symptomatic (SYMP) vs. asymptomatic (ASYMP) individuals and HLA-A*0201 transgenic rabbits. Compared to higher frequencies of multifunctional effector memory CD8+ TEM cells in ASYMP individuals, the SYMP individuals presented dysfunctional CD8+ TEM cells, expressing major exhaustion pathways. Compared to protected ASYMP HLA transgenic rabbits, the trigeminal ganglia of non-protected SYMP HLA transgenic rabbits had higher frequencies of dysfunctional tissue-resident CD8+ TRM cells. Moreover, blockade of T cell exhaustion pathways restored the function of CD8+ T cells, reduced virus reactivation, and diminished recurrent disease in HLA transgenic rabbits. These findings reveal unique molecular signatures of protective CD8+ T cells and pave the way for T-cell-based immunotherapy to combat recurrent ocular herpes.

Adoption of Innovation in Herpes Simplex Virus Keratitis.

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.

Development, Implementation, and Evaluation of Treatment Guidelines for Herpes Simplex Keratitis in Sydney, Australia.

PURPOSE: To develop and measure the uptake of a local guideline for herpes simplex keratitis (HSK) and to standardize initial antiviral therapy in Australia. METHODS: The Registered Nurses' Association of Ontario Toolkit: "Implementation of Best Practice Guidelines" was used to develop, implement, and evaluate the guideline at Sydney Eye Hospital. An implementation team was established to reach consensus on antiviral therapy guidelines through review of available evidence, identifying stakeholders, facilitators and barriers, creating strategies for implementation, and developing a sustainability plan. An audit of all adult HSK cases during a 6-month postguideline implementation period was conducted, and the results were compared with a preimplementation audit. A web-based survey was created to assess clinician awareness, usage, and level of knowledge of the guideline. RESULTS: Clinicians, pharmacists, and administrative staff were identified as stakeholders. Changing clinician's behavior was the major barrier to implementation. Implementation strategies included printed and online materials and lectures to clinicians. A postimplementation audit included 85 patients, and 95 clinicians received a web-based survey. The dose of the prescribed antiviral medication was in alignment with the local guideline in 80% (51/64) of the patients compared with 73% (163/223) before implementation (P = 0.331). Stromal HSK with ulceration and keratouveitis were excluded because there were no recommendations before implementation. Over 70% of clinicians (30/41) were aware of the guideline and accessed them through educational resources. CONCLUSIONS: Guidelines for the management of HSK may improve standardization of initial antiviral therapy in HSK. In practice, most clinicians were aware of and adhered to the local guideline.

Successful Descemet Membrane Endothelial Keratoplasty in Proven Herpetic Endothelial Decompensation Requires Intensive Antiviral Therapy.

PURPOSE: To report the outcomes of Descemet membrane endothelial keratoplasty (DMEK) with intensive antiviral therapy for corneal edema secondary to herpes simplex virus type 1 (HSV-1)-mediated endotheliitis. METHODS: All eyes with polymerase chain reaction positive for HSV-1 undergoing DMEK for endothelial decompensation between January 2014 and January 2018 were followed up prospectively at our tertiary referral center. All eyes had been free of active inflammation for a minimum of 9 months and were treated prophylactically with high-dose systemic and topical antivirals, which were continued for a prolonged period of time. Primary outcomes were the occurrence of immunological rejection and/or recurrence of endotheliitis, eventually resulting in graft failure. Secondary outcomes were best spectacle-corrected visual acuity and endothelial cell loss. RESULTS: Four consecutive eyes of 4 patients were included with a mean (±SD) patient age of 68.5 ± 15.1 years. The postoperative follow-up averaged 22 months. No eyes exhibited any signs of immunologic rejection, recurrence of endotheliitis, or graft failure. Mean (±SD) decimal best spectacle-corrected visual acuity improved from 0.2 ± 0.1 to 0.7 ± 0.2 (P = 0.007), whereas mean (±SD) endothelial cell loss was 56% ± 10.2% at the final postoperative follow-up. CONCLUSIONS: DMEK is an effective option to treat corneal edema secondary to HSV-1-related endotheliitis. Intensive antiviral prophylaxis may reduce the risk of recurrence and subsequent graft failure.

Herpes Simplex Virus Keratitis.

Herpes simplex virus (HSV) is a highly prevalent infection in the United States. One complication of HSV is HSV keratitis, an ocular HSV infection thought to be the leading cause of corneal blindness in the United States. Home care clinicians with knowledge of the signs and symptoms of HSV and HSV keratitis can aid in early detection and treatment of this potentially serious infection. This article discusses signs and symptoms of HSV keratitis, preventive measures, and treatment.

Queratopatía neurotrófica postherpética: etiopatogenia, clínica y terapias actuales / Post-herpes neurotrophic keratopathy: Aetiopathogenesis, clinical signs and current therapies

La queratopatía neurotrófica (QN) es una enfermedad corneal degenerativa causada por un daño en la inervación del nervio trigémino. Esta situación produce defectos epiteliales, ulceración y, eventualmente, perforación. Tanto la queratitis por herpes simple como por varicela zoster constituyen la principal causa de QN. Además, el pronóstico en este tipo de QN es pobre. Los hallazgos clínicos clásicos en la QN postherpética incluyen la rotura epitelial espontánea, defectos epiteliales ovalados y centrales de bordes suaves, queratolisis con adelgazamiento del estroma, cicatrización y neovascularización. Aunque se han descrito tratamientos médicos y quirúrgicos prometedores, actualmente no hay un tratamiento definitivo para restaurar la sensibilidad de la córnea. Por tanto, la QN sigue siendo un reto terapéutico. En esta revisión resumimos la patogenia, la clínica y el tratamiento actual de la QN postherpética. Se discute el papel del tratamiento antiviral y de las vacunas contra el virus de la varicela-zoster. Se describen nuevas terapias médicas y quirúrgicas, como los agentes regenerativos y la neurotización corneal

Neurotrophic keratopathy (NK) is a degenerative corneal disease caused by damage of trigeminal innervation. This leads to epithelial defects, ulceration and, eventually, perforation. Both herpes simplex and varicella zoster keratitis are reported to be the main causes of NK. Furthermore, prognosis in this type of NK is poor. Classic clinical findings in post-herpes NK are spontaneous epithelial breakdown, round and central epithelial defects with smooth edges, stromal melting and thinning, scarring, and neovascularisation. Although several medical and surgical treatments have been reported, no therapies are currently available to definitely restore corneal sensitivity. Therefore, NK remains a challenging disease to treat. In this review a summary is presented of the pathogenesis, manifestations, and current management of post-herpes NK. The role of antiviral treatment and varicella-zoster vaccination is also discussed. A description is also presented on both medical and surgical novel therapies, such as regenerative drugs and corneal neurotization

Bilateral herpes simplex keratitis: lactation a trigger for recurrence!

A young lactating woman presenting to us with simultaneous bilateral corneal lesions was clinically diagnosed to have herpes simplex keratitis, which was confirmed by herpes simplex virus (HSV) PCR. The patient was administered topical and systemic acyclovir therapy and therapeutic penetrating keratoplasty was done in right eye. She was advised to continue breast feeding under strict hygienic conditions. Diagnosis and management of HSV keratitis in a lactating patient can be particularly challenging for both clinician and patient and adoption of a multidisciplinary approach is necessary to ensure safety of mother and child. At 3 months follow-up, the baby was clinically healthy, there were no side effects of acyclovir therapy in the mother or the baby and the patient showed no evidence of recurrence in either eye.

Risk factors influencing survival of acellular porcine corneal stroma in infectious keratitis: a prospective clinical study.

BACKGROUND: A worldwide lack of donor corneas demands the bioengineered corneas be developed as an alternative. The primary objective of the current study was to evaluate the efficacy of acellular porcine corneal stroma (APCS) transplantation in various types of infectious keratitis and identify risk factors that may increase APCS graft failure. METHODS: In this prospective interventional study, 39 patients with progressive infectious keratitis underwent therapeutic lamellar keratoplasty using APCS and were followed up for 12 months. Data collected for analysis included preoperative characteristics, visual acuity, graft survival and complications. Graft survival was evaluated by the Kaplan-Meier method and compared with the log-rank test. RESULTS: The percentage of eyes that had a visual acuity of 20/40 or better increased from 10.3% preoperatively to 51.2% at 12 months postoperatively. Twelve patients (30.8%) experienced graft failure within the follow-up period. The primary reasons given for graft failure was noninfectious graft melting (n = 5), and the other causes included recurrence of primary infection (n = 4) and extensive graft neovascularization (n = 3). No graft rejection was observed during the follow-up period. A higher relative risk (RR) of graft failure was associated with herpetic keratitis (RR = 8.0, P = 0.046) and graft size larger than 8 mm (RR = 6.5, P < 0.001). CONCLUSIONS: APCS transplantation is an alternative treatment option for eyes with medically unresponsive infectious keratitis. Despite the efficacy of therapeutic lamellar keratoplasty with APCS, to achieve a good prognosis, restriction of surgical indications, careful selection of patients and postoperative management must be emphasized. Trial registration Prospective Study of Deep Anterior Lamellar Keratoplasty Using Acellular Porcine Cornea, NCT03105466. Registered 31 August 2016, ClinicalTrails.gov.

Management of Herpes Simplex Virus Keratitis in the Pediatric Population.

Herpes simplex virus (HSV) keratitis is a highly prevalent and visually disabling disease in both the pediatric and adult population. While many studies have investigated the treatment of HSV keratitis in adult patients, few have focused on managing this condition in children. Children are at particularly high risk for visual morbidity due to unique challenges in diagnosis and treatment, and the often more aggressive disease course that results in corneal scarring, and subsequently amblyopia. This review presents the pathogenesis and most current recommendations for the medical and surgical management of HSV keratitis in the pediatric population.

[Deep anterior lamellar keratoplasty combined with antiviral therapy in the treatment of severe herpes necrotizing stromal keratitis].

Objective: To evaluate the efficacy of modified deep lamellar keratoplasty (DLKP) combined with antiviral medications for severe herpes necrotizing stromal keratitis. Methods: Retrospective case series study. Modified DLKP was performed in combination with antiviral medications in fifty patients (50 eyes) with severe necrotizing stromal keratitis, which was unresponsive to systemic and topical antiviral treatment for 1 week, at Shandong Eye Hospital. Before surgery, the operated eyes were examined using slit-lamp microscopy. The size of corneal ulceration and inflammatory infiltration and the depth of ulceration were observed in all of the patients. Corneal scraping and microbial culture and confocal laser scanning microscopy were used to exclude fungal, bacterial, Acanthamoeba, or other infections, and check the number of corneal endothelial cells. Anterior segment optical coherence tomography was used to examine the depth of infiltration, especially the thickness of the remaining cornea below the deepest ulceration. Antiviral drugs were used topically and systemically to control the infection and inflammation. Postoperatively, both antiviral drugs and low-dose corticosteroids were used. The ocular inflammation, corneal graft status and viral recurrence were monitored intraoperatively and postoperatively. Results: All of the fifty patients showed obvious inflammatory infiltration and stromal ulcers, and the corneal stroma in 23 patients (46%) remained less than 1/5 of the corneal thickness. Nine (18%) of the patients presented with descemetocele. The depth of infiltration ranged from 128 µm to 519 µm [mean, (265±84) µm]. The depth of corneal ulcers was deeper than 2/3 of the corneal thickness in 36 eyes (72%). The endothelial cells were visible in 26 eyes. The density of endothelial cells ranged from 1 275 cells/mm(2) to 2 994 cells/mm(2) [mean, (2 053±507) cells/mm(2)]. No fungal or bacterial infection was detected by corneal scraping. The microbial culture results were negative. All the inflammations in patients with severe herpes necrotizing stromal keratitis were under control by DLKP. No intraoperative corneal perforation occurred, and 6 eyes (12%) healed following amniotic membrane transplantation due to slow corneal epithelial healing. The infection was exacerbated two days following the surgery in two eyes (4%). These infections were controlled with enhanced antiviral medications in addition to the immediate withdrawal of corticosteroids. The corneal grafts returned to transparency at 1-2 weeks in 42 eyes (84%). Ten eyes (20%) exhibited recurrence due to medication withdrawal without the doctors' advice and a lack of regular visit during 2-year follow-up. Two patients (4%) developed stromal graft rejection for the same reasons. Conclusions: DLKP can achieve the results of ulcer healing for severe herpes necrotizing stromal keratitis. Combined antiviral therapy and close follow-up can reduce the viral recurrence. (Chin J Ophthalmol, 2018, 54: 97-104).

Blockade of LAG-3 Immune Checkpoint Combined With Therapeutic Vaccination Restore the Function of Tissue-Resident Anti-viral CD8+ T Cells and Protect Against Recurrent Ocular Herpes Simplex Infection and Disease.

Recurrent viral diseases often occur after the viruses evade the hosts' immune system, by inducing exhaustion of antiviral T cells. In the present study, we found that functionally exhausted herpes simplex virus type 1 (HSV-1) -specific CD8+ T cells, with elevated expression of lymphocyte activation gene-3 (LAG-3), an immune checkpoint receptor that promotes T cell exhaustion, were frequent in symptomatic (SYMP) patients with a history of numerous episodes of recurrent corneal herpetic disease. Similarly, following UV-B induced virus reactivation from latency the symptomatic wild-type (WT) B6 mice that developed increase virus shedding and severe recurrent corneal herpetic disease had more exhausted HSV-specific LAG-3+CD8+ T cells in both trigeminal ganglia (TG) and cornea. Moreover, a therapeutic blockade of LAG-3 immune checkpoint with antagonist antibodies combined with a therapeutic immunization with gB498-505 peptide immunodominant epitope of latently infected B6 mice significantly restored the quality and quantity of functional HSV-1 gB498-505 specific CD8+ T cells in both TG and cornea and protected against UV-B induced recurrent corneal herpes infection and disease. In contrast to dysfunctional HSV-specific CD8+ T cells from WT B6 mice, more functional HSV-specific CD8+ T cells were detected in LAG-3-/- deficient mice and were associated with less UV-B induced recurrent corneal herpetic disease. Thus, the LAG-3 pathway plays a fundamental role in ocular herpes T cell immunopathology and provides an important immune checkpoint target that can synergizes with T cell-based therapeutic vaccines against symptomatic recurrent ocular herpes.

Lack of TNF-α signaling through p55 makes the mice more susceptible to acute infection but does not alter state of latency and reactivation of HSV-1.

TNF-α has been shown to play an important role in pathogenesis and latency of HSV-1 infections. TNF-α signals through TNFR1 (p55) and TNFR2 (p75), and signaling through p55 generally results in gene activation leading to induction of inflammatory responses. Here, we studied the role of TNF-α signaling in latent virus reactivation in p55-knock out (KO) mouse model of ocular HSV-1 infection. We found that KO mice are more susceptible to HSV-1 infection compared to wild type C57Bl/6 mice. While the absence of TNFRI signaling enhanced the ganglion latent DNA content by two folds, there was no difference in the maintenance and reactivation of latent HSV-1. Strikingly, interfering with inflammatory responses through PGE2 synthesis by treating latently infected wild type mice with indomethacin (COX inhibitor) prior to UV-exposure prevented HSV-1 reactivation. These results suggest that reactivation of latent HSV-1 might result from the cumulative effects of a cascade of inflammatory cytokines including TNF-α.

New Therapeutic Perceptions in a Patient with Complicated Herpes Simplex Virus 1 Keratitis: A Case Report and Review of the Literature.

BACKGROUND Keratitis caused by herpes simplex virus (HSV) can have detrimental effects on the cornea leading to loss of vision. Modern therapies can contribute to the prevention of anatomical and functional damage. CASE REPORT An 80-year-old male with complicated HSV-1 keratitis of the left eye (confirmed diagnosis after microbiological investigation) presented three months after antiviral treatment with corneal blurring, severe epitheliopathy, thinning of the stroma, and neovascularization. At the time he was referred, the visual acuity of his left eye was very low, as he could only count fingers at a one-foot distance. He was initially started on oral acyclovir (800 mg once daily) and topical poly-carboxymethyl glucose sulfate; afterwards he underwent amniotic membrane (AM) transplantation and localized treatment with anti-VEGF factors. One month after the AM transplantation there was an obvious improvement of the corneal surface. Ophthalmic suspension of cyclosporine-A 1% was also added to his treatment. After three months, a transplantation of stem cells (deriving from the sclerocorneal junction of his right eye) was carried out at the sclerocorneal junction, as the corneal damage and neovascularization was more severe at this anatomical area. Four months after the last surgery, his visual acuity was 1/10 (note, he had a history of an old vascular episode) and the cornea was sufficiently clear with no signs of epitheliopathy and almost complete subsidence of the neovascularization. CONCLUSIONS Transplantation of AM and stem cells in combination with anti-VEGF factors and topical administration of cyclosporine-A 1% and poly-carboxymethyl glucose sulfate (a regenerative factor of corneal matrix) contributed substantially in the management of herpetic keratitis complications.

Self-Retained Amniotic Membrane Combined With Antiviral Therapy for Herpetic Epithelial Keratitis.

PURPOSE: To evaluate the therapeutic benefit of self-retained cryopreserved amniotic membrane in conjunction with oral antiviral therapy in herpetic epithelial keratitis. METHODS: Retrospective review of 4 patients with primary (1 eye) and recurrent (3 eyes) unilateral herpetic epithelial keratitis treated with cryopreserved amniotic membrane through the placement of the PROKERA Slim (PKS) (Bio-Tissue, Inc) in conjunction with oral acyclovir. Their symptoms, conjunctival inflammation, corneal staining, and visual acuity were compared before and after treatment. RESULTS: Herpetic epithelial keratitis presented as dendritic (3 eyes) and geographic (1 eye) epithelial lesions. After epithelial debridement and placement of the PKS for 5 ± 3.7 days, all patients reported significant relief of symptoms, rapid corneal epithelialization, and reduction of ocular surface inflammation. The visual acuity was also improved in all eyes from 0.7 ± 0.7 to 0.4 ± 0.7 logarithm of the minimum angle of resolution (P = 0.2). They remained symptom-free during a follow-up period of 2.7 to 50.8 (20.3 ± 21.7) months. CONCLUSIONS: The PKS in conjunction with oral acyclovir facilitates the ease of early intervention to accelerate restoration of a normal corneal epithelium in herpetic epithelial keratitis.