Trabeculotomy ab interno with internal limiting membrane forceps for open-angle glaucoma.

PURPOSE: To describe a new technique to perform trabeculotomy ab interno on eyes with open-angle glaucoma (OAG). METHODS: This was a retrospective study. We inserted a 25-gauge forceps that is usually used for internal limiting membrane peeling into the anterior chamber, and grasped and pulled the inner wall of Schlemm's canal away from the canal. The inner wall of Schlemm's canal was stripped for about 100° to 120° in 26 eyes of 23 patients. The intraocular pressure (IOP) and number of glaucoma medications were recorded before, and 1 day, 1 week, 2 weeks, and 1, 3, 6, 10, 12, 15, 17, 19, 24, 27, 30, and 33 months after the surgery. The intra- and postoperative complications were recorded. RESULTS: The mean ± standard deviation of the preoperative IOP was 20.0 ± 6.8 mmHg with a range from 10 to 38 mmHg (n = 26). The IOP was significantly reduced (P < 0.05; paired t-tests) at 1 week, 2 weeks, and 1, 3, 6, 10, 12, 15, 17, 24, 19, 27, 30, and 33 months after the surgery. The mean preoperative number of glaucoma medications was significantly reduced (P < 0.001; paired t-tests) at 1 week, 2 weeks, and 1, 3, 6, 10, 12, 15, 17, 19, 24, 27, 30, and 33 months after the surgery. No vision-threatening complications were found in any of the cases, but there were blood clots in the anterior chamber postoperatively in 92.3 % of the cases. CONCLUSIONS: Trabeculotomy ab interno for OAG is effective but with some minor complications. A larger number of patients with longer follow-up periods are needed to determine the long-term effectiveness of this procedure.

Interleukin 1 beta promoter polymorphism is associated with keratoconus in a Japanese population.

PURPOSE: Polymorphisms in the interleukin 1 alpha (IL1A) and IL1B gene regions were previously associated with keratoconus in a Korean population. In the present study, we investigated whether the IL1A and IL1B polymorphisms are associated with keratoconus in a Japanese population. METHODS: A total of 169 Japanese patients with keratoconus and 390 Japanese healthy controls were recruited. We genotyped one IL1A single nucleotide polymorphism (SNP; rs2071376) and two IL1B SNPs (rs1143627 and rs16944) to compare the frequencies of alleles, genotypes, and haplotypes between cases and controls. RESULTS: Statistically significant association was observed for rs1143627 (-31 T>C) in the IL1B promoter region; the T allele of rs1143627 was associated with an increased risk of keratoconus (p=0.014, corrected p value [pc]=0.043, odds ratio=1.38). The C allele of rs16944 (-511 C>T) in the IL1B promoter region had a 1.33-fold increased risk of keratoconus, although this increase did not reach statistical significance (p=0.033, pc=0.098). The TT genotype of rs1143627 was weakly associated with an increased risk of keratoconus (p=0.033, pc=0.099, odds ratio=1.52). However, no significant differences were found in the allele and genotype frequencies between the cases and controls for rs2071376 in IL1A. Regarding haplotypic diversity, the haplotype created by the T allele of rs1143627 and C allele of rs16944 was associated with a 1.72-fold increased risk of keratoconus (p=4.0×10(-5), pc=1.6×10(-4)). CONCLUSIONS: Our results replicate associations reported recently in a Korean population. Thus, IL1B may play an important role in the development of keratoconus through genetic polymorphisms.

Staining internal limiting membrane with a mixture of BBG and sodium hyaluronate.

AIMS: To evaluate the intraoperative applicability and safety of a mixture of brilliant blue G and sodium hyaluronate (visco-BBG) for staining the inner limiting membrane (ILM). METHODS: A retrospective consecutive case series. Seventy-four eyes that had undergone ILM peeling were studied. During vitrectomy, ILM peeling with visco-BBG (visco-BBG group) was performed on 40 eyes; 12 with a macular hole (MH), 26 with an epimacular membrane (ERM) and 2 with a retinal detachment due to a MH (MHRD). ILM peeling with BBG dissolved in balanced salt solution (BSS-BBG group) was performed on 34 eyes; 9 with a MH, 23 with an ERM and 2 with a MHRD. The main outcome measures were the distribution of the dye within the vitreous cavity and the retinal sensitivity in the MH patients of the two groups by microperimetry. RESULTS: The visco-BBG was injected over the retina where the ILM was intended to be peeled, and it stained the ILM in all cases. It did not disperse throughout the vitreous cavity or into the subretinal space. The BSS-BBG dispersed throughout the vitreous cavity, and its distribution was difficult to control. The two solutions did not stain the epiretinal membranes or any residual posterior hyaloid membrane. The difference in the retinal sensitivity between the two patients with MH of two groups was not significant. No complications were found in the visco-BBG group, although an accidental retinal perforation was found in one eye of the BSS-BBG group. Transmission electron microscopy confirmed that the membrane peeled was the ILM. CONCLUSIONS: Visco-BBG can be a useful method to assist macular surgery and can overcome some of the disadvantages of conventional BBG solutions dissolved in BSS.

Genetic characterization and susceptibility for sarcoidosis in Japanese patients: risk factors of BTNL2 gene polymorphisms and HLA class II alleles.

PURPOSE: Sarcoidosis is a heterogeneous and multisystem granulomatous disorder. The etiology still is uncertain, but the disease currently is thought to be triggered by various genetic as well as environmental factors. Recently, an association between sarcoidosis and the butyrophilin-like 2 (BTNL2) gene located in close proximity to the HLA-DRB1 gene was reported. The purpose of our study was to verify the relationship between BTNL2 and HLA risk alleles for the susceptibility to sarcoidosis, and to assess whether the BTNL2 association is independent of the HLA risk alleles. METHODS: In our study, 11 single nucleotide polymorphisms (rs28362677, rs2076533, rs2076530, rs2076529, rs2294881, rs3763304, rs2076523, rs28362682, rs3806156, rs9268499, rs3763317), including the functional rs2076530 (G > A) of the BTNL2 gene, and HLA-DRB1 and -DQB1 alleles, were genotyped in 237 Japanese patients diagnosed with sarcoidosis and 287 healthy Japanese control subjects. RESULTS: In the patient group, the HLA-DRB1*08:03 (P = 6.15 × 10(-5), odds ratio [OR] = 2.43) and BTNL2 rs2076530_A (P = 6.90 × 10(-6), OR = 1.84) were associated with disease susceptibility. Upon stratification analysis in search for a synergistic effect given the extensive linkage disequilibrium between BTNL2 rs2076530_A and HLA-DRB1*08:03, our results suggested that the risk-bearing allele of these two loci interact negatively. No significant differences were observed in allele frequencies for alleles in patients with ocular and other systemic sarcoidosis. CONCLUSIONS: Our studies implicated that the HLA-DRB1 allele is a major contributing genetic factor in the development of sarcoidosis in Japan. However, further studies are needed to verify how HLA or BTNL2 alleles confer the disease phenotype, severity of sarcoidosis.

Treatment of pterygium by ligation and bevacizumab injection.

PURPOSE: To describe a technique for treating pterygium by combining a subpterygial injection of bevacizumab followed by pterygial ligation. METHODS: Bevacizumab (1.25 mg/0.05 mL) was injected into the base of pterygia in 4 patients, and the pterygial necks were ligated. RESULTS: The heads of the pterygia regressed and disappeared within 7 days after treatment. The bodies also partially regressed and well-defined vessels were not seen on the bodies; however, the concentration of microvessels was higher on the pterygial bodies than in the normal conjunctiva after 1 month. A recurrence was defined as fibrovascular growth of conjunctival tissue that extended beyond the limbus. No complications or recurrences were noted during the follow-up period. CONCLUSIONS: Although only 4 cases were studied, the uniform finding demonstrated that combined subpterygial bevacizumab injection and pterygial ligation is a potential effective procedure for removing pterygium.

Common variants in the COL4A4 gene confer susceptibility to lattice degeneration of the retina.

Lattice degeneration of the retina is a vitreoretinal disorder characterized by a visible fundus lesion predisposing the patient to retinal tears and detachment. The etiology of this degeneration is still uncertain, but it is likely that both genetic and environmental factors play important roles in its development. To identify genetic susceptibility regions for lattice degeneration of the retina, we performed a genome-wide association study (GWAS) using a dense panel of 23,465 microsatellite markers covering the entire human genome. This GWAS in a Japanese cohort (294 patients with lattice degeneration and 294 controls) led to the identification of one microsatellite locus, D2S0276i, in the collagen type IV alpha 4 (COL4A4) gene on chromosome 2q36.3. To validate the significance of this observation, we evaluated the D2S0276i region in the GWAS cohort and in an independent Japanese cohort (280 patients and 314 controls) using D2S0276i and 47 single nucleotide polymorphisms covering the region. The strong associations were observed in D2S0276i and rs7558081 in the COL4A4 gene (Pc = 5.8 × 10(-6), OR = 0.63 and Pc = 1.0 × 10(-5), OR = 0.69 in a total of 574 patients and 608 controls, respectively). Our findings suggest that variants in the COL4A4 gene may contribute to the development of lattice degeneration of the retina.

Immediate removal of posteriorly dislocated lens fragments through sclerocorneal incision during cataract surgery.

AIM: To describe a new method of removing dislocated nuclear fragments smaller than one-fourth the size of the lens nucleus through the sclerocorneal incision made for cataract surgery. METHODS: Dislocated lens nuclear fragments on the surface of the retina were removed from six eyes of six consecutive patients. An anterior vitreous cutter with a 27-gauge chandelier endoilluminator (Twinlight illumination) tied to its sleeve was inserted into the eye through the incision made for cataract surgery and used for core vitrectomy. A fragmatome with another 27-gauge chandelier endoilluminator (Twinlight illumination) fibre was used to grasp and move the larger dislocated nuclear fragments into the anterior chamber where they were divided and removed. RESULTS: All dislocated nuclear fragments were removed through the incision for cataract surgery, and a posterior chamber lens was implanted in each patient without major complications. CONCLUSIONS: The procedure can be used to remove dislocated lens nuclear fragments from the surface of the retina through the incision for cataract surgery. Neither a second surgery, which would require three ports, nor the body of instruments for vitreal surgery are needed with this procedure.

Lack of association between IL10 polymorphisms and sarcoidosis in Japanese patients.

PURPOSE: To investigate whether interleukin 10 (IL10) gene polymorphisms are associated with the development of sarcoidosis in Japanese patients. METHODS: Two hundred and eighty-eight Japanese sarcoidosis patients and 310 Japanese healthy controls were recruited. We genotyped 9 single-nucleotide polymorphisms in IL10 and assessed the allelic diversity between cases and controls. RESULTS: No significant differences in the frequency of IL10 alleles, genotypes, and haplotypes in the sarcoidosis cases compared to the controls were detected. CONCLUSIONS: Our results suggest that IL10 polymorphisms are not significantly related to the pathogenesis of sarcoidosis in the Japanese population.

Factors associated with enlargement of chorioretinal atrophy after intravitreal bevacizumab for myopic choroidal neovascularization.

PURPOSE: To determine the factors significantly associated with an enlargement of the area of a chorioretinal atrophy (ChRA) after intravitreal bevacizumab (IVB) to treat myopic choroidal neovascularization (mCNV). METHODS: The medical charts of 27 eyes with a mCNV that had received IVB were reviewed. The ophthalmic examinations included measurements of the best-corrected visual acuity, visual fields with the Humphrey 10-2 Field Analyzer, fluorescein angiography, and indocyanine green angiography. The area of the mCNV and the chorioretinal atrophy (ChRA) were measured on the FA images. RESULTS: Eyes with an enlargement of the ChRA had significantly larger mCNVs at the baseline, a greater reduction in the size of the mCNV, a higher incidence of subretinal hemorrhage, longer duration of follow-up, received more injections of IVB, and had a greater decrease of retinal sensitivity (P ≤ 0.041). Multiple regression analyses showed that the factors most significantly associated with an enlargement of the ChRA were the CNV size at baseline, the number of IVB injections, and the duration of the follow-up period (P < 0.0001). CONCLUSIONS: Our findings showed that eyes with a larger CNV at the baseline and longer follow-up period had a greater risk of developing a ChRA like non-treatment, even if IVB treatment was performed for mCNV.

Thermocautery for inferior conjunctivochalasis.

PURPOSE: To describe a thermocautery technique to treat symptomatic inferior conjunctivochalasis. METHODS: Thirty-nine eyes of 23 patients with symptomatic inferior conjunctivochalasis were treated with thermocautery. The mean age of the patients was 78.6 ± 5.4 years (±SD) with a range of 69-89 years. Patients with symptomatic inferior conjunctivochalasis were initially treated with topical medication, and the eyes that were unresponsive underwent a ligation test. We treated those eyes in which symptoms improved or disappeared during the ligation test. The redundant bulbar conjunctival tissue was grasped with smooth forceps and cauterized with the OPTEMP variable low temperature cauterizer until the redundant conjunctival tissue was gone. The mean follow-up period was 469.5 ± 234.6 days (range, 101-823 days). RESULTS: After the thermocautery, the symptoms disappeared in 36 of 39 eyes (92.3%) and improved in the remaining 3 eyes (7.7%). The conjunctival laxity disappeared in 36 of 39 eyes (92.3%) and improved in 3 eyes (7.7%). There were no recurrences of the conjunctival laxity during the follow-up period. CONCLUSIONS: Thermocautery is a simple and effective treatment for symptomatic inferior conjunctivochalasis.

Investigation of association between TLR9 gene polymorphisms and VKH in Japanese patients.

PURPOSE: Vogt-Koyanagi-Harada (VKH) disease is an autoimmune disorder affecting melanocytes in the skin, eyes, inner ear, and meninges. The Epstein-Barr virus and cytomegalovirus (CMV) antigen have been hypothesized as possible triggering factors for the disease. Toll-like receptors (TLRs) play an important role in the induction of defense mechanisms of the innate and adaptive immune responses to microbial pathogens. Among TLRs, TLR9 recognizes unmethylated 2'-deoxyribo (cytidine-phosphate guanosine)(CpG) DNA motifs that are frequently present in viruses and plays a central role in the host defense against viral infection. The aim of this study was to investigate whether TLR9 polymorphisms were associated with VKH in a Japanese population. METHODS: Ninety-four Japanese patients diagnosed with VKH and 125 healthy control subjects were recruited. Five single-nucleotide polymorphisms (SNPs: rs187084, rs5743836, rs352139, rs352140, rs5743845) in the TLR9 gene were genotyped, and allelic and phenotypic diversity was assessed between cases and control subjects. RESULTS: Strong linkage disequilibrium was observed among three SNPs (D' > 0.99), which were located in one haplotype block. Two SNPs (rs5743836 and rs5743845) were monopolymorphic in both cases and controls. No statistically significant association was observed for any of the SNPs between cases and controls. CONCLUSION: Three SNPs in the TLR9 gene were not significantly associated with susceptibility to VKH.

Investigation of the association between SLC1A3 gene polymorphisms and normal tension glaucoma.

PURPOSE: To investigate whether the solute carrier family 1, member 3 (SLC1A3) gene, which encodes the glutamate aspartate transporter, is associated with normal tension glaucoma (NTG) in Japanese patients. METHODS: Two hundred and ninety-five Japanese patients with NTG and 518 Japanese healthy controls were recruited. Patients exhibiting comparatively early NTG onset were selected because early onset suggests that genetic factors may show stronger involvement. We genotyped 5 single-nucleotide polymorphisms (SNPs) in SLC1A3 and assessed the allelic and genotypic diversity among cases and controls. RESULTS: There were no statistically significant differences in the frequency of SLC1A3 alleles and genotypes between cases and controls. CONCLUSIONS: Our study showed no association between SLC1A3 and NTG, suggesting that the SLC1A3 gene may not be an associated factor in NTG pathogenesis.

Association analysis of Toll-like receptor 7 gene polymorphisms and Behçet's disease in Japanese patients.

Action of Toll-like receptors (TLRs) is deeply associated with defense mechanisms of the innate and adaptive immune responses to microbial pathogens. There have been reports of genetic polymorphisms within the TLR7 gene being closely related to a variety of inflammatory and infectious diseases. Behçet's disease (BD) is an autoinflammatory disease, and the pathogenesis has yet to be fully discovered. We investigated whether polymorphisms of Toll-like receptor 7 (TLR7) are associated with BD by analyzing the frequency of eight single nucleotide polymorphisms (SNPs) within 200 Japanese BD patients and 102 randomized controls. We genotyped nine SNPs in the TLR7 gene and assessed the allele/genotype diversity between cases and controls for all SNPs. In all eight SNPs, statistically significant differences were not observed between cases and controls.

Investigation of the association between Toll-like receptor 2 gene polymorphisms and Behçet's disease in Japanese patients.

Behçet's disease (BD) is a chronic systemic inflammatory disorder characterized by recurrent ocular symptoms, oral and genital ulcers, and skin lesions. The etiology of BD is still uncertain, but genetic and environmental factors likely both play an important role in BD development. In the present study, we investigated whether polymorphisms of Toll-like receptor 2 (TLR2), previously reported to recognize BD candidate antigens, are associated with BD. Two hundred Japanese patients with BD and 128 Japanese healthy controls were recruited. We genotyped five single-nucleotide polymorphisms (SNPs) in the TLR2 gene and assessed the allele/genotype diversity between cases and controls for all SNPs. No significant differences in the frequency of TLR2 alleles, genotypes, and haplotypes in the BD cases were detected compared with the controls. These data indicate that TLR2 polymorphisms do not play an important role in the development of BD.