Characterization of Ebola Virus-Associated Eye Disease.

Importance: Survivors of Ebola virus disease (EVD) may experience ocular sequelae. Comparison with antibody-negative individuals from the local population is required to characterize the disease. Objective: To assess features of ophthalmic disease specific to EVD. Design, Setting, and Participants: This baseline cross-sectional analysis of survivors of EVD and their close contacts was conducted within PREVAIL III, a 5-year, longitudinal cohort study. Participants who enrolled at John F. Kennedy Medical Center in Liberia, West Africa from June 2015 to March 2016 were included in this analysis. Close contacts were defined as household members or sex partners of survivors of EVD. Data were analyzed from July 2016 to July 2020. Exposures: All participants, both survivors and close contacts, underwent testing of IgG antibody levels against Ebola virus surface glycoprotein. Main Outcomes and Measures: Ocular symptoms, anterior and posterior ophthalmologic examination findings, and optical coherence tomography images were compared between antibody-positive survivors and antibody-negative close contacts. Results: A total of 564 antibody-positive survivors (320 [56.7%] female; mean [SD] age, 30.3 [14.0] years) and 635 antibody-negative close contacts (347 [54.6%] female; mean [SD] age, 25.8 [15.5] years) were enrolled in this study. Survivors were more likely to demonstrate color vision deficit (28.9% vs 19.0%, odds ratio [OR], 1.6; 95% CI, 1.2-2.1) and lower intraocular pressure (12.4 vs 13.5 mm Hg; mean difference, -1.2 mm Hg; 95% CI, -1.6 to -0.8 mm Hg) compared with close contacts. Dilated fundus examination revealed a higher percentage of vitreous cells (7.8% vs 0.5%; OR, 16.6; 95% CI, 5.0-55.2) and macular scars (4.6% vs 1.6%; OR, 2.8; 95% CI, 1.4-5.5) in survivors than in close contacts. Uveitis was present in 26.4% of survivors and 12.1% of close contacts (OR, 2.4; 95% CI, 1.8-3.2). Among all participants with uveitis, survivors were more likely than close contacts to have intermediate uveitis (34.2% vs 6.5% of all cases; OR, 7.8; 95% CI, 3.1-19.7) and had thicker mean central subfield thickness on optical coherence tomography (222 vs 212 µm; mean difference, 14.4 µm; 95% CI, 1.9-26.9 µm). Conclusions and Relevance: In this cross-sectional study, survivors of EVD had a distinct spectrum of ocular and neuro-ophthalmologic findings compared with close contacts that potentially require medical and surgical treatment.

Indications and outcomes of pediatric keratoplasty in a tertiary eye care center: A retrospective review.

To evaluate indications and outcomes of pediatric keratoplasty in a tertiary eye center, and identify factors that affect visual outcomes.We performed a retrospective review of penetrating keratoplasty in children aged 0 to 18 years between 1995 and 2011 in the Asociación para Evitar la Ceguera en México IAP, Hospital "Dr. Luis Sánchez Bulnes".A total of 574 penetrating keratoplasties were performed during the study interval. Median follow-up was 5.0 years. Main indications included keratoconus (55.58%), postherpetic scarring (9.58%), traumatic opacities (7.49%), and bullous keratopathy (6.09%). Rejection rates at 5 years were 27% overall, and among indications, keratoconus showed the best graft survival at 60-months follow-up (85%). The percentage of patients with best corrected visual acuity (BCVA) posttransplant >20/400 at 5 years in the nonrejection group was 81.25% and 82.74% in < and > 10 years of age (YOA) groups, respectively, versus a BCVA posttransplant > 20/400 at 5 years in the rejection group of 53.68% and 51.72% in < and > 10 YOA groups, respectively. There was a statistically significant reduced rejection rate between genders at 18 months of follow-up, favoring males.Despite being considered a high-risk procedure in children, penetrating keratoplasty can achieve good results, especially in patients with keratoconus. It can achieve significative improvements of visual acuity, provided there is an adequate follow-up and treatment adherence.

Clinicopathologic Features of Hydroa Vacciniforme-Like Lymphoma: A Series of 9 Patients.

Hydroa vacciniforme-like lymphoma is a recently recognized cutaneous T-cell lymphoma associated with Epstein-Barr virus. The disease is observed in children of Latin American or Asian ethnicity. The authors report the clinical, histopathological, and immunophenotypical features of 9 new Mexican patients (M:F = 2:1; mean age, 14.5 years; median age, 13.3 years; age range, 4-27 years), expanding on previous observations of this elusive disease. The most common clinical aspects were persistent facial edema with necroses and pitted scars. Histopathological analyses revealed variably dense lymphoid infiltrates with common angiodestructive features. Neoplastic cells expressed CD3 and cytotoxic markers in all cases and were constantly positive for Epstein-Barr virus (EBER-1). Expression of other markers was variable. Follow-up data revealed that all patients died within 6 months or less, thus showing a very aggressive course with poor prognosis.

Cutaneous cytomegalovirus infection on multi dermatomal herpes zoster scars: an isotopic immune response.

As more patients with human immunodeficiency virus (HIV) are surviving, despite severe immune suppression, clinicians are faced with atypical manifestations of both common and uncommon dermatoses. A 30-year-old black South African woman presented with a 10-month history of multiple chronic ulcers appearing on a multidermatomal herpes zoster (HZ) scar. The woman was infected with HIV, and her CD4 count was 45 cells/µL. Histology and PCR revealed cytomegalovirus (CMV) infection. This case highlights an unusual presentation of cutaneous CMV occurring as an isotopic immune response on a pre-existing multidermatomal HZ scar.

Langerin+ dermal DC, but not Langerhans cells, are required for effective CD8-mediated immune responses after skin scarification with vaccinia virus.

Skin scarification (s.s.) with vaccinia virus (VACV) is essential for generation of an optimal protective T-cell memory immune response. Dendritic cells (DCs), which are professional antigen-presenting cells, are required for naive T-cell priming and activation. At least three subsets of skin-resident DC have been identified: Langerhans cells (LCs), dermal Langerin+ DC (Lang+ dDC), and dermal Langerin- DC (Lang- dDC). Using Langerin-diphtheria toxin receptor mice and established mouse model of VACV delivered by s.s., we demonstrated that Lang+ dDC, but not LC, are absolutely required for the induction of a rapid and robust antigen-specific CD8+ T-cell response after s.s. with VACV. The depletion of Lang+ dDC led to a significant delay in the priming and proliferation of antigen-specific CD8+ T cells. Moreover, CD8+ T cells generated after VACV s.s. in the absence of Lang+ dDC lacked effector cytotoxic functions both in vitro and in vivo. While s.s.-immunized wild-type and LC-depleted mice controlled the progression of OVA257-264 expressing T-cell lymphoma EG7 (injected intradermally), the depletion of Lang+ dDC led to rapid lymphoma progression and mortality. These data indicate that of all skin DC subsets, Lang+ dDC is the most critical for the generation of robust CD8+ T-cell immunity after s.s. with VACV.

Focal high-concentration trichloroacetic acid peeling for treatment of atrophic facial chickenpox scar: an open-label study.

BACKGROUND: Despite their prevalence, there is a paucity of information in the medical literature on the treatment of atrophic chickenpox scars. OBJECTIVE: To evaluate the efficacy and safety of using the chemical reconstruction of skin scar technique for the treatment of atrophic facial chickenpox scars. METHODS AND MATERIALS: One hundred patients (mean age 23 years; Fitzpatrick skin types II-IV) were treated with focal chemical peeling with 70% trichloroacetic acid (TCA) for a maximum of six sessions. Improvement rate, frequency of adverse events and patient satisfaction were assessed. RESULTS: Five hundred thirty-three peeling sessions in 100 consecutive patients were performed. Final assessment at 12-week follow-up visit after the last treatment revealed improvement in 95% of patients: mild improvement in 12 cases, moderate improvement in 42 cases, and marked improvement in 41 cases. The appearance of scars did not change in five patients. Seventy-nine patients expressed moderate to high satisfaction with the results. Post-treatment side effects were mild and transient, resolving gradually within the study period. CONCLUSION: Focal peeling with high-concentration TCA appears to be a safe and effective alternative in the treatment of atrophic facial chickenpox scars.

Herpes zoster developing within recent subciliary incision scar.

Herpes zoster is a common dermatologic disease characterized by unilateral pain and vesicular lesions over the unilateral sensory dermatomes being caused by the reactivation of varicella zoster virus, and its incidence seems to be increasing recently. In case of involving the ganglion of the fifth cranial nerve (trigeminal nerve), it can descend down the affected nerve into the skin, then producing an eruption in the dermatome. Among the patients with this disease, about 40% to 50% had associated conditions such as diabetes mellitus, hypertension, pulmonary tuberculosis, liver diseases, peptic ulcer, hypothyroidism, or pharyngitis but rarely facial trauma. Generally, herpes zoster was commonly associated with systemic disorders, and the treatment duration was prolonged in associated diseases. However, herpes zoster occurring specifically at the site of previously traumatized facial bone has not yet been reported. Retrospective study of 1 case of herpes zoster with blow-out fracture, which had been treated with acyclovir and steroid, was done. Follow-up length was about 3 months. After treatment, the patient became stable, and there was no complication. We treated herpes zoster developing within a recent operative subciliary scar, and the case is presented with the review of literature. Finally, facial trauma or reconstruction of the orbital floor with alloplastic implant might be a risk factor for herpes zoster in traumatized patient.

Bitoric rigid gas permeable contact lens fitting for the management of a corneal scar caused by herpes zoster ophthalmicus.

Empirical fitting of a bitoric rigid gas permeable contact lens for the management of a scarred irregular cornea caused by herpes zoster ophthalmicus is described. Two corneal scars, which affect the pupil axis, caused an irregular cornea and produced low visual acuity and anisometropia. Two contact lenses were necessary to complete the fitting. Visual acuity improved from 0.2 to 1.0. The rigid gas permeable lenses can be a good alternative in the management of patients with irregular corneas caused by herpes zoster ophthalmicus.

Immunization with different viral antigens alters the pattern of T cell exhaustion and latency in herpes simplex virus type 1-infected mice.

We have shown previously that immunization with herpes simplex virus type 1 (HSV-1) glycoprotein K (gK) exacerbated corneal scarring (CS) in ocularly infected mice. In this study, we investigated whether higher levels of CS were correlated with higher levels of latency and T cell exhaustion in gK-immunized mice. BALB/c mice were vaccinated with baculovirus-expressed gK or gD or mock immunized. Twenty-one days after the third immunization, mice were ocularly infected with 2 × 10(4) PFU/eye of virulent HSV-1 strain McKrae. On day 5 postinfection, virus replication in the eye was measured, and on day 30 postinfection, infiltration of the trigeminal ganglia (TG) by CD4, CD8, programmed death 1 (PD-1), and T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) was monitored by immunohistochemistry and quantitative real-time PCR (qRT-PCR). This study demonstrated that higher levels of CS were correlated with higher levels of latency, and this was associated with the presence of significantly higher numbers of CD4(+)PD-1(+) and CD8(+)PD-1(+) cells in the TG of the gK-immunized group than in both the gD- and mock-immunized groups. Levels of exhaustion associated with Tim-3 were the same among gK- and mock-vaccinated groups but higher than levels in the gD-vaccinated group. In this study, we have shown for the first time that both PD-1 and Tim-3 contribute to T cell exhaustion and an increase of latency in the TG of latently infected mice.

The outcome of deep anterior lamellar keratoplasty in herpes simplex virus-related corneal scarring, complications and graft survival.

AIMS: To determine the visual outcome, graft survival and complications after deep anterior lamellar keratoplasty (DALK) in patients with herpes simplex virus (HSV)-related corneal scarring. METHODS: A retrospective analysis of the patients who had DALK for HSV-related corneal scarring between January 2004 and February 2007 was performed. Mean follow-up was 30 months (range 16-48 months). The statistical significance of host corneal vascularisation was determined using Fisher's exact test. RESULTS: There were 18 eyes from 18 patients and the mean age was 57 years. Preoperative visual acuity ranged from hand movements (HM) to 6/12. Fifty per cent of the eyes achieved visual acuity of 6/12 or better postoperatively. Six eyes (33%) had recurrence of HSV-related inflammation, eight eyes (including four eyes with recurrence of HSV-related inflammation) developed graft rejection and four eyes (including two eyes with recurrence of HSV-related inflammation) had bacterial keratitis. The graft survival rate was 83%. Three eyes developed glaucoma and one eye required trabeculectomy. Immunohistochemistry revealed that HSV was focally positive or equivocal in four recipient corneal buttons, and transmission electron microscopy showed intracellular HSV virions in two of them. CONCLUSIONS: This is the largest series of DALK for herpetic corneal scarring that shows a comparable visual outcome and better graft survival rate than penetrating keratoplasty. There is significant risk of recurrence of HSV-related inflammation and graft rejection that requires timely recognition and adequate management.

Selective changes in human corneal sensation associated with herpes simplex virus keratitis.

PURPOSE: To determine corneal sensitivity to selective mechanical, chemical, and thermal (heat and cold) stimulation in patients with a history of herpes simplex virus (HSV) keratitis. METHODS: Corneal sensitivity to different modalities of stimulus was determined in both eyes of 16 patients with unilateral HSV keratitis diagnosed 1 to 12 months before the study. On slit lamp examination, 13 HSV-affected eyes showed corneal scarring or opacities, and three had no signs of previous keratitis. Corneal sensitivity was determined with the Belmonte gas esthesiometer. Mechanical, chemical, heat, and cold stimuli were applied on the central cornea. Eyes from 10 healthy subjects served as controls. RESULTS: In all control and contralateral eyes, selective mechanical, chemical, heat, and cold stimulation evoked sensations of subjective intensity proportional to the magnitude of the applied stimulus. In one HSV patient, the affected cornea was unresponsive to all types of stimuli, four lost only corneal sensitivity to mechanical stimulation, and three lost only sensitivity to heat. Mechanical (P<0.005) and heat (P<0.05) thresholds were raised in HSV eyes, whereas thresholds for CO2 were not modified. Also, HSV subjects identified poorly the intensity of mechanical, chemical, and heat stimuli, whereas sensitivity to cold stimulation was unaffected. CONCLUSIONS: In eyes that had had HSV keratitis, corneal sensitivity to mechanical forces and heat was significantly impaired, suggesting that axonal damage and/or altered expression of membrane ion channels involved in transduction and membrane excitability affects primarily the mechano- and polymodal nociceptor terminals. Corneal cold-sensitive terminals remain largely unaffected.

Exacerbation of corneal scarring in HSV-1 gK-immunized mice correlates with elevation of CD8+CD25+ T cells in corneas of ocularly infected mice.

We have shown previously that exacerbation of corneal scarring (CS) in HSV-1 glycoprotein K (gK) immunized mice was associated with CD8+ T cells. In this study, we investigated the type and the nature of the immune responses that are involved in the exacerbation of CS in gK-immunized animals. BALB/c mice were vaccinated with baculovirus expressed gK, gD, or mock-immunized. Twenty-one days after the third immunization, mice were ocularly infected with 2 x 10(5) PFU/eye of virulent HSV-1 strain McKrae. Infiltration of the cornea by CD4+, CD8+, CD25+, CD4+CD25+, CD8+CD25+, CD19+, CD40+, CD40L+, CD62L+, CD95+, B7-1+, B7-2+, MHC-I+, and MHC-II+ cells was monitored by immunohistochemistry, qRT-PCR and FACS at various times post-infection (PI). This study demonstrated for the first time that the presence of CD8+CD25+ T cells in the cornea is correlated with exacerbation of CS in the gK-immunized group.

Development of a contagious ecthyma vaccine for goats.

OBJECTIVE: To identify a strain of contagious ecthyma virus from goats that possesses the appropriate characteristics for an effective vaccine for goats. ANIMALS: 25 goat kids used for vaccine development and 100 goat kids used for evaluation of vaccine efficacy. PROCEDURES: 5 strains of contagious ecthyma virus were tested in a vaccination-challenge study to identify the best strain to be the seed strain for a contagious ecthyma vaccine. The vaccine derived from the chosen viral stain was tested at 2 concentrations for efficacy in a vaccination-challenge study. RESULTS: 2 of 5 viral strains induced moderate to severe scabs following infection, and 3 viral strains protected the goats from wild-type virus challenge following vaccination. Viral strain 47CE was selected as the seed source for the production of a contagious ecthyma vaccine because of the larger vaccine-to-challenge scab formation ratio. Vaccine 47CE protected all goat kids (48/48) following challenge with the wild-type contagious ecthyma virus; all goat kids (32/32) in the control group had scab formation following challenge with the wild-type contagious ecthyma virus, which indicated no protection following administration of vaccine diluent. CONCLUSIONS AND CLINICAL RELEVANCE: A vaccine containing a caprine strain of contagious ecthyma virus used in goats appeared to provide the characteristics needed for an effective vaccine, including good scab production and protection from wild-type infection. This vaccine may potentially provide better protection for goats from contagious ecthyma than currently available vaccines labeled for sheep.

Keloids: A viral hypothesis.

The triggering cause of keloid formation on a healing wound remains an enigma. In fact, the hypotheses put forward so far to explain this phenomenon seem inconsistent with some clinical features of the disease. The recently established bonds between infectious agents and some pathologies of unknown origin such as peptic ulcer disease, Kaposi's sarcoma or cervical cancer among others led us to consider a potential infectious origin for keloids. This paper presents an infection-based hypothesis (specifically, a viral hypothesis) intended to account for most of their clinical features. Essentially, we hypothesize that healthy individuals carrying a virus, whether known or unknown, associated to some adjuvant, and having some genetic susceptibility, may develop keloids during the scar maturation process in the following manner: the virus would make the bone marrow or lymphatic system its reservoir, residing there in a silent state, and reach the wound via two different mechanisms. The primary mechanism might use an internal circuit through which the viral genome would be transported from its myeloid reservoir to the wound via bone marrow or circulating fibrocytes chemotactically attracted to the damaged skin region. The secondary mechanism might involve an external circuit by which infecting virions via saliva would be shed in the wound directly (preferentially in the sternal or deltoid region) or indirectly (other satellite regions) via the hands or some fomites. A combination of both mechanisms might also be possible. Once in the wound, the virus would switch from a silent state to a latent state by effect of some chemical stimulus probably generated during the tissue repair process; in the new state, the transcription of some of the powerful viral proteins might cause thorough derailment of the normal repair process. As a result, keloid growth might depend both on individual susceptibility and on the viral load deposited into the wound; the greater the susceptibility and viral load were, the more markedly the keloid would develop and the more aggressive it would be.