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Purpose: To assess the effect of corneal scar location on corneal nerve regeneration in patients with herpes simplex virus (HSV) keratitis in their affected and contralateral eyes over a 1-year period by in vivo confocal microscopy (IVCM), and to correlate these findings to corneal sensation measured by Cochet-Bonnet Esthesiometer., Methods: Prospective, longitudinal, case-control study. Bilateral corneal nerve density and corneal sensation were analyzed centrally and peripherally in 24 healthy controls and 23 patients with unilateral HSV-related corneal scars using IVCM., Results: In the central scar (CS) group, total nerve density in the central cornea remained significantly lower compared to controls at follow-up (11.05 ± 1.97mm/mm2, p < 0.001), and no significant nerve regeneration was observed (p = 0.090). At follow-up, total nerve density was not significantly different from controls in the central and peripheral cornea of the peripheral scar (PS) group (all p > 0.05), but significant nerve regeneration was observed in central corneas (16.39 ± 2.39mm/mm2, p = 0.007) compared to baseline. In contralateral eyes, no significant corneal nerve regeneration was observed in central or peripheral corneas of patients with central scars or peripheral scars at 1-year follow-up, compared to baseline (p > 0.05). There was a positive correlation between corneal nerve density and sensation in both central (R = 0.53, p < 0.0001) and peripheral corneas (R = 0.27, p = 0.0004). In the CS group, the corneal sensitivity was <4 cm in 4 (30.8%) and 7 (53.8%) patients in the central and peripheral corneas at baseline, and in 5 (38.5%) and 2 subjects (15.4%) at follow-up, whereas in the PS group only 1 patient (10%) showed a corneal sensation < 4 cm in the central cornea at baseline, and only 1 (10.0%), 3 (30.0%) and 1 (10.0%) patients at follow-up in the central, affected and opposite area of the cornea, respectively., Conclusion: The location of HSV scarring in the cornea affects the level of corneal nerve regeneration. Eyes with central corneal scar have a diminished capacity to regenerate nerves in central cornea, show a more severe reduction in corneal sensation in the central and peripheral corneas that persist at follow-up, and have a reduced capability to restore the corneal sensitivity above the cut-off of 4 cm. Thus, clinicians should be aware that CS patients would benefit from closer monitoring for potential complications associated with neurotrophic keratopathy, as they have a lower likelihood for nerve regeneration., Competing Interests: Declaration of competing interest No conflicting relationship exists for any author., (Copyright © 2023. Published by Elsevier Inc.)

Background: Herpes simplex virus (HSV) keratitis remains a leading infectious cause of blindness worldwide. Although all forms of HSV keratitis are commonly recurrent, the risk is greatest in stromal keratitis, which is the most likely to result in corneal scarring, thinning, and neovascularization. Recent studies showed the ability of Optical Coherence Tomography Angiography (OCTA) to detect and study vascular abnormalities in the anterior segment, including abnormal corneal vessels. This study intends to investigate the potential of OCTA device to image and describe quantitatively the vascularization in eyes diagnosed with herpetic leucoma and to discuss and review the usefulness of this technique in this pathology., Methods: A Cross-sectional study was made, including 17 eyes of 15 patients with leucoma secondary to herpetic keratitis. All eyes underwent anterior segment Slit-Lamp photography (SLP), and OCTA with en-face, b-scans and c-scans imaging. The vessel density (VD) was analyzed in the inferior, nasal and temporal corneal margin in all patients, and in the central area, in eyes with central corneal neovascularization (CoNV). The measurements were calculated after binarization with ImageJ software, using OCTA scans with 6 × 6 mm in a depth of 800 μm., Results: Patients included had a mean age 53.267 ± 21.542 (years ± SD). The mean total vessel area was 50.907% ± 3.435%. VD was higher in the nasal quadrant (51.156% ± 4.276%) but there were no significant differences between the three analyzed areas (p = 0.940). OCTA was able to identify abnormal vessels when SLP apparently showed no abnormal vessels; OCTA was able to distinguish between larger and smaller vessels even in central cornea; OCTA scans allowed the investigation of several corneal planes and the relation of them with clinical findings., Conclusions: OCTA can be useful in both qualitative and quantitative follow-up of patients and may become a non-invasive alternative to objectively monitor treatment response in eyes with corneal vascularization due to herpetic infection., (© 2022. The Author(s).)

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.

Background/objectives: To describe the predisposing factors, pathogens and outcomes in patients with clinical presumed concomitant microbial and herpes simplex keratitis (HSK) at Sydney Eye Hospital, Australia over a 5-year period., Subjects/methods: A retrospective case review was conducted. Patients with clinical presumed concomitant microbial and HSK from 2012 to 2016 were identified from pathology and hospital coding databases. Data were extracted from the medical records. VA was converted to the logarithm of the minimum angle of resolution (logMAR). 'Poor' outcome was defined as final VA worse than 6/60, or decrease in VA during treatment, or presence of complication, or needed surgical intervention., Results: 126 episodes in 121 patients were included; median age 70 years (range 18-96); 56% male. Predisposing factors included blepharitis 20/126 (16%) cases, and corneal transplantation 19 (15%). Forty-six (37%) cases had prior HSK. Coagulase-negative staphylococci 51/116 (44%), Staphylococcus aureus 11 (9%), and Pseudomonas aeruginosa 11 (9%) were the most common isolates. The median VA at initial visit was 1.7 logMAR (range 0.04-2.7) and at final visit, 0.98 logMAR (range 0-2.7) (P < 0.05). Complications occurred in 70 episodes: persistent epithelial defect in 38 (30%); intraocular pressure elevation in 15 (12%), and corneal perforation in 12 (10%). 'Poor' outcome was recorded in 46/75 (61%) episodes., Conclusions: Patients with clinical presumed concomitant microbial and HSK face significant ocular morbidity and poor visual outcome. In our setting, previous HSK, corneal and ocular surface disease, were common predisposing factors and Gram-positive bacteria were the most commonly associated organisms., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

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.)

To investigate the acute clinical, immunological, and corneal nerve changes following corneal HSV-1 KOS-63 strain inoculation. Corneas of C57BL/6 mice were inoculated with either low dose (Ld) or high dose (Hd) HSV-1 KOS-63 or culture medium. Clinical evaluation was conducted up to 7 days post inoculation (dpi). Viral titers were assessed by standard plaque assay. Excised corneas were stained for CD45 and beta-III tubulin. Corneal flow cytometry was performed to assess changes in leukocyte subpopulations. Corneal sensation was measured using a Cochet-Bonnet esthesiometer. Naïve, sham-infected (post scarification), and McKrae-infected C57BL/6 corneas served as two negative and positive controls, respectively. Compared to Ld infected mice, Hd HSV-1 KOS-63 demonstrated higher incidence of corneal opacity (1.5 ×) and neovascularization (2.6 × ; p < 0.05). At 7 dpi Hd infected mice showed more severe corneal opacity (2.23 vs. 0.87; p = 0.0003), neovascularization (6.00 vs. 0.75; p < 0.0001), and blepharitis (3.11 vs. 2.06; p = 0.001) compared to the Ld group. At 3 dpi epitheliopathy was significantly larger in the Hd group (23.59% vs. 3.44%; p = 0.001). Similarly, corneal opacity was significantly higher in Hd McKrae-infected corneas as compared with Ld McKrae-infected corneas at 3 and 5 dpi. No significant corneal opacity, neovascularization, blepharitis, and epitheliopathy were observed in naïve or sham-infected mice. Higher viral titers were detected in corneas (1 and 3 dpi) and trigeminal ganglia (TG) (3 and 5 dpi) in Hd versus Ld KOS-63 groups (p < 0.05). Leukocyte density showed a gradual increase over time from 1 to 7 dpi in both KOS-63 and McKrae-infected corneas. Corneal flow cytometric analysis (3 dpi) demonstrated a higher percentage of Gr-1 + (71.6 vs. 26.3) and CD11b + (90.6 vs. 41.1) cells in Hd versus Ld KOS-63 groups. Corneal nerve density significantly decreased in both Hd KOS-63 and Hd McKrae infected corneas in comparison with naïve and sham-infected corneas. At 3 dpi corneal nerve density was lower in the Hd versus Ld KOS-63 groups (16.79 vs. 57.41 mm/mm2; p = 0.004). Corneal sensation decreased accordingly at 5 and 7 dpi in both Ld and Hd KOS-63-infected mice. Corneal inoculation with HSV-1 KOS-63 strain shows acute keratitis and nerve degeneration in a dose-dependent fashion, demonstrating virulence of this strain.

Purpose: The purpose of this study is to examine the expression of tenascin-C and matrilin-2 in three different disorders, which frequently require corneal transplantation. These pathological conditions include bullous keratopathy (BK), Fuchs' endothelial corneal dystrophy (FECD), and corneal scarring in herpetic keratitis., Methods: Histological sections of corneal buttons removed during keratoplasty were analyzed in BK (n = 20), FECD (n = 9), herpetic keratitis (n = 12), and cadaveric control (n = 10) groups with light microscopy following chromogenic immunohistochemistry. The sections were evaluated by three investigators, and semiquantitative scoring (0 to 3+) was applied according to standardized methods at 400X magnification. Each layer of the cornea was investigated; moreover, the stroma was subdivided into subepithelial, middle, and pre-Descemet's membrane areas for more detailed analysis., Results: Excessive epithelial and stromal expression of tenascin-C was identified in all investigated conditions; the results were most pronounced in the pre-Descemet's membrane. Regarding matrilin-2, when examined in BK, there was increased labeling intensity in the epithelium (p<0.001) and stromal layers (p<0.05), and a decrease in the endothelium (p<0.001). In the other investigated conditions, only a low degree of stromal localization (p<0.05) of matrilin-2 was detected., Conclusions: The expression of tenascin-C and matrilin-2 differs when examined in various corneal pathologies resulting in opacification. Both molecules seem to be involved in regeneration and wound healing of the corneal matrix in these diseases., (Copyright © 2021 Molecular Vision.)

Background/objectives: The aim of this study was to identify risk factors, prognosis, and management in patients with concomitant herpetic keratitis and acute retinal necrosis (ARN)., Subjects/methods: In this retrospective observational series, ARN patients in the Greater Vancouver area from 2004 to 2018 were identified through key words, billing codes, and dispensing data from medical records of affiliate researchers and the pharmacy at Vancouver General Hospital., Results: Twenty-eight patients were diagnosed with ARN during this period. Five of those were also diagnosed with herpetic keratitis. Thus, the incidence of combined keratitis and ARN was 18% of patients with ARN. The two diseases occurred concomitantly in four out of five patients. Mean age at diagnosis was 55 ± 17 years. Of the five patients with both corneal and retinal involvement, three patients were immunocompromised and three had a history of herpetic diseases. Three developed disciform keratitis and two developed stromal immune keratitis. Clinical management and outcomes of these patients did not differ from patients with ARN alone, except for a lower rate of retinal detachment (p = 0.006) and a higher proportion with visual acuity ≥ 20/200 (p = 0.01)., Conclusions: Keratitis may complicate the clinical picture of one out of five to six patients with ARN. Comprehensive ophthalmic examination, including careful anterior segment exams in patients with ARN and sequential dilated fundus exams in patients with herpetic keratitis, should always be conducted to identify cases of concomitant disease.

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.

Purpose: To report the outcomes of initial high-dose and extended taper of antiviral and steroid prophylaxis for the treatment of eyes with high-risk vascularized herpetic corneal scars that underwent 2-piece mushroom keratoplasty (MK)., Design: Prospective interventional case series., Methods: In this single-center study, 52 consecutive eyes with vascularized (≥2 quadrants) herpetic corneal scars underwent 2-piece microkeratome-assisted MK. Initial high-dose and extended taper of combined oral and topical antiviral and steroid prophylaxis was administered. Outcome measures were best spectacle-corrected visual acuity (BSCVA), refractive astigmatism (RA), endothelial cell density, immunologic rejection, herpetic recurrence, and graft failure rates., Results: Excluding patients with vision-impairing comorbidities, baseline BSCVA (1.73 ± 0.67 logMAR) significantly improved annually during the first 2 years (P < .001, P = .016), reaching 0.17 ± 0.18 logMAR at year 2, and remaining stable up to 10 years (P = .662). At 2 years, 86% of eyes saw ≥20/40, 55% saw ≥20/25, and 18% saw ≥20/20 Snellen BSCVA. RA exceeded 4.5 diopters in 7% of cases after wound revision for high-degree astigmatism in 7 cases. Endothelial cell loss was 40.9% at 1 year with an annual decline of 3.1% over 10 years. The 10-year cumulative risk for immunologic rejection, herpetic recurrence, and graft failure was 9.7%, 7.8%, and 7.6%, respectively., Conclusions: Initial high dose and extended taper of antiviral and steroid prophylaxis for MK in high-risk, vascularized herpetic corneal scars achieves clinical outcomes that remain stable for up to 10 years after surgery with minimal risk of immunologic rejection, herpetic recurrence and graft failure., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Corneal opacity and neovascularization (NV) are often described as outcomes of severe herpes simplex virus type 1 (HSV-1) infection. The current study investigated the role of colony-stimulating factor 1 receptor (CSF1R)+ cells and soluble factors in the progression of HSV-1-induced corneal NV and opacity., Methods: MaFIA mice were infected with 500 plaque-forming units of HSV-1 in the cornea following scarification. From day 10 to day 13 post-infection (pi), mice were treated with 40 µg/day of AP20187 (macrophage ablation) or vehicle intraperitoneally. For osteopontin (OPN) neutralization experiments, C57BL/6 mice were infected as above and treated with 2 µg of goat anti-mouse OPN or isotypic control IgG subconjunctivally every 2 days from day 4 to day 12 pi. Mice were euthanized on day 14 pi, and tissue was processed for immunohistochemistry to quantify NV and opacity by confocal microscopy and absorbance or detection of pro- and anti-angiogenic and inflammatory factors and cells by suspension array analysis and flow cytometry, respectively., Results: In the absence of CSF1R+ cells, HSV-1-induced blood and lymphatic vessel growth was muted. These results correlated with a loss in fibroblast growth factor type 2 (FGF-2) and an increase in OPN expression in the infected cornea. However, a reduction in OPN expression in mice did not alter corneal NV but significantly reduced opacity., Conclusions: Our data suggest that CSF1R+ cell depletion results in a significant reduction in HSV-1-induced corneal NV that correlates with the loss of FGF-2 expression. A reduction in OPN expression was aligned with a significant drop in opacity associated with reduced corneal collagen disruption.

Purpose: To report the clinical outcome and postoperative course of Descemet membrane endothelial keratoplasty (DMEK) in irreversible corneal edema due to herpes simplex virus (HSV) endotheliitis., Methods: This is a retrospective, noncomparative, interventional case series. Nineteen eyes of 19 patients underwent standard DMEK combined with cataract surgery (triple DMEK) between May 2016 and April 2018. All patients received perioperative oral acyclovir (ACV) and prednisolone. Patients were followed up on day 1, on day 7, at 1 month, and then at 3 monthly intervals. Preoperative and postoperative best spectacle-corrected visual acuity (BSCVA), graft clarity, pachymetry, and endothelial cell loss after 1 year were recorded. Postoperative complications and HSV recurrence were noted until the last follow-up visit., Results: All eyes were phakic with variable grades of cataract with a preoperative BSCVA of 1.0 logarithm of the minimum angle of resolution or worse. The mean follow-up period was 19.3 ± 5.4 months. After 1 year, 14 (73.7%) eyes achieved a BSCVA of 0.3 or better. Seventeen (89.5%) patients had a clear graft at the last visit without any rejection episode. One graft failed after 16 months. After 3 months, the mean pachymetry reduced from 667.1 ± 62.1 to 512.8 ± 27.1 μm (P < 0.001). The mean endothelial cell loss after 1 year was 36.7 ± 13.4%. Three (15.8%) eyes had recurrence: one with recurrent endotheliitis and 2 with dendritic keratitis despite oral ACV, which responded to oral valacyclovir and ACV eye ointment. One patient had re-recurrence of endotheliitis after 20 months., Conclusions: DMEK in persistent corneal edema after HSV endotheliitis remains challenging but has encouraging outcomes. The postoperative course may be complicated by HSV recurrence. Prophylactic oral antivirals for 1 year or more and topical antivirals are useful for the prevention of recurrence.

Whether complement dysregulation directly contributes to the pathogenesis of peripheral nervous system diseases, including sensory neuropathies, is unclear. We addressed this important question in a mouse model of ocular HSV-1 infection, where sensory nerve damage is a common clinical problem. Through genetic and pharmacologic targeting, we uncovered a central role for C3 in sensory nerve damage at the morphological and functional levels. Interestingly, CD4 T cells were central in facilitating this complement-mediated damage. This same C3/CD4 T cell axis triggered corneal sensory nerve damage in a mouse model of ocular graft-versus-host disease (GVHD). However, this was not the case in a T-dependent allergic eye disease (AED) model, suggesting that this inflammatory neuroimmune pathology is specific to certain disease etiologies. Collectively, these findings uncover a central role for complement in CD4 T cell-dependent corneal nerve damage in multiple disease settings and indicate the possibility for complement-targeted therapeutics to mitigate sensory neuropathies., Competing Interests: DR, JE, LL, GG, RM, DS, VP, DC No competing interests declared, (© 2019, Royer et al.)

Purpose: To examine the outcomes of phacoemulsification cataract surgery in eyes with herpes zoster-related keratitis and/or uveitis and evaluate the risks for recurrent disease., Setting: Public ophthalmology service, Auckland, New Zealand., Design: Retrospective case series., Methods: Patients with herpes zoster-related keratitis and/or uveitis who had cataract surgery in the ipsilateral eye were reviewed. Outcome measures were intraoperative and postoperative complications, postoperative visual acuity, and recurrent disease., Results: Fifty-seven eyes of 57 patients were included. Thirty-eight patients (66.7%) had recurrent disease before cataract surgery. Intraoperative complications occurred in 8 patients (14.0%) and included posterior capsule tear in 2 patients (3.5%). Postoperative complications included intraocular pressure of 30 mm Hg or higher in 2 patients (3.5%) and central corneal edema in 8 patients (14.0%); all resolved by 1 month. Cystoid macular edema occurred in 2 patients (3.5%). The median corrected distance visual acuity at 12 months was 20/40 (interquartile range, 20/30-20/50). Corneal scarring was associated with poorer vision (P = .003). Herpes zoster recurred in 23 patients (40.4%) after surgery. An increased risk for recurrence was associated with shorter periods of quiescence (P = .029) and greater number of recurrences before surgery (P = .039). One eye was eviscerated because of the severity of the disease., Conclusions: Phacoemulsification in eyes with previous herpes zoster-related keratitis or uveitis posed a mildly increased risk for intraoperative and postoperative complications; however, herpes zoster disease recurrence after surgery was common and was severe in some cases. Consideration should be given to maximizing the period of quiescence before surgery and the potential role of antiviral prophylaxis., (Copyright © 2019 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Background and objectives: The purpose of this study was to describe corneal sensitivity and the morphological changes of sub-basal corneal nerves using in vivo laser scanning confocal microscopy (LSCM) in herpes simplex virus (HSV) keratitis-affected eyes, and to compare with both contralateral eyes and with the eyes of patients with a previous history of herpes labialis but no history of herpetic eye disease, and with healthy patients with no history of any HSV diseases, during the acute phase of the disease and after six months. Materials and Methods: A prospective clinical study included 269 patients. All of them underwent a complete ophthalmological examination, Cochet-Bonnet aesthesiometry and LSCM within the central 5 mm of the cornea. After six months, all the patients with herpetic eye disease underwent the same examination. Serology tests of the serum to detect HSV 1/2 IgG and IgM were performed. Results: HSV-affected eyes compared with contralateral eyes, herpes labialis and healthy control group eyes demonstrated a significant decrease in corneal sensitivity, corneal nerve fibre density, corneal nerve branch density, corneal nerve fibre length and corneal nerve total branch density ( p < 0.05). During follow up after six months, corneal sensitivity and sub-basal nerve parameters had increased but did not reach the parameters of contralateral eyes ( p < 0.05). Previous herpes labialis did not influence corneal sensitivity and was not a risk factor for herpetic eye disease. Conclusions: Corneal sensitivity and sub-basal nerve changes in HSV-affected eyes revealed a significant decrease compared with contralateral eyes, and with the eyes of patients with a previous history of herpes labialis, and of healthy controls. Following six months, corneal sensitivity and sub-basal nerve parameters increased; however, they did not reach the parameters of contralateral eyes and the eyes of healthy controls. The best recovery of corneal sensitivity was seen in patients with epithelial keratitis. Herpes labialis was not a risk factor for herpetic eye disease., Competing Interests: The authors declare that they have no competing interests.

Purpose: To describe the functional outcome, postoperative complications, and complication management of Descemet's membrane endothelial keratoplasty (DMEK) in corneal decompensation secondary to Herpes simplex eye disease (HED)., Methods: This retrospective interventional case series included 17 eyes that received DMEK for endothelial decompensation secondary to HED. Complete ophthalmological examination, including corrected-distance visual acuity (CDVA), anterior segment slit-lamp, and optical coherence tomography assessment, were performed preoperatively and postoperatively at regular follow-up intervals. Visual outcome and complication rates were compared with those of 72 consecutive eyes that received DMEK for Fuchs endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK) during the same period., Results: Mean follow-up time was 11.1 ± 5.9 months (range 6-27). CDVA improved from 1.16 ± 0.46 logMAR to 0.62 ± 0.44 logMAR (P = 0.001). Corneal pachymetry significantly decreased from 695 ± 53 μm at day 1 to 569 ± 88 μm at 2 months (P < 0.001). Postoperative complications occurred in 12 eyes, including primary graft failure (12%), endotheliitis (29%), corneal ulcers (35%), and cystoid macular edema (18%). Most complications occurred shortly after surgery, with a median delay of 2.5 months. In comparison, the complication rates for DMEK in FECD and PBK were significantly lower (no graft failure, P = 0.005; no endotheliitis, P < 0.001; no corneal ulcers, P < 0.001 and 3% cystoid macular edema, P = 0.046)., Conclusions: DMEK surgery significantly improved CDVA in patients with endothelial decompensation due to HED. The rate of postoperative complications was higher than for FECD and PBK. Close follow-up is mandatory and the rate of postoperative inflammatory events suggests that patients should be kept on high doses of oral valacyclovir.

Rationale: To report a case of herpes simplex virus (HSV) linear endotheliitis in a 57-year-old male who had underwent keratoplasty 10 years ago. The characteristic linear keratic precipitates (KPs) resembled the Khodadoust line in graft rejection. The differential diagnosis is essential, because the treatment regimen is different between HSV linear endotheliitis and graft rejection., Patient Concerns: The patient developed a sudden onset of ocular pain and a decrease in visual acuity in his right eye. The patient had received penetrating keratoplasty in the eye 10 years ago., Diagnoses: The ocular disease was evaluated using several ocular examinations, including best-corrected visual acuity (BCVA), intraocular pressure, slit lamp examination, fundus examination, and aqueous humor tap. Characteristic linear endothelial KPs were found both in the host cornea and graft cornea. Stromal edema was evident in both the donor and recipient corneas. The aqueous humor was sampled for viral polymerase chain reaction (PCR) analysis. The sample was investigated for the possible presence of HSV I, HSV II, cytomegalovirus, and varicella zoster virus. The PCR was positive for HSV I and negative for HSV II, cytomegalovirus, and varicella zoster virus., Interventions: The patient was treated with both antiviral and steroid treatments for 1 month. Thereafter, prophylactic antiviral treatment was continued., Outcomes: The subjective symptoms had improved and the cornea edema and the linear endothelial KPs had disappeared. The BCVA improved from 20/200 to 20/80., Lessons: HSV linear endotheliitis is the most severe form of HSV endotheliitis. This case showed characteristic endothelial KPs, which were different from the Khodadoust line of graft rejection.

Purpose: To evaluate the long-term alterations of corneal nerves in patients with herpes simplex virus (HSV) keratitis using in vivo confocal microscopy (IVCM)., Design: Prospective, longitudinal, cross sectional., Methods: This study included 16 patients with a history of HSV keratitis and 15 age-matched normal controls. Slit-scanning IVCM was performed in all subjects at baseline and then after a mean follow-up of 37.3 ± 1.7 months in the patient group. Corneal subbasal nerve density and corneal sensation were compared between groups at baseline and follow-up., Results: At baseline, the mean subbasal nerve density was significantly lower in both affected eyes (1.4 ± 0.6 mm/mm 2 ) and contralateral unaffected eyes (6.4 ± 0.7 mm/mm 2 ) compared with the controls (14.1 ± 1.6 mm/mm 2 ; all P < .001). At the end of follow-up, the mean nerve density in affected eyes increased to 2.8 ± 0.7 mm/mm 2 (P = .006), with no significant change in contralateral unaffected eyes (6.5 ± 1.0 mm/mm 2 , P = .72). However, both eyes had lower nerve density than controls (all P < .001). Corneal sensation was significantly lower in affected eyes (2.6 ± 0.6 cm) than in the control group (6.0 ± 0.0, P < .001) and showed no significant change at the end of follow-up (2.5 ± 0.6 cm, P = .80). Corneal sensation in contralateral unaffected eyes was not different in comparison with controls at both baseline and follow up (all p > .05)., Conclusions: Our results demonstrate that although corneal nerve regeneration occurs in patients with HSV keratitis, this change is not clinically significant and does not results in changes of corneal sensation. Therefore, these patients need to be followed closely for complications of neurotrophic keratopathy and might benefit from neuro-regenerative therapies., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To study corneal innervation in eyes with history of herpetic keratitis and its correlation with corneal sensitivity and biomechanical properties., Methods: A total of 56 eyes were included, of which 16 had a history of unilateral immune stromal herpetic keratitis, 16 were their contralateral eyes, and 20 were healthy controls. Structural analysis of corneal nerve plexus was performed by confocal microscopy. Biomechanical properties were measured with the Ocular Response Analyzer. Corneal sensitivity was assessed by contact (Cochet-Bonnet) and non-contact (Belmonte) esthesiometry., Results: The eyes with a history of herpetic keratitis had reduced sensitivity for mechanical stimuli when compared to healthy eyes (1441.88 ± 83 ml/min vs. 67.9 ± 7.86 ml/min). Nerve fiber density in the corneas with a history of herpetic disease was lower (4.13 ± 2.19 U/image) than in the contralateral eyes (7.44 ± 2.9 U/image, p value = 0.01) and than in healthy controls (10.35 ± 2.01, p value < 0.0001). The best structural and functional correlation was established between the total length of nerves per section and mechanic threshold assessed by Belmonte esthesiometer (Coef. -0.58 p value < 0.0001) and between total length of nerves and corneal resistance factor (CRF) (Coef. -0.64, p value < 0.0001)., Conclusions: The corneal sensitivity impairment in eyes with immune stromal herpetic keratitis can be explained by the loss of nerve fibers. Biomechanical corneal properties are affected as well. Corneal hysteresis (CH) and CRF are lower for the eyes with a history of herpetic keratitis, and also for the contralateral eye when compared to healthy controls.

Iridocorneal (ICE) syndrome is a rare ocular disease characterized by abnormal proliferation of corneal endothelial cells, progressive obstruction of irido-corneal angle and atrophy of iris. ICE syndrome progressed slowly, but can cause serious complications such as secondary glaucoma in late stage. Because the etiology of ICE syndrome is not clear, there is still no effective treatment in clinical practice. Previous studies have detected herpes simplex virus (HSV) DNA inside patient's aqueous humor. However, no further explanation for HSV-related etiology of ICE syndrome was established. Besides, construction of animal models using HSV all failed, leaving behind a blank space about how HSV infection finally led to ICE syndrome. By summarizing findings from previous studies, we came up with a hypothesis about etiology of ICE syndrome: HSV infection initiated ICE syndrome by integration of viral genetic material into human genome. Infection of HSV changed activity and morphology of endothelial cells, making them regain the ability of mitosis. Proof of such hypothesis will provide a theoretical foundation for construction of animal models and effective intervention of the disease., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Herpes uveitis has been previously reported to present with hyphema, but hemorrhagic hypopyon is rarely reported as a herpetic uveitis manifestation. We report a case of herpes simplex virus (HSV) presenting with hemorrhagic hypopyon, and speculate on the underlying pathophysiology with relation to an intravascular lymphoma which was subsequently diagnosed as a result., Case Presentation: We present a case wherein a 62-year-old Japanese rheumatoid arthritis woman, with HSV uveitis, presented with hemorrhagic hypopyon in the anterior chamber and a fever with photophobia. Patient was treated with antiviral drugs which improved the hyphema and corneal lesions, but lesions recurred 3 months later. This rare presentation of HSV induced uveitis, and its subsequent recurrence, aroused suspicion of an additional hypopyon-inducing pathology. On account of previous history of lung opacities and elevated LDH, intravascular lymphoma was eventually diagnosed via lung biopsy. She was treated for the lymphoma which also completely resolved all ocular symptoms without any recurrence as of 1.5 years later., Conclusion: The exceedingly rare presentation of hemorrhagic hypopyon may have been enabled by an interaction of the HSV with the intravascular lymphoma. HSV involvement was indicated by the dendritic lesions, IgG assay, and response to anti-viral drugs. The ocular involvement of the intravascular lymphoma seems to be indicated by virtue of the anti-tumor drugs completely resolving all ocular symptoms.

Objective: To describe the clinical findings of a patient with tyrosinemia type I with noncompliance to a protein-restricted diet, treated with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC)., Methods: Clinical findings at the initial examination and after strict compliance to a protein-restricted diet after 4 weeks follow-up are described in a patient with tyrosinemia type I on NTBC treatment, who had been treated with presumed herpetic keratitis., Results: A 10-year-old girl diagnosed with hereditary tyrosinemia type I and on NTBC treatment presented with photophobia and ocular discomfort in both eyes. An ophthalmologic examination demonstrated bilateral dendritiform epithelial lesions in the central cornea, staining faintly with fluorescein. These lesions were subsequently intermittently treated with topical antivirals for presumed herpes simplex virus keratitis and lubricant eye drops for 9 months without resolution; however, when strict compliance with a protein-restricted diet was instituted, nearly a complete resolution of the lesions was noted at the 4-week follow-up., Conclusions: Although type II tyrosinemia is known to have corneal involvement, the natural course of tyrosinemia type I has not been shown to have corneal involvement. Corneal involvement in type I tyrosinemia may be an indicator of dietary noncompliance and may show complete resolution with a strict compliance to protein-restricted diet only.

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.)

Purpose:: To determine the outcomes of penetrating keratoplasty (PK) for treatment of corneal scarring caused by Herpes simplex virus (HSV) keratitis, and whether the corneal scar type affects treatment outcome., Methods:: A retrospective analysis of patients who underwent PK for HSV-related corneal scarring between January 2008 and July 2011 was performed. The patients were categorized into two groups. Group 1 consisted of patients with a quiescent herpetic corneal scar and group 2 consisted of patients who developed a corneal descemetocele or perforation secondary to persistent epithelial defects with no active stromal inflammation. The mean follow-up was 21.30 ± 14.59 months. The main parameters evaluated were recurrence of herpetic keratitis, graft rejection, graft failure, visual acuity, and graft survival rate., Results:: There were 42 patients in group 1 and 13 in group 2. Preoperative BCVA varied from hand movements to 0.7 logMAR. Postoperatively, 34 patients (61.8%) achieved visual acuity of 0.6 logMAR or more. Recurrence of HSV keratitis was noted in 12 (28.57%) eyes in group 1 and 4 (30.76%) eyes in group 2 (p=0.40). Graft rejection occurred in 4 eyes (9.52%) in group 1 and in 3 (23.07%) eyes in group 2 (p=0.58). The 1-, 2-, and 3-year graft survival rates were 91.9%, 76.0%, and 65.1% in group 1, and 89.5%, 76.0%, and 63.6% in group 2 (p=0.91), respectively., Conclusions:: Although there were different recurrence and graft rejection rates for two groups, the graft survival rates at 3 years were similar. According to our results, without inflammation, corneal herpetic scarring with a descemetocele or perforation achieved similar graft survival rates with quiescent herpetic corneal scars.

Purpose: Most of the inflammation in murine herpes simplex virus type 1 (HSV-1)-induced stromal keratitis (HSK) is due to exposure stress resulting from loss of corneal nerves and blink reflex. Corneal grafts often fail when placed on corneal beds with a history of HSK. We asked if corneal exposure contributes to the severe pathology of corneal grafts on HSV-1-infected corneal beds., Methods: Herpes simplex virus type 1-infected corneas were tested for blink reflex. Opacity and vascularization were monitored in allogeneic and syngeneic corneal grafts that were transplanted to corneal beds with no blink reflex or to those that retained blink reflex in at least one quadrant following infection., Results: Retention of any level of blink reflex significantly reduced inflammation in HSV-1-infected corneas. Corneal allografts placed on HSV-1-infected beds lacking corneal blink reflex developed opacity faster and more frequently than those placed on infected beds that partially or completely retained blink reflex. Corneal grafts placed on infected corneal beds with no blink reflex rapidly became opaque to a level that would be considered rejection. However, protecting these grafts from exposure by tarsorrhaphy prevented or reversed the opacity in both syngeneic and allogenic grafts., Conclusions: Exposure due to HSV-1-engendered hypoesthesia causes rapid, severe, persistent, but reversible opacification of both allogeneic and syngeneic corneal grafts. This opacity should not be interpreted as immunologic rejection. Exposure stress may contribute to the high rate of corneal graft pathology in patients with recurrent HSK.

Purpose: To evaluate corneal higher-order aberrations (HOAs) in eyes with corneal scars due to herpes simplex keratitis (HSK)., Methods: Forty-four eyes of 41 consecutive patients who were diagnosed with corneal scars due to HSK and 18 control eyes were included. HOAs of the anterior and posterior surfaces and the total cornea were analyzed using anterior segment optical coherence tomography. Corneal opacity grades were assigned on the basis of slit-lamp examinations., Results: HOAs within a 4-mm diameter were significantly larger in eyes with HSK (anterior surface, 1.01 ± 1.18 μm; posterior surface, 0.25 ± 0.24; total cornea, 1.00 ± 1.00) compared with controls (0.10 ± 0.02, 0.02 ± 0.00, and 0.09 ± 0.01, respectively; all P < 0.001). HOAs within a 6-mm diameter were significantly larger in eyes with HSK (anterior surface, 1.87 ± 1.75; posterior surface, 0.42 ± 0.44; total cornea, 1.85 ± 1.46) compared with controls (0.19 ± 0.04, 0.06 ± 0.01, and 0.17 ± 0.03, respectively; all, P < 0.001). The logarithm of the minimum angle of resolution (logMAR) decreased with the corneal opacity score (0.42 ± 0.61 in grade 1, 1.30 ± 0.96 in grade 2, and 1.58 ± 0.90 in grade 3). LogMAR was significantly correlated with HOAs (R = 0.65, P < 0.0001). HOAs of the posterior surface increased from 0.15 ± 0.15 in grade 1 to 0.37 ± 0.33 in grade 3 (P = 0.005), whereas there was no difference in HOAs of the anterior surface and the total cornea among the different corneal opacity grades., Conclusions: Increased HOAs of the anterior and posterior surfaces occur in eyes with corneal opacity due to HSK. Larger corneal HOAs are associated with poorer visual acuity.

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.)

Purpose: To investigate the visual prognosis and ocular complications in patients with herpetic versus HLA-B27 associated anterior uveitis (AU)., Methods: This was a retrospective, observational study conducted at the ophthalmology department of the University Medical Center of Groningen. Sixty-two herpetic and 113 HLA-B27-associated AU patients were included. The main outcome measures were visual acuity and ocular complications., Results: Visual acuity over time was significantly lower in herpetic as compared to HLA-B27 AU, mainly due to corneal scarring. The incidence rate of any ocular complication was higher in herpetic AU compared to HLA-B27-associated AU (0.140/EY versus 0.076/EY, p = <0.001), which was mainly due to glaucoma (0.033/EY versus 0.004/EY, p < 0.001) and cataract (0.059/EY versus 0.023/EY, p < 0.001)., Conclusions: The most prominent finding was a worse visual prognosis in herpetic AU, which is probably related to higher prevalence of corneal scarring and glaucoma. In addition, herpetic AU patients have more ocular complications overall.

Purpose: 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., Methods: 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., Results: 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., Conclusions: 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.

Ocular Baylisascaris procyonis infection results from ingestion of infective eggs of B. procyonis, the raccoon ascarid. Herpes simplex virus type 2 (HSV-2) infection of the retina is the result of either primary infection or reactivated disease. Herein, we report a case of a 12-year-old female resident of the Bronx in New York City, who presented with pan-uveitis and vision loss. Initial evaluation for etiologic causes was nondiagnostic. Serology for anti-Baylisascaris procyonis antibodies in serum and vitreous fluid were both positive. Polymerase chain reaction (PCR) of vitreous fluid was positive for HSV-2. Treatment with vitrectomy, albendazole, and acyclovir resulted in mild improvement of visual acuity. The atypical presentation of B. procyonis in this case, as ocular larva migrans with a peripheral granuloma and retinal detachment, underscores the importance of maintaining a high degree of suspicion for this pathogen even in non-diffuse unilateral subacute neuroretinitis (DUSN) patients in urban areas. This case further illustrates that it is possible to have coexisting infections in cases of posterior uveitis., (© The American Society of Tropical Medicine and Hygiene.)

Purpose: To evaluate and compare the ocular surface condition in herpetic interstitial stromal keratitis and neurotrophic ulcer groups and their normal fellow eyes., Methods: In this observational, cross-sectional case-control study, 85 consecutive patients were included, including 56 cases of treated herpetic interstitial keratitis and 29 patients with neurotrophic ulcers. Fifty-six age- and sex-matched participants were also recruited from a normal population as the control group. We evaluated and scored the subjective and objective measures of dry eye for both eyes of all patients. Then, we compared the score of the groups with one another and also with the control group. The main outcome measures were the discomfort level, visual symptoms of dry eye, conjunctival injection, conjunctival staining, corneal staining, corneal tear signs of dry eye, meibomian gland dysfunction, tear break-up time, Schirmer test score with anesthesia, and tear osmolarity., Results: The normal fellow eye of the herpetic keratitis group had significantly higher discomfort levels (1.4 ± 0.9 vs. 1.3 ± 0.5, P = 0.003), visual symptoms (1.7 ± 0.8 vs. 1.3 ± 0.7, P = 0.002), tear break-up time (8.3 ± 3.2 vs. 12.1 ± 3.3 seconds, P = 0.003), Schirmer test scores (9.2 ± 3.9 vs. 12.9 ± 3 mm, P = 0.04), and tear osmolarity (9.2 ± 3.9 vs. 12.9 ± 3 mm, P = 0.003) in comparison with normal controls. The normal fellow eyes of the neurotrophic ulcer group had significantly worse values for discomfort level (1.9 ± 0.9 vs. 1.3 ± 0.5, P < 0.001), tear break-up time (7.9 ± 4 vs. 12.1 ± 3.3, P = 0.004), Schirmer test score (8.1 ± 3.9 vs. 12.9 ± 3, P = 0.005), and tear osmolarity (295 ± 9.2 vs. 292.7 ± 5.9, P = 0.02) compared with normal controls., Conclusions: Both eyes of patients with neurotrophic ulcer and interstitial herpetic keratitis have a significantly poorer ocular surface condition compared with that of normal controls.

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.

A 20-year-old man presented with a recurrent episode of herpetic keratouveitis in his right eye. The patient was treated with oral acyclovir and topical steroids. One week later the patient reported a sudden diminution of vision. Slitlamp biomicroscopy revealed the presence of a central anterior capsular defect and anterior subcapsular cataract. Dosage of steroids was temporarily increased and progression of cataract monitored. Subsequently, the anterior chamber reaction decreased and steroids were tapered., (2014 BMJ Publishing Group Ltd.)

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.

We present the case of a 42-year-old man with AIDS who had lost complete vision of his left eye for the past 15 days. MRI and brightness scan ultrasonography were performed on his eyes that suggested of endophthalmitis with dendritic involvement in the left eye. Viral DNA PCR was performed in aqueous humour sample that confirmed the presence of herpes simplex virus and showed a negative result for cytomegalovirus. The patient was treated with a high dose of oral acyclovir for 10 days and long-term topical acyclovir. Neodymium-doped yttrium aluminum garnet procedure was performed to clear up the cornea, and intraocular pressure was controlled with brimonidine and timolol maleate. The patient was diagnosed to have disseminated tuberculosis (tuberculoma of the brain) and was started with antituberculosis therapy. His condition improved significantly after the treatment, and keratitis in cornea started to clean up.

The herpes simplex virus is one of the most common pathogens in humans, who are seropositive for the virus in 90% of the cases at the adult age. It determines reccurent infections in more than a third of the population and these infections depend on the immune response of the host. Ocular infections of newborns are due to the herpes simplex virus type 2, meanwhile type 1 is found predominantly at adults; almost all ocular structures can be affected. HSV-1 in the most frequent etiologic agent in infectious anterior uveitis (with the varicelo-zosterian virus) and it is responsible for 6-10% of all cases of anterior uveitis. More than half of the keratouveitides due to HSV will develop intraocular hypertension and open-angle secondary glaucoma, during reccurences and most of them will resolve after proper control of inflammation.

Aims: To analyse high-order aberrations (HOA), modulation transfer function (MTF) and Strehl ratio in patients with a history of herpes simplex keratitis (HSK) and apparently normal vision., Methods: Fifteen patients with a history of recurrent unilateral HSK and normal Snellen visual acuity (0 logMAR) were enrolled. Eyes with HSK (HSK group) were statistically compared with normal fellow eyes (Control group). HOA, MTF and Strehl ratio were measured using the OPD-SCAN II (Nidek Co, Gamagori, Japan) aberrometer. Measures were performed at least 3 months after the last episode of herpes. Statistical significance was indicated by p<0.05., Results: Despite apparently normal vision in both eyes (as assessed by routine visual acuity charts), significantly higher total HOA, trefoil and tetrafoil were present in the HSK group compared with the Control group. The MTF and strehl ratio were lower in the HSK group compared with the Control group. In the HSK group, eyes with corneal opacities tended to present with greater optical aberrations than eyes with a clear cornea., Conclusions: Using patients as their own controls, the outcomes of this study indicate that eyes with recurrent HSK with no apparent decrease in visual acuity (0 logMAR) have significantly greater optical aberrations than eyes with no past history of herpetic disease. This outcome may explain some visual complaints of HSK patients, such as a decrease in contrast quality or reduced colour perception, compared with the unaffected contralateral eye despite apparently normal vision in both eyes.

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.)

When the cornea of the eye dissolves, most commonly secondary to infection or trauma, the ventral wall of the anterior chamber of the eye is no longer supported and thus bulges forward, enlarging the anterior chamber volume. This is referred to as a corneal melt, and it has a unique CT appearance that has not been previously described.

Ocular infection with HSV causes corneal neovascularization (CV), an essential step in the pathogenesis of the blinding immunoinflammatory lesion stromal keratitis. The infection results in IL-17A production, which contributes to CV in ways that together serve to shift the balance between corneal concentrations of vascular endothelial growth factor A (VEGF-A) and the soluble vascular endothelial growth factor receptor 1 molecule, which binds to VEGF-A and blocks its function (a so-called VEGF trap). Accordingly, animals lacking responses to IL-17A signaling, either because of IL-17 receptor A knockout or wild-type animals that received neutralizing mAb to IL-17A, had diminished CV, compared with controls. The procedures reduced VEGF-A protein levels but had no effect on the levels of soluble vascular endothelial growth factor receptor 1. Hence the VEGF trap was strengthened. IL-17A also caused increased CXCL1/KC synthesis, which attracts neutrophils to the inflammatory site. Neutrophils further influenced the extent of CV by acting as an additional source of VEGF-A, as did metalloproteinase enzymes that degrade the soluble receptor, inhibiting its VEGF-blocking activity. Our results indicate that suppressing the expression of IL-17A, or increasing the activity of the VEGF trap, represents a useful approach to inhibiting CV and the control of an ocular lesion that is an important cause of human blindness.

Innate immune deficiencies result in a spectrum of severe clinical outcomes following infection. In particular, there is a strong association between loss of the signal transducer and activator of transcription (Stat) pathway, breach of the blood-brain barrier (BBB), and virus-induced neuropathology. The gene signatures that characterize resistance, disease, and mortality in the virus-infected nervous system have not been defined. Herpes simplex virus type 1 (HSV-1) is commonly associated with encephalitis in humans, and humans and mice lacking Stat1 display increased susceptibility to HSV central nervous system (CNS) infections. In this study, two HSV-1 strains were used, KOS (wild type [WT]), and Δvhs, an avirulent recombinant lacking the virion host shutoff (vhs) function. In addition, two mouse strains were used: strain 129 (control) and a Stat1-deficient (Stat1(-/-)) strain. Using combinations of these virus and mouse strains, we established a model of infection resulting in three different outcomes: viral clearance without neurological disease (Δvhs infection of control mice), neurological disease followed by viral clearance (Δvhs infection of Stat1(-/-) mice and WT infection of control mice), or neurological disease followed by death (WT infection of Stat1(-/-) mice). Through the use of functional genomics on the infected brain stems, we determined gene signatures that were representative of the three infection outcomes. We demonstrated a pathological signature in the brain stem of Stat1-deficient mice characterized by upregulation of transcripts encoding chemokine receptors, inflammatory markers, neutrophil chemoattractants, leukocyte adhesion proteins, and matrix metalloproteases. Additionally, there was a greater than 100-fold increase in the inflammatory markers interleukin 1β (IL-1β) and IL-6. Consistent with this gene signature, we demonstrated profound CNS inflammation with a concomitant lethal breach of the BBB. Taken together, our results indicated an essential role for normal Stat1-dependent signaling in mediating a nonpathological immune response to viral CNS infection.