Association study of genetic variants on chromosome 7q31 with susceptibility to normal tension glaucoma in a Japanese population.

The caveolin 1 to caveolin 2 (CAV1-CAV2) gene region on chromosome 7q31 has been reported to be associated with susceptibility to primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) in previous studies. We investigated whether genetic variants in the CAV1-CAV2 region are associated with NTG in Japanese patients. Two hundred and ninety-two Japanese patients with NTG and 352 Japanese healthy controls were recruited. We genotyped three single-nucleotide polymorphisms; that is, rs1052990, rs4236601, and rs7795356, in the CAV1-CAV2 gene region and assessed the allelic diversity among cases and controls. The frequency of the minor allele (G) of rs1052990 was significantly decreased in NTG cases compared with controls (P=0.014, OR=0.71), whereas NTG or POAG cases had a significantly higher frequency of the allele than controls in previous studies. Conversely, rs7795356 did not show any significant association with NTG cases, and rs4236601 was monomorphic in the Japanese study population. Our findings did not correspond with previous positive results, suggesting that CAV1-CAV2 variants studied in the present study are not important risk factors for NTG susceptibility in all populations. Further studies are needed to elucidate the possible contribution of the CAV1-CAV2 region to the development of glaucoma.

A remote operating slit lamp microscope system. Development and its utility in ophthalmologic examinations.

OBJECTIVES: To develop a remote-operating slit lamp microscope system (the remote slit lamp) as the core for highly specialized ophthalmology diagnoses, and to compare the utility of this system with the conventional slit lamp microscope system (the conventional slit lamp) in making a diagnosis. METHODS: The remote slit lamp system was developed. Three factors were evaluated in comparison to the conventional slit lamp. The ability to acquire skills was investigated using a task loading system among specialists and residents in ophthalmology. Participants repeated a task up to ten times and the time required for each task was analyzed. The consistency of the two systems in making a diagnosis was investigated using eyes of patients with ocular diseases as well as healthy volunteers. RESULTS: The remote slit lamp is composed of a patient's unit and ophthalmologist's unit connected by high-speed internet. The two units share images acquired by the slit lamp in addition to the images and voices of patients and ophthalmologists. Both ophthalmology specialists and residents could minimize the completion times after several trials. The remote slit lamp took more time than the conventional slit lamp. Both systems showed a high consistency in evaluations among eyes with healthy eyes or those with ocular diseases. CONCLUSIONS: The remote slit lamp has a similar diagnostic ability, but required more examination time in comparison to the conventional slit lamp. The currently developed remote slit lamp has the potential to be employed for tele-medicine purposes in the field of ophthalmology.

Investigation of the association between the GLC3A locus and normal tension glaucoma in Japanese patients by microsatellite analysis.

PURPOSE: To investigate whether the GLC3A locus harboring the CYP1B1 gene is associated with normal tension glaucoma (NTG) in Japanese patients. MATERIALS AND METHODS: One hundred forty-two Japanese patients with NTG and 101 Japanese healthy controls were recruited. Patients exhibiting a comparatively early onset were selected as this suggests that genetic factors may show stronger involvement. Genotyping and assessment of allelic diversity was performed on 13 highly polymorphic microsatellite markers in and around the GLC3A locus. RESULTS: There were decreased frequencies of the 444 allele of D2S0416i and the 258 allele of D2S0425i in cases compared to controls (P = 0.022 and P = 0.034, respectively). However, this statistical significance disappeared when corrected (Pc > 0.05). We did not find any significant association between the remaining 11 microsatellite markers, including D2S177, which may be associated with CYP1B1, and NTG (P > 0.05). CONCLUSIONS: Our study showed no association between the GLCA3 locus and NTG, suggesting that the CYP1B1 gene, which is reportedly involved in a range of glaucoma phenotypes, may not be an associated factor in the pathogenesis of NTG.

Microsatellite analysis of the GLC1B locus on chromosome 2 points to NCK2 as a new candidate gene for normal tension glaucoma.

AIMS: The aim of this study was to investigate the association between normal tension glaucoma and the candidate disease locus glaucoma 1, open angle, B (GLC1B) on chromosome 2. There are many reports describing the results of association or linkage studies for primary open angle glaucoma (POAG), with GLC1B as one of the loci associated with normal or moderately elevated intraocular pressure. However, there are few reports about the association of genes or defined genomic regions with normal tension glaucoma, which is the leading type of glaucoma in Japan. The GLC1B locus is hypothesized to be a causative region for normal tension glaucoma. METHODS: Genomic DNA was extracted from whole blood of normal tension glaucoma (n = 143) and healthy controls (n = 103) of Japanese origin. RESULTS: Fifteen microsatellite markers within and/or near to the GLC1B locus were genotyped, and their association with normal tension glaucoma was analysed. Two markers D2S2264 and D2S176 had significant positive associations. CONCLUSION: The D2S176 marker had the strongest significant association and it is located 24 kb from the nearest gene NCK2, which now becomes an important new candidate gene for future studies of its association with normal tension glaucoma.

A sequence change (Arg158Gln) in the leucine zipper-like motif region of the MYOC/TIGR protein.

The myocilin/trabecular meshwork-inducible glucocorticoid response (MYOC/TIGR) gene was identified as a gene that caused open angle glaucoma (OAG). Single-strand conformation polymorphism analysis and subsequent sequence analysis were performed for the MYOC/TIGR gene in 120 unrelated Japanese OAG patients with increased intraocular pressure (IOP), 116 unrelated OAG patients without increased IOP, and 106 unrelated control subjects without glaucoma. An Arg158Gln sequence change in the leucine zipper-like motif (LZM) region in the myosin-homology domain was found in 2 OAG patients with or without increased IOP, and in a 56-year-old control subject without glaucoma. This is the first report of missense sequence change in the LZM region of the MYOC/TIGR protein in subjects showing various phenotypes, including a control subject. These findings suggest that Arg158Gln in the LZM region is probably a rare nondisease-causing polymorphism, despite its important role in this region, because it was found in a control subject, although Arg158Gln was previously reported as a probable disease-causing mutation.

Analysis of myocilin gene mutations in Japanese patients with normal tension glaucoma and primary open-angle glaucoma.

The myocilin gene was identified as a gene (MYOC) that caused primary open-angle glaucoma (POAG). Although a normal tension glaucoma (NTG) patient with the myocilin gene mutation was previously reported, no study using large numbers of patients with NTG has been reported. Single-strand conformation polymorphism analysis and subsequent sequence analysis were performed for genotyping the myocilin gene in 114 unrelated Japanese patients with NTG. One hundred and nineteen patients with POAG and 100 control subjects without glaucoma were studied as reference subjects. Five amino acid sequence changes of the myocilin were identified: Arg46Stop (one NTG), Arg76Lys (four NTG, 10 POAG, seven control), Arg158Gln (one NTG, one POAG, one control) found in only Japanese, Asp208Glu (four NTG, three POAG, one control), Pro481Ser (one control). Pro481Ser was novel. Arg76Lys always occurred with 1-83 from G to A in the promoter as it was reported in Chinese. Although some Japanese patients with NTG had sequence changes of the myocilin gene, there were no apparent specific mutations in patients with NTG.

Pars plana filtration with multiple laser perforation of the uvea for neovascular glaucoma following proliferative diabetic retinopathy.

PURPOSE: To evaluate the effect of pars plana filtration with multiple laser perforation of the uvea in neovascular glaucoma patients following proliferative diabetic retinopathy. METHODS: In 18 eyes of 13 patients, after a fornix-based conjunctival incision, two 9 x 3 mm, thin, rectangular scleral flaps were created 3-6 mm posterior to the limbus. The remaining layers of sclera under each flap were removed. The exposed uvea was irradiated at a mean of 60.6 spots with an argon laser just to the point of perforation. After the posterior chamber fluid escaped, the flaps were sutured. RESULTS: The mean preoperative intraocular pressure (IOP) was 36.4 +/- 9.0 mm Hg. After an average follow-up of 16.6 +/- 5.9 months, the mean final postoperative IOP was 16.6 +/- 4.4 mm Hg. The postoperative IOP was below 21 mm Hg in 3 (16.7%) of the 18 eyes without medication, in 14 (77.8%) on anti-glaucoma eye drops, and in 16 (88. 9%) on anti-glaucoma eye drops and an oral carbonic anhydrase inhibitor. Snellen visual acuity improved by more than 2 lines in 7 of the 18 eyes, worsened by this amount in 3, and remained within baseline +/- 2 lines in 8. CONCLUSION: This procedure is an effective treatment for neovascular glaucoma patients following proliferative diabetic retinopathy.