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Purpose: To investigate the choroidal structures in the enhanced depth imaging optical coherence tomographic images in eyes with retinitis pigmentosa (RP) and to determine correlations between the choroidal structures and visual functions. Methods: The enhanced depth imaging optical coherence tomographic images of 100 eyes with typical RP and 60 age-, sex-, and axial length–matched normal eyes were binarized using ImageJ. The cross-sectional luminal and stromal areas of the inner and outer subfoveal choroid of 1,500-µm width were measured. The inner choroid included the choriocapillaris and medium vessel layer, and the outer choroid included the larger vessel layer. Results: In the inner choroid, the luminal area and the ratio of luminal/total choroidal area (L/C ratio) were significantly smaller in RP than in controls (P = 0.010, P < 0.001, respectively), whereas the stromal area was not significantly different (P = 0.114). The inner choroidal L/C ratio was significantly correlated with the best-corrected visual acuity, mean deviation, foveal sensitivity, width of the ellipsoid zone, and central foveal thickness in RP after adjusting for the axial length, age, and sex (all P < 0.005). Conclusion: The significant correlations between the inner choroidal structures and the visual functions and retinal structures indicate that the choroidal structures are altered in association with the progression of RP.

Bentonite-based engineered barrier materials transfer from unsaturated state as emplaced to saturated state after closure of deep geological disposal facilities for radioactive waste, while decrease in saturation could occur due to heat and gas generation from the wastes. Modelling for mechanical characteristics and water retention properties of unsaturated “bentonite-based engineered barrier materials” are indispensable to predict such important transient behavior. In this study the following characteristics are obtained based on controlled-suction oedometer or triaxial compression tests : i) swelling and shrinking caused by respectively wetting and drying, ii) consolidation under constant matric suctions, iii) shear strength depending on matric suction, iv) hysteresis of water retention. In addition, applicability of existing constitutive models such as Barcelona basic model, Komine’s model, vG model, and suction stress concept are discussed based on these results., Peer Reviewed, Postprint (published version)

Gen Miura, Takayuki Baba, Toshiyuki Oshitari, Shuichi Yamamoto Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan Purpose: The aim of this study is to determine the effect of pupil size of eyes with cataracts on the flicker electroretinograms (ERGs) elicited and recorded with the RETeval system.Patients and methods: Forty-one eyes of 41 patients (mean age, 76.5±7.3 years) that had grade 2 nuclear or cortical cataract without any other abnormalities were studied. Flicker ERGs were recorded before and after mydriatic drops instillation. The ERGs were elicited by the white light delivered at the frequency of 28.3 Hz and intensities of 2, 8, and 32 Td-s. The amplitudes and the implicit times of the flicker ERGs before and after mydriasis were compared.Results: There were no significant differences between the amplitudes before and after mydriasis (P=0.35, 2 Td-s; P=0.31, 8 Td-s; P=0.50, 32 Td-s). There were also no significant differences between the implicit times before and after mydriasis (P=0.86, 2 Td-s; P=0.98, 8 Td-s; P=0.95, 32 Td-s). The mean amplitudes and implicit times of the nuclear and cortical cataracts groups before the mydriasis were also not significantly different from those after mydriasis for all stimulus intensities.Conclusion: The lack of significant differences in the amplitudes and the implicit times of the flicker ERG of cataractous eyes before and after mydriasis indicated that the RETeval flicker ERGs in cataractous eyes is less affected by the pupil diameter. With our earlier study, it was assumed that the effect of cataracts on the RETeval flicker ERGs was due to the opacity of the crystalline lens, and the influence of the cataract would not be reduced or increased by mydriasis. Keywords: electroretinogram, ERG, flicker ERG, cataract, RETeval

Guzel Bikbova,1,2 Toshiyuki Oshitari,1 Takayuki Baba,1 Mukharram Bikbov,2 Shuichi Yamamoto1 1Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan; 2Cornea and Refractive Surgery Department, Ufa Eye Research Institute, Ufa, Russia Abstract: Diabetic keratopathy is characterized by impaired innervation of the cornea that leads to decreased sensitivity, with resultant difficulties with epithelial wound healing. These difficulties in wound healing put patients at risk for ocular complications such as surface irregularities, corneal infections, and stromal opacification. Pathological changes in corneal innervations in diabetic patients are an important early indicator of diabetic neuropathy. The decrease in corneal sensitivity is strongly correlated with the duration of diabetes as well as the severity of the neuropathy. This review presents recent findings in assessing the ocular surface as well as the recent therapeutic strategies for optimal management of individuals with diabetes who are susceptible to developing diabetic neuropathy. Keywords: diabetes mellitus, cornea, innervation, neuroprotective therapy

Tomohiro Nizawa, Takayuki Baba, Masayasu Kitahashi, Toshiyuki Oshitari, Shuichi Yamamoto Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan Purpose: To determine the differences in the retinal sensitivities obtained by microperimetry with a single cross or a circular fixation target in normal individuals.Methods: Thirty-two eyes of 16 healthy volunteers (mean age 28.9±1.4 years, range 24–44 years) were studied. The retinal sensitivity of the central 0 degrees and of the mean central 2 degrees consisting of 8 points were determined independently using the two different fixation targets with Microperimeter 3. The Goldmann III stimulus with a luminance of 1.0 cd/m2 was presented for 200 ms on a white background.Results: The retinal sensitivity of the central 0 degrees was significantly better with the circular target than that with the cross target (P=0.003, right eyes; P=0.001, left eyes). The mean retinal sensitivity in the central 2 degrees was not significantly different between the cross and circular fixation targets. (P=0.07, right eyes; P=0.08, left eyes).Conclusion: These results indicate that the circular fixation target is a better target to use to evaluate the central retinal sensitivity. The difference in the retinal sensitivity is most likely due to the cross fixation target overlapping the test stimulus target. Keywords: microperimetry, retinal sensitivity, fixation targets, stimuli

Nana Furuya, Toshiyuki Oshitari, Jiro Yotsukura, Takayuki Baba, Shuichi Yamamoto Department of Ophthalmology and Visual Science, Chiba University, Graduate School of Medicine, Chuo-ku, Chiba, Japan Abstract: We were presented with two cases of relapsing polychondritis (RP) associated with different types of ocular inflammation. The first case was a 35-year-old man who had bilateral hyperemic conjunctiva and ocular pain, and was referred to Chiba University Hospital with a diagnosis of episcleritis refractory. He was treated with dexamethasone eye drops. He developed tinnitus, deafness in both ears, and left auriculitis. A left auricular biopsy showed an infiltration of lymphocytes surrounding the cartilage. He was diagnosed with RP and treated with 30 mg/day oral prednisolone. After tapering the prednisolone, the scleritis in both eyes improved. The second case was a 71-year-old man who was deaf in both ears and had bilateral scleritis. At the first visit to our hospital, his left eyelid and right auricula were reddish and swollen, and he reported some pain. He was treated with intravenous antibiotics, and the left orbital cellulitis quickly improved. However, he developed right scleritis and left gonitis. Magnetic resonance imaging showed bilateral posterior scleritis and right auricular perichondritis. Auricular biopsy showed an infiltration of lymphocytes into the periauricular tissue. He was diagnosed with RP, and 40 mg/day oral prednisolone was given and his symptoms improved. Although RP is rare, it is a life-threatening disease. Thus, ophthalmologists should consider RP in patients with both ocular and auricular inflammation. Keywords: relapsing polychondritis, scleritis, oral prednisolone, ocular cellulitis

Toshiyuki Oshitari, Sakiko Nonomura, Miyuki Arai, Yoko Takatsuna, Eiju Sato, Takayuki Baba, Shuichi Yamamoto Department of Ophthalmology and Visual Science, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan Purpose: To compare the effects of sub-Tenon's capsule triamcinolone acetonide (STTA) injection to that of STTA injection combined with microaneurysm photocoagulation (MAPC; STTA + MAPC) on eyes with diabetic macular edema (DME). Patients and methods: The medical records of 138 eyes of 138 patients with DME treated by either STTA or STTA + MAPC were reviewed. The degree of DME was determined by the optical coherence tomographic features: patients with serous retinal detachment (SRD+; 38 eyes) and patients without SRD (non-SRD; 100 eyes). The central macular thickness (CMT) and the best-corrected visual acuity (BCVA) were measured periodically for 6 months after the treatments. Results: The BCVA was significantly improved in the non-SRD group after STTA + MAPC. The CMT was significantly improved in all groups and improved considerably more in the non-SRD group than in the SRD+ group after STTA + MAPC. Conclusion: Our findings indicate that MAPC has an additive effect in the non-SRD type. Keywords: diabetic macular edema, sub-Tenon's triamcinolone acetonide injection, microaneurysm photocoagulation, best-corrected visual acuity, central macular thickness

Masayasu Kitahashi,1 Takayuki Baba,1 Madoka Sakurai,1 Hirotaka Yokouchi,1 Mariko Kubota-Taniai,1 Yoshinori Mitamura,2 Shuichi Yamamoto1 1Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, 2Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan Background: The purpose of this study was to compare the effectiveness of pneumatic displacement combined with intravitreal bevacizumab (IVB) with that of pneumatic displacement (PD) alone to treat massive submacular hemorrhage (SMH) secondary to polypoidal choroidal vasculopathy (PCV). Methods: Thirty-two eyes of 32 patients with massive SMH secondary to PCV were studied. Twenty-two eyes were treated with a combination of PD and 1.25 mg of intravitreal bevacizumab (PD + IVB group), and ten eyes with pneumatic displacement alone (PD group). Results: Pretreatment, the differences in best-corrected visual acuity and size of the SMH between the two groups were not significant (P=0.59 and P=0.72, respectively). Complete displacement of the hemorrhage from under the fovea was achieved in 19 of 22 eyes (86.4%) in the PD + IVB group and in five of ten eyes (50%) in the PD group. The best-corrected visual acuity in the PD + IVB group was significantly better than that in the PD group at one, 3, and 6 months after treatment (P<0.001, P<0.001, and P<0.001, respectively). Improvement in best-corrected visual acuity by >0.3 logMAR units was obtained in 18 eyes (81.8%) in the PD + IVB group and two eyes (20%) in the PD group (P<0.001). The number of eyes that required additional treatments was significantly fewer in the PD + IVB group than in the PD group (P=0.0001). Conclusion: The combination of PD and IVB may be a better therapeutic procedure for eyes with massive SMH due to PCV in the short term because of the better visual outcome and less need for additional treatments. Keywords: pneumatic displacement, intravitrea

Sakiko Nonomura, Toshiyuki Oshitari, Miyuki Arai, Eiju Sato, Yoko Takatsuna, Takayuki Baba, Shuichi YamamotoDepartment of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, JapanPurpose: To compare the effect of posterior sub-Tenon’s capsule triamcinolone acetonide (STTA) injection to that of pars plana vitrectomy (PPV) for diabetic macular edema (DME).Patients and methods: The medical records of 50 patients (52 eyes) with DME were reviewed. Twenty-six eyes underwent STTA (20 mg) and the other 26 eyes underwent vitrectomy combined with cataract surgery. The central macular thickness (CMT), measured by optical coherence tomography, and best-corrected visual acuity (BCVA) were determined before and 1, 3, and 6 months after treatment.Results: The differences in the BCVA and the CMT between the STTA group and the PPV group were not significant before or at any time after the treatment. In both the STTA and PPV groups, there were significant differences between the pre-treatment CMT and BCVA at any time after treatment.Conclusion: We recommend STTA injection for the treatment of DME.Keywords: diabetic macular edema, posterior sub-Tenon’s capsule triamcinolone acetonide injection, pars plana vitrectomy, central macular thickness

Madoka Sakurai, Takayuki Baba, Masayasu Kitahashi, Hirotaka Yokouchi, Mariko Kubota-Taniai, Guzel Bikbova, Toshiyuki Oshitari, Shuichi YamamotoDepartment of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, JapanPurpose: To compare the 1-year results of intravitreal ranibizumab combined with reduced-fluence photodynamic therapy (RF-PDT) to intravitreal ranibizumab (IVR) alone for eyes with polypoidal choroidal vasculopathy (PCV).Methods: We reviewed the medical records from 47 consecutive patients with PCV (47 naïve eyes). Seventeen eyes from 17 patients had one IVR treatment combined with RF-PDT followed by two additional IVR treatments (combined group), and 30 eyes from 30 patients were treated with 3 monthly IVR treatments (IVR group). All eyes had a follow-up period of at least 12 months.Results: At 12 months, the mean logarithm of the minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA) significantly improved from 0.55 to 0.38 logMAR units in the combined group (P=0.041) but did not change significantly in the IVR group (P=0.371). The central foveal thickness (CFT) was significantly thinner in both groups at 6 months (P<0.01). Additional IVR injections were required less frequently in the combined group (n=3; 17%) than in the IVR group (n=16; 53%) during the 12 month follow-up (P=0.029).Conclusion: The IVR and RF-PDT combination led to significant BCVA improvements and required fewer additional IVR treatments for at least 12 months in eyes with PCV.Keywords: intravitreal ranibizumab, reduced-fluence photodynamic therapy, polypoidal choroidal vasculopathy

We report a class of the mathematics in which an animation technology (calculating and plotting capabilities) of the software Mathematica is utilized. This class is taught for university students in a computer laboratory during a second semester. It is our purpose to make a student realize the usefulness and the importance of mathematics easily through visualization. In addition, we hope that students will acquire a new power of mathematics needed in the 21st century. For several years, we have continued this kind of class, and have continued to investigate the effectiveness that our teaching method (especially visualization) brings in the understanding of the mathematics. In this paper, we present some of this teaching method, which is performed in our class. From the questionnaire survey, it is found that our teaching method not only convinces students that the mathematics is useful or important but also deepens the mathematic understanding of students more.

We report a class of the mathematics in which an animation technology (calculating and plotting capabilities) of the software Mathematica is utilized. This class is taught for university students in a computer laboratory during a second semester. It is our purpose to make a student realize the usefulness and the importance of mathematics easily through visualization. In addition, we hope that students will acquire a new power of mathematics needed in the 21st century. For several years, we have continued this kind of class, and have continued to investigate the effectiveness that our teaching method (especially visualization) brings in the understanding of the mathematics. In this paper, we present some of this teaching method, which is performed in our class. From the questionnaire survey, it is found that our teaching method not only convinces students that the mathematics is useful or important but also deepens the mathematic understanding of students more.

Yuzhu Chai1, Hiroko Yamazaki1, Akihide Kondo2, Toshiyuki Oshitari3, Shuichi Yamamoto31Department of Ophthalmology, Kohnodai Hospital, National Center for Global Health and Medicine, Chiba, 2Department of Neurosurgery, Juntendo University, School of Medicine, Tokyo, 3Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, JapanAbstract: We present detailed ophthalmic findings in a case of tuberculum sellae meningioma with acute visual symptoms due to optic canal involvement. A 62-year-old Japanese woman reported a 1-week history of headaches and blurred vision in her left eye. Her visual acuity was 0.3 in the left eye with no ophthalmoscopic abnormalities. A relative afferent pupillary defect and inferior temporal field defect were found in the left eye. Pattern visual evoked potentials were undetectable in the left eye. Enhanced magnetic resonance imaging showed a 9 mm intracranial lesion around the left optic nerve anterior to the chiasm. She was diagnosed with granulomatous inflammation because of the increased cell counts and protein concentration in the cerebrospinal fluid. She was treated with steroid pulse therapy, and her visual acuity and visual field defect improved to normal in 3 weeks. However, 16 months after the onset, she suffered from headaches again and had a complete loss of vision in her left eye. There was no response to steroid pulse therapy. Enhanced magnetic resonance imaging revealed that the lesion had extended into the left optic canal, and emergency tumor removal surgery was carried out. The histopathological diagnosis was meningioma. One month after the surgery, her left visual acuity improved to 1.2, and her visual field was almost normal. Pattern visual evoked potentials were present but had a prolonged P100 latency of 170 ms. A thinning of the ganglion cell complex was detected by optical coherence tomography. Ophthalmologists should be aware that a small tuberculum sellae meningioma

Tomohiro Nizawa1, Toshiyuki Oshitari1, Ryuta Kimoto1, Fusae Kajita1, Jiro Yotsukura1, Kaoru Asanagi1, Takayuki Baba1, Yoko Takahashi2, Takashi Oide2, Takako Kiyokawa2, Takashi Kishimoto2, Shuichi Yamamoto11Department of Ophthalmology and Visual Science, 2Department of Molecular Pathology, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, JapanAbstract: We present the findings of an early-stage primary mucinous sweat gland adenocarcinoma in the lower eyelid of a Japanese patient. The patient was a 73-year-old man who had had a nodule on the left lower eyelid for two years. He was referred to our hospital with a diagnosis of a swollen chalazion. The clinical and histopathological records were reviewed and the mass was excised. Histopathological examination revealed a mucinous sweat gland adenocarcinoma. Postoperative magnetic resonance imaging and positron emission tomography excluded systemic metastases. After the histopathological findings, a complete surgical excision of the margins of the adenocarcinoma was performed, with histopathological confirmation of negative margins. After the final histopathological examination, the patient was diagnosed with a primary mucinous sweat gland adenocarcinoma of the left eyelid. Six months after the surgery, no recurrence has been observed. Because the appearance of mucinous sweat gland adenocarcinoma of the eyelid is quite variable, the final diagnosis can only be made by histopathological examination. A complete surgical excision is recommended.Keywords: complete surgical excision, eyelid, initial stage, mucinous sweat gland adenocarcinoma

Takayuki Baba, Tomoaki Tatsumi, Toshiyuki Oshitari, Shuichi YamamotoDepartment of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, JapanAbstract: We report a patient with cognitive disorder who had a rhegmatogenous retinal detachment (RRD). A 17-year-old Japanese man presented with a RRD with a vitreous hemorrhage in his right eye. An unusual vertical splitting of the macula accompanied by a giant retinal tear was observed intraoperatively. The retina was successfully reattached by pars plana vitrectomy with silicone oil tamponade and scleral buckling. Visual function appeared to have improved from the behavior of the patient. Although the precise mechanism causing the break which split the macula was not determined, self-inflicted blunt trauma to the eye was suspected.Keywords: macular break, cognitive disorder, retinal detachment&nbsp

Mariko Kubota-Taniai1,2, Toshiyuki Oshitari2, Maya Handa2, Takayuki Baba2, Jiro Yotsukura2, Shuichi Yamamoto21Department of Ophthalmology, National Hospital Organization, Chiba Medical Center, Chiba, Japan; 2Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, JapanPurpose: To describe a case of choroidal osteoma with choroidal neovascularization (CNV) that was successfully treated with two intravitreal injections of bevacizumab (IVB).Design and methods: Case report on a 12-year-old Japanese girl who presented with a sudden decrease in vision in her left eye. At the first visit, 2 days after the onset of her symptoms, her visual acuity (VA) in her left eye was 0.2. Ophthalmoscopy showed a hemorrhage of 5 disc diameters under the retinal pigment epithelium and a serous retinal detachment at the posterior pole of the left eye. These findings were confirmed by optical coherence tomography. Fluorescein angiography (FA) and indocyanine green angiography (ICGA) showed several points of leakage around the fovea, which suggested a CNV. From these findings, the patient was diagnosed with choroidal osteoma with a CNV. The submacular hemorrhage was from the CNV associated with the choroidal osteoma. We treated her with two injections of 1.25 mg/0.05 mL IVB with a 4-month interval.Results: The patient's VA in her left eye improved to 0.7, and this vision was maintained for 4 years. The CNV disappeared in the FA and ICGA images and no recurrence was observed after 4 years.Conclusion: Our findings indicate that IVB is effective in resolving CNV in eyes with an osteoma and prevents a decrease of vision in eyes with a choroidal osteoma with a CNV.Keywords: choroidal osteoma, CNV, IVB, visual acuity

Yuzhu Chai1, Hiroko Yamazaki1, Kaoru Fujinami2, Kazushige Tsunoda2, Shuichi Yamamoto31Department of Ophthalmology, Kohnodai Hospital, National Center for Global Health and Medicine, Chiba, Japan; 2National Institute of Sensory Organs, Tokyo, Japan; 3Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, JapanAbstract: Electrophysiological and morphological findings were studied in a case of acute zonal occult outer retinopathy (AZOOR) showing abnormal pattern visual evoked potentials (VEPs) at the onset and significant functional recovery in the natural course.  A 21-year-old woman presented with acute onset of photopsia and a large scotoma in the right eye of 2 weeks duration. Her visual acuity was 20/20 in both eyes with no ophthalmoscopic and fluorescein angiographic abnormalities. However, a relative afferent pupillary defect and an enlarged blind spot were found in the right eye. The pattern VEPs were severely reduced when the right eye was stimulated. The amplitudes of both rod and cone full-field electroretinographics (ERGs) were reduced in the right eye. The amplitudes of the multifocal ERGs were reduced in the area of the enlarged blind spot. Irregularities in the inner segment/outer segment (IS/OS) line of the photoreceptors were observed over the nasal fovea by optical coherence tomography (OCT). The patient was followed without treatment. The enlarged blind spot disappeared in 3 months after the onset. At 5 months, reappearance of the IS/OS line was detected by OCT. At 6 months, the P100 recovered to normal values. At 1 year, the reduced full-field ERGs were almost normal size and the multifocal ERGs in the area corresponding to the enlarged blind spot were also improved. ERG findings are crucial for differentiating AZOOR from retrobulbar neuritis, especially in patients with abnormal pattern VEPs. The pattern VEPs, full-field ERGs, multifocal ERGs, and OCT images can be abnormal in the early phase o

Kazumi Oomachi1, Kazuha Ogata2, Takeshi Sugawara2, Akira Hagiwara2, Akira Hata1, Shuichi Yamamoto21Department of Public Health; 2Department of Ophthalmology, Chiba University Graduate School of Medicine, Chiba, JapanBackground: The purpose of this study was to determine visual acuity at different contrast levels under photopic and mesopic conditions in patients with retinitis pigmentosa.Methods: Sixty eyes of 31 normal controls, 92 eyes of 52 patients with retinitis pigmentosa without other ocular disorders (RP-1 group), and 20 eyes of 14 patients with retinitis pigmentosa with cataracts and without other ocular disorders (RP-2 group) were studied. Conventional visual acuity was measured using a conventional Landolt ring chart with 100% contrast and luminance of 150 cd/m2. All of the patients with retinitis pigmentosa had a decimal visual acuity better than 1.0. Contrast visual acuity was measured with the same Landolt ring chart with contrasts of 100% and 10% and under photopic (200 cd/m2) and mesopic (10 cd/m2) conditions. Decimal visual acuities were converted to logMAR units for the analyses.Results: The 100% contrast visual acuity and the 10% contrast visual acuity determined under both photopic and mesopic conditions were significantly poorer in both the RP-1 and RP-2 groups than in the controls. The differences between the conventional visual acuity and the 100% contrast visual acuity were significantly greater in the RP-1 and RP-2 groups than in the controls under both photopic and mesopic conditions. The differences between the 100% contrast visual acuity and the 10% contrast visual acuity were not significant among the three groups under photopic and mesopic conditions.Conclusion: Contrast visual acuities were greatly reduced in patients with retinitis pigmentosa with relatively well preserved conventional visual acuity, and the contrast visual acuity was largely influenced by ambient light levels in patients with retinitis pigmentosa. Although a longitudi

Fusae Kajita1, Toshiyuki Oshitari1, Jiro Yotsukura1, Kaoru Asanagi1, Takayuki Baba1, Takashi Kishimoto2, Shuichi Yamamoto11Department of Ophthalmology and Visual Science, 2Department of Molecular Pathology, Chiba University Graduate School of Medicine, Chiba, JapanAbstract: The purpose of this study was to determine the characteristics of primary diffuse large B-cell lymphoma (DLBCL) of the lacrimal sac. A 77-year-old man had epiphora of the right eye for three years. After visiting five clinics and hospitals, he was referred to our hospital, and the preoperative magnetic resonance imaging findings suggested a lacrimal sac mass. Dacryocysteography showed an obstruction of the right nasolacrimal duct, so we performed dacryocystectomy. After a histopathologic examination of the specimen, the patient was diagnosed with a DLBCL. Positron emission tomography scanning excluded metastases, and the final diagnosis was made of a primary DLBCL of the right lacrimal sac. He underwent radiotherapy with 30.6 Gray in total to the right lacrimal sac. After radiotherapy, no recurrence has been observed anywhere in his body for one year. Although a malignant lymphoma of the lacrimal sac is rare, clinicians should consider a primary malignant lymphoma in the differential diagnosis in patients with chronic dacryocystitis.Keywords: lacrimal sac, diffuse large B-cell lymphoma, radiotherapy, dacryocystectomy, Japanese

Toshiyuki Oshitari1, Jiro Yotsukura1, Kaoru Asahagi1, Takayuki Baba1, Takashi Kishimoto2, Shuichi Yamamoto11Department of Ophthalmology and Visual Science, 2Department of Molecular Pathology, Chiba University Graduate School of Medicine, Chiba, JapanAbstract: The purpose of this study is to present a case of chronic sclerosing dacryoadenitis with high level of IgG4 in a patient diagnosed earlier with Castleman disease. A 79-year-old man noticed a swelling of his lower left jaw that was first seen 8 years earlier. He was diagnosed with Castleman disease from the histopathological examination of a biopsy of the submandibular gland. Since then, the size of the gland had not changed, and he had no systemic inflammatory signs or symptoms. He developed diplopia a year earlier, and CT scans showed bilateral swelling of the lacrimal glands. He was referred to our hospital for further examinations. The patient underwent partial dacryoadenectomy. From the histopathological examinations, he was diagnosed with chronic sclerosing dacryoadenitis with high level of the serum IgG4. He underwent oral steroid therapy and the swollen lacrimal glands were significantly improved. The results suggest that there may be pathological links between IgG4-related dacryoadenitis and Castleman disease.Keywords: IgG4, dacryoadenitis, Castleman disease, steroid

Kyoko Okada, Mariko Kubota-Taniai, Masayasu Kitahashi, Takayuki Baba, Yoshinori Mitamura, Shuichi YamamotoDepartment of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, JapanPurpose: To determine the correlation between the changes in the central retinal sensitivity and the changes in the foveal thickness (FT) after photodynamic therapy (PDT) for age-related macular degeneration (AMD).Methods: Nineteen eyes of 19 patients with choroidal neovasularizations (CNVs) secondary to AMD were studied. The pretreatment values of the central retinal sensitivity determined by Micro Perimeter 1 (MP1; Nidek Technologies), best-corrected visual acuity (BCVA), and optical coherence tomography (OCT)-determined FT were compared to the postoperative values at three and six months after PDT.Results: At six months, the retinal sensitivity within the central 10° was significantly improved (P = 0.02) and the FT was significantly thinner (P = 0.016). The BCVA, however, did not change significantly (P = 0.80). The changes in the retinal sensitivities were significantly correlated with the changes in the decrease in the FT (r = -0.59, P = 0.012 within the central 10°) at six months after PDT.Conclusion: Significant improvements in retinal sensitivities within the central 10° and a decrease in FT were observed even though the BCVA was not significantly improved. The measurement of retinal sensitivity by MP1 may be a better method to assess central visual function than the conventional visual acuity after PDT.Keywords: age-related macular degeneration, fundus-related microperimetry, optical coherence tomography, photodynamic therapy

Toshiyuki Oshitari1,2, Natsuyo Hata1, Shuichi Yamamoto11Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba City, Chiba, Japan; 2Department of Ophthalmology, Kimitsu Central Hospital, Kisarazu City, Chiba, JapanAbstract: Endoplasmic reticulum (ER) stress is involved in the pathogenesis of several diseases including Alzheimer disease and Parkinson disease. Many recent studies have shown that ER stress is related to the pathogenesis of diabetes mellitus, and with the death of pancreatic β-cells, insulin resistance, and the death of the vascular cells in the retina. Diabetic retinopathy is a major complication of diabetes and results in death of both neural and vascular cells. Because the death of the neurons directly affects visual function, the precise mechanism causing the death of neurons in early diabetic retinopathy must be determined. The ideal therapy for preventing the onset and the progression of diabetic retinopathy would be to treat the factors involved with both the vascular and neuronal abnormalities in diabetic retinopathy. In this review, we present evidence that ER stress is involved in the death of both retinal neurons and vascular cells in diabetic eyes, and thus reducing or blocking ER stress may be a potential therapy for preventing the onset and the progression of diabetic retinopathy.Keywords: endoplasmic reticulum stress, diabetic retinopathy, vascular cell death, neuronal cell death

Natsuyo Hata1, Toshiyuki Oshitari1,2, Akiko Yokoyama1,3, Yoshinori Mitamura1, Shuichi Yamamoto11Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan; 2Department of Ophthalmology, Kimitsu Central Hospital, Kisarazu City, Chiba, Japan; 3Department of Ophthalmology, Inoue Memorial Hospital, Chuo-ku, Chiba, JapanAbstract: The purpose of this study was to determine whether the expression of ER stress-related factors IRE1α, apoptosis signal-regulating kinase 1 (ASK1), SAPK/ERK kinase 1 (SEK1) and c-Jun N-terminal kinase (JNK) is associated with the damaged retinal neurons induced by ischemia-reperfusion injury. After 60 minutes of ischemia, the rat retinas were reperfused, and retinas were isolated and fixed after 6, 9, 12, 18, and 24 hours, and 2, 5, and 9 days of reperfusion. Cryosections were immunostained with Fluoro-Jade B, a degenerating neuron marker to label degenerating neurons. Semi-quantitative analysis of the expression of IRE1α, ASK1, SEK1, and JNK were performed in both control and ischemic retinas. In ischemic retinas, the intensities of IRE1α immunoreactivity in the ganglion cell layer (GCL) were significantly higher than in the control retinas. In ischemic retinas, the numbers of SEK1-, ASK1-, and JNK-positive cells were significantly increased in the GCL compared to those in the control retinas. In addition, the cells that were positive for SEK1-, ASK1-, and JNK were also positive for Fluoro-Jade B-positive cells. These results indicate that the increased expression of ER stress-related factors was, in part, associated with the retinal neuronal abnormalities after ischemia-reperfusion injury in rat retinas.Keywords: endoplasmic reticulum, IRE1α, apoptosis signal-regulating kinase 1, SAPK/ERK kinase 1, c-Jun N-terminal kinase, Fluoro-Jade B, ischemia-reperfusion injury

type:text, [Abstract] Diabetic retinopathy is one of the most frequent complications of diabetes and is a leading cause of vision loss in adulthood. To better understand the molecular pathophysiology of diabetic retinopathy, we performed comprehensive gene expression analysis of the mouse retina under diabetic conditions with an in-house cDNA microarray system that was designed to be suitable for the small amount of RNA available from a single mouse retina. Diabetes was induced in male C57BL/6 mice by an intraperitoneal injection of streptozotocin, and the changes in retinal mRNA levels were examined in three pairs of diabetic and age-matched control mice at 1 and 3 months after the injection of streptozotocin. Northern blot analysis with amplified total cRNA confirmed the increase in mRNA levels of several selected genes. Most of the significantly up-regulated genes could be classified into two functional categories: oxidative phosphorylation and protein turnover. All mitochondrial DNA-encoded and most of the nuclear DNA-encoded genes for oxidative phosphorylation were up-regulated in the diabetic retina. This was in sharp contrast with a previous report of a down-regulation of these genes in skeletal muscles of streptozotocin-induced diabetic mice and type 2 diabetic humans. Genes for protein synthesis and ubiquitin were also up-regulated in the diabetic retina, suggesting the increase in turnover rates for at least a part of the protein population. Taken together, the diabetic retina appears to be in a state activated for intermediary metabolism, presumably because of an increase in insulin-independent glucose influx. These results provide insights into possible preventive and therapeutic intervention of diabetic retinopathy.

Separation of acetic acid from palm oil mill effluent (POME) to increase its concentration by an anion exchange resin was examined as a preliminary study for its recovery from POME that had been anaerobically treated by sludge from a palm oil mill. This paper concerns the acetic acid thus separated for producing bacterial polyhydroxyalkanoate (PHA) by Alcaligenes eutrophus. It was found that sludge particles in POME strongly inhibited the adsorption of acetic acid on the anion exchange resin. Removing the sludge particles from the POME facilitated the separation of acetic acid from the POME efficiently. The concentrated acetic acid thus obtained from anaerobically treated POME could be used as a substrate in the fed-batch production of polyhydroxyalkanoate by Alcaligenes eutrophus.

Separation of acetic acid from palm oil mill effluent (POME) to increase its concentration by an anion exchange resin was examined as a preliminary study for its recovery from POME that had been anaerobically treated by sludge from a palm oil mill. This paper concerns the acetic acid thus separated for producing bacterial polyhydroxyalkanoate (PHA) by Alcaligenes eutrophus. It was found that sludge particles in POME strongly inhibited the adsorption of acetic acid on the anion exchange resin. Removing the sludge particles from the POME facilitated the separation of acetic acid from the POME efficiently. The concentrated acetic acid thus obtained from anaerobically treated POME could be used as a substrate in the fed-batch production of polyhydroxyalkanoate by Alcaligenes eutrophus.