Optical coherence tomography angiography in herpetic leucoma.

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.

Loss of Osteopontin Expression Reduces HSV-1-Induced Corneal Opacity.

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.

Sympathetic ophthalmia with incidental finding of chicken pox supported by histopathology and immunohistochemistry.

Sympathetic ophthalmia (SO) is a rare bilateral diffuse granulomatous panuveitis that occurs in few days to several years after penetrating injury. This intraocular inflammation can occur in any age group without a sex predilection. Pathology and immunohistochemistry-supported evidence is important to know the disease in a better way. We present a case of a 24-year-old female with clinical diagnosis of SO with an atypical past history of chicken pox in that eye and residual corneal opacity.

CCR6-Positive γδ T Cells Provide Protection Against Intracorneal HSV-1 Infection.

Purpose: γδ T cells offer an important early immune defense against many different pathogens, both bacterial and viral. Herein, we examined the capacity of γδ T cell subsets to provide protection in the cornea against herpes simplex virus-1 (HSV-1). Methods: C57Bl/6 (wild-type [WT]), γδ T-cell deficient (TCRδ-/-) and CCR6-deficient (CCR6-/-) mice were infected intracorneally with HSV-1. At multiple time points following infection, corneas were excised, and cells were immunostained for surface markers, intracellular cytokines, and analyzed using flow cytometry. WT and CCR6-/- γδ T cells were adoptively transferred into TCRδ-/- mice and corneal scores and survival were measured. Results: Intracorneal infection of mice lacking γδ T cells exhibited increased corneal opacity scores, elevated viral titers, and higher mortality compared with WT mice. Both CCR6+ and CCR6neg γδ T cell subsets were observed in corneas after virus infection. CCR6+ γδ T cells produced IL-17A and were predominantly CD44+CD62L+, consistent with natural IL-17+ γδ T cells. In contrast IL-17A production by CCR6neg γδ T cells was infrequent, and this subset was largely single positive for CD62L or CD44. The CCR6+ subset appeared to provide protection against HSV-1 as follows: (1) CCR6-/- mice had more severe corneal opacity compared with WT mice; and (2) adoptive transfer of γδ T cells from WT mice restored protection in TCRδ-/- mice whereas transfer of γδ T cells from CCR6-/- mice did not. Conclusions: γδ T cells in the cornea can be divided into CCR6+ and CCR6neg subsets with the former conferring protection early after intracorneal HSV-1 infection.

Corneal Opacity in Domestic Ducks Experimentally Infected With H5N1 Highly Pathogenic Avian Influenza Virus.

Domestic ducks can be a key factor in the regional spread of H5N1 highly pathogenic avian influenza (HPAI) virus in Asia. The authors performed experimental infections to examine the relationship between corneal opacity and H5N1 HPAI virus infection in domestic ducks (Anas platyrhyncha var domestica). A total of 99 domestic ducks, including 3 control birds, were used in the study. In experiment 1, when domestic ducks were inoculated intranasally with 2 H5N1 HPAI viruses, corneal opacity appeared more frequently than neurologic signs and mortality. Corneal ulceration and exophthalmos were rare findings. Histopathologic examinations of the eyes of domestic ducks in experiment 2 revealed that corneal opacity was due to the loss of corneal endothelial cells and subsequent keratitis with edema. Influenza viral antigen was detected in corneal endothelial cells and some other ocular cells by immunohistochemistry. Results suggest that corneal opacity is a characteristic and frequent finding in domestic ducks infected with the H5N1 HPAI virus. Confirming this ocular change may improve the detection rate of infected domestic ducks in the field.

Long-term comparison of full-bed deep lamellar keratoplasty with penetrating keratoplasty in treating corneal leucoma caused by herpes simplex keratitis.

PURPOSE: To compare long-term outcomes of full-bed deep lamellar keratoplasty (DLK) with penetrating keratoplasty (PK) for treating corneal leucoma caused by herpes simplex keratitis (HSK). DESIGN: Retrospective, comparative, interventional case series. METHODS: setting: Institutional. patients: Inclusion criteria were patients with corneal scarring induced exclusively by HSK who underwent primary graft of full-bed DLK or PK and completed a minimum of 12 months postoperative follow-up. There was no significant difference of corneal scarring and vascularization between the 2 groups before surgery. Choosing PK or full-bed DLK depended on the patient's own willingness, except those patients with a preoperative endothelial cell count of less than 700 cells/mm(2) or whose endothelial cell count was undetectable were encouraged to undergo only PK. Exclusion criteria were patients with a past history of corneal perforation, nonprimary graft, non-HSK-related corneal scars, and failure to complete a minimum of 12 months of postoperative follow-up. Fifty-eight eyes of 58 patients in the full-bed DLK group and 63 eyes of 63 patients in the PK group met the inclusion criteria. main outcome measures: Postoperative managements, recurrence of HSK, graft rejection, graft survival rate, visual acuity, and corneal endothelial density. RESULTS: The mean postoperative follow-up duration was 45.8 ± 30.9 months in the full-bed DLK group and 47.9 ± 27.2 months in the PK group (P = .70). As compared with the PK group, the full-bed DLK group experienced earlier suture removal (P = .01), needed fewer postoperative visits (P < .001), and had a higher proportion of eyes with full withdrawal of oral acyclovir (P < .001) and topical corticosteroid (P < .001). There were a total of 21 episodes of recurrent HSK in the PK group, more frequent than the 7 episodes in the full-bed DLK group, among which recurrent epithelial keratitis amounted to 13 episodes in the PK group, remarkably more frequent than the 1 episode in the full-bed DLK group. Twenty-six eyes (41.3%) encountered rejection episodes in the PK group, but no rejection episode was found in the full-bed DLK group (P < .001). In 14 eyes in the PK group, graft failure developed because of graft rejection, recurrence of HSK, or both, whereas only in 1 eye in the full-bed DLK group did graft failure develop because of recurrence of HSK (P = .001). The clear graft survival rate in the full-bed DLK group was significantly higher than that in the PK group (P = .01). Corneal endothelial cell density was stable from 1 month through 5 years in the full-bed DLK group, but 51.3% cell loss was found in the PK group at 5 years after surgery. At the last visit, 66.1% of eyes with full-bed DLK grafts and 50.9% of eyes with PK grafts achieved a best-correct visual acuity of 0.5 or better (P = .10). CONCLUSIONS: Advantages of full-bed DLK over PK are no allograft rejection, longer graft survival, earlier drug withdrawal of topical steroid and oral acyclovir, less recurrence of HSK, and fewer follow-up visits. Full-bed DLK is preferable for treating HSK-induced corneal scarring with relatively healthy endothelium and with no history of perforation.

Phototherapeutic keratectomy for the treatment of corneal opacities after epidemic keratoconjunctivitis.

PURPOSE: To assess visual results and compare methods of measuring central corneal thickness (CCT) and corneal opacity thickness (COT) in patients with corneal opacities induced by epidemic keratoconjunctivitis (EKC) and treated with phototherapeutic keratectomy (PTK) using low-dose mitomycin C (MMC). DESIGN: Prospective consecutive case series. METHODS: Patients with chronic adenoviral corneal opacity underwent transepithelial PTK with MMC 0.002% for 1 minute. The presence of photophobia, the best spectacle-corrected visual acuity (BSCVA), and the contrast sensitivity were evaluated. CCT measurements were obtained with ultrasound pachymeter (US), ultrasound biomicroscopy (UBM), Scheimpflug tomography (Pentacam Oculus), and optical coherence tomography (OCT Visante). COT measurements were obtained with UBM, Pentacam, and OCT. RESULTS: Thirty-one eyes of 23 patients, comprising 15 women (65.2%) and 8 men (34.8%), mean age 41.8 years, were enrolled in the study. Duration of visual disturbance was 19.1 ± 14 months. The number of patients with photophobia was reduced from 100% to 29% after surgery. BSCVA improved 2 or more lines in 78% of the patients at 12 months. A hyperopic shift of 1.52 ± 0.91 diopters was achieved. Contrast sensitivity improved in both photopic and mesopic conditions. For each of the instruments, the CCT postoperative mean was significantly smaller than the preoperative measurement (P < .0001) and COT values were significantly reduced in comparison to the preoperative values (P < .001). CONCLUSION: Improvements in photophobia, BSCVA, and contrast sensitivity were observed in patients treated using excimer laser PTK with low-dose MMC for subepithelial infiltrates.

Ocular lesions in HTLV-1 infected patients from Salvador, State of Bahia: the city with the highest prevalence of this infection in Brazil / Lesões oculares em pacientes infectados pelo HTLV-1 em Salvador, Estado da Bahia: a cidade com maior prevalência desta infecção no Brasil

In order to determine the prevalence of ocular lesions in HTLV-1 infected patients in Salvador Bahia, a transversal study was conducted on 140 HTLV-1 infected patients (90 asymptomatic and 50 tropical spastic paraparesis/HTLV-1-associated myelopathy) between June 2004 and November 2005. The ophthalmological examination included visual acuity measurement, ocular motility, biomicroscopy of the anterior and posterior chambers, intraocular pressure and evaluation of lachrymal secretion. Observation verified 4 (2.8 percent) out of 140 patients with uveitis (two patients had intermediate uveitis and two had pan-uveitis) and 39 (36.4 percent) out of 107 patients with keratoconjunctivitis sicca. The prevalence of Keratoconjunctivitis sicca was significantly higher among the TSP/HAM patients (OR age adjusted=3.64; 95 percentCI 1.59-8.32). Uveitis and corneal opacities were also important findings, indicating the strong need for periodic ophthalmological follow-up in all HTLV-1 subjects.

Com o objetivo de determinar a prevalência de lesões oculares, em portadores de HTLV-1 em Salvador, Bahia, foi realizado um estudo transversal em 140 pacientes (90 assintomático e 50 com paraparesia espática tropical/mielopatia associada ao vírus linfotrópico de células T humanas) entre junho de 2004 e novembro de 2005. O exame oftalmológico incluiu medida da acuidade visual, exame da motilidade ocular, biomicroscopia anterior e posterior, pressão intraocular e avaliação do filme lacrimal. Observamos 4.0 (2.8 por cento) pacientes com uveites (dois com uveíte intermediária e dois com panuveíte) e 39 (36,4 por cento) pacientes com ceratoconjuntivite seca. A prevalência de Ceratoconjuntivite seca foi significantemente mais elevada entre os pacientes com TSP/HAM (RC ajustada para idade = 3,64; IC 95 por cento 1,59-8,32). As uveítes e opacidades corneanas foram também, patologias importantes, indicando a necessidade de acompanhamento oftalmológico periódico nos portadores de HTLV-1.

Ocular lesions in HTLV-1 infected patients from Salvador, State of Bahia: the city with the highest prevalence of this infection in Brazil.

In order to determine the prevalence of ocular lesions in HTLV-1 infected patients in Salvador Bahia, a transversal study was conducted on 140 HTLV-1 infected patients (90 asymptomatic and 50 tropical spastic paraparesis/HTLV-1-associated myelopathy) between June 2004 and November 2005. The ophthalmological examination included visual acuity measurement, ocular motility, biomicroscopy of the anterior and posterior chambers, intraocular pressure and evaluation of lachrymal secretion. Observation verified 4 (2.8%) out of 140 patients with uveitis (two patients had intermediate uveitis and two had pan-uveitis) and 39 (36.4%) out of 107 patients with keratoconjunctivitis sicca. The prevalence of Keratoconjunctivitis sicca was significantly higher among the TSP/HAM patients (OR age adjusted=3.64; 95%CI 1.59-8.32). Uveitis and corneal opacities were also important findings, indicating the strong need for periodic ophthalmological follow-up in all HTLV-1 subjects.

Effect of human apolipoprotein E genotype on the pathogenesis of experimental ocular HSV-1.

The isoform-specific role of human apolipoprotein E (apoE) has been assessed in a mouse model of ocular herpes. Female, age-matched transgenic mice knocked-in for the human allele apoE3 or apoE4 and their parent C57Bl/6 mice were inoculated corneally with HSV-1 strain KOS. Ocular HSV-1 pathogenesis was monitored through viral replication and clinical progression of stromal opacity and neovascularization by slit-lamp examination. Establishment of latency was determined by analysis of HSV-1 DNA (copy number) by specific real-time PCR in the cornea, trigeminal ganglia (TG), and brain. Representative groups of transgenic mice were sacrificed for the analysis of gene expression of vascular endothelial growth factor (VEGF) by reverse-transcription PCR, and apoE expression by Western blot analysis. At 6days post-infection (P.I.), the ocular infectious HSV-1 titer was significantly higher (p<0.05) in apoE4 mice compared with apoE3 and C57Bl/6 mice. Corneal neovascularization in apoE4 mice was significantly higher (p<0.05) than apoE3 and C57Bl/6 mice. The onset of corneal opacity in apoE4 mice was accelerated during days 9-11 P.I.; however, no significant difference in severity was seen on P.I. days 15 and beyond. At 28 days P.I., infected mice of all genotypes had no significant differences in copy numbers (range 0-15) of HSV-1 DNA in their corneas, indicating that HSV-1 DNA copy numbers in cornea are independent of apoE isoform regulation. At 28 days P.I., both apoE4 and C57Bl/6 mice had a significantly higher (p=0.001) number of copies of HSV-1 DNA in TG compared with apoE3. ApoE4 mice also had significantly higher (p=0.001) copies of HSV-1 DNA in their TGs compared with C57Bl/6 mice. In brain, both apoE4 and C57Bl/6 mice had significantly higher numbers (p

Subepithelial infiltrates associated to viral keratoconjunctivitis following photorefractive keratectomy.

PURPOSE: To report three cases of adenoviral keratoconjunctivitis in patients who have undergone photorefractive keratectomy and that just developed subepithelial infiltrates. METHODS: Description of patients that developed postoperative adenoviral keratoconjunctivitis after photorefractive keratectomy without influence in the final visual outcome. RESULTS: All patients presented adenoviral keratoconjunctivitis 2-3 months after refractive surgery. They developed multiple pinpoint subepithelial infiltrates in six eyes, without haze development. The final uncorrected visual acuity was better or equal to 20/30. CONCLUSION: Although patients undergoing photorefractive keratectomy might develop severe corneal scarring following ocular infections, such events may follow their natural evolution.

Effect of oral acyclovir after penetrating keratoplasty for herpetic keratitis: a placebo-controlled multicenter trial.

OBJECTIVE: To determine the prophylactic effect of oral acyclovir on the recurrence rate of herpetic eye disease after penetrating keratoplasty. DESIGN: A randomized, double-masked, placebo-controlled multicenter trial. PARTICIPANTS: Sixty-eight consecutive patients (68 eyes) with corneal opacities due to herpetic eye disease who underwent penetrating keratoplasty. INTERVENTION: Oral acyclovir 400 mg twice daily or placebo tablets for 6 months. MAIN OUTCOME MEASURES: The recurrence rate of herpetic eye disease-related events and rejection episodes, proven by viral cell culture or polymerase chain reaction. RESULTS: During the 2-year follow-up period, there were 3 culture-proven herpetic eye disease recurrences in the acyclovir group and 9 in the placebo group. Lifetime survival analysis of the probability of remaining free from recurrence revealed a significantly reduced risk of recurrent herpetic disease in the acyclovir-treated group. CONCLUSION: This study suggests that oral acyclovir effectively prevents herpes-related recurrences after penetrating keratoplasty in herpetic eye disease.

Therapeutic vaccination with vhs(-) herpes simplex virus reduces the severity of recurrent herpetic stromal keratitis in mice.

Virion host shutoff (vhs)-deficient herpes simplex virus (HSV) was tested as a therapeutic vaccine in a mouse model of UV light-induced recurrent herpetic stromal keratitis. Four weeks after primary corneal infection, mice were vaccinated intraperitoneally with vhs(-) vaccine or control. Four weeks after vaccination, the eyes of latently infected mice were UV-B irradiated to induce recurrent virus shedding and disease. Post-irradiation corneal opacity in latently infected, vhs(-)-vaccinated mice was significantly reduced compared to control-vaccinated mice (P=0.007 to 0.035). The incidence and duration of recurrent virus shedding were the same in both groups. Antibody titres were increased (P=0.05) and delayed type hypersensitive responses were unaffected by vhs(-) vaccination. Combined with studies using different vaccination timing and vhs(-) genotypes, these data suggest that deletion of vhs is a useful strategy in the development of a therapeutic HSV vaccine, and that temporal and genetic factors influence vaccination outcome.

Linkage of IL-6 with neutrophil chemoattractant expression in virus-induced ocular inflammation.

PURPOSE: Herpes simplex virus (HSV)-1 infection of the murine cornea is known to stimulate a vigorous interleukin (IL)-6 response, but whether this pleiotropic cytokine is an essential participant in corneal inflammation is unclear. This study was designed to compare the early inflammatory response in IL-6 gene-deficient mice to that in wild-type hosts. METHODS: Gene knockout and wild-type mice (C57BL/6 background) were infected intracorneally with HSV-1 (strain RE) and observed through clinical examination and immunohistochemistry for the development of corneal opacity. Virus corneal titers were determined by standard plaque assay on Vero cells. Cytokine and chemokine levels in corneal lysates were measured with commercial ELISA kits. RESULTS: Corneal opacity in IL-6(-/-) mice was substantially diminished in comparison with IL-6(+/+) hosts 24 to 48 hours after intracorneal viral infection, and corneal levels of (MIP)-2 and MIP-1alpha were significantly reduced. Local administration of IL-6 at the time of infection restored corneal opacity and chemokine levels to that of wild-type hosts. Antibody neutralization of endogenous IL-6 in IL-6(+/+) animals reduced corneal opacity scores and MIP-2 levels to that of IL-6(-/-) mice. Ex vivo studies with excised corneal buttons revealed that uninfected IL-6(-/-) corneas injected with IL-6 produced MIP-2 and MIP-1alpha at levels comparable to that seen in IL-6(+/+) hosts. CONCLUSIONS: Collectively, these results suggest that IL-6 promotes corneal inflammation by acting in an autocrine-paracrine fashion to induce resident corneal cells to make MIP-2 and MIP-1alpha, which in turn recruit neutrophils to the virus infection site.