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Purpose: To evaluate the quality of life (QoL) in patients with quiescent herpes simplex keratitis compared with control patients without ocular herpes., Design: Prospective, case-control study., Participants: Thirty-three patients with a unilateral and relapsing herpes simplex keratitis (HSK group) that was quiescent during evaluation (no acute episode in the past 3 months) and 66 patients with no history of HSK (control group). Both groups were age and gender matched., Methods: Three previously validated QoL questionnaires were used in this study: the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25), Glaucoma Quality of Life 17 (Glau-QoL17) questionnaire, and Ocular Surface Disease Quality of Life (OSD-QoL) questionnaire. Each questionnaire covered various aspects of the disease., Main Outcome Measures: The outcomes of the 3 questionnaires were compared between groups. For the HSK group, the results were correlated to the clinical findings and the history of herpetic disease., Results: The mean total questionnaire scores of the 3 QoL questionnaires were significantly lower in the HSK group compared with controls (NEI VFQ-25: 70.5±3.8 vs. 91.1±0.8, P < 0.0001; Glau-QoL17: 68.2±3.1 vs. 87.9±1.0, P < 0.0001; and OSD-QoL: 65.4±2.9 vs. 93.1±0.6, P < 0.0001, respectively). In the HSK group, the level of visual acuity (VA) in the affected eye had the greatest impact on QoL, inducing lower QoL results related to "general vision," "distance activities," "dependency," "peripheral vision," "self-image," "daily living," and "driving" dimensions. Decreased VA in the unaffected eye also negatively affected "self-image" and "driving" results. Patients with frequent HSK relapses had lower QoL related to "ocular pain" and "acknowledgement.", Conclusions: Even during a quiescent phase of the disease, unilateral and relapsing HSK significantly impairs the QoL of patients to a similar level as most sight-threatening diseases. The decrease of VA has the greatest overall effect, but other factors also significantly affect QoL, such as the frequency of relapses., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Herpes simplex virus type 1 (HSV-1) is a leading cause of neurotrophic keratitis characterized by decreased corneal sensation because of damage to the corneal sensory fibers. We and others have reported regression of corneal nerves during acute HSV-1 infection. To determine whether denervation is caused directly by the virus or indirectly by the elicited immune response, mice were infected with HSV-1 and topically treated with dexamethasone (DEX) or control eye drops. Corneal sensitivity was measured using a Cochet-Bonnet esthesiometer and nerve network structure via immunohistochemistry. Corneas were assessed for viral content by plaque assay, leukocyte influx by flow cytometry, and content of chemokines and inflammatory cytokines by suspension array. DEX significantly preserved corneal nerve structure and sensitivity on infection. DEX reduced myeloid and T-cell populations in the cornea and did not affect viral contents at 4 and 8 days post infection. The elevated protein contents of chemokines and inflammatory cytokines on infection were greatly suppressed by DEX. Subconjunctival delivery of neutralizing antibody against IL-6 to infected mice resulted in partial preservation of corneal nerve structure and sensitivity. Our study supports a role for the immune response, but not local virus replication in the development of HSV-1-induced neurotrophic keratitis. IL-6 is one of the factors produced by the elicited inflammatory response to HSV-1 infection contributing to nerve regression., (Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

MicroRNAs (miRNAs) are small regulatory molecules that control diverse biological processes that include angiogenesis. Herpes simplex virus (HSV) causes a chronic immuno-inflammatory response in the eye that may result in corneal neovascularization during blinding immunopathological lesion stromal keratitis (SK). miR-132 is a highly conserved miRNA that is induced in endothelial cells in response to growth factors, such as vascular endothelial growth factor (VEGF). In this study, we show that miR-132 expression was up-regulated (10- to 20-fold) after ocular infection with HSV, an event that involved the production of both VEGF-A and IL-17. Consequently, blockade of VEGF-A activity using soluble VEGF receptor 1 resulted in significantly lower levels of corneal miR-132 after HSV infection. In addition, low levels of corneal miR-132 were detected in IL-17 receptor knockout mice after HSV infection. In vivo silencing of miR-132 by the provision of anti-miR-132 (antagomir-132) nanoparticles to HSV-infected mice led to reduced corneal neovascularization and diminished SK lesions. The anti-angiogenic effect of antagomir-132 was reflected by a reduction in angiogenic Ras activity in corneal CD31-enriched cells (presumably blood vessel endothelial cells) during SK. To our knowledge, this is one of the first reports of miRNA involvement in an infectious ocular disease. Manipulating miRNA expression holds promise as a therapeutic approach to control an ocular lesion that is an important cause of human blindness., (Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

The last decade has seen herpes simplex virus (HSV)-induced stromal keratitis (SK) research shift from being a topic only of interest to vision researchers to one that fascinates the general field of inflammatory disease. Studies on experimental mouse lesions have uncovered several fundamental processes that explain lesion development. In this model, the chronic immuno-inflammatory lesions are mainly orchestrated by CD4+ T cells, but multiple early events occur that set the stage for the subsequent pathology. These include virus replication, the production of key cytokines and chemokines, neovascularization of the avascular cornea and the influx of certain inflammatory cell types. Many of these early events are subject to modulation, providing an approach to controlling this important cause of human blindness. We also comment on events ongoing during chronic SK, debating whether or not these represent virus-induced or autoimmune lesions.

Ocular neovascularization often results in vision impairment. Frequently vascular endothelial cell growth factors (VEGFs) are mainly responsible for the pathological neovascularization as in the case in neovascularization induced by CpG oligodeoxynucleotides and herpes simplex virus infection in this report. siRNAs targeting either VEGFA, VEGFR1, VEGFR2, or a mix of the three were shown to significantly inhibit neovascularization induced by CpG when given locally or systemically. The efficacy of systemic administration was facilitated by the use of a polymer delivery vehicle. Additional experiments showed a significant inhibitory effect of the siRNAs mix when given either locally or systemically in vehicle against herpes simplex virus-induced angiogenesis as well as against lesions of stromal keratitis. These results indicate that the use of VEGF pathway-specific siRNAs represents a useful therapy against neovascularization-related eye diseases.

Purpose: To evaluate the efficacy of multilayer amniotic membrane transplantation for reconstruction of corneal epithelium and stroma in the context of deep corneal ulcers., Design: Prospective, noncomparative, interventional case series., Participants: Eleven consecutive patients with deep corneal ulcers refractory to conventional treatment; six patients had herpetic keratitis and five had other forms of neurotrophic keratitis., Intervention: Multilayer amniotic membrane transplantation with kryopreserved human amniotic membrane., Main Outcome Measures: Integrity of corneal epithelium and stroma, opacification, and appearance of grafted membrane during 12 months follow-up., Results: Amniotic membrane transplantation markedly reduced ocular inflammation in all patients. Epithelium healed above all corneal ulcers within 4 weeks and remained stable in 9 of 11 patients for 1 year. Two patients with recurrent epithelial defect suffered from severe neurotrophic keratitis. Following transplantation the amniotic membranes gradually dissolved over a period of 12 months, but stromal thickness remained stable., Conclusion: Amniotic membrane transplantation allows corneal surface reconstruction in patients with persistent epithelial defects. The multilayer technique is useful for treating deep corneal ulcers and even descemetoceles. Because the procedure results in stability of the ocular surface over a period of more than 12 months in most patients, it may be considered an alternative to conventional surgical techniques for ocular surface reconstruction.

Objective: This study aimed to describe the clinical characteristics of uveitis presenting de novo in the elderly., Design: The study design was a description of a retrospectively identified case series., Participants: A population of 138 patients (209 eyes) with uveitis beginning after age 60 was analyzed., Results: Uveitis in the elderly accounted for 10.4% of the authors' uveitis population. The localization of uveitis was anterior in 56.5% of patients, intermediate uveitis was diagnosed in two patients (1.4%), posterior uveitis was found in 25.4%, while 16.7% of patients presented with panuveitis. Idiopathic uveitis accounted for the majority of cases (31.2%), whereas herpes zoster ophthalmicus (11.6%), herpes simplex virus (6.5%), presumed sarcoidosis (5.8%), syphilis (4.3%) ankylosing spondylitis (4.3%), and birdshot chorioretinopathy (3.6%) were the most frequent specific diagnostic entities. Secondary elevation of intraocular pressure was common (67 eyes, or 32%). The development of macular edema complicated 28.7% of cases (60 eyes). Two cases of intraocular lymphoma were identified in 19 diagnostic vitreous biopsy specimens. Fifty-two percent of eyes retained visual acuity of 20/40 or more; 32.6% had final visual acuity worse than 20/100., Conclusions: Uveitis presenting for the first time in the elderly is not uncommon. Idiopathic uveitis accounts for the majority of cases, and herpes zoster ophthalmicus and herpes simplex virus are particularly prevalent. Intraocular lymphoma does not predominate in this age group. With adequate control of intraocular inflammation and its sequelae, the visual prognosis in patients in this age group with uveitis is relatively good.

Purpose: The authors compare the incidence and clinical course of herpes simplex virus (HSV) keratitis among patients who are positive and negative for human immunodeficiency virus (HIV)., Methods: A retrospective cohort study was designed. Outcomes measured in both groups included incidence of HSV keratitis, lesion type (epithelial vs. stromal), lesion location (central vs. peripheral), treatment time, time to first recurrence, and recurrence rate., Results: There was no statistically significant difference between the groups for any of the outcomes measured except for recurrence rate. The recurrence rate was 2.48 times more frequent among patients positive for HIV (1 recurrence per 587 person-days of follow-up among patients positive for HIV vs. 1 per 1455 person-days among patients negative for HIV)., Conclusions: Except for recurrence rate, the incidence and clinical course of HSV keratitis in this study were no different among patients positive and negative for HIV.