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Toshihiko Inoue,1 Yoshishige Okuno,1 Iku Nishiguchi,1 Koji Ikenaga,1 Osamu Mimura2 1Department of Radiation Oncology, Ashiya Radiotherapy Clinic Nozomi, Ashiya, Japan; 2Department of Neuro-Ophthalmological Therapeutics, Hyogo College of Medicine, Nishinomiya, Japan Purpose: To report the outcomes of early intervention with fractionated stereotactic radiotherapy (FSRT) in a patient with primary optic nerve sheath meningioma (ONSM).Patient and methods: A male patient in his early 40s underwent 5-beam FSRT at a prescribed dose of 50 Gy in 25 fractions over 35 days. The patient had an 11-month history of progressive visual impairment at the time of FSRT.Results: On day 14 of treatment, the patient reported early improvement in his vision. Two weeks after the completion of FSRT, his left eye visual acuity and field recovered completely. However, the tumor regressed only slightly in the 2 years of follow-up.Conclusion: Early intervention with FSRT for optic nerve sheath meningioma resulted in a rapid response and complete improvement of visual impairment. Keywords: fractionated stereotactic radiotherapy, optic nerve sheath meningioma, early intervention, rapid recovery of visual impairment

Yutaro Nishi,1,2 Tomohiro Ikeda,1 Kayo Nishi,2 Osamu Mimura1 1Department of Ophthalmology, Hyogo College of Medicine, Hyogo, 2Nishi Eye Hospital, Osaka, Japan Background and objective: We investigated the yttrium aluminum garnet (YAG) capsulotomy rates in various intraocular lenses (IOLs). Study design/patients and methods: We retrospectively analyzed 23,440 eyes implanted with either MA60BM, MA60AC, VA-60BB, CeeOnEdge, Clariflex, Technis Z9002, SI-40NB, or UV26T IOLs. We calculated the YAG capsulotomy rates at 1, 3, 5, and 10 years post lens implantation. Results: YAG capsulotomy rates at 3 years postimplantation for the eight groups of IOLs were, respectively, 3.7%, 3.9%, 23.7%, 3.4%, 4.5%, 4.7%, 10.4%, and 21.0%. YAG capsulotomy rates at 10 years postimplantation for the MA60BM and SI-40NB IOLs were, respectively, 9.1% and 15% (P

Mana Okamoto, Akiko Kimura, Akiko Masuda, Osamu Mimura Department of Ophthalmology, Hyogo College of Medicine Hospital, Nishinomiya, Japan Abstract: Nasal transposition of the inferior rectus (IR) muscle, which is transposed nasally with the insertion parallel to the spiral of Tillaux, could correct excyclotropia. However, as far as we are aware, there have been no reports examining the surgical effects of this procedure in multiple cases. Therefore, we examined the surgical effects of IR nasal transposition in 135 cases with acquired trochlear nerve palsy at Hyogo College of Medicine Hospital, Nishinomiya, Japan. One muscle width of IR nasal transposition corrected an average 5.6° in excyclotorsion, while bilateral IR nasal transposition corrected average 10.9°. This result shows this procedure is accurate quantitatively. Moreover, IR nasal transposition in combination with IR recession or resection can correct vertical deviation and excyclotorsion simultaneously. The results of this study suggest that IR nasal transposition should become first-line treatment for acquired superior oblique palsy. Keywords: spiral of Tillaux, strabismus surgery, excyclotropia, acquired trochlear nerve palsy

Osamu Mimura,1 Hiroto Ishikawa,1,2 Naoki Kimura,1 Akiko Kimura,1 Cesar V Borlongan2 1Department of Ophthalmology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan; 2Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL, USA Purpose: Periodic alternating nystagmus (PAN) is a spontaneous horizontal nystagmus observed in disorders of the central nervous system. Patients with congenital PAN complain of oscillating vision at high rates. Medication is the first-choice treatment for PAN; however, clinicians still seek better therapy. The aim of this study was to evaluate outcomes of recession of four horizontal rectus muscle (R-FHR) in patients with congenital PAN.Patients and methods: This study reports a retrospective case series of ten patients (seven males and three females; mean age 24.4±10.9) with congenital PAN who underwent R-FHR between 2007 and 2012, which was performed by the same surgeon at the Hyogo College of Medicine. Patients were evaluated for complications, recession amount, deviation angle, eye movements including a nystagmus amplitude, and visual acuity during pre- and post-operative periods.Results: Pre-operatively, patients complained of oscillating vision, abnormal head posture, esotropia, and congenital superior oblique palsy. Post-operatively, changes from the previous observations of nystagmus amplitudes and abnormal head posture demonstrated a complete reversal in all patients. In addition, visual acuity determined with a Snellen chart improved in two patients. However, esotropia occurred in three patients who underwent additional strabismus surgery 2 days after R-FHR. R-FHR was particularly effective in eight patients who pre-operatively had periodic oscillating vision with a regular pattern of periodic nystagmus.Conclusion: We demonstrated that ten patients with congenital PAN had improved vision following R-FHR, indicating that R-FHR was an effective procedure, especially in patients suffering PAN with periodic oscillating vision. Keywords: congenital nystagmus, null point nystagmus, strabismus surgery, ocular torticollis, oscillating vision, electro-oculogram

Kohji Hoshina,1 Yuichi Tagami,2 Osamu Mimura,3 Hiroshi Edagawa,4 Masao Matsubara,5 Teiichi Nakayama6 1Hoshina Eye Clinic, Nishinomiya, Japan; 2Department of Ophthalmology, Kobe Century Memorial Hospital, Kobe, Japan; 3Department of Ophthalmology, Hyogo College of Medicine, Nishinomiya, Japan; 4Edagawa Eye Clinic, Tokyo, Japan; 5Department of Ophthalmology, Tokyo Women's Medical University Medical Center East, Tokyo, Japan; 6Ritsumeikan University, Kyoto, Japan Background: It seemed that visual functions might have some effects on the performance of baseball players. We measured static, kinetic, and dynamic visual acuity (SVA, KVA, and DVA, respectively) of Japanese professional baseball players to ascertain whether there would be any difference in SVA, KVA, and DVA among player groups stratified according to their performance level. Methods: The subjects were 102 male professional baseball players with a mean age of 26 years who were members of a Japanese professional baseball club from 2000 to 2009. They were stratified into three groups according to their performance level: A (players who were on the roster of the top-level team all the time throughout the study period), B (players who were on the roster of the top-level team sometimes but not all the time), and C (players who were never on the roster of the top-level team). They were interviewed for the use of corrective visual aids, and examined for SVA, KVA, and DVA. The measurements of these parameters were compared among groups A, B, and C. We also investigated and analyzed the association of KVA or DVA with player position (pitchers or fielders) and with hand dominance for batting. KVA was compared between the pitchers and the fielders because they each require different playing skills. DVA was compared between the right-handed and the left-handed batters. Results: There was no statistically significant difference among groups A, B, and C. There was a statistically significant difference in KVA between the pitchers and the fielders (t-test; P < 0.05) There was no statistically significant difference in DVA between the right-handed and the left-handed batters. Conclusions: There was no significant difference in the examined visual functions among player groups with different performance levels. Keywords: static visual acuity, kinetic visual acuity, dynamic visual acuity, Japanese professional baseball players

Kazuaki Nakauchi,1 Hidenori Mito,2 Osamu Mimura11Hospital of Hyogo College of Medicine, Hyogo, 2Ide Eye Hospital, Yamagata, JapanBackground: The frontalis suspension technique is the surgical method of choice in patients with ptosis and a levator function of 4 mm or less. Several types of materials have been used, including Gore-Tex®, which has been used successfully as a frontalis sling material since 1986. Recently, a Gore-Tex sheet (wider than a sling or strip) suspension was reported. This paper reports the results of 27 eyes from 20 patients with congenital ptosis treated using the frontalis suspension technique with the newly developed Gore-Tex Most Versatile Patch (MVP) sheet.Methods: All patients underwent surgery between April 2007 and September 2011 and were followed up for at least one year. The average follow-up duration was 18 months, with a range of 12–36 months. The average patient age was 45 (5–85) years, and the group included 11 males and nine females. Thirteen cases demonstrated ptosis in one eye, and seven cases involved both eyes. The patients were divided by age into a younger group and an older group. All ptosis procedures were performed using the Gore-Tex MVP sheet. The implant was normally 7 mm wide for adults and 5 mm wide for children. The implantation method was the same as that used for the sheet shape fascia.Results: In all patients, satisfactory functional results were observed at the 6-month follow-up examination. Eyelid opening heights were also obtained. The average marginal reflex distance (MRD) was -0.5 mm preoperatively, which improved to +1.9 mm after surgery. After one year, average MRD was +1.6 mm. MRD attenuation was more frequent in the younger group. There were no cases requiring redo surgery and only one case of exposure.Keywords: polytetrafluoroethylene, Gore-Tex®, frontalis suspension, congenital ptosis, recurrence

Kazuaki Nakauchi, Osamu MimuraDepartment of Ophthalmology, Hospital of Hyogo College of Medicine, Nishinomiya, Hyogo, JapanPurpose: Involutional entropion is a common condition in Asian countries, including Japan. One cause of involutional entropion is weakening of the capsulopalpebral fascia (CPF). The aged, thin, membranous nature of the CPF limits the results of correction by the original Jones procedure (CPF tightening) alone, so we added the modified Hotz procedure to the entropion repair. We then compared the recurrence rates and operation times in corrections performed with and without this additional procedure.Cases: From April 2010 to December 2011, one surgeon performed lower-lid surgery using the Jones procedure with the addition of the modified Hotz procedure. Fifteen patients (a total of 21 eyes) underwent this combined procedure. Previously, the same surgeon performed the Jones procedure alone for eight patients (a total of nine eyes).Results: The average age of the two groups was 76.4 years, with an age range of 66–85 years. All cases reported acceptable ciliary orientation at the end of the surgery. However, patients who underwent the Jones procedure alone (nine eyes total) reported three cases of recurrence after at least 6 months of follow-up. Patients who underwent the combined procedure reported two complications: one recurrence and one ectropion. The recurrence rate was 5%. The Jones procedure using eyelid pinch required an average of 22.6 minutes to complete; the combined method required 33.4 minutes to complete.Conclusion: The combined method resulted in a significantly higher success rate than the Jones procedure alone (P < 0.05). The 5% failure rate of the combined method was found to be superior to the 30% recurrence rate of the Jones procedure. As a result, the Hotz procedure enhanced the results of the entropion correction and required only 10 additional minutes of surgery. We now perform this combined procedure for all cases.Keywords: Jones procedure, Hotz procedure, entropion, recurrence, operation time

Kazuaki Nakauchi, Osamu MimuraOphthalmology, Hyogo College of Medicine, Hyogo, JapanPreface: The Asian race has a high prevalence of congenital entropion. It was reported that over 20% of Japanese children have congenital entropion at the age of 1 year. One of the structural causes of this condition is the development of epiblepharon, which attaches the lower eyelid to the upper eyelid, and is also common among Asians. However, designing a procedure for modifying an epicanthus flap is relatively difficult, and epicanthoplasty is not a popular procedure in Japan. In the present study, we developed an easy method of designing the surgery, and we describe both the surgical procedure and the outcome.Cases: Between January 2010 and August 2011, one surgeon performed surgery to correct congenital entropion in 28 patients. We analyzed this series of 28 cases retrospectively. The patients consisted of 17 females and eleven males with an average age of 7.6 years. Ten patients with a thick epicanthal fold required epicanthoplasties in addition to lower lid procedures, and 18 patients with a thin epicanthal fold required only lower lid procedures.Surgical method: On the epicanthus, a small, triangular “fish-tail” flap that was 2 mm wide was designed and was located adjacent to a “fish-body” marking on the subciliary lower eyelid. After fish-tail resection, the residual medial edge was sutured to the corner of the epicanthus. A C-shaped epicanthus was changed into an L-shape by means of this procedure.Result: The fish-tail resection diminished the tension of the orbicularis in the superior direction. After a minimum of 6 months, the shape of the medial canthus remained L-shaped, and the cilia had stable orientations.Conclusion: This plasty is easy to design in conjunction with a Hotz procedure, and it is an effective means of correcting Asian congenital entropion. Recognizing the shape of a congenital entropion that is accompanied by epiblepharon is important for its radical treatment.Keywords: epiblepharon, congenital entropion, asian, modified Hotz, fish tail

Increasing evidences show that immune response affects the reparative mechanisms in injured brain. Recently, we have demonstrated that CD4+T cells serve as negative modulators in neurogenesis after stroke, but the mechanistic detail remains unclear. Glucocorticoid-induced tumor necrosis factor (TNF) receptor (GITR), a multifaceted regulator of immunity belonging to the TNF receptor superfamily, is expressed on activated CD4+T cells. Herein, we show, by using a murine model of cortical infarction, that GITR triggering on CD4+T cells increases poststroke inflammation and decreases the number of neural stem/progenitor cells induced by ischemia (iNSPCs). CD4+GITR+T cells were preferentially accumulated at the postischemic cortex, and mice treated with GITR-stimulating antibody augmented poststroke inflammatory responses with enhanced apoptosis of iNSPCs. In contrast, blocking the GITR-GITR ligand (GITRL) interaction by GITR-Fc fusion protein abrogated inflammation and suppressed apoptosis of iNSPCs. Moreover, GITR-stimulated T cells caused apoptosis of the iNSPCs, and administration of GITR-stimulated T cells to poststroke severe combined immunodeficient mice significantly reduced iNSPC number compared with that of non-stimulated T cells. These observations indicate that among the CD4+T cells, GITR+CD4+T cells are major deteriorating modulators of poststroke neurogenesis. This suggests that blockade of the GITR-GITRL interaction may be a novel immune-based therapy in stroke. [ABSTRACT FROM AUTHOR]

Purpose: To objectively assess visual function in Leber's Hereditary Optic Neuropathy (LHON) patients; this study evaluated pre- and post-idebenone treatment changes in primary visual cortical (V1) responses using functional magnetic resonance imaging (fMRI), given the challenges in subjective testing due to central retinal ganglion cell damage., Study Design: A descriptive study involving four confirmed LHON patients., Methods: Four patients received 900 mg/day of oral idebenone for 24 weeks. Baseline and post-treatment visual acuity, visual fields, and BOLD fMRI responses while passively viewed drifting contrast pattern visual stimuli were compared with self-reported symptoms., Results: Post-idebenone, one patient showed positive trends across subjective tests, reported symptoms, and fMRI. Two patients had stable symptoms and fMRI responses; one improved on subjective tests, and another worsened slightly. Another patient improved in visual field tests despite worsening symptoms and fMRI trends., Conclusion: fMRI may offer a valuable objective measure of visual functions in LHON and appears to be more relevant in assessing symptoms. Further research with more participants is needed to ascertain fMRI's role in developing objective visual assessments and treatment evaluation., (© 2024. Japanese Ophthalmological Society.)

Superior sagittal sinus (SSS) obstruction causes intracranial hypertension, often requiring surgical stenting. Consensus on treating brain venous sinus stenosis, another cause, is lacking. This study reports a case of SSS stenosis and intracranial hypertension treated with venous stenting, improving bilateral papilledema. A 51-year-old with a headache and visual disturbance had papilledema and visual field loss. MR venography showed SSS stenosis, leading to a neurosurgery referral. Lumbar puncture confirmed intracranial hypertension (>35 cmH2O), prompting venous stenting. Post-procedure, papilledema, headache, and visual field loss improved. Venous stenting could be effective for SSS stenosis with clinically proven or recurrent pressure differences. Further cases are needed for standardization., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Miyoshi et al.)

Purpose: Leber's hereditary optic neuropathy (LHON) is a mitochondrial neuropathy that causes acute vision loss. Idebenone, a short-chain ubiquinone analog that preserves mitochondrial function is thought to suppress disease progression in early-onset LHON patients. We investigated the effects of idebenone in Japanese LHON patients., Study Design: Prospective, interventional, non-comparative study in patients with definite LHON diagnosis, under trial registration number UMIN000017939., Methods: Fifty-seven patients received 900 mg/day idebenone for 24 weeks. We measured baseline best-corrected visual acuity, visual fields, critical fusion frequency and retinal ganglion cell layer complex thickness; we assessed efficacy at 24 and 48 weeks, and safety throughout., Results: Patients were predominantly male (91.2%) and most had an mt.11778G>A mutation (94.7%). All patients tolerated idebenone therapy well. Data from the 51 mt.11778 patients were compared with their baseline data. At 48 weeks, significant improvement in best-corrected visual acuity was observed in 17 patients (33.3%). Furthermore, 25.5% of patients showed improvements in visual fields and 33.3% in critical fusion frequency. However, retinal ganglion cell layer complex thickness was significantly reduced. Among patients who started idebenone >1 year after disease onset, visual improvement was found in 12 (38.7%). Among patients who developed LHON before 19 years of age, visual improvement was found in 11 (42.3%)., Conclusion: Idebenone's potential and favorable safety profile were confirmed in Japanese LHON patients. However, this study had no placebo group; therefore, we need to undertake a prospective intervention study to further investigate the therapeutic effects of Idebenone in Japanese LHON patients.

Purpose: To evaluate the efficacy and safety of intravenous "freeze-dried sulfonated human normal immunoglobulin (GGS)" in patients with steroid-resistant optic neuritis (ON)., Study Design: Multicenter, prospective, double-blind, parallel-group, randomized controlled trial., Methods: Patients with steroid-resistant acute ON were randomly assigned to receive either intravenous GGS (GGS group) or intravenous methylprednisolone (steroid pulse [SP] group). Visual acuity (logarithm of the minimum angle of resolution [logMAR]), mean deviation (MD) value of the Humphrey Field Analyzer, and critical flicker fusion frequency were measured as efficacy endpoints; adverse events (AEs) were assessed as the safety endpoint., Results: Thirty-two patients (16 patients/group) received the study drugs. The primary endpoint, change in logMAR at week 2 compared to baseline, showed no statistically significant intergroup difference. However, compared with the SP group, change in the GGS group was increasingly indicative of visual improvement, with least squares mean difference of > 0.3 logMAR. On post-hoc analyses, the percentage of patients in the GGS and SP groups with improvement by ≥ 0.3 logMAR at week 2 were 75.0% and 31.3%, respectively. Changes in MD values at week 2 compared to baseline were 9.258  ±  8.296 (mean ± standard deviation) dB and 3.175  ±  6.167 dB in the GGS and SP groups, respectively. These results showed statistically significant intergroup differences (visual acuity improvement, P = 0.032; change in MD values, P = 0.030). No clinically significant AEs were observed., Conclusion: Our results suggest that intravenous immunoglobulin could be a safe and efficacious therapeutic option for prompt treatment of steroid-resistant acute ON., Trial Registration: JapicCTI-132080.

Purpose: To clarify the factors predictive of progression from ocular myasthenia gravis (OMG) to generalized MG (GMG) among patients with positive antiacetylcholine receptor antibodies (AChRAb) and to evaluate the efficacy of our OMG treatment protocol including tacrolimus (TAC)., Study Design: Retrospective study., Methods: Fifty-two patients with AChRAb positivity and ptosis and/or eye movement disturbance showing diurnal fluctuation and fatigability were included. First, we compared the clinical characteristics of patients without OMG progression (p-OMG) with those of patients whose OMG transformed to GMG (TMG). Second, we subdivided the p-OMG patients according to the time of approval of TAC into the Before group and the After group. We compared the dosage and period of prednisolone administration (PSL) of the 2 groups. Third, we evaluated the responses to OMG treatment using the Myasthenia Gravis Foundation of America Postintervention Status (MGFA-PS) scale., Results: Forty-one patients were classified into the p-OMG group, and 11, into the TMG group. The AChRAb level (P = 0.0006) and prevalence of thymoma (P = 0.001) were significantly higher in the TMG group than in the p-OMG group. In the p-OMG group, the MG composite score (P ≤ 0.0001) and AChRAb level (P = 0.005) improved after treatment. The periods of PSL administration at ≥ 20 mg/day (P = 0.009) and at 10 to 19 mg/day (P = 0.002) were significantly shorter in the After group. At the last follow-up, 78.0% of the p-OMG group patients had achieved MGFA-PS minimal manifestations or better status with PSL ≤ 5 mg/day., Conclusions: The TMG cases were characterized by higher AChRAb levels and presence of thymoma. The P-OMG patients could be managed with our treatment protocol. Combined use of TAC was efficacious in patients with steroid-dependent p-OMG.

Purpose: The Glaucoma Module Premium Edition (GMPE) software for the SPECTRALIS optical coherence tomography (OCT) is able to automatically track the anatomic centers of both the fovea and the optic disc. We investigated the efficacy of the OCT in measuring the ocular torsion angle before and after strabismus surgery., Methods: Between June 2017 and December 2018, 40 patients with cyclodeviation who had undergone strabismus surgery at Hyogo College of Medicine were enrolled. Ocular torsion angle measurements, including OCT and nonmydriatic fundus camera for objective measurements and synoptophore for subjective measurements, were performed before surgery and 1 day after surgery., Results: The ocular torsion angles were measured as follows: synoptophore preoperative (-8.8° ± 4.1°) and postoperative (-3.1° ± 2.8°), fundus photography preoperative (-27.2° ± 6.4°) and postoperative (-18.6° ± 5.9°), and OCT preoperative (-25.9° ± 6.8°) and postoperative (-18.2° ± 5.8°). In all cases, symptoms related to cyclodeviation resolved postoperatively. All measurements were positively correlated before surgery. Postoperatively, changes in all measurements were also correlated. However, all synoptophore-related data were underestimated when compared with OCT and fundus photography., Conclusions: For measuring the ocular torsion angle, the OCT-based technology GMPE appears to provide information regarding anatomic fundus torsion that is similar to that obtained using fundus photography., Translational Relevance: This new objective measurement for the ocular torsion angle is helpful for treating cyclotropia., Competing Interests: Disclosure: K. Yamadera, None; H. Ishikawa, None; A. Imai, None; M. Okamoto, None; A. Kimura, None; O. Mimura, None; F. Gomi, None, (Copyright 2020 The Authors.)

Purpose: To investigate the characteristics of tear abnormalities with benign essential blepharospasm (BEB) and the effect of botulinum toxin type A (BTX-A) treatment., Study Design: Prospective and clinical study., Methods: Forty eyes of 40 patients (12 men and 28 women, ages 63.5 ±12.9) with BEB and tear abnormalities were enrolled., Results: The average scores for subjective symptoms as evaluated by the visual analog scale (VAS) were 46.3 and Dry Eye-Related Quality-of-Life Score (DEQS) were 63.7. The fluorescein breakup time (FBUT) was 2.7 ± 1.6 sec. Among fluorescein breakup patterns (FBUPs), dimple break, with the corresponding mechanism of decreased wettability was the most frequent, observed in 29 eyes (73%). The NEI score was 0.4 ± 0.7 and the van Bijesterveld score was 0.6 ± 0.8; the Schirmer 1 test value was 13.1 ± 9.4 mm. Eighteen patients received BTX-A treatment, and significant improvement was found in severity of subjective symptoms both on VAS and DEQS as well as for FBUT. The main FBUPs changed from dimple break to random break., Conclusion: Tear abnormalities seen in BEB correspond to short BUT-type dry eye (DE), subclassified into decreased wettability DE in view of FBUPs.

Purpose: Congenital fibrosis of the extraocular muscles (CFEOM) is a rare nonprogressive disorder characterized by bilateral ptosis, with severely limited ocular motility. We report the treatment outcomes and problems in 3 cases of pediatric CFEOM in which extraocular muscle surgery was performed., Cases: All the cases showed bilateral ptosis and a chin-up abnormal head posture (AHP). Case 1 A 6-year-old girl. Both eyes were fixed downward with esotropia and could not elevate above the horizontal midline. She underwent simultaneous bilateral inferior rectus (IR) and medial rectus (MR) recession. Postoperatively, 8-prism-diopter (PD) exotropia was observed, and the AHP were improved, but MR advancement in the right eye was necessary because A-pattern exotropia became prominent starting about 10 months postoperatively. Case 2 A 7-year-old girl. Both eyes were fixed downward and did not elevate over the midline. She underwent bilateral IR recession. Postoperatively, 8-PD exotropia was observed; however, A-pattern exotropia became prominent gradually at about 1 year and 7 months postoperatively, and bilateral lateral rectus (LR) recession was added. Case 3 A 6-year-old girl. Both eyes were fixed downward but could be elevated above the horizontal midline by upward effort. She underwent bilateral IR recession, which resulted in improvement of the AHP and ptosis. About 8 months postoperatively, exotropia was evident only in the downward gaze., Conclusions: Bilateral IR recession in pediatric patients with CFEOM was effective in improving AHP, but postoperative exotropia appeared to be inevitable owing to the diminished adducted function caused by IR recession. Thus, horizontal strabismus surgery should be planned after the results of IR recession become evident.

Purpose: To elucidate the clinical and epidemiologic characteristics of optic neuritis in Japan., Design: Multicenter cross-sectional, observational cohort study., Participants: A total of 531 cases of unilateral or bilateral noninfectious optic neuritis identified in 33 institutions nationwide in Japan., Methods: Serum samples from patients with optic neuritis were tested for anti-aquaporin-4 antibodies (AQP4-Abs) and anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) using a cell-based assay and were correlated with the clinical findings., Main Outcome Measures: Antibody positivity, clinical and radiologic characteristics, and visual outcome., Results: Among 531 cases of optic neuritis, 12% were AQP4-Ab positive, 10% were MOG-Ab positive, 77% were negative for both antibodies (double-negative), and 1 case was positive for both antibodies. Pretreatment visual acuity (VA) worsened to more than a median 1.0 logarithm of the minimum angle of resolution (logMAR) in all groups. After steroid pulse therapy (combined with plasmapheresis in 32% of patients in AQP4-Ab-positive group), median VA improved to 0.4 logMAR in the AQP4-Ab-positive group, 0 logMAR in the MOG-Ab-positive group, and 0.1 logMAR in the double-negative group. The AQP4-Ab-positive group showed a high proportion of females, exhibited diverse visual field abnormalities, and demonstrated concurrent spinal cord lesions on magnetic resonance imaging (MRI) in 22% of the patients. In the MOG-Ab-positive group, although posttreatment visual outcome was good, the rates of optic disc swelling and pain with eye movement were significantly higher than those in the AQP4-Ab-positive and double-negative groups. However, most cases showed isolated optic neuritis lesions on MRI. In the double-negative group, 4% of the patients had multiple sclerosis. Multivariate logistic regression analysis of all participants identified age and presence of antibodies (MOG-Ab and AQP4-Ab) as significant factors affecting visual outcome., Conclusions: The present large-scale cohort study revealed the clinicoepidemiologic features of noninfectious optic neuritis in Japan. Anti-aquaporin-4 antibody-positive optic neuritis has poor visual outcome. In contrast, MOG-Ab positive cases manifested severe clinical findings of optic neuritis before treatment, but few showed concurrent lesions in sites other than the optic nerve and generally showed good treatment response with favorable visual outcome. These findings indicate that autoantibody measurement is useful for prompt diagnosis and proper management of optic neuritis that tends to become refractory., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

During precision radiotherapy to treat optic nerve sheath meningioma, early improvement in visual function has been seen. This has been difficult to explain biologically. In the present study, we aimed to investigate this rapid improvement in visual function. To this end, we prospectively tested a single patient's visual field (VF) using Humphrey automated perimetry at weekly intervals. The patient exhibited significant stepwise improvement in VF during an intensity-modulated radiotherapy course., Competing Interests: Conflict of interestNo author has any conflict of interest to disclose.

Background: There has been a paradigm shift in the treatment for optic nerve sheath meningioma (ONSM) from surgery to fractionated stereotactic radiotherapy (FSRT) in other countries. However, FSRT has seldom been performed in Japan. The purpose of this retrospective study is to reconfirm the effectiveness of early intervention with precision radiotherapy for ONSM reported in our previous study., Methods: Five consecutive patients with ONSM were retrospectively analyzed. All patients underwent intensity-modulated radiotherapy (IMRT) or FSRT. They received the early interventions between 1.5 and 7 months after deterioration of the disease. The median dose was 52.8 Gy (range 46.0-59.4 Gy) and the median number of fractions was 25 (range 22-33)., Results: All patients experienced reestablishment of vision at the median follow-up time of 36 months (range 18-54 months). Four of them noted early improvement of visual deficits during the treatment course (range 2-4 weeks) and the remaining patient improved 3 weeks after completion of IMRT. The median tumor reduction was 53% (range 39-75%). One patient with diabetes mellitus developed retinal bleeding as a result of radiation retinopathy 16 months after IMRT, although the doses were acceptable. The remaining 4 patients have no late toxicity at the follow-up time of 31-54 months., Conclusions: A paradigm shift is necessary from surgery to early intervention using precision radiotherapy for the treatment of ONSM in Japan.

Background/aims: To evaluate the effects of botulinum toxin type A (BTX-A) treatment in patients with benign essential blepharospasm (BEB) by monitoring the ocular surface and ocular higher-order aberrations (HOAs) before and after treatment., Methods: The present study reports a prospective case series of 38 patients (76 eyes, 11 men and 27 women; mean age 66.8 ± 9.8 years) with BEB who underwent BTX-A treatment at Kokura Memorial Hospital between 2013 and 2014. Patients were evaluated for ophthalmoscopic findings, Schirmer I test, tear film break-up time (t-BUT), HOAs, fluctuation index (FI), stability index (SI) using a wavefront aberrometer, 15 subjective symptoms using the Dry Eye-Related Quality of Life Score (DEQS), and complications before and after the treatment., Results: After BTX-A treatment, the Schirmer I test score improved significantly from 5.9 ± 5.4 to 8.7 ± 6.1 mm and t-BUT recovered from 5.2 ± 1.7 to 7.3 ± 1.7 s. HOAs were classified into four patterns: stable (60.5 %), small fluctuation (14.5 %), sawtooth (17.1 %), and reverse sawtooth (7.9 %), and they significantly reduced after the treatment. Only FI (not SI) showed a marked reduction, and the DEQS significantly improved from 44.7 ± 21.6 to 37.6 ± 21.0 after the treatment (p < 0.05). There were no complications during the observations., Conclusion: BTX-A is a treatment with a high potential to improve ocular surface disorders induced by BEB.

Background: We report a case of a corneal disorder after breast cancer treatment with a microtubule inhibitor, nab-paclitaxel (Abraxane)., Case: A 55-year-old woman, who was referred to our clinic, presented with blurred vision. 2 weeks previously, she had been undergoing treatment with nab-paclitaxel, trastuzumab and pertuzumab. Visual acuity was 20/60 in right eye and 20/40 in left eye. Slit-lamp examination showed an atypical epithelium invasion of the cornea in both eyes and small epithelial defect in left eye. After the nab-paclitaxel treatment was discontinued the corneal findings improved. 4 months later, visual acuity was 20/15 in right eye and 20/20 in left eye., Conclusions: Nab-paclitaxel can cause severe corneal disorders, but the possibility that trastuzumab and pertuzumab combination therapy is associated with these disorders cannot be denied. Clinicians should consider the possibility of the side effects caused by systemic administration in cases of corneal disorders of uncertain etiology.

Designation criteria for Leber's hereditary optic neuropathy (LHON) have been established by a working group for retino-choroidal and optic atrophy funded by the Ministry of Health, Labor, and Welfare (MHLW) of Japan in collaboration with the Japanese Neuro-ophthalmology Society. The criteria are composed of three major symptoms and three ancillary test findings. According to the number and the combination of these symptoms and findings, subjects are classified into definite, probable, and possible LHON cases and asymptomatic carriers. The major symptoms include bilateral involvement with a time-lag, a papillomacular bundle atrophy, both characteristic optic disc findings at the acute phase. In the ancillary testings, mitochondrial DNA mutations specific for LHON are detailed with a table listing the mutation loci being attached. To enhance readers' understanding of description of the major symptoms and ancillary test findings, explanatory remarks on 11 parameters are supplemented. The establishment of the criteria facilitates epidemiological survey of LHON by MHLW and contributes to improvement of welfare for patients with LHON in Japan.

Purpose: To determine the clinical symptoms of Fisher syndrome (FS)., Methods: We performed a retrospective study of 19 patients who had been diagnosed as having FS., Results: The study involved 19 patients (13 men and 6 women) whose mean age of onset was 42.0 years. Ophthalmoplegia included 16 cases of abducens nerve palsy, 2 cases of total external ophthalmoplegia, and 1 combined case of abducens nerve palsy and impaired eye elevation. Although all cases of abducens nerve palsy were bilateral, in 5 cases the degree of the affliction was asymmetric. Other neurologic symptoms included 5 cases of nystamus, 5 cases of pain on eye movement, 5 cases of pupillary defects, 6 cases of blepharoptosis, 2 cases of facial palsy, 9 cases of dysesthesia in the limbs, 3 cases of ataxia and 1 case of bulbar palsy. Anti-GQ1b antibodies were detected in 74% of the patients. Sixteen patients were followed without treatment while 1 patient, was given oral vitamin B12 and 2 patients received intravenous immunoglobulin. Double vision improved in all cases, and the mean duration of double vision was approximately 70 days., Conclusions: FS develops in people of all ages and is more common in men. Also, abducens nerve palsy is common in FS. While it is rare to observe the triad of ophthalmoplegia, ataxia and areflexia, the frequency in which the disorder is complicated by neurologic symptoms other than the triad is high. Double vision has a good prognosis and improves even without treatment.

Purpose: We carried out a national clinical investigation of anti-aquaporin-4 seropositive optic neuritis which is resistant to steroid pulse therapy., Methods: A questionnaire of clinical training institutions authorized by the Japanese Ophthalmological Society regarding anti-aquaporin-4 seropositive optic neuritis., Results: We received responses from 44 facilities (40%). There were 188 anti-aquaporin-4 seropositive cases (24 men, 162 women), with a mean age of 52.4 +/- 15.5 (14-88 years old, median 54). Visual acuity at the time of the first medical examination was 3.4 to -0.18 logMAR (median 1.30) and at the last 3.4 to -0.18 logMAR (median 0.70). The average number of times of recurrence and steroid pulse therapy were 1.5 +/- 2.3 (median 1) and 3.3 +/- 4.1 (median 2) respectively. There was no significant difference in visual acuity between patients who received additional therapy such as plasma exchange therapy and immunoadsorption therapy and patients who were not treated additionally., Conclusions: Clinical characteristics of anti-aquaporin-4 seropositive optic neuritis were revealed. A well-designed prospective study is needed to obtain evidence of availability of plasma exchange therapy and other related issues.

Purpose: To investigate the ability of patients with strabismus and/or amblyopia to see 3D images., Methods: A questionnaire survey conducted for children aged 6 to 19 years and adults aged 20 to 39 years on their experience of viewing 3D images (movies, motion attractions, television, games), asking whether they could see stereoscopically, with or without adverse effects. A retrospective investigation of ophthalmological examinations was followed., Results: Of 507 cases, 342 had had the experience of veiwing 3D images. In 212 (62%) cases of strabismus and/or amblyopia, stereopsis was lacking in 17 to 18% of the subjects for movies, in 6 to 7% for attractions, in 32% in children and 50% in adults for television and 23% in children and 17% in adults for games. Adults complained of a higher rate of adverse effects, 65% for movies and 75% for games, as compared with 34% for movies and 26% for games in children(p < 0.01). The lack of stereopsis for games and movies was higher in the subgroup of Fly (-) and convergence insufficiency (p < 0.05)., Conclusions: Since many patients with strabismus and/or amblyopia found some difficulty in stereoscopic viewing, precise examinations for stereopsis and convergence are needed to assess individual aptitude for 3D viewing.

Background and Purpose: Despite the reported functional recovery in transplanted stroke models and patients, the mechanism of action underlying stem cell therapy remains not well understood. Here, we examined the role of stem cell-mediated vascular repair in stroke., Methods: Adult rats were exposed to transient occlusion of the middle cerebral artery and 3 hours later randomly stereotaxically transplantated with 100K, 200K, or 400K human cerebral endothelial cell 6 viable cells or vehicle. Animals underwent neurological examination and motor test up to day 7 after transplantation then euthanized for immunostaining against neuronal, vascular, and specific human antigens. A parallel in vitro study cocultured rat primary neuronal cells with human cerebral endothelial cell 6 under oxygen-glucose deprivation and treated with vascular endothelial growth factor (VEGF) and anti-VEGF., Results: Stroke animals that received vehicle infusion displayed typical occlusion of the middle cerebral artery-induced behavioral impairments that were dose-dependently reduced in transplanted stroke animals at days 3 and 7 after transplantation and accompanied by increased expression of host neuronal and vascular markers adjacent to the transplanted cells. Some transplanted cells showed a microvascular phenotype and juxtaposed to the host vasculature. Infarct volume in transplanted stroke animals was significantly smaller than vehicle-infused stroke animals. Moreover, rat neurons cocultured with human cerebral endothelial cell 6 or treated with VEGF exhibited significantly less oxygen-glucose deprivation-induced cell death that was blocked by anti-VEGF treatment., Conclusions: We found attenuation of behavioral and histological deficits coupled with robust vasculogenesis and neurogenesis in endothelial cell-transplanted stroke animals, suggesting that targeting vascular repair sets in motion a regenerative process in experimental stroke possibly via the VEGF pathway.

Background: Refractive change can be caused by systemic illnesses such as Lupus erythematosus, thyroid deficiency, and diabetes mellitus. However, refractive change after pituitary tumor removal has so far not been reported., Case Presentation: A 62-year-old woman presented with blurred near vision 10 days after trans-sphenoidal surgery (TSS) for a pituitary tumor. Around the same time, she experienced intercurrent hyponatremia. The corrected visual acuity of both eyes was 20/20, the spherical equivalent of the right eye was -2.125 diopters, and of the left eye was -2.0 diopters before TSS. However, 11 days after TSS, the spherical equivalent of the right eye changed to -0.75 diopters, and that of left eye changed to -1.125 diopters without hyperglycemia. There were no changes in the corrected visual acuity during the follow-up., Conclusion: We demonstrated a case with transient refractive change after TSS. The following mechanism is proposed: Hyponatremia induced by the pituitary tumor removal causes an osmotic change in the aqueous humor with lens swelling. This case report is a reminder to both ophthalmologists and neurosurgeons that ophthalmological factors such as lens thickness and axial length should be taken into account when conducting preoperative examinations especially for patients undergoing TSS.

Background and Purpose: Ischemic stroke is a leading cause of mortality and morbidity in the world and may be associated with cardiac myocyte vulnerability. However, it remains uncertain how an ischemic brain contributes to cardiac alternations. Here, we used experimental stroke models to reveal the pathological effects of the ischemic brain on the heart., Methods: For the in vitro study, primary rat neuronal cells were subjected to 90-minute oxygen-glucose deprivation (OGD). Two hours after OGD, the supernatant was collected and cryopreserved until further biological assays. Primary rat cardiac myocytes were exposed to ischemic-reperfusion injury and subsequently to the supernatant derived from either the OGD or non-OGD-exposed primary rat neuronal cells for 2, 6, 24, or 48 hours. Thereafter, we measured cell viability and mitochondrial activity in rat cardiac myocytes. For the in vivo study, we subjected adult rats to transient middle cerebral artery occlusion, and their brains and hearts were harvested for immunohistochemical analyses at 3 months later., Results: The supernatant from the OGD, but not the non-OGD-exposed primary rat neuronal cells, caused significant reduction in cell viability and mitochondrial activity in rat cardiac myocytes. Ischemic stroke animals displayed phenotypic expression of necrosis, apoptosis, and autophagy in their hearts, which paralleled the detection of these same cell death markers in their brains., Conclusions: Ischemic stroke was accompanied by cardiac myocyte death, indicating a close pathological link between brain and heart. These results suggest a vigilant assessment of the heart condition in stroke patients, likely requiring the need to treat systemic cardiac symptoms after an ischemic brain episode.

Peripheral nerve injury activates spinal glial cells, which may contribute to the development of pain behavioral hypersensitivity. There is growing evidence that activated microglia show dynamic changes in cell morphology; however, the molecular mechanisms that underlie the modification of the membrane and cytoskeleton of microglia are not known. Here, we investigated the phosphorylation of ezrin, radixin, and moesin (ERM) proteins in the spinal cord after peripheral nerve injury. ERM is known to function as membrane-cytoskeletal linkers and be localized at filopodia- and microvilli-like structures. ERM proteins must be phosphorylated at a specific C-terminal threonine residue to be in the active state. The nature of ERM proteins in the spinal cord of animals in a neuropathic pain model has not been investigated and characterized. In the present study, we observed an increase in the phosphorylated ERM in the spinal microglia following spared nerve injury. The intrathecal administration of lysophosphatidic acid induced the phosphorylation of ERM proteins in microglia along with the development of mechanical pain hypersensitivity. Intrathecal administration of ERM antisense locked nucleic acid suppressed nerve injury-induced tactile allodynia and decreased the phosphorylation of ERM, but not the Iba1 staining pattern, in spinal glial cells. These findings suggest that lysophosphatidic acid induced the phosphorylation of ERM proteins in spinal microglia and may be involved in the emergence of neuropathic pain. These findings may underlie the pathological mechanisms of nerve injury-induced neuropathic pain., (Copyright © 2012 Wiley Periodicals, Inc.)

Purpose: We present a case of idiopathic orbital inflammatory disease with dilatation and tortuosity of the retinal veins., Case: A 74-year-old man presented at his local eye hospital with left conjunctival edema and pain. He was referred to our hospital. At the initial examination, the intraocular pressure was 19 mmHg OD and 40 mmHg OS. Examination of the left eye revealed conjunctival edema with dilated and tortuous blood vessels, and dilatation and tortuousity of the retinal veins. Magnetic resonance imaging showed marked thickening of the left extraocular muscles, and suspected compression of the left superior and inferior ophthalmic veins. We diagnosed left idiopathic orbital inflammatory disease, and administered a tapering course of prednisolone starting at 40 mg daily. Thirteen days later, the conjunctival findings improved, but the left fundus showed signs of non-ischaemic central retinal vein occlusion. Subsequently, the dilatation and tortuousity of the retinal veins gradually improved. At the final examination, recurrence was not noted., Conclusion: We report a case of idiopathic orbital inflammatory diseases with central retinal vein occlusion. The dilatation and tortuousity of the conjunctiva and central retinal vein occlusion improved with steroid therapy only. These Conditions improved because the inflammatory swelling of the extraocular muscle disappeared and the pressure to the vein was relieved.

Purpose: To investigate the effects of transcorneal electrical stimulation (TES) on eyes that have a branch retinal artery occlusion (BRAO)., Subjects and Method: We studied two eyes having a BRAO, with an interval between the onset of symptoms and the beginning of treatment of >16 weeks (longstanding cases), and in three eyes with an interval of <16 weeks (fresh cases). The visual functions of the eyes were assessed by the best-corrected visual acuity (BCVA), multifocal electroretinograms (mfERGs), and automated static perimetry with the Humphrey field analyzer (HFA). The mfERGs were recorded before and 1 month after the TES, and perimetry with the HFA was done before and at 1 and 3 months after the TES. The amplitudes and implicit times of the N1, P1, and N2 components of the mfERGs were analyzed., Results: TES did not alter the BCVA significantly in all eyes, but it led to a significant increase in the amplitude of the N2 wave of the mfERGs (P < 0.01). The amplitude of the N1-P1 was also increased but not significantly. The implicit times of N1 (P < 0.01) and P1 (P < 0.05) were significantly shorter than that before the TES. The mean deviation of the HFA was increased after the TES but only in the longstanding cases., Conclusion: Our results indicate that TES improves the visual function in eyes with BRAO, mainly in longstanding cases.

Purpose: The aim of this article is to investigate the effect of transcorneal electrical stimulation (TES) on chorioretinal blood flow in healthy human subjects., Methods: The chorioretinal blood flow of 10 healthy subjects was measured before and after TES by laser speckle flowgraphy and expressed as the square blur rate (SBR). The chorioretinal blood flow was determined before and immediately after TES and 0.5, 1, 1.5, 2, 2.5, 3, 24, and 40 h after TES in three different areas: the margin of the optic disc, a point located midway between the optic disc and macula, and the macula area. The SBR of the stimulated eye is expressed relative to the value of the fellow eye. The mean standardized blur ratio was calculated as the ratio of the standardized SBR to the baseline SBR. The changes of intraocular pressure (IOP), blood pressure (BP), and pulse rate (PR) were determined after each measurement of the SBR. The ocular perfusion pressure (OPP) was calculated from BP and IOP., Results: The mean standardized blur ratio at the optic disc did not change significantly throughout the course of the experiment. However, the mean standardized blur ratio midway between the optic disc and macula and at the macula area were significantly higher after TES than that after sham stimulation at 3 and 24 h (P < 0.05, P < 0.01, respectively). At all times, the mean BP, PR, IOP, and OPP were not significantly different from the prestimulation values., Conclusions: TES increases the chorioretinal blood flow in normal subjects with minimal effects on the systemic blood circulation and the IOP. The increase in chorioretinal blood flow may be one of the beneficial effects that TES has on ischemic retinal diseases.

IL-33, a member of the IL-1 family of cytokines, is the ligand for ST2 (IL-33Ralpha chain). IL-33 has the capacity to induce T(h)2 cytokine production from T(h)2 cells, mast cells and basophils, indicating that IL-33 has the potential to induce T(h)2 cytokine-mediated allergic inflammation of the eye. Thus, we tested the pathological role of IL-33 in allergic conjunctivitis (AC). As reported elsewhere, animals immunized with ragweed pollen (RW)/alum and boosted with RW/PBS developed AC promptly (within 15 min) and conjunctival eosinophilic inflammation after a delay (within 24 h) in response to eye drop challenge with RW. Furthermore, RW-immunized mice, when topically challenged with both RW and IL-33, developed more striking eosinophilia in their conjunctiva without exacerbation of the clinical AC score. This in vivo IL-33 treatment significantly increased the capacity of T cells in the cervical lymph nodes of RW-immunized mice to produce IL-4, IL-5 and IL-13 upon challenge with anti-CD3 and anti-CD28 antibodies in vitro. Furthermore, the infiltrating cells were largely eosinophils and a small proportion of CD4(+) T cells, both of which express ST2. We also found that even splenic eosinophils express ST2 and show increased expression in response to IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF) or IL-33. Eosinophils, stimulated with IL-5 and/or GM-CSF, are responsive to IL-33, which induces production of IL-4 and chemokines. Finally, we showed that conjunctival tissues constitutively express biologically active IL-33, suggesting that IL-33 might play a crucial role in the induction and augmentation of AC.

Background: A case of acute lymphoblastic leukemia in which a variety of ophthalmic findings were observed., Case: A 27-year-old woman with acute lymphoblastic leukemia. Ocular findings were Roth's spot and serous retinal detachment. Fluorescein angiography revealed no clear leak point. Subsequently, the serous retinal detachment disappeared. Within 4 months after the initial diagnosis, cytomegalovirus (CMV) retinitis occurred, and further keratoconjunctivitis and serous retinal detachment recurred due to Graft-versus-Host Disease (GVHD), thus resulting in death 4 months later., Conclusions: Cases in which patients with leukemia complicated by serous retinal detachment during the course often result in death. In the present case, CMV retinitis and keratoconjunctivitis occurred due to GVHD after serous retinal detachment, thus resulting in death 8 months after the initial diagnosis, therefore if serous retinal detachment is observed in a leukemia patient, it is necessary to perform periodical ophthalmologic examinations even after the ocular symptoms disappear.

To evaluate the pharmacological properties of cilostazol (CLZ), we examined its intraocular pressure (IOP) -lowering effect. CLZ is an inhibitor of Type III phosphodiesterase that increases intracellular cyclic AMP levels by restraining platelet aggregation, and has a potential protective effect against atherosclerosis. We attempted to apply it for use as an anti-glaucoma agent; however, the application of CLZ in the ophthalmic field is limited due to its poor water solubility. We attempted to enhance CLZ solubility using 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD). The solubility of CLZ increased with increasing HPbetaCD concentrations, and 0.05% CLZ was dissolved in 10% HPbetaCD. Moreover, fine particle suspension of 0.5% CLZ in 5% HPbetaCD (soluble CLZ: ca. 0.027%) were prepared using a Microfluidizer, an impact-type emulsifying comminution device. In an in vitro transcorneal penetration experiment through the rabbit cornea, the CLZ penetration rate was dependent on the CLZ content of the solutions and suspensions. When a 0.05% CLZ ophthalmic solution was instilled into a rabbit eye, the absorption rate constant for CLZ into an aqueous humor was 0.0059+/-0.001 min(-1), and the elimination rate constant was 0.048+/-0.024 min(-1). Also CLZ ophthalmic solutions and fine particle suspension were examined to for their ability to reduce enhanced intraocular pressure (IOP) of rabbits in a darkroom. The instillation of 0.05% CLZ ophthalmic solutions and 0.5% CLZ fine particle suspensions into rabbit eyes reduced the enhanced IOP. These results demonstrate that the instillation of CLZ ophthalmic solutions and fine particle suspensions may represent an effective anti-glaucoma formulation.

Objective: The visual efficiency scale currently adopted to determine the legal grade of visual disability associated with visual field loss in Japan is not appropriate for the evaluation of disability regarding daily living activities. We investigated whether Esterman disability score (EDS) is suitable for the assessment of mobility difficulty in patients with visual field loss., Methods: The correlation between the EDS calculated from Goldmann's kinetic visual field and the degree of subjective mobility difficulty determined by a questionnaire was investigated in 164 patients with visual field loss. The correlation between the EDS determined using a program built into the Humphrey field analyzer and that calculated from Goldmann's kinetic visual field was also investigated., Results: The EDS based on the kinetic visual field was correlated well with the degree of subjective mobility difficulty, and the EDS measured using the Humphrey field analyzer could be estimated from the kinetic visual field-based EDS., Conclusion: Instead of the currently adopted visual efficiency scale, EDS should be employed for the assessment of mobility difficulty in patients with visual field loss, also to establish new judgment criteria concerning the visual field.

The ectopic distribution of synaptic ribbons in dendrites of mouse retinal bipolar cells was examined by using genetic ablation of metabotropic glutamate receptor subtype 6 (mGluR6), electron microscopy, and immunocytochemistry. Ectopic ribbons were observed in dendrites of rod and ON-cone bipolar cells in the mGluR6-deficient mouse but not in those of wild-type mice. The number of rod spherules facing the ectopic ribbons in mGluR6-deficient rod bipolar dendrites increased gradually during early growth and reached a plateau level of about 20% at 12 weeks. These ectopic ribbons were immunopositive for RIBEYE, a ribbon-specific protein, but the associated vesicles were immunonegative for synaptophysin, a synaptic-vesicle-specific protein. The presence of ectopic ribbons was correlated with an increase in the roundness of the invaginating dendrites of the rod bipolar cells. We further confirmed ectopic ribbons in dendrites of OFF-cone bipolar cells in wild-type retinas. Of the four types of OFF-cone bipolar cells (T1-T4), only the T2-type, which had a greater number of synaptic ribbons at the axon terminal and a thicker axon cylinder than the other types, had ectopic ribbons. Light-adapted experiments revealed that, in wild-type mice under enhanced-light adaptation (considered similar to the mGluR6-deficient state), the roundness in the invaginating dendrites and axon terminals of rod bipolar cells increased, but no ectopic ribbons were detected. Based on these findings and known mechanisms for neurotransmitter release and protein trafficking, the possible mechanisms underlying the ectopic ribbons are discussed on the basis of intracellular transport for the replenishment of synaptic proteins.