Assessment of objective visual function following idebenone administration in patients with leber hereditary optic neuropathy.

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.

A Case of Bilateral Papilledema With Improved Clinical Symptoms by Venous Stenting for Superior Sagittal Sinus Stenosis.

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.

Intravenous immunoglobulin treatment for steroid-resistant optic neuritis: a multicenter, double-blind, randomized, controlled phase III study.

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.

Characteristics of Japanese patients with Leber's hereditary optic neuropathy and idebenone trial: a prospective, interventional, non-comparative study.

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.

Clinical features and treatment status of antiacetylcholine receptor antibody-positive ocular myasthenia gravis.

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.

A Novel Method for Evaluation of Ocular Torsion Angle by Optical Coherence Tomography.

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.

Surgical management of pediatric patients with congenital fibrosis of the extraocular muscles.

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.

Characteristics of tear abnormalities associated with benign essential blepharospasm and amelioration by means of botulinum toxin type A treatment.

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.

Epidemiologic and Clinical Characteristics of Optic Neuritis in Japan.

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.

The rapid improvement in visual field defect observed with weekly perimetry during intensity-modulated radiotherapy for optic nerve sheath meningioma.

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.

Early intervention using high-precision radiotherapy preserved visual function for five consecutive patients with optic nerve sheath meningioma.

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.

Rapid recovery of vision following early intervention with fractionated stereotactic radiotherapy for optic nerve sheath meningioma.

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.

Changes in ocular higher-order aberrations following botulinum toxin treatment in patients with blepharospasm : BTX improves dry eye in patients with BEB.

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.

[A Case of a Corneal Disorder after Breast Cancer Treatment with Nab-paclitaxel].

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.

Epidemiological evaluation of YAG capsulotomy incidence for posterior capsule opacification in various intraocular lenses in Japanese eyes.

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<0.05). The average YAG rates for all sharp-edged and round-edged IOLs at 5 years postimplantation were, respectively, 5.2%±0.7% and 25.6%±9.0% (P<0.05). CONCLUSION: In all studied IOLs, posterior capsule opacification prevention seemed to be associated with the posterior optic sharp-edge design. Round-edged silicone IOLs may also retard posterior capsule opacification formation, though not as much as sharp-edged IOLs. As the follow-up period progressed, round-edged silicone IOLs showed significantly higher YAG rates than sharp-edged IOLs.

[Designation criteria for Leber's hereditary optic neuropathy].

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.

Surgical effects of nasal transposition of inferior rectus muscle - 135 cases of acquired superior oblique palsy.

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.

[Clinical features of 19 cases of Fisher syndrome].

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.