Initial trabeculectomy with mitomycin C in eyes with uveitic glaucoma with inactive uveitis.

PURPOSE: To analyse clinical outcomes of trabeculectomy with mitomycin C (MMC) in eyes with uveitic glaucoma (UG) with inactive uveitis and compare them to those in eyes with primary open-angle glaucoma (POAG). DESIGN: Retrospective non-randomized comparative interventional case series. METHODS: A total of 53 eyes with UG and 80 eyes with POAG that received MMC trabeculectomy as an initial ocular surgery with average follow-up of 5.4 years were reviewed retrospectively. The intraocular pressure (IOP) control and persistence of filtering bleb were analysed using the Kaplan-Meier life-table method based on two definitions of successful IOP control, ie complete success (IOP

Heterogeneity of the fibre sequence in subgenus C adenoviruses.

AIMS: To determine the nucleotide sequences of adenovirus (Ad) types 1 and 6 fibre genes; to clarify the molecular basis of the distinct haemagglutination properties of subgenus C Ads and their phylogenetic relations. METHODS: Human Ad1 and Ad6 fibre genes were sequenced from genomic DNA by direct sequencing. Primer selection was based on alignment of the fibre gene of human Ad serotypes Ad2 and Ad5. Fibre based subgenus C specific polymerase chain reaction (PCR) was performed to check for deletions in field isolates of Ad6, as revealed by sequence analysis of the Ad6 prototype. A phylogenetic tree was constructed from the predicted amino acid (AA) sequences of the fibre gene of important Ads. RESULTS: Ad1 and Ad6 comprise 1746 and 1584 nucleotides, encoding 582 and 528 AA, respectively. Ad6 showed deletions in motifs 15-17 (51 AA) of the shaft when compared with Ad1, Ad2, and Ad5. Subgenus C specific PCR with both prototype and field isolates also showed deletions in Ad6. In the shaft and knob, AA homology was 58.82-72.91% and 68.89-74.59%, respectively. The tail was 100% conserved. Phylogenetically, Ad1 and Ad6, including Ad2 and Ad5, formed a subgenus specific cluster, like other serotypes. CONCLUSIONS: The fibre gene (including the knob region) of subgenus C Ads is heterogeneous, providing the molecular basis for lack of crossreactivity in the haemagglutination inhibition test. This heterogeneity could be helpful in fibre based genotyping of subgenus C field isolates. Phylogeny might be useful for subgenus specific identification of important field strains.

Serological and genetic characterisation of a unique strain of adenovirus involved in an outbreak of epidemic keratoconjunctivitis.

AIMS: To characterise a novel strain of adenovirus (Ad) type Ad8 (genome type Ad8I) involved in an epidemic keratoconjunctivitis (EKC) outbreak in Hiroshima city using serological testing and sequence analysis of the fibre and hexon gene. METHODS: A neutralisation test (NT) was performed in microtitre plates containing a confluent monolayer of A549 cells using 100 tissue culture infectious doses of virus and type specific antisera. The haemagglutination inhibition test was also carried out in microtitre plates with rat erythrocytes using four haemagglutination units of virus and twofold dilutions of serum. The fibre gene was sequenced by generating overlapping polymerase chain reaction products or by direct sequencing of genomic DNA. Primer selection was based on alignment of the fibre genes of human adenovirus serotypes Ad8, Ad19, Ad37, Ad9, and Ad15 available from Gene Bank. RESULTS: The virus strain was specifically neutralised by anti-Ad8 antibodies, although there was a major crossreaction with anti-Ad9 antibodies. Haemagglutination was equally inhibited by anti-Ad8 and anti-Ad9 antibodies. The predicted amino acid sequences of the hypervariable regions (HVRs) of the Ad8I hexon gene showed higher homology with Ad9 (83.3%) than with Ad8 (62.0%). However, the Ad8I fibre knob was more homologous to Ad8 (94.4%) than to Ad9 (91.6%). CONCLUSIONS: Ad8I is a unique strain of adenovirus because of its lower genomic homology with Ad8, major crossreactivity with Ad9 in NT, and mixed genetic organisation of HVRs of the hexon gene. These factors may have enabled the virus to circumvent acquired immunity, resulting in the outbreak.

Characterisation of hexon and fibre genes of a novel strain of adenovirus involved in epidemic keratoconjunctivitis.

AIMS: To characterise a novel strain (M86) of adenovirus (Ad) involved in epidemic keratoconjunctivitis (EKC). METHODS/RESULTS: The virus strain was neutralised by antisera to both Ad35 and Ad11. Restriction endonuclease analysis of genomic DNA showed 98% and 88% homology with Ad11 and Ad35, respectively. The deduced amino acid sequence of the hypervariable regions of (HVRs) of the hexon gene showed a higher homology with Ad35 (94.4%) than with Ad11 (83.7%). However, it was 100% homologous to Ad35 in HVRs 1, 2, 3, and 6 and to Ad11 in HVRs 4 and 6. In the fibre knob, the isolate was more homologous to Ad11 (99.4%) than to Ad35 (29.1%). CONCLUSION: This novel strain of adenovirus showed similarities with both Ad11 and Ad35. The isolation of a novel strain like Ad35+11 is important because of its association with EKC.

Genetic characterisation of adenovirus type 8 isolated in Hiroshima city over a 15 year period.

AIMS: To investigate the genetic differences among the strains of adenovirus type 8 (Ad8) circulating in Hiroshima city, Japan, and to study their circulation pattern. METHODS: One hundred and twenty nine strains of adenovirus type 8 (Ad8) were isolated in Hiroshima City over a 15 year period (1983-97) from patients with keratoconjunctivitis, and analysed with six restriction enzymes-BamHI, HindIII, PstI, SacI, SalI, and SmaI-to investigate possible relations among the isolates and their genetic variability. Seven hypervariable regions of the hexon gene that carry the type specific epitope were also sequenced to investigate the variation among the genome types. RESULTS: Restriction endonuclease analyses yielded three known genome types (Ad8A, 13 samples; Ad8B, seven samples; and Ad8E, 35 samples) and a novel genome type (Ad8I, 74 samples). Ad8A, Ad8B, and Ad8E were closely related, with 96% homology, whereas Ad8I had only 71% homology. Ad8A, Ad8B, and Ad8E shared 91.8% and 96.4% homology with regard to their amino acid and nucleotide sequences, respectively, with the isolate 1127 (accession no X74663). However, when compared with Ad8A, Ad8B, Ad8E, and isolate 1127, Ad8I shared only 62.7% and 69.9% homology with regard to amino acid and nucleotide sequences, respectively. Ad8A, Ad8B, and Ad8E had a unique 31 amino acid deletion in the hypervariable region 1 of the hexon gene, whereas Ad8I had a 33 residue deletion. The Ad8E strain that circulated from 1984 to 1995 was stable among the study population. Ad8I was isolated from an outbreak of epidemic keratoconjunctivitis in 1995 and was also isolated from sporadic cases until 1997. CONCLUSIONS: These results confirmed that genetic variability occurs in Ad8 in the microenvironment and revealed the emergence of a new genome type (Ad8I).

Ultrasound biomicroscopic study of sclerotomy sites after implantation of sustained release drug devices.

BACKGROUND/AIMS: To evaluate the potential of ultrasound biomicroscopy (UBM) as a tool to study the precise location and changes of sclerotomy sites of the eye with an intraocular drug delivery device. METHODS: Eight eyes of six patients (13 sites) who received ganciclovir implants were examined by UBM. Examinations were performed 1-26 months (mean 12.8 months) postoperatively. Serial transverse and radial sections of the anterior ciliary body around the sclerotomy sites were obtained. RESULTS: The ganciclovir implant contour was successfully viewed using an UBM with high reflectivity. Three implants were deviated anteriorly and they were very close to the ciliary body and the lens (anterior deviation), while four implants were deviated posteriorly and away from the lens (posterior deviation). The other six implants were located at the appropriate position as intended. A solitary homogeneous mass with a medium reflectivity around the suture tab was observed at 12 out of 13 sites in seven eyes. Thick membranes extending from sclerotomy sites to the ora serrata were found at two sites in two eyes. CONCLUSION: UBM is helpful in detecting abnormal manifestations around ganciclovir implants and is a valuable tool to assess the changes of the sclerotomy sites of the sustained released intraocular devices.

Ocular and systemic factors relevant to diabetic keratoepitheliopathy.

PURPOSE: This study examines the contribution of ocular and systemic factors to diabetic keratoepitheliopathy. METHODS: The presence and severity of keratoepitheliopathy was investigated in 114 eyes of patients with diabetes and 59 eyes of patients without diabetes. The ocular factors examined were the status of the lipid layer of the tear fluid assessed with the specular reflection video-recording system, corneal sensitivity using the Cochet-Bonnet method, tear volume by the cotton thread test, tear film stability by tear breakup time, and grade of diabetic retinopathy. The systemic factors examined included patient age, hemoglobin A1c value, and duration of diabetes mellitus. Multivariate regression analysis was performed to assess the factors related to keratoepitheliopathy. RESULTS: The incidence of keratoepitheliopathy was 22.8% and 8.5% in patients with and without diabetes, respectively. Ocular measures, such as nonuniformity of tear lipid layer, corneal sensitivity, and tear breakup time, were significantly worse in patients with diabetes than in patients without diabetes ( p < 0.05). Multivariate regression analysis showed that the status of the tear lipid layer was significantly relevant to diabetic keratoepitheliopathy ( p < 0.05). CONCLUSION: Qualitative abnormalities in tear secretion seem relevant to the development of diabetic keratoepitheliopathy. The tear lipid layer interference pattern may yield useful information for the elucidation of the mechanism and treatment of diabetic keratoepitheliopathy.

Rapid detection and typing of oculopathogenic strain of subgenus D adenoviruses by fiber-based PCR and restriction enzyme analysis.

PURPOSE: To develop a new detection and typing method of oculopathogenic strains of subgenus D adenoviruses directly from conjunctival scrapings by a combination of polymerase chain reaction (PCR) and restriction enzyme analysis (REA). METHODS: A new PCR method using primer pairs of AF2/AR2, which are specific for the fiber genes, were developed to amplify 1150-bp products from nine oculopathogenic prototypes of subgenus D adenoviruses. Amplicons were cleaved with three restriction enzymes: DdeI, HinfI, and RsaI. Clinical specimens of 102 conjunctival scrapings were also evaluated by this PCR method. Restriction patterns of prototypes were used for the typing of clinical samples. Detection limit was determined by the PCR amplification of a known amount of purified adenovirus serotype 8 DNA. RESULTS: A novel PCR method based on the fiber genes allowed the amplification of nine oculopathogenic serotypes of subgenus D (Ad8, Ad9, Ad15, Ad17, Ad19, Ad22, Ad28, Ad37, and Ad39). As little as 38.4 fg of adenovirus type 8 could be detected by this method. Positive results were obtained from 48 of 102 samples (47%) by both hexon- and fiber-based PCR, whereas only 29 of 102 (28.4%) yielded positive results by culture isolation/neutralization test (NT). All positive specimens (29 samples) of culture isolation and PCR-RFLP methods showed positive results by our new fiber-based PCR method, and no positive products were detected from other subgenus of adenovirus or nonadenoviral DNA. CONCLUSIONS: A newly developed fiber-based PCR-REA method for the detection and typing of adenoviruses is faster than any former PCR methods. This all-in-1-day detection and typing method will be quite useful to the rapid diagnosis of subgenus D adenovirus infection.

A case of multiple sclerosis with granulomatous uveitis in Japan--use of the antilipoarabinomannan (LAM)-B test in differential diagnosis.

PURPOSE: To report a patient with multiple sclerosis and associated with granulomatous uveitis, and how anti-lipoarabinomannan (LAM)-B antibody can play a key role in differential diagnosis. METHODS: Case report. RESULTS: A 35-year-old Japanese woman with multiple sclerosis, diagnosed 3 years ago, presented with blurred vision in her left eye. Ophthalmological examinations revealed granulomatous iridocyclitis in her left eye and retinal periphlebitis in both eyes. The diagnosis of tuberculosis was suspected because of a positive tuberculin skin test. However, a further examination by an anti-LAM-B antibody test excluded active tuberculosis. Her clinical findings were thought most likely to be caused by multiple sclerosis and treated with corticosteroids. CONCLUSION: We should consider the possibility of multiple sclerosis as the underlying origin in patients with granulomatous uveitis. A measurement of anti-LAM-B antibody titer may be useful in the differential diagnosis of granulomatous uveitis.

Glycemic control and lens transparency in patients with type 1 diabetes mellitus.

PURPOSE: To assess quantitatively the cumulative effect of hyperglycemia on lens transparency in patients with juvenile type 1 diabetes mellitus. METHODS: Subjects were 30 patients (30 eyes) with type 1 diabetes mellitus who had well-documented records on the duration of diabetes mellitus and condition of glycemic control from the onset. They were 35 years of age or younger (mean, 26.0 years), had a history of type 1 diabetes mellitus at least 5 years (mean, 8.4 years), had corrected visual acuity of 20/20 or better, and showed no clinically apparent cataract on slit-lamp examination. Twenty-one eyes of 21 subjects served as age-matched normal controls. They were 35 years of age or younger (mean, 25.7 years), had no diabetes mellitus, had corrected visual acuity of 20/20 or better, and showed no signs of cataract on slit-lamp examination. The degree of lens opacity was quantified using the anterior eye segment analysis system based on the Scheimpflug principle. An index was created to represent the cumulative effect of long-term glycemic control (hyperglycemic accumulation) by multiplying the average hemoglobin A(1c) value and the number of months from the onset. RESULTS: The patients with diabetes mellitus exhibited significantly greater degree of lens opacity than the normal controls (P =.017, Mann-Whitney U-test). Among the patients with diabetes mellitus, the lens opacity was greater in eyes with retinopathy than those without retinopathy (P =.011). Multiple regression analysis revealed that only the index of hyperglycemic accumulation significantly correlated with the degree of lens opacity (P =.042). CONCLUSION: Accumulated effect of hyperglycemia is related to the lens transparency in patients with diabetes.

Anterior capsular contraction after cataract surgery in eyes of diabetic patients.

AIM: To investigate change in the area of anterior capsular opening (ACO) after cataract surgery and its relation to the degree of postoperative anterior inflammation in patients with diabetes mellitus (DM). METHODS: 31 eyes of 31 patients with DM and 30 eyes of 30 normal controls scheduled to undergo cataract surgery were examined prospectively. The area of ACO was measured with an anterior eye segment analysis system (EAS-1000) on the day following surgery and 3, 6, and 12 months after surgery. Comparative analyses were made on the area of ACO relative to the presence of DM and diabetic retinopathy (DR). The percentage reduction of area of ACO was calculated from values 1 day and 12 months after surgery, and multiple regression analysis was performed on the presence of DM, patient age, ACO area on the first postoperative day, and aqueous flare intensity 1 day and 12 months after surgery. RESULTS: The area was significantly smaller in the DM group at 3 (p=0.015, Student's t test), 6 (p=0.011), and 12 (p=0.010) months postoperatively. Patients having DR showed significantly smaller ACO area than the non-DR group 3 (p=0.039), 6 (p=0.033), and 12 (p=0.028) months after surgery. Multiple regression analysis revealed that presence of DM (p=0.003) and aqueous flare intensity 12 months after surgery (p=0.039) significantly correlated with the percentage reduction of area of ACO. Age, ACO area at 1 day postoperatively, and aqueous flare intensity immediately after surgery were not relevant to ACO contraction. CONCLUSIONS: Anterior capsular contraction after cataract surgery was greater in eyes of DM patients, especially in those with DR and increased permeability of the blood-aqueous barrier.

An ocular cat-scratch disease patient positive for cytoplasmic anti-neutrophil cytoplasmic antibody.

BACKGROUND: We report a case of ocular cat-scratch disease with permanent vision reduction in a patient who was cytoplasmic anti-neutrophil cytoplasmic antibody (C-ANCA) positive. METHODS: Case report and review of the literature. RESULTS: While taking steroids and antibiotics, a 52-year-old man with uveitis associated with cat-scratch disease developed retinal vein occlusion and a macular exudate. His final visual acuity was poor because of residual macular degeneration and optic atrophy. Serum C-ANCA increased and decreased in parallel with ocular inflammatory activity. CONCLUSION: C-ANCA is an indicator of vasculitis and may be useful as an indicator of severe cat-scratch disease.

Optic disk pallor and retinal atrophy in Sotos syndrome (cerebral gigantism).

PURPOSE: To report a case of Sotos syndrome (cerebral gigantism) with megalophthalmos, optic disk pallor, and retinal atrophy. METHODS: Case report. RESULTS: A 22-year-old man was diagnosed with Sotos syndrome with optic atrophy. His corneal diameters were 13 mm horizontally, and his optic disks were pale. His retinal vessels were attenuate in diameter, and small white spots were found on the retina. The results of a Goldmann visual field test were normal. His visually evoked potential to flash stimuli showed extended latent times and normal amplitudes. Keratometry was 40.5 diopters (8.33 mm) in both eyes. The axial length was 25.9 mm in the right eye and 25.4 mm in the left eye. CONCLUSION: Sotos syndrome may be associated with optic disk pallor and retinal atrophy.

Bilateral choroidal metastases secondary to uterocervical carcinoma of the squamous cell type.

PURPOSE: To report a patient with bilateral choroidal metastases secondary to uterocervical carcinoma of the squamous cell type. METHODS: Case report. RESULTS: A 55-year-old woman complained of visual field loss and decreasing vision. Seven months earlier, uterocervical carcinoma of the squamous cell type was diagnosed and treated with chemotherapy and irradiation. Serous retinal detachment and choroidal masses were present in both eyes. Retinal detachment was lessened in both eyes after radiotherapy. The patient died of respiratory insufficiency 3 months after the appearance of choroidal metastases. At autopsy, there was no second cancer to cause the choroidal metastases. Tumor embolization was present in the choriocapillaries. CONCLUSION: Choroidal metastasis may develop from hematogenous spread of uterocervical squamous cell carcinoma.

Influence of rapid glycemic control on lens opacity in patients with diabetes mellitus.

PURPOSE: To report the influence of rapid glycemic control on lens opacity in patients with diabetes mellitus. METHODS: In a prospective study, nine patients with adult onset diabetes mellitus and glycosylated hemoglobin values over 9% were divided into two groups, rapid glycemic control and slow glycemic control groups, based on the time course of glycosylated hemoglobin values after the initiation of glycemic control. The lens thickness and opacity were measured using the anterior eye segment analysis system. RESULTS: One week after onset of treatment, the lens in rapid glycemic control group became significantly thicker than in pretreatment, but returned to the baseline level at the subsequent measurement points. The lens opacity index in the rapid glycemic control group increased significantly (P <.01, paired t test) 4 months after the glycemic control, which persisted throughout the 1-year study period. The lens thickness and opacity in the slow glycemic control group did not change significantly. CONCLUSION: It was suggested that rapid glycemic control can induce an irreversible increase in lens opacification.