Tomoko Yokoyama

High frequency of open-angle glaucoma in Japanese patients with Alzheimer's disease

The clinical and genetic relationships between Alzheimers disease (AD) and glaucoma remain obscure. The aim of this study was to determine the prevalence of open-angle glaucoma (OAG) in patients with AD and whether the apolipoprotein E (APOE) 4 allele is associated with AD, with or without OAG, in Japanese. The groups consisted of 172 patients with the diagnostic criteria of AD and 176 age-matched controls. Ophthalmic examinations were conducted, and genomic analysis was performed by PCR and digestion of products with an enzyme. OAG was found in 41 (23.8%) of the AD patients, which was a significantly (p = 0.0002) higher prevalence than that in the controls (9.9%). Furthermore, there was no significant difference between intraocular pressures (IOPs) in AD patients with OAG and without OAG. The percentage of AD patients who carried an APOE epsilon4 allele (29.5%) was significantly (p = 0.0007) higher than that of the controls (9.1%). However, the percentage of AD patients with OAG who carried an APOE epsilon4 allele (35.7%) was not significantly different than that of AD patients without OAG (27.7%, p = 0.42). In summary, the prevalence of OAG is high in Japanese patients with AD, suggesting that common factors other than APOE may contribute to the two diseases.

Twenty-four-hour ocular hypotensive effects of 0.0015% tafluprost and 0.005% latanoprost in healthy subjects

PurposeTo compare the intraocular pressure (IOP) reduction over 24 h achieved with tafluprost (0.0015%) with that achieved with latanoprost (0.005%).MethodsTwenty-seven healthy volunteers were studied. After a 24-h IOP baseline measurement was taken, one ophthalmic solution was applied to the right eye daily for 7 days. The drug was then withdrawn for 2 weeks. The other agent was then applied to the left eye in the same manner. IOP was measured every 3 h for 24 h on the seventh day of treatment.ResultsThe 24-h IOP after 7 days’ treatment with latanoprost decreased from 11.5 mmHg at baseline to 9.7 mmHg (−1.8 mmHg) and that with tafluprost from 11.8 to 9.8 mmHg (−1.9 mmHg). Tafluprost was statistically more effective after 24 h (P = 0.007; paired t test). The number of subjects with a 24-h mean IOP reduction of <10% was 8/27 (29.6%) with latanoprost versus 4/27 (14.8%) with tafluprost. The incidence of conjunctival hyperemia with latanoprost was 4/27 (14.8%) and that with tafluprost was 8/27 (29.6%).ConclusionThe overall efficacies of the two agents were not different, but tafluprost was associated with a greater reduction in IOP at 24 h after administration. Tafluprost showed a higher rate of conjunctival hyperemia.

Prevalence of glaucoma in adults with Down's syndrome.

PurposeTo compare the prevalence of glaucoma in adults with Downs syndrome (DS) to that in non-DS control adults.MethodsTwenty-six patients (14 men and 12 women) with DS and 188 control subjects (105 men and 83 women) were studied. The mean age was 35.1 ± 6.9 (± SD) years in the DS group and 36.9 ± 5.2 years in the control group. There were no significant differences in age or sex distribution between the two groups. Glaucoma was diagnosed by two glaucoma specialists based on the optic disc findings obtained through dilated pupils.ResultsThe prevalence of patients with glaucoma in the DS group was 11.5%, significantly higher (P = 0.014) than that in the control group, 1.1%. There was no significant difference in intraocular pressure between glaucomatous eyes (12.2 ± 3.2 mmHg) and nonglaucomatous eyes (11.1 ± 4.1 mmHg) in the DS group (P = 0.465).ConclusionsThe prevalence of glaucoma in adult patients with DS was significantly higher than that in age-matched control subjects. Jpn J Ophthalmol 2006;50:274–276

Glaucoma in Atomic Bomb Survivors

Radiation has been associated with increases in noncancerous diseases. An effect of low-dose radiation on the prevalence of clinically detected glaucoma has not been previously reported. We therefore investigated the prevalence of glaucoma in A-bomb survivors and its possible association with radiation dose. A total of 1,589 people who participated in the clinical examination program for A-bomb survivors at the Radiation Effects Research Foundation (RERF) between October 2006 and September 2008 and who had reconstructed radiation doses, were recruited into this cross-sectional screening study. The prevalence of glaucoma and its dose-response relationship to A-bomb radiation were measured. Each subject underwent an initial screening consisting of an interview and ophthalmological examination. Questionable cases with any indication of ocular disease, including glaucoma, were referred to local hospitals for more comprehensive evaluation. A diagnosis of glaucoma was made based on specific optic disc appearance, perimetric results and other ocular findings. Of 1,589 eligible people, we detected 284 (17.9%) cases of glaucoma overall, including 36 (2.3%) cases of primary open-angle glaucoma with intraocular pressure levels greater than 21 mmHg, 226 (14.2%) cases of normal-tension glaucoma and 25 (1.6%) cases of primary angle-closure glaucoma. Seven glaucoma risk factors were examined as potential confounders but only two needed to be included in the final model. Binary regression using a generalized estimating equation method, with adjustment for gender, age, city, cataract surgery or diabetes mellitus, revealed an odds ratio at 1 Gy of 1.31 (95% confidence interval 1.11–1.53, P = 0.001) in the case of normal-tension glaucoma, but no association for other types of glaucoma. The prevalence of normal-tension glaucoma may increase with A-bomb radiation dose, but uncertainties associated with nonparticipation (59% participation) suggest caution in the interpretation of these results until they are confirmed by other studies.

Proteomic study of DBA/2J mice retina: Down-regulation of Integrin β7 correlated with retinal ganglion cell death

To identify and determine the function of the proteins associated with the death of retinal ganglion cells (RGCs) in DBA/2J mice, an animal model of glaucoma, retinas of DBA/2J mice, were analyzed by proteomics at 5‐, 7‐, and 11‐months‐of‐age. The proteins showing significant alterations were selected for identification by MS and 18 proteins were differentially expressed and the identified proteins included cell membrane receptors and proteins associated with intracellular signaling pathways. Among of identified proteins, the expression of Integrin β7 at 7‐months‐of‐age was decreased by about 89% of that at 5‐months‐of‐age. Integrin β7 was expressed in the RGCs. The effect of glutamate toxicity on the expression pattern of Integrin β7 in a RGC line was also investigated and the glutamate‐induced death of RGC was inhibited by the RNA knockdown of Integrin β7. Our data showed also that the expression of 18 proteins in the DBA/2J was significantly altered in DBA2 mice and down‐regulation of Integrin β7 may have a protective effect on glutamate‐induced death of RGCs.

Proteomics of Vitreous Fluid

Vitreous and serum samples were obtained from subjects with diabetic retinopathy (DR; 33 cases) and idiopathic macular hole (MH; 26 cases), at the time of pars plana vitrectomy. The expressed proteins were separated by 2D gel electrophoresis. Separated protein spots were then visualized by silver staining and analyzed by mass spectrometry. For the MH vitreous samples, more than 400 spots were detected on 2D gels, of which 78 spots were identified as 18 unique proteins, including pigment epithelium-derived factor (PEDF), prostaglandin-D2 synthase, plasma glutathione peroxidase, and interphotoreceptor retinoid-binding protein (IRBP), which were not identified in the corresponding serum samples. For the DR vitreous samples, more than 600 spots were detected on gels, and 141 spots were identified as 38 unique proteins, some of which were derived from serum. Enolase and catalase were identified among four detected spots; neither of them was found in MH vitreous or DR serum samples. The increased protein expression observed in DR vitreous samples may be due to barrier dysfunction and/or production in the eye.