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Purpose: Additional analyses of outcomes of laser-assisted subepithelial keratectomy (LASEK) are still necessary to improve the safety of LASEK. Therefore, in our study, outcomes were assessed retrospectively in 561 eyes that underwent LASEK treatment. Methods: Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA) and residual spherical equivalent were analyzed at 3 and 6 months postoperatively. We assessed four subgroups based on the degree of preoperative myopia considering mean BSCVA and loss of two or more lines. Results: Mean UCVAs and BSCVAs were obtained at 3 and 6 months postoperatively (1.23/1.35 and 1.23/1.37, respectively). The mean predictability was within ±0.125 diopters. Conversely, the safety indexes were 0.94 and 0.96 respectively, and the efficacy indexes were 0.86 and 0.86 at 3 and 6 months postoperatively, respectively. 8.4% eyes and 5.2% eyes lost two or more lines of BSCVA at 3 and 6 months postoperatively, respectively. The mean BSCVAs of the high or ultra-high groups were significantly lower than those of the low or mild groups both 3 months and 6 months postoperatively. The incidence rates of losing two or more lines of BSCVA in the high or ultra-high myopia groups were significantly greater than in the low or mild groups at 3 months and 6 months postoperatively. Conclusion: LASEK predictably corrected myopia achieving >1.2 in UCVA and BSCVA. However, the safety and efficacy indexes were

Purpose To measure the concentration of brilliant blue G (BBG) in vitreous and plasma after use as a surgical adjuvant for staining and peeling of the internal limiting membrane to determine potential systemic adverse effects. Methods This study was designed as a prospective, interventional, clinical, case series. Five eyes from five patients with macular hole or epiretinal membrane underwent BBG-assisted internal limiting membrane and epiretinal membrane removal. The vitreous samples were obtained and stored at the end of surgery in all five cases. The plasma specimens were extracted and stored at the end of the operation, after 4 hours, and after 7 days post operation. For BBG analysis of plasma and vitreous, high-performance liquid chromatography coupled with tandem mass spectrometric detection was used. Results Brilliant blue G was not detected in plasma from all five cases at the three points of measurement. The mean vitreous BBG concentration was 34.5 ± 23.7 ng/mL (range, 11.3-70.9 ng/mL). Postoperative progress was good, and adverse effects were not observed in any of the five cases. Conclusion Brilliant blue G, which remained at low levels in the vitreous cavity, was not found in the systemic blood flow after the operation. Thus, any adverse effects of systemic BBG would be avoided.

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.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.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.

Purpose: Systemic metastatic retinal lymphoma (SMRL) originates in systemic organs. It has been reported to exhibit clinical features similar to those of primary vitreoretinal lymphoma (PVRL). We report six cases of SMRL in a single-center survey in Japan.Methods: The clinical and pathologic features in SMRL at the Kyushu University Hospital were retrospectively studied.Results: The mean patient age at the onset of ocular involvement was 75.3 years. Four patients had brain involvement. The primary sites were: breast (2); chest (1); testis (1); intestinal tract (1); and nasal sinus (1). In all patients, the cytology of vitreous samples indicated diffuse large B-cell lymphoma (DLBCL).Conclusions: DLBCL is the most common subtype in our study. The prevalence of CNS involvement in patients with SMRL is similar to that with PVRL. The testis and breast may be common sites of origin for SMRL.

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 Conclusion Recovery of corneal sensation had begun 3 months after LASIK and appeared complete after 12 months.

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 > .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.

· Background: The focus of these studies was to determine whether the Y79 human retinoblastoma cell line could function as a good in vitro model system for studying human cytomegalovirus (HCMV) infection. · Methods: Y79 cells were exposed to an HCMV mutant carrying a LacZ gene, and the resulting β-galactosidase expression in infected cells was assessed by flow cytometry. The extent to which the three classes of viral gene products – immediate early, early, and late proteins – were expressed was analyzed by immunohistochemical staining and Western blotting. Infected Y79 cells were also co-cultivated on human foreskin fibroblast (SF cell) cultures to recover virus. · Results: Infection of Y79 cells with the virus resulted in β-galactosidase expression as detected by flow-cytometric analysis. Immunohistochemical staining revealed that a portion of Y79 cells expressed antigens reactive to monoclonal antibodies against immediate early, early, and late HCMV proteins. The 43-kDa early gene product was also detected by Western blotting. Infected Y79 cells co-cultivated on SF cell cultures yielded infectious foci, which turned blue following X-gal staining, demonstrating productive HCMV infection in the Y79 cells. · Conclusion: These results demonstrate that while HCMV can productively infect Y79 cultures, it does so in a highly inefficient manner, leading these authors to conclude that this cell line does not provide a particularly good model system to study HCMV infection.

• Background: We examined four patients who exhibited both idiopathic retinal vasculitis and elevated serum IgD levels. Uveitis caused by Behcet's disease is also associated with high levels of serum IgD. Therefore, the clinical features of these patients were investigated and the possible relationship between retinal vasculitis and elevated serum IgD was examined after undertaking a study of increased IgD levels in patients diagnosed with uveitis. • Methods: The study population was composed of 110 patients: 49 with Behcet's disease, 15 with sarcoidosis, 10 with Vogt-Koyanagi-Harada disease, and 36 with other forms of uveitis. IgD measurements were performed using modifications of the latex photometric immunoassay. Surface IgD (sIgD) expression in peripheral lymphocytes was determined by immunofluorescence, and the correlation between serum IgD levels and the percentage of sIgD-positive cells was examined. • Results: Twelve of the 110 patients had an elevated serum IgD. Eight of the 12 had Behcet's disease, and 4 were diagnosed with idiopathic retinal vasculitis. These 4 patients were HLA-A24+ females whose ages ranged from 8 to 25 years. A linear correlation between the serum IgD levels and the percentage of sIgD-positive cells was found. • Conclusion: Hyperimmunoglobulinemia D state was found in Behcet's disease and idiopathic retinal vasculitis. These diseases may represent a new clinical entity characterized by signs of retinal vasculitis and hyperimmunoglobulinemia D that results from abnormal B cell activation and immune complex-mediated responses.

Purpose To describe a Japanese patient with lattice corneal dystrophy type I (LCD I) who lacked the typical lattice lines. Design Interventional case report. Methods A complete ophthalmologic examination was performed on a 54-year-old woman, and the TGFBI gene was analyzed by direct genomic sequencing. Results The patient had diffuse opacification of the central corneal stroma but without lattice lines and corneal epithelial erosions bilaterally. Molecular genetic analysis identified a lattice corneal dystrophy I–associated heterozygous missense alteration (C417T) that changed arginine in codon 124 to cysteine (R124C) in the TGFBI gene. Conclusions The cornea of the patient appeared to represent late-stage lattice corneal dystrophy I, which suggests the existence of interactions of modifier genes, environmental factors during corneal aging, or both. The molecular genetic analysis of TGFBI can offer rapid, accurate diagnosis of patients with atypical corneal appearance.

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.

Surgical treatment and the results of esophageal cancers at our institution in a recent one decade were analyzed with special reference to the combination chemo-radiation therapy. Eighty-one patients who underwent esophagectomy for esophageal cancer were divided into two patient groups; the first half group (1981-1985: 28 patients) and the last half (1986-1991: 53 patients). The first half group received radical esophagectomy including 2-field lymph node dissection with preoperative irradidiation (30Gy). The last half received 3-field lymph node dissection with preoperative chemotherapy (CBDCA, 5FU and PEP) and postoperative irradiation (45Gy) combined with chemotherapy. In the last half, 56.8% received 3-field lymph node dissection and 51.0% received combined chemotherapy. No difference in the operative mortality rate was observed between the groups. Side effects of chemo-radiation therapy were pharyngitis and leucocytopenia. The five-year survival rate of over-all patients who received esophagectomy were 20.9% in the first half and 32.2% in the last half. The five-year survival rate of patients receiving curative operation were 25.0% in the first half and 48.4% in the last half. Postoperative anastomotic disruptin was improved from 39.4% to 9.4% by the modification of the procedure in the last half. In conclusion, our pre-and postoperative chemo-radiation therapy combined with 3-field lymph node dissection can be safely applied without severe side effects to the patients with esophageal cancer, and was effective to improve the survival rate.

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.

Recently three strains of herpes simplex virus type 1 (HSV-1), which did not react with Micro Trak 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.

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 inocu

Recent studies of the corneal dystrophies (CDs) have shown that most cases of granular CD, Avellino CD, and lattice CD type I are caused by mutations in the human transforming growth factor beta-induced (TGFBI) gene. The aim of this study was to develop a rapid diagnostic assay to detect mutations in the TGFBI gene. Sixty-six patients from 64 families with TGFBI-associated CD were studied. A primer probe set was designed to examine the genome from exons 4 and 12 of the TGFBI gene in order to identify mutant and wild-type alleles. A region spanning the mutations was amplified by the polymerase chain reaction (PCR) in a commercial cycler. Mutations were then identified by melting curve analysis of the hybrid formed between the PCR product and a specific fluorescent probe. Using this system, we clearly distinguished each CD genotype (homozygous and heterozygous 418G--A, heterozygous 417C--T, heterozygous 1710C--T, and wild-type) of all the patients by means of the clearly distinct melting peaks at different temperatures. One thermal cycling took approximately 54 min, and all results were completely in concordance with the genotypes determined by conventional DNA sequencing. Thus, the technique is accurate and can be used for routine clinical diagnosis. We expect that our new method will help in making precise diagnoses of patients with atypical CDs and aid the revision of the clinical classification of inherited corneal diseases based on the genetic pathogenesis.

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.

· Background: Cytomegalovirus retinitis remains a serious problem in AIDS patients, and the species specificity of human cytomegalovirus (HCMV) has hindered the development of animal models suitable for testing new therapeutic agents. Having previously described an in vivo model of HCMV retinal infection, we investigated its ability to reproduce the antiviral effects of the established anti-HCMV agent ganciclovir in order to determine the model’s potential for evaluating novel agents. · Methods: Athymic rats had human fetal retinal tissue implanted in both anterior chambers. At 14 or 28 days post implantation, a suspension of a β-galactosidase (lacZ+) mutant of HCMV was injected into each anterior chamber. Commencing 3 days prior to the injection of virus, rats in the treatment group received twice-daily intraperitoneal injections of ganciclovir (≡ a total of 100 mg/kg per day) for the duration of the study. The control rats received no drug. Twenty days after virus injection, the eyes of all rats were removed, sectioned and developed with X-gal substrate to detect any β-galactosidase expression in the human tissue implants. · Results: Blue-staining foci of infection were detected in the implanted retinal tissue in 8 of 10 eyes from untreated control rats, but no β-galactosidase expression was found in any of 12 eyes from animals which had received ganciclovir treatment. · Conclusion: Intraperitoneal administration of ganciclovir successfully prevented HCMV replication in the intraocular retinal implants. This model of HCMV retinal infection is therefore suitable for preliminary evaluation of systemically administered antiviral agents.

Gelatinous drop-like corneal dystrophy (GDLD) is a rare autosomal recessive disorder that is most often seen in Japan. This bilateral dystrophy usually presents in the first decade of life and is associated with a decrease of visual acuity. Typically, a mulberry-like opacity is present with protuberant subepithelial mounds that grow with age. Corneal neovascularisation (NV) also accompanies advanced cases.1 Corneal transplantation is the major therapeutic option for GDLD, but because NV can significantly increase the risk of graft rejection, a better understanding of the mechanism(s) for the corneal NV would be valuable. A 39 year old Japanese man with GDLD was studied. His right eye had band-shaped corneal opacities in the interpalpebral area with a number of gelatinous prominences, and vascular invasions from the superior limbus into the clear cornea (Fig 1A). Because the visual acuity of the right eye had decreased to 20/800, penetrating keratoplasty was performed, and the diagnosis of GDLD was …

Recurrent stromal keratitis induced by herpes simplex virus (HSV) type 1 is one of the most important problems in herpetic ocular diseases and has been considered to represent the host’s immunopathologic response to the virus. In the pathogenicity of this disease, glycoprotein C (gC) of HSV-1 has been shown to be essential, because it is reported as immunodominant antigen to induce HSVspecific memory cytotoxic T lymphocytes. gC also functions as a receptor of complement C3b and has been thought to play an important role in natural infection of HSV. Recently, we isolated HSV-1 strains from a patient with recurrent herpetic keratitis. Interestingly, these viruses were shown to be gCnegative by using two different anti-HSV-1, gC-specific monoclonal antibodies. The clinical isolation of the gC-negative HSV strain is an extremely rare event. Molecular analyses of the gC-negative phenotype of these HSV-1 strains revealed that a premature termination of the translation due to a point mutation of the nucleotide occurred in the mid portion of the gC open reading frame and consequently, a truncated, immature gC molecule lacking the transmembrane domain was secreted to the extracellular fluid. We also demonstrated the important role of gC in protection of the virion envelope against complement-mediated damage, by using the gC-positive recombinant viruses derived from one of these clinical isolates. It is thus expected that these rare HSV-1 strains will provide us with valuable information concerning the in vivo functions of gC, especially in ocular disease. The requirement of gC in herpetic stromal keratitis is also discussed.

A recombinant murine interferon -β (rMuIFN-β) 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 × 10 5 or 8 × 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 × 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 × 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.

The effect of monoclonal antibody (MCA) to glycoprotein gB of herpes simplex virus (HSV) was studied in athymic nude mice inoculated with HSV intracutaneously in the midflank. HS1, the MCA used in the study, had a high neutralizing titer (1:2048) and had antibody-dependent cell-mediated cytotoxicity. HS1 was injected intraperitoneally at various intervals after HSV infection. HS1 injected 3 h after infection inhibited the development of skin lesions and most mice survived. Administration of HS1 at the time the local skin erosions appeared at the inoculated site (4–7 days after infection) was also effective, and in four of eight mice skin lesions completely healed. Furthermore, in three of the four mice that survived, latent infections in the ganglia were also prevented as evidenced by the failure to detect HSV by co-cultivation with Vero cells. Administration of HS1 after the development of zosteriform skin lesions (5–9 days after infection) reduced virus in the ganglia and prolonged the survival time, though the disease was not completely arrested and all the mice died eventually.

The participation of T lymphocytes in the immunopathogenesis of corneal opacity in herpetic stromal keratitis was investigated. In BALB/c mice infected intracorneally with herpes simplex virus type 1, corneal opacity was manifested 10 days after infection, while in athymic mice corneas remained almost clear. Histologically, all opaque corneas revealed stromal edema accompanied by the diffuse presence of polymorphonuclear cells and lymphocytes. When complement (C')-treated immune spleen cells were adoptively transferred into athymic mice 6 or 72 h after corneal infection, stromal keratitis with mild opacity was observed 10 days after transfer. The athymic mice given anti-Thy 1.2+C'-treated immune spleen cells failed to develop corneal opacity. The difference, as revealed by light and electron microscopy, was the presence or absence of lymphocytic infiltration and edema in the posterior third layers of the stroma and endothelial lesions. The endothelium was infiltrated by lymphocytes or macrophages and showed various stages of destruction. The main cause of corneal opacity in the early stage of herpetic stromal keratitis is thought to be stromal edema due to an adverse effect on the endothelium by immune T lymphocytes.

Herpes 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-beta-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.