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Shin Asami, Masahiko Sugimoto, Hideyuki Tsukitome, Kumiko Kato, Hisashi Matsubara, Mineo Kondo Department of Ophthalmology, Mie University Graduate School of Medicine, Tsu, Mie, JapanCorrespondence: Masahiko Sugimoto, Department of Ophthalmology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan, Tel +81-59-231-5027, Fax +81-59-231-3036, Email sugmochi@clin.medic.mie-u.ac.jpPurpose: To compare the therapeutic effects of anti-vascular endothelial growth factor (anti-VEGF) agents in eyes with macular edema associated with branch retinal vein occlusion (BRVO-ME) with glaucoma to those without glaucoma.Patients and Methods: This retrospective study was conducted using the medical records of Mie University Hospital from 2013 to 2017. Patients were recruited if they had received anti-VEGF agents for BRVO-ME treatment and included 30 patients (30 eyes) without glaucoma (G[-] group) and 27 patients (27 eyes) with glaucoma (G[+] group). The central retinal thickness (CRT) and best-corrected visual acuity (BCVA) at 3 months after a single injection of anti-VEGF agents were compared between the two groups.Results: Before treatment, the mean±standard deviation of the CRT was 514.2± 117.3 μm for the G[-] group, which was not significantly different from that for the G[+] group (533.4± 171.4 μm). The CRT in the G[-] and G[+] groups significantly reduced to 321.1± 114.6 μm and 347.8± 134.7 μm, respectively, at 1 month after the injection and to 360.4± 159.5 μm and 352.4± 151.9 μm, respectively, at 3 months after the injection (P< 0.01 for each group). The difference in the degree of CRT reduction between the two groups was not significant. Before treatment, the BCVA was 0.42± 0.32 logMAR units in the G[-] group and 0.57± 0.33 logMAR units in the G[+] group, showing no significant difference. The BCVA in the G[-] and G[+] groups improved significantly to 0.27± 0.26 logMAR units and 0.34± 0.42 logMAR units, respectively, at 1 month, and to 0.18± 0.20 logMAR units and 0.39± 0.34 logMAR units, respectively, at 3 months (P< 0.01). The BCVA in the G[-] group was significantly better than that in the G[+] group at 3 months (P=0.02).Conclusion: The therapeutic response of anti-VEGF agents for BRVO-ME is affected by the presence of glaucoma.Keywords: anti-vascular endothelial growth factor treatment, branch retinal vein occlusion, glaucoma, macular edema

To determine the characteristics and cause of the increase in the amplitude of flicker electroretinography (ERG) after cataract surgery.Prospective, observational clinical study.Thirty patients who underwent cataract surgery.Flicker ERGs were recorded with the RETeval system without mydriasis. The central macular thickness (CMT) was measured by OCT and the aqueous flare value (AFV) by laser flare-cell photometry. These examinations were performed before surgery and 1 day, 1 week, 1 month, 2 months, and 3 months after surgery. Linear regression analysis through the origin was used to compare the correlations between the relative changes in flicker ERG amplitudes and the changes in the CMT and AFV at different times after the surgery.The amplitude of flicker ERGs, CMT, and AFV.The mean amplitude of flicker ERGs increased significantly by 31% at 1 week after surgery (These results suggest that the increase in the amplitude of flicker ERGs after cataract surgery is a transient phenomenon that has a peak at 1 week after surgery. The increase of flicker ERG amplitude was associated with measures that are frequently used to evaluate postoperative inflammation.Proprietary or commercial disclosure may be found after the references.

Aims/Introduction To determine the current clinical preferences of anti‐vascular endothelial growth factor (VEGF) treatment protocols for diabetic macular edema (DME) in Japan. Materials and Methods This was a descriptive cross‐sectional study. Answers to a questionnaire consisting of 16 questions were obtained from 176 of 278 (63.3%) surveyed ophthalmologists. Results The results showed that 81.2% preferred intravitreal injections of anti‐VEGF antibodies as the first‐line therapy. The most important indicators for beginning anti‐VEGF therapy were: the best‐corrected visual acuity in 44.3% and the retinal thickness in 30.7%. In the loading phase, 53.4% preferred a single injection, and in the maintenance phase, 75.0% preferred the pro re nata regimen. Financial limitation (85.8%) was reported as the most important difficulty in the treatment. For combination therapy with anti‐VEGF treatment, panretinal photocoagulation, focal photocoagulations and a sub‐Tenon steroid injection were preferred. The contraindications for anti‐VEGF therapy were: prior cerebral infarction (72.7%). Regarding the use of both approved anti‐VEGF agents in Japan, ranibizumab and aflibercept, 39.8% doctors used them appropriately. Conclusions Our results present the current clinical preferences of anti‐VEGF treatment for DME in Japan. The best‐corrected visual acuity and the retinal thickness are important indicators to institute this therapy. The majority of the ophthalmologists use anti‐VEGF treatment as first‐line therapy and prefer the 1 + pro re nata regimen.

The aim of this study was to determine the prevalence and progression of diabetic retinopathy (DR) with hyperglycemic disorders during pregnancy (HDPs) in Japan between 2013 and 2018 using two cohorts. The patients with HDPs were classified as those with pre-existing DM (pexD), gestational DM (GDM), and overt DM (ODM). Cohort 1 was obtained from the health claims database whose diseases were classified by the International Classification of Diseases-10. Cohort 2 was derived from a retrospective, multicenter analysis of the medical records of 225 patients from 10 ophthalmological institutions. In Cohort 1, there were 5268 patients with an HDP prevalence of 8.4%. Among them, 73 of 1139 patients had pexD (6.4%) and 61 of 4129 patients with GDM (1.5%) had DR; the overall prevalence of DR was 2.5%. In Cohort 2, 36 of 225 patients (16.0%) had DR, and 149 patients were followed at the early and late stages of pregnancy. Moreover, 10 of the 102 patients with pexD (9.8%) and two of five patients with ODM (40.0%) had a progression of DR. In conclusion, the prevalence and progression of DR in patients with pexD is lower than previously reported. More attention should be given to pexD and ODM.

To determine the annual incidence of visual impairment in a Japanese population during a 10-year period. We examined the physical disability certificates issued yearly between 2004 and 2013 in Mie prefecture, Japan. During this period 2468 visually impaired people were registered under the newly defined Act on Welfare of the Physically Disabled Persons’ criteria. The age, sex distribution, and causes of visual impairment were determined from the certificates. The major causes of visual impairment during the ten-year period were glaucoma (23.3%), diabetic retinopathy (17.3%), retinitis pigmentosa (12.2%), macular degeneration (9.0%), chorioretinal degeneration or high myopia (7.4%), optic atrophy (5.8%), stroke or brain tumor (5.4%) and cataracts (3.7%). The incidence of glaucoma was significantly higher throughout the period (2004–2013), and that of diabetic retinopathy was lower between 2007 and 2013. The incidence of retinitis pigmentosa did not change significantly during the 10-year period. The incidence of macular degeneration tended to increase between 2004 and 2007, but it decreased significantly between 2007 and 2013. The results indicate that in Japan, the rates of the major causes of visual impairment altered in the most recent 10-year period reflecting the recent changes in the social background and advances in ocular and systemic treatment.

Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are widely used to treat neovascular age-related macular degeneration (nAMD). Although these treatments are effective, multiple injections have recently been recommended to ensure that there is a good long-term prognosis. However, sustained intraocular pressure (IOP) elevations have been reported to develop after multiple injections of anti-VEGF agents. We present our findings of a case of uncontrolled and persistent IOP elevation after switching from intravitreal ranibizumab injections to intravitreal aflibercept injections. A 74-year-old Japanese man without a history of glaucoma underwent 22 ranibizumab injections for nAMD and suddenly developed an elevated IOP after the 22nd injection. Although the subsequent medical treatment led to normalization of his IOP, the subretinal fluid under the central fovea remained even after the 25th injection of ranibizumab. Thus, ranibizumab treatment was switched to bimonthly intravitreal aflibercept injections in conjunction with glaucoma medications. His IOP recovered to within the normal range; however, after the 11th aflibercept injection, there was a sudden elevation of his IOP in spite of the continued glaucoma medications. Due to this sustained IOP elevation, his aflibercept injections were suspended for 16 weeks. Because his IOP could not be normalized by a full glaucoma medication regimen, the patient underwent trabeculotomy, which resulted in a lowering of the IOP to normal levels. We conclude that patients who receive serial intravitreal injections of anti-VEGF agents need to be closely monitored because severe and sustained ocular hypertension can develop.

Intravitreale Injektionen mit Wirkstoffen gegen den vaskulären endothelialen Wachstumsfaktor (VEGF) sind eine gängige Behandlungsmaßnahme bei neovaskulärer altersbedingter Makuladegeneration (nAMD). Obwohl diese Behandlungen sehr effektiv sind, sind in jüngster Zeit multiple Injektionen empfohlen worden, um auch langfristig für eine günstige Prognose zu sorgen. Es liegen jedoch Berichte über einen Anstieg des Augeninnendrucks (AID) nach multiplen Injektionen mit Anti-VEGF-Wirkstoffen vor. Wir präsentieren hier einen Fall von unkontrollierter persistierender AID-Erhöhung nach der Umstellung von intravitrealen Ranibizumab- auf Aflibercept-Injektionen. Bei einem 74-jährigen japanischen Mann ohne Glaukom in der Vorgeschichte, der zur Behandlung einer nAMD 22 Ranibizumab-Injektionen erhalten hatte, stieg nach der 22. Injektion der AID unvermittelt an. Die daraufhin eingeleitete medikamentöse Therapie führte zwar zur Normalisierung des AID, doch unterhalb der Fovea centralis lag auch nach der 25. Ranibizumab-Injektion noch subretinale Flüssigkeit vor. Daher erfolgte eine Umstellung der Therapie von Ranibizumab auf 2-monatliche intravitreale Injektionen mit Aflibercept, begleitet von Glaukom-Medikamenten. Der AID kehrte daraufhin in den Normalbereich zurück. Nach der 11. Aflibercept-Injektion kam es trotz der weiterhin angewandten Glaukom-Medikamente wiederum zu einem plötzlichen AID-Anstieg. Aufgrund dieser anhaltenden AID-Erhöhung wurden die Aflibercept-Injektionen für 16 Wochen ausgesetzt. Da es auch mit einem umfassenden Glaukom-Medikationsschema nicht gelang, den AID zu normalisieren, unterzog sich der Patient einer Trabekulotomie, die zur Rückkehr des AID in den Normalbereich führte. Wir gelangen zu der Schlussfolgerung, dass Patienten, die serielle intravitreale Injektionen eines Anti-VEGF-Wirkstoffs erhalten, aufmerksam überwacht werden müssen, da sich eine schwere und anhaltende okuläre Hypertension entwickeln kann.

Purpose To study changes in the opening angle of the optic nerve and the angle of the ocular orbit with increasing age in normal Japanese children. Methods We studied 147 normal children (aged 6 months to 18 years) who had undergone CT as a diagnostic procedure. Measurements were performed on axial CT images that included the entire optic nerve of both eyes. The opening angle of the optic nerve was defined as the angle formed by the intersection of a line running through the left optic nerve and a vertical line passing through the centre of the nose. The opening angle of the orbit was defined as the angle formed by the intersection of a line running tangentially along the deep lateral wall of the left orbit and a vertical line passing through the centre of the nose. The relationship between age and these opening angles was analysed by regression analysis. Results The correlation between age and opening angle of the optic nerve was not significant. In contrast, the opening angle of the orbit decreased relatively rapidly until about 2–3 years of age, and then it stabilised. The decrease in the opening angle of the orbit with increasing age was significant (p

We report a patient with frosted branch-like appearance retinal vasculitis associated with peripheral capillary nonperfusion and full-field electroretinographic changes. A 62-year-old man presented with sudden bilateral decreased vision accompanied by headaches. His best-corrected visual acuity was 0.01 in both eyes. Fundus examination and fluorescein angiography showed bilateral frosted branch-like appearance retinal vasculitis, and spectral-domain optical coherence tomography showed severe macular edema in both eyes. The cerebrospinal fluid analyses showed an increased lymphocyte count and protein levels. He was treated with systemic corticosteroid therapy, and his best-corrected visual acuity improved to 0.8 OD and 1.0 OS at 6 months after onset. However, fluorescein angiography showed a lack of capillary perfusion in the periphery, and the oscillatory potentials on full-field electroretinography were severely reduced in both eyes. These findings indicated extensive retinal ischemia and inner retinal dysfunction, and that fluorescein angiography and full-field electroretinograms can be useful during follow-up of eyes with frosted branch-like appearance retinal vasculitis.

Purpose To report the development of bilateral retinal detachment in a patient with Werner syndrome. Methods Retrospective chart review. A 44-year-old woman diagnosed with Werner syndrome developed bilateral retinal detachment. The fundus in both eyes showed patchy chorioretinal atrophy similar to that seen in high myopia, with the retinal detachment limited to the posterior pole. Two weeks after performing vitrectomy in the right eye, vitrectomy was performed in the left eye. Results After the surgeries, both retinas were reattached. During the surgeries, we observed an excessively liquefied vitreous and a posterior hyaloid membrane that was tightly attached to the retina. The retinal break was located along the superotemporal arcade and over an area of the patchy chorioretinal atrophy in both eyes. The chorioretinal atrophy and vitreous liquefaction appeared to be excessive for the patient's age and axial lengths (right: 26.66 mm, left: 27.04 mm). Conclusion Vitreoretinal changes found in this case might have been partially because of the premature aging associated with Werner syndrome.

To investigate genetic and clinical features of patients with Leber congenital amaurosis (LCA) caused by RPE65 mutations.Five Japanese families with LCA were recruited. We performed complete ophthalmic examinations, with optical coherence tomography, fundus autofluorescence imaging, and full-field electroretinography (ERG). Genetic analysis was performed with whole-exome sequencing analysis and Sanger sequencing.We identified RPE65 mutations in two unrelated LCA patients from two families. Case 1: A 5-month-old girl was diagnosed with LCA because of nystagmus, loss of vision and non-recordable ERG. She was the only one affected in her non-consanguineous family, and exhibited novel compound heterozygous RPE65 mutations (c.177CG, p.H59Q and c.183_184insT, p.D62X). Case 2: A 30-year-old woman, who had night blindness and poor ocular pursuit during the first year of life, exhibited severe retinal degeneration and non-recordable ERG. She was the only affected in her non-consanguineous family, and showed a homozygous RPE65 mutation (c.1543CT, p.R515W).By using whole-exome sequencing analysis, three RPE65 mutations were identified in two Japanese patients with LCA. This approach would be useful for identification of disease-causing mutations of LCA.

The purpose of this study was to determine the causes of visual impairment in Mie prefecture during a five-year period.The study was conducted between April 2004 and March 2009 in Mie Prefecture. 1,322 visually impaired people as defined by the Act on Welfare of Physically Disabled Persons were enrolled. We reviewed age, sex, causes of visual impairment, degree of disability and medical conditions according to their physical disability certificate.The four major causes of visual impairment were glaucoma (20.3%), diabetic retinopathy (18.9%), retinitis pigmentosa (12.2%), and macular degeneration (9.1%), followed by chorioretinal degeneration, stroke or brain tumor, optic atrophy, and cataract. The average ages of the four major causes were glaucoma (77.1 years), diabetic retinopathy (65.1 years), retinitis pigmentosa (62.5 years) and macular degeneration (77.7 years).The most common cause of visual impairment in Mie prefecture was glaucoma. The four major causes in Mie prefecture were the same as the results of the nation-wide investigation reported in 2006.

A male neonate was delivered normally in the 38th week of gestation. The patient weighed 2730 g and was 48.8 cm long at birth. The Apgar score was 10. He was referred to the Department of Ophthalmology, Mie University Hospital by a local ophthalmologist for megalophthalmos and elevated IOP in both eyes (OU) on the 10th day after birth. He had no significant family history. Family history revealed that the mother of the patient was a 20-year-old primipara receiving systemic steroid therapy for chronic nephritis. Obstetric ultrasonography at 30 gestational weeks had revealed the neonate to have megalophthalmos OU. At 35 gestational weeks, the ocular axial length measurements OU were 23–25 mm (Fig. 1) and about 24 mm based on B-scan ultrasonography and magnetic resonance imaging (MRI) images (Fig. 2), respectively. A disproportion in volume between eye and orbit was noticed, but no other abnormal findings were detected on the images. An ophthalmic examination revealed diffuse corneal opacification and corneal edema OU; consequently, the fundus could not be observed. The horizontal corneal diameter was 14 mm in the right eye (OD) and 13 mm in the left eye (OS). The intraocular pressure on a Perkins hand-held applanation tonometer was 34 mmHg OD and 42 mmHg OS. The diagnosis was bilateral early-onset developmental glaucoma. On his 17th day of life, the patient underwent a trabeculotomy of about 120 dextent OU with a scleral flap at

Benzoyl peroxide (BzPO), a free-radical generator, has tumor-promoting activity. As a method for approaching the mechanism of tumor promoter function, the ability of oxidative DNA damage by BzPO was investigated by using (32)P-labeled DNA fragments obtained from the human p53 tumor suppressor gene and c-Ha-ras-1 protooncogene. BzPO induced piperidine-labile sites at the 5'-site guanine of GG and GGG sequences of double-stranded DNA in the presence of Cu(I), whereas the damage occurred at single guanine residues of single-stranded DNA. Both methional and dimethyl sulfoxide (DMSO) inhibited DNA damage induced by BzPO and Cu(I), but typical hydroxyl radical ((*)OH) scavengers, superoxide dismutase (SOD) and catalase, did not inhibit it. On the other hand, H(2)O(2) induced piperidine-labile sites at cytosine and thymine residues of double-stranded DNA in the presence of Cu(I). Phenylhydrazine, which is known to produce phenyl radicals, induced Cu(I)-dependent damage at thymine residues but not at guanine residues. These results suggest that the BzPO-derived reactive species causing DNA damage is different from (*)OH and phenyl radicals generated from benzoyloxyl radicals. BzPO/Cu(I) induced 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation in double-stranded DNA more effectively than that in single-stranded DNA. Furthermore, we observed that BzPO increased the amount of 8-oxodG in human cultured cells. Consequently, it is concluded that benzoyloxyl radicals generated by the reaction of BzPO with Cu(I) may oxidize the 5'-guanine of GG and GGG sequences in double-stranded DNA to lead to 8-oxodG formation and piperidine-labile guanine lesions, and the damage seems to be relevant to the tumor-promoting activity of BzPO.