Akiko Miyazawa

Polymorphisms in ARMS2 (LOC387715) and LOXL1 Genes in the Japanese With Age-Related Macular Degeneration

a t e a g The point of this is to say that we do not believe that evaluation of the posterior curvature, Descemet membrane stripping, and careful peripheral scraping is the ONLY way to make the tissue attach, but we do believe that these steps decrease the rate of detachment to less than 3%, not only in this setting, but also for our published series of hundreds of routine cases. We also have observed that thinner donor tissue has a greater propensity to conform to the variable curvature of the recipient bed. It may be that Mifflin and associates were using tissue thinner than prior reports of endothelial keratoplasty under PK and, because of this, had better conformation of their tissue to the posterior protuberances of the PK edge recipient beds, enhancing their adherence rate in this unique setting. In our series, by fitting the tissue between protuberances, we could use donor tissues of any thickness, without worrying about conforming to the recipient bed edges. We recommend that Mifflin and associates perform donor tissue thickness analysis when they submit their longer manuscript for peer review of their study. Finally, although adherence of the donor tissue is enhanced by the removal of interface fluid, we caution Mifflin and associates about the routine use of venting incisions to accomplish this. There is now a plethora of publications demonstrating the short-term and the longterm liabilities, such as infections, melting, and epithelial downgrowth, that can occur because of these incisions. We have used surface sweeping without venting incisions to evacuate interface fluid for essentially all of our 1300 cases over the past 11 years and have avoided these liabilities, yet retained the lowest dislocation rates in the world. Once again, we thank Mifflin and associates for their interest in our article, and we look forward to reading their expanded manuscript in the future.

A comparison of preservative-free diclofenac and preserved diclofenac eye drops after cataract surgery in patients with diabetic retinopathy.

PURPOSE The aim of this study was to compare the anti-inflammatory efficacy of preservative-free and preserved 0.1% diclofenac eye drops for the management of postoperative inflammation after cataract surgery in patients with nonproliferative diabetic retinopathy and in normal controls. METHODS Forty-two diabetic patients and 50 normal control patients who underwent small-incision phacoemulsification cataract surgery bilaterally received topical preservative-free diclofenac in 1 eye and preserved diclofenac in the other eye. The corrected distance visual acuity (CDVA) as determined by a logarithm of the minimum angle of resolution (logMAR) chart, intraocular pressure (IOP), foveal thickness (FT) using optical coherence tomography (OCT), and the anterior chamber flare (ACF) score measured with a laser flare cell meter were monitored for 12 weeks after surgery. RESULTS In the eyes with diabetic retinopathy, there were no significant differences in CDVA, IOP, FT, and ACF score between the right and left eyes at the initial exam. After cataract surgery, changes in CDVA, IOP, and FT were not influenced by the preservative in the diclofenac eye drops. In contrast, the ACF score in the eyes treated with preserved diclofenac showed slower recovery from postoperative inflammation than the eyes treated with preservative-free diclofenac. In the normal control eyes, similar but milder changes were observed in each of the clinical parameters. CONCLUSIONS Because preservative suppressed the anti-inflammatory efficacy of topical diclofenac after cataract surgery, preservative-free diclofenac may have an improved safety profile during postoperative treatment, especially in patients with diabetic retinopathy.

Mutation spectrum of the CYP1B1 gene for congenital glaucoma in the Japanese population

PurposeMutations of the CYP1B1 gene cause primary congenital glaucoma (PCG), Peters anomaly, and juvenile open-angle glaucoma (JOAG). The aim of this study was to determine the spectrum and role of the CYP1B1 gene in Japanese patients with PCG or JOAG.MethodsGenomic DNA was extracted from the leukocytes of 18 unrelated patients with PCG and 21 unrelated patients with JOAG. All of the patients developed high intraocular pressure (IOP) before the age of 35 years. One hundred unrelated healthy adults with normal IOP were examined in the same way. The three exons of the CYP1B1 gene were amplified by polymerase chain reaction and directly sequenced.ResultsMutational screening and sequence analyses of the CYP1B1 gene revealed four mutations in four patients with PCG: p.Asp192Val, c.4776insAT, p.Val364Met, and p.Asp430Glu. The first three mutations have been reported in other Japanese PCG patients, but Asp430Glu is a new mutation. No mutations were found in the CYP1B1 gene of the JOAG patients.ConclusionsPCG in approximately 20% of Japanese patients may be associated with CYP1B1 mutations, but JOAG is not. The three mutations p.Asp192Val, c.4776insAT, and p.Val364Met appear to be common in the Japanese population and might be useful in genetic screening for PCG.

Association of HK2 and NCK2 with normal tension glaucoma in the Japanese population.

Although family studies and genome-wide association studies have shown that genetic factors play a role in glaucoma, it has been difficult to identify the specific genetic variants involved. We tested 669 single nucleotide polymorphisms (SNPs) from the region of chromosome 2 that includes the GLC1B glaucoma locus for association with primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG) in the Japanese population. We performed a two-stage case-control study. The first cohort consisted of 123 POAG cases, 121 NTG cases and 120 controls: the second cohort consisted of 187 POAG cases, 286 NTG cases, and 271 controls. Out of six SNPs showing significant association with POAG in the first round screening, seven SNPs were tested in the second round. Rs678350 in the HK2 gene coding sequence showed significant allelic (p = 0.0027 in Stage Two, 2.7XE-4 in meta-analysis) association with POAG, and significant allelic (p = 4.7XE-4 in Stage Two, 1.0XE-5 in meta-analysis) association with NTG. Although alleles in the TMEM182 gene did not show significant association with glaucoma in the second round, subjects with the A/A allele in TMEM182 rs869833 showed worse visual field mean deviation (p = 0.01). Even though rs2033008 in the NCK2 gene coding sequence did not show significant association in the first round, it had previously shown association with NTG so it was tested for association with NTG in round 2 (p = 0.0053 in Stage Two). Immunohistochemistry showed that both HK2 and NCK2 are expressed in the retinal ganglion cell layer. Once multi-testing was taken into account, only HK2 showed significant association with POAG and NTG in Stage Two. Our data also support previous reports of NCK2 association with NTG, and raise questions about what role TMEM182 might play in phenotypic variability. Our data suggest that HK2 may play an important role in NTG in the Japanese population.

Pre-seasonal Treatment With Topical Olopatadine Suppresses the Clinical Symptoms of Seasonal Allergic Conjunctivitis

PURPOSE To evaluate the effectiveness of pre-seasonal treatment with topical olopatadine on the reduction of clinical symptoms of seasonal allergic conjunctivitis (SAC). DESIGN Prospective interventional case series. METHODS Eleven patients with SAC received topical olopatadine in one eye at least two weeks before the onset of allergy symptoms, and the other eye served as the control. After the onset of allergic conjunctivitis, both eyes were treated with topical olopatadine. Visual analogue scale (VAS), which evaluated the subjective symptoms of ocular allergy, and the tear levels of histamine and substance P were measured up to six weeks. RESULTS At the onset of allergy symptoms, the VAS score in the pretreatment eyes was statistically significantly lower than that in the control eyes. The VAS score in the control eyes decreased with time but did not decrease to the level seen in the pretreatment eyes until four weeks later. The tear level of substance P at the onset of allergy symptoms was significantly suppressed in the pretreatment eyes, while the level of histamine was not suppressed. Alteration of the VAS scores in the pretreatment eyes significantly correlated with the level of substance P, but not of histamine. CONCLUSIONS To suppress clinical symptoms in patients with SAC, pre-seasonal treatment with topical olopatadine is effective. The effectiveness of treatment correlates with the tear level of substance P.