Yuji Kumano

Corneal sensation after correction of myopia by photorefractive keratectomy and laser in situ keratomileusis.

Purpose: To compare the effects of photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) on corneal sensation. Setting: Ohshima Hospital of Ophthalmology, Fukuoka, Japan. Methods: Corneal sensation was measured with a Cochet‐Bonnet esthesiometer in 35 patients before and 3 days, 1 week, and 1 and 3 months after correction of myopia by PRK (22 patients) or LASIK (13 patients). Results: After PRK, corneal sensitivity was decreased slightly at 3 days, began to recover at 1 week, and returned to preoperative values at 3 months; none of the changes was statistically significant (P gt; .05). After LASIK, corneal sensation was significantly decreased at 3 days, 1 week, and 1 month; it recovered slightly at 3 months, although it remained significantly less than preoperatively. Conclusions: Laser in situ keratomileusis was associated with a negative effect on corneal sensation, which was markedly greater than the effect with PRK and was evident for at least 3 months after surgery.

Recovery of corneal sensation after myopic correction by laser in situ keratomileusis with a nasal or superior hinge

Purpose: To measure corneal sensitivity after laser in situ keratomileusis (LASIK) to determine the time required for recovery of this parameter. Setting: Ohshima Hospital of Ophthalmology, Fukuoka, Japan. Methods: Corneal sensation was measured with a Cochet‐Bonnet‐type esthesiometer in 75 patients before and 1, 3, 6, and 12 months after correction of myopia by photorefractive keratectomy (n = 21) or LASIK (n = 54). Results: Photorefractive keratectomy did not affect corneal sensation. In the LASIK group, a large and significant decrease in corneal sensitivity was apparent at 1 month (P<.05). Although corneal sensitivity appeared to have recovered slightly at 3 months, it remained significantly decreased (P<.05). By 6 or 12 months, the corneal sensitivity in LASIK patients was not statistically different from the preoperative values in the study patients. A significantly greater decrease in corneal sensitivity was apparent in the LASIK patients with a nasal hinge than in those with a superior hinge (F = 7.54, P<.01). Corneal sensitivity was in the normal range in 31.5% of LASIK patients at 3 months and in 57.4% and 82.1% at 6 and 12 months, respectively. Conclusion: Recovery of corneal sensation had begun 3 months after LASIK and appeared complete after 12 months.

Characterization of glycoprotein C-negative mutants of herpes simplex virus type 1 isolated from a patient with keratitis

SummaryRecently three strains of herpes simplex virus type 1 (HSV-1), which did not react with MicroTrak Herpes (Syva Co.), were isolated by us from a patient with recurrent herpetic keratitis. In this study we characterized these strains of HSV-1 and found them to be HSV-1 gC− mutants which are very rare isolates from humans. The properties of the HSV-1 strains regarding plaque morphology on Vero cells and chick embryo fibroblasts and viral DNA analysis were the same as those of the usual HSV-1 strains. An immunofluorescence study using anti-gC-1 monoclonal antibody and SDS-PAGE analysis of radiolabeled viral glycoproteins showed that these strains are deficient in gC-1. They were virulent for mice and sensitive to acyclovir and bromovinyldeoxyuridine. Furthermore the infectivity of the strains was inactivated by complement though the phenomenon was not observed in the usual HSV-1 strains. This finding suggests that protection from damages by complement is an important function of gC. In keratitis the effects of complement are thought to be minimal because of the scanty blood supply and this may be the reason why these strains were isolated from the cornea.

Protection against herpes simplex virus infection in mice by recombinant murine interferon-β in combination with antibody

A recombinant murine interferon -beta (rMuIFN-beta) was used to suppress the development of skin lesions and death of mice after challenge with herpes simplex virus (HSV) type 1 (HSV-1). Depilated female BALB/c mice were inoculated intradermally with HSV-1, Hayashida strain, and were administered various concentrations of interferon (IFN) intraperitoneally 3 h later. The treatment with IFN was given once a day for 10 successive days. Under the conditions in which almost all control mice died after development of severe zosteriform skin lesions, the mortality of mice treated with IFN (8 X 10(5) or 8 X 10(4) U/mouse) was less than 50% (9/20 and 4/10, respectively), though all mice treated with a lower dose of IFN (8 X 10(3) U/mouse) died. Titration revealed that there was no significant suppression of virus growth by IFN in the skin or dorsal root ganglia, but it was significantly suppressed in the brain. The protective effect of IFN was enhanced when it was used in combination with human anti-HSV antibody having a neutralizing titer (NT) of 1:16. All mice treated with IFN (8 X 10(5) U/mouse) and antibody (NT, 1:16) survived, and only 40% of them developed slight zosteriform skin lesions. The effect of the combination was observed even when both IFN and antibody were diluted 1:10. The protective effect of IFN was also observed when athymic nude mice were used as the host. In this system, though the IFN-treated nude mice survived significantly longer than the controls, they finally died. In antibody- or acyclovir (ACV)-treated nude mice, there was also a prolongation of survival time as compared with control mice. The effect of antibody was enhanced by the addition of IFN, but IFN did not potentiate the effect of ACV.

Two brothers with gelatinous drop-like dystrophy at different stages of the disease: role of mutational analysis.

PURPOSE A report of two Japanese brothers with gelatinous drop-like corneal dystrophy, one with and one without the typical gelatinous drop-like region. DESIGN Interventional case report and observational case report. METHODS After penetrating keratoplasty, the corneal button, right eye, of the elder brother, 39 years of age, was stained and examined by microscopy. The M1S1 and BIGH3 genes were examined for mutations using the polymerase chain reaction and direct sequencing. Corneal abnormalities in the younger brother, 37 years of age, were observed. RESULTS The elder brother had bilateral gelatinous prominences and band-shaped corneal opacities, whereas the younger brother had only bilateral band-shaped opacities. Histologically, corneal deposits beneath the epithelium stained with Congo red. Molecular genetic analysis revealed that M1S1 was homozygously mutated in both brothers (Q118X). CONCLUSION The Q118X mutation of the M1S1 gene can produce either a gelatinous drop-like region or band-shaped opacities.

An acyclovir-resistant strain of herpes simplex virus type 2 which is highly virulent for mice

SummaryHerpes simplex virus type 2 (HSV-2), strain YS-4 C-1, isolated by plaque cloning from a clinical isolate was found to be resistant to acyclovir (ACV; acycloguanosine) in vitro. It was sensitive to phosphonoacetic acid and 9-β-D-arabinofuranosyladenine. Thymidine kinase (TK) activity of YS-4 C-1 was less than 1% of that of other strains from the same clinical source. However, thymidine plaque autoradiography showed that YS-4 C-1 was not completely deficient in TK activity. YS-4 C-1 showed high virulence for mice like other HSV-2 strains which were sensitive to ACV. YS-4 C-1 was able to establish latent infection in mice. Virus isolated from the brain of a mouse died after being inoculated with YS-4 C-1 was also resistant to ACV. ACV was not effective in mice inoculated with YS-4 C-1. This study shows that not all ACV-resistant strains are avirulent for mice.

Detection of Varicella-Zoster Virus Genome Having a Pstl Site in the Ocular Sample from a Patient with Acute Retinal Necrosis

We detected the virus genome in ocular samples from a 65-year-old woman with clinically diagnosed acute retinal necrosis using DNA amplification. She exhibited occlusive retinal vasculitis, confluent necrotizing retinitis, mainly peripheral, and iridocyclitis. For DNA amplification, we used recently published primers specific for varicella-zoster virus (VZV) and herpes simplex virus. Using VZV primers, we detected the VZV genome in the aqueous humor, but not in the vitreous, by amplifying a DNA fragment 642 base pairs in length. HSV DNA was not detected. After detecting the VZV genome, PstI restriction endonuclease was used because an epidemiological study found that about 25% of the VZV strains in Japan carry a mutation lacking a PstI recognition site. The VZV genome from the patient had a PstI cleavage pattern, while the positive control had a VZV genome that carried a PstI-site-less mutation. We considered our patient with acute retinal necrosis to be infected with VZV having a PstI site.

An analysis of BIGH3 mutations in patients with corneal dystrophies in the Kyushu District of Japan

PURPOSE To assess the involvement of BIGH3 in corneal dystrophies (CD) with an autosomal dominant trait, in patients referred to a hospital in the Kyushu district of Japan. METHODS Forty-five CD patients from 44 families were studied. Genomic DNA was extracted from peripheral blood, and exons 4 and 12 of the BIGH3 gene were amplified by polymerase chain reaction followed by direct sequencing. RESULTS In exon 4, an R124H mutation associated with Avellino corneal dystrophy (ACD) was found in 39/44 families (86.4%) and an R124C mutation associated with lattice corneal dystrophy type 1 (LCD1) was detected in 2/44 families (4.5%). In exon 12, an R555W mutation associated with granular corneal dystrophy (GCD) was detected in 4/44 families (9.1%). CONCLUSIONS Codons R124 and R555 of the BIGH3 gene represent mutational hotspots in the genomes of Japanese patients with autosomal-dominant CD.

Symptomatic and morphological differences between choroidal excavations.

Purpose The purpose of this report is to describe the morphological and clinical features of two patients with focal choroidal excavation in an attempt to understand more about this rare condition. Case Report Spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography, and indocyanine green angiography were used to assess the morphological characteristics of the patients’ choroidal excavations. Both patients showed the following features on SD-OCT: (1) the retinal pigment epithelium band and inner/outer segment junction followed the contour of the choroidal excavation, which involved the outer nuclear layers up to the outer limiting membrane; (2) the sclerochoroidal junction was smooth and undisturbed, but large choroidal vessels were present beneath each excavation. The patient with metamorphopsia showed separation between the photoreceptor outer segment and the retinal pigment epithelium as well as disturbance of the inner/outer segment junction on SD-OCT volume scans and hyperfluorescence and hypofluorescence in the foveal region on indocyanine green angiography. Conclusions Symptomatic and morphological differences between focal choroidal excavations suggested anatomical alterations between the photoreceptor tips and the retinal pigment epithelium or location of choroidal excavation as the cause of metamorphopsia. We speculate that the pathogenesis of focal choroidal excavation involves outward traction on the macula caused by choroidal vascular abnormalities because of embryonic developmental failure of the choroid.

Recurrent Herpetic Keratitis: Failure to Detect Herpes simplex Virus Infection Using the Syva MicroTrakTM HSV1/HSV2 Direct Specimen Identification/Typing Test

A 35-year-old man had developed recurrent herpetic keratitis characterized by dendritic keratitis at intervals of a year. We were able to culture cytopathic agents repeatedly from his lesions by inoculating Vero cells. The cultures yielded definitive evidence of a virus that caused a cytopathic effect within 3 days. However, these virus strains could not be identified as herpes simplex virus (HSV) in immunofluorescence assays using the Syva MicroTrak HSV1/HSV2 direct specimen identification/typing test. Rather they were identified as strains of HSV type 1 (HSV-1) on the basis of plaque morphology, neutralization tests, electron-microscopic examination and DNA restriction endonuclease analysis. Our results allow us to assume the existence of HSV-1 strains isolated clinically that are negative to analysis using the Syva Micro-Trak HSV1/HSV2 direct specimen identification/typing test.