Potentially compromised systemic and local lactate metabolic balance in glaucoma, which could increase retinal glucose and glutamate concentrations.

To investigate the association between lactate metabolism and glaucoma, we conducted a multi-institutional cross-sectional clinical study and a retinal metabolomic analysis of mice with elevated intraocular pressure (IOP) induced by intracameral microbead injection. We compared lactate concentrations in serum and aqueous humor in age-matched 64 patients each with primary open-angle glaucoma (POAG) and cataract. Neither serum nor aqueous humor lactate concentrations differed between the two groups. Multiple regression analysis revealed that only body mass index showed a significant positive correlation with serum and aqueous humor lactate concentration in POAG patients (rs = 0.376, P = 0.002, and rs = 0.333, P = 0.007, respectively), but not in cataract patients. L-Lactic acid was one of the most abundantly detected metabolites in mouse retinas with gas chromatography and mass spectrometry, but there were no significant differences among control, 2-week, and 4-week IOP elevation groups. After 4 weeks of elevated IOP, D-glucose and L-glutamic acid ranked as the top two for a change in raised concentration, roughly sevenfold and threefold, respectively (ANOVA, P = 0.004; Tukey-Kramer, P < 0.05). Glaucoma may disrupt the systemic and intraocular lactate metabolic homeostasis, with a compensatory rise in glucose and glutamate in the retina.

Impact of glaucoma medications on subsequent Schlemm's canal surgery outcome: Cox proportional hazard model and propensity score-matched analysis.

PURPOSE: The impact of various preoperative glaucoma medications on Schlemm's canal surgery outcomes remains unclear. This study aimed to investigate the impact of preoperative glaucoma medications on the postoperative 1-year outcomes of µTLO. METHODS: We analyzed the medical records of 218 patients who underwent their first µTLO to investigate the 1-year postoperative outcomes. Cox proportional hazard regression analysis was performed with surgical failure as the dependent variable and each type of preoperative medication as the independent variable. We also compared the 1-year outcomes of µTLO between users and non-users of specific medications using propensity score matching. Surgical success was defined as a postoperative intraocular pressure ranging from 5 to 21 mmHg, a ≥20% reduction in IOP from baseline, and no additional glaucoma surgery within 1 year postoperatively. RESULTS: The Cox proportional hazard analysis showed that all drugs that do not increase the conventional outflow exhibited hazard ratios greater than 1.0, and the preoperative use of ß-blockers and oral CAI was a significant surgical risk factor (hazard ratio: 2.65 and 2.45, p = 0.04 and <0.001). In the propensity score matching analysis, success rates at 1 year postoperatively were 55/85, 54/79, 60/73, and 40/76% for users/non-users of ß-blockers, topical CAIs, an alpha-2 adrenergic agonist, and an oral CAI, respectively. Kaplan-Meier survival curves in these comparisons also demonstrated that preoperative ß-blockers and oral CAI use were significant surgical risks (p = 0.01, <0.001). CONCLUSION: Our study suggests that preoperative medications that do not involve conventional pathway outflow have a detrimental effect on subsequent Schlemm's canal surgery outcomes.

Randomized Multicenter Clinical Trial Comparing 0.1% Brimonidine/0.5% Timolol Versus 1% Dorzolamide/0.5% Timolol as Adjuncts to Prostaglandin Analogues: Aibeta Crossover Study.

INTRODUCTION: This multicenter, randomized, comparative, and investigator-masked crossover clinical trial sought to compare the efficacy and tolerability of fixed combinations of 0.1% brimonidine/0.5% timolol (BTFC) versus 1% dorzolamide/0.5% timolol (DTFC) as adjunctive therapies to prostaglandin analogues. METHODS: A total of 110 patients with open-angle glaucoma or ocular hypertension previously treated with prostaglandin analogue monotherapy were randomized to receive either BTFC or DTFC as adjunctive therapy for 8 weeks. These patients were then crossed over to the alternative treatment arm for another 8 weeks. The reduction in intraocular pressure (IOP) (primary outcome), occurrence of adverse events, ocular discomfort after instillation, and patient preference (secondary outcomes) were recorded through patient interviews. RESULTS: BTFC instillation for 8 weeks reduced IOP by 3.55 mmHg, demonstrating non-inferiority to DTFC instillation (3.60 mmHg; P < 0.0001, mixed-effects model). Although adverse events were rare with both combinations, patients reported greater discomfort with DTFC than with BTFC (P < 0.0001). More patients preferred BTFC (P < 0.0001) over DTFC, as BTFC caused minimal or no eye irritation. CONCLUSION: As BTFC offered better tolerability than DTFC with comparable reduction in IOP, we recommend it as an alternative for patients who experience ocular discomfort with DTFC-prostaglandin analogue combination therapy. TRIAL REGISTRATION NUMBER: jRCTs051190125.

Patients with glaucoma who require further reduction in intraocular pressure while undergoing monotherapy with prostaglandin analogue ophthalmic solution have been prescribed two enhanced treatment options: 0.1% brimonidine/0.5% timolol fixed combination ophthalmic solution (BTFC) and 1% dorzolamide/0.5% timolol fixed combination ophthalmic solution (DTFC). The Aibeta Crossover Study Group in Japan compared the efficacy and tolerability of fixed combinations of BTFC versus DTFC when an additional fixed combination ophthalmic solution was prescribed in patients with open-angle glaucoma or ocular hypertension who had been treated with prostaglandin analogue monotherapy. We recruited 110 patients previously treated with prostaglandin analogue monotherapy at 20 clinical centers in Japan, then randomly assigned them to two alternative treatment groups: the BTFC to DTFC group or the DTFC to BTFC group, as an adjunctive therapy to prostaglandin analogues for total of 16 weeks. We compared the reduction in intraocular pressure, occurrence of side effects, eye discomfort after instillation, and patient preference between BTFC versus DTFC instillations. The intraocular pressure reduction of BTFC instillation was comparable to that of DTFC instillation, showing non-inferiority to DTFC (3.55 mmHg vs. 3.60 mmHg; P < 0.0001, mixed-effects model). Both eye drops caused few side effects; however, patients felt greater eye discomfort with DTFC than with BTFC (P < 0.0001). Because of less eye irritation, more patients preferred BTFC (P < 0.0001) over DTFC. We can recommend using BTFC for patients who feel eye discomfort with DTFC­prostaglandin analogue combination therapy.

Test-retest repeatability of the imo binocular random single-eye test and Humphrey monocular test in patients with glaucoma.

PURPOSE: To evaluate the reproducibility of the imo binocular random single-eye test (BRSET) and Humphrey Field Analyzer (HFA) monocular test in patients with glaucoma. STUDY DESIGN: Retrospective observational study. METHODS: We measured the visual fields (VF) of patients with glaucoma using the BRSET and HFA. All tests were repeated two months later. Mean sensitivity (MS), mean deviation (MD), sensitivity at each test location, and reliability indices were compared between the test days. Wilcoxon signed-rank test, interclass correlation coefficient (ICC), correlation coefficients, and Bland-Altman plots were generated for analysis. RESULTS: We analyzed the VFs of 46 patients with glaucoma. There were no test-retest differences for MS and MD, and ICCs were > 0.9 for MS and MD in both perimeters. Inter-test correlations for MS and MD were high. The limits of agreement (LoAs) (lower, upper limit) between test days for MS were (- 3.4, 4.0) for BRSET and (-3.3, 3.0) for HFA. The LoA for MD was (- 3.3, 3.8) for BRSET and (- 3.2, 2.9) for HFA. Sensitivity at each testing location was more variable between testing days for BRSET than for HFA. For reliability indices, LoAs between testing days were wider for BRSET than for HFA. CONCLUSION: The imo BRSET showed similar reproducibility to HFA in MS and MD. However, sensitivity at each test location varied more for BRSET than for HFA. Further studies are needed to verify the reproducibility of the imo BRSET.

Detection of Relative Afferent Pupillary Defect and Its Correlation with Structural and Functional Asymmetry in Patients with Glaucoma Using Hitomiru, a Novel Hand-Held Pupillometer.

Patients with asymmetric glaucomatous optic neuropathy (GON) present a relative afferent pupillary defect (RAPD) in the eye with more advanced damage. Although useful, pupillometric RAPD quantification is not widely used as it is not portable. Whether asymmetry of the peripapillary capillary perfusion density (CPD) detected using optical coherence tomography angiography correlates with the severity of RAPD remains unknown. This study assessed RAPD in 81 patients with GON using Hitomiru, a novel hand-held infrared binocular pupillometer. The correlation and ability to detect clinical RAPD based on the swinging flash light test of two independent RAPD parameters (the maximum pupil constriction ratio and the constriction maintenance capacity ratio) were assessed. The coefficient of determination (R2) was calculated between each of the two RAPD parameters and asymmetry of the circumpapillary retinal nerve fiber layer thickness (cpRNFLT), ganglion cell layer/inner plexiform layer thickness (GCL/IPLT), and CPD. The two RAPD parameters showed a correlation coefficient of 0.86 and areas under the receiver operating characteristic (ROC) curve of 0.85-0.88, with R2 being 0.63-0.67 for the visual field, 0.35-0.45 for cpRNFLT, 0.45-0.49 for GCL/IPLT, and 0.53-0.59 for CPD asymmetry. Hitomiru has high discriminatory performance in detecting RAPD in patients with asymmetric GON. CPD asymmetry may better correlate with RAPD than cpRNFLT and GCL/IPLT asymmetry.

Favorable effect of ripasudil use on surgical outcomes of microhook ab interno trabeculotomy.

PURPOSE: We have previously demonstrated that prolonged use of glaucoma medications was associated with a poor surgical outcome of ab interno trabeculotomy (µTLO). Given that almost all types of glaucoma eye drop either enhance the drainage through the uveoscleral pathway or reduce aqueous humor production, we hypothesized that prolonged use of these medications might cause disuse atrophy of the conventional pathway. In contrast, ripasudil increases the conventional outflow and eventually shows a favorable outcome of µTLO. This study aimed to evaluate the effect of ripasudil use on µTLO outcomes. METHOD: The medical charts of 218 patients who underwent µTLO were analyzed retrospectively. We compared the 1-year outcome between ripasudil users versus nonusers by using propensity score matching. We set the covariates as age, sex, glaucoma types, preoperative intraocular pressure (IOP), the mean deviation values of visual field tests, the presence or absence of concomitant cataract surgery, trabecular meshwork incision range, the presence or absence of any glaucoma medication except ripasudil and duration of glaucoma medical therapy. Success was defined as a postoperative IOP between 5 and 21 mmHg, a ≥ 20% IOP reduction from baseline, and no additional glaucoma surgery at postoperative 1 year. RESULT: Fifty-seven patients each were allocated to the ripasudil users or nonusers. The 1-year success rates were 74% in ripasudil users and 51% in nonusers (p = 0.01). Kaplan‒Meier survival curves also showed that the ripasudil users had a higher survival distribution (p = 0.01). CONCLUSION: The patients who took ripasudil showed a favorable 1-year outcome of µTLO.

Risk of surgical failure and hemorrhagic complications associated with antithrombotic medication in glaucoma surgery.

PURPOSE: The purpose of this retrospective study was to determine the extent to which the use of antithrombotic drugs during glaucoma surgery contributes to surgical failure and postsurgical hemorrhagic complications. METHODS: Glaucoma surgeries were categorized into three groups: trabeculotomy (TLO), trabeculectomy (TLE), and long-Tube shunt surgery (Tube). At 1 year after surgery, the following criteria for surgical success were met: intraocular pressure (IOP) in the 5-21-mmHg range, IOP reduction of at least 20% from the preoperative level, and no additional glaucoma surgeries. We compared the percentages of the success rates and hemorrhagic complications between antithrombotic medication experiencers and non-experiencers. Furthermore, we adjusted the preoperative factors between the two groups using a propensity score analysis in TLO and TLE surgeries. RESULTS: A total of 910 glaucoma surgeries were included, with TLO, TLE, and Tube accounting for 353, 444, and 113 surgeries, respectively. Preoperative antithrombotic medications were administered to 149 patients in all glaucoma surgeries: 37 patients used only anticoagulants, 102 used only antiplatelets, and 10 used both. There was no significant difference in the success rates of any of the procedures. The hemorrhagic complications (hyphema and vitreous hemorrhage rate) were significantly higher in the patients who underwent TLE and Tube. The surgical success rates of TLO and TLE were not significantly different after the two groups were matched by propensity score. CONCLUSION: The perioperative use of antithrombotic drugs did not affect success for any of the procedures. However, it increased early postoperative hemorrhagic complications for TLE and Tube.

Association of the prolonged use of anti-glaucoma medications with the surgical failure of ab interno microhook trabeculotomy.

PURPOSE: This study examined the perioperative factors affecting surgical success in ab interno microhook trabeculotomy (µTLO). METHODS: A total of 146 consecutive patients who underwent µTLO were included in this retrospective study. We performed Cox proportional hazard modelling by setting surgical success at 1 year as an objective variable. The explanatory variables included age, sex, glaucoma type, preoperative intraocular pressure (IOP), glaucoma drug score, mean deviation (MD) of the Humphrey visual field test, duration of glaucoma drug use, antithrombotic drug use, combined cataract surgery, incision range and diabetes mellitus. Additionally, we performed 1:1 matching using propensity score analysis and compared the perioperative parameters between durations of glaucoma drug use of <4.5 years and ≥ 4.5 years (50 patients each). We defined surgical success as satisfaction of all three criteria: IOP 5-21 mmHg, IOP reduction of ≥20% from the preoperative IOP and no additional glaucoma surgery. RESULTS: The Cox proportional hazard model revealed that a longer duration of anti-glaucoma medication was significantly associated with surgical failure. Propensity score matching analysis showed that the <4.5-year users of anti-glaucoma drugs had significantly higher success rates than the ≥4.5-year users (72% versus 52%; p = 0.04). CONCLUSIONS: The prolonged use of multiple glaucoma drugs adversely affected the outcome of µTLO at least at 1 year postoperatively.

The beneficial impact of filtration surgery on antiviral therapy cessation in patients with cytomegalovirus-related secondary glaucoma.

PURPOSE: Cytomegalovirus (CMV)-related keratouveitis elevates intraocular pressure (IOP). Antiviral therapy does not always control IOP and some patients do not tolerate systemic antiviral therapy because of the side effects. The purpose of this study is to evaluate the clinical characteristics of patients with CMV-related keratouveitis and determine the impact of glaucoma surgeries on the postoperative antiviral therapy regimen. METHODS: We enrolled twenty-two patients with CMV-DNA-positive keratouveitis between June 2012 and July 2019 in Kobe University Hospital. The following clinical parameters were collected: gender, age, history of previous intraocular surgery, antiviral medications, visual acuity, IOP, glaucoma drug score, corneal endothelial cells density, and the mean deviation of a Humphrey visual field test at the first visit and before and 1 year after glaucoma surgery. RESULTS: All twenty-two patients started on oral and/or topical antiviral therapy. Eighteen patients needed glaucoma surgery despite their antiviral medications. Nine patients underwent trabeculotomy (TLO) and nine underwent trabeculectomy (TLE) as the first surgical intervention. Six of patients who initially underwent TLO and two of the patients who initially underwent TLE required additional TLE within 1 year. Each of the 15 patients who underwent at least 1 TLE showed a reduction in the magnitude and variation of IOP and glaucoma drug scores and 13 patients were able to discontinue antiviral therapy. For the remaining 4 patients, IOP and inflammation were controlled but with antiviral medications. CONCLUSIONS: In patients with CMV-related keratouveitis, TLE decreases and stabilizes IOP and contributes to withdrawal from antiviral medications.

Protocol to test the efficacy and safety of frequent applications of skin electrical stimulation for Leber hereditary optic neuropathy: a single-arm, open-label, non-randomised prospective study.

INTRODUCTION: Leber hereditary optic neuropathy (LHON) is an acute or subacute inherited optic neuropathy caused by mitochondrial mutations. More than 90% of patients with LHON have one of three point mutations (ie, G3460A, G11778A and T14484C). We previously reported that a 12-week session of skin electrical stimulation (SES) with a 2-week interval significantly improved visual acuity and field tests 1 week after the last stimulation and without adverse effects in 10 cases of LHON carrying the mt DNA G11778A mutation. In the present study, we will examine the magnitude and persistence of the efficacy and presence or absence of adverse events using SES with a more frequent stimulation protocol. METHODS AND ANALYSIS: This study will be a single-arm, open-labelled, non-randomised clinical study that analyses 15 cases of LHON with G11778A mutation. All participants will take a portable SES device home and perform SES by themselves every other day for 12 weeks. The logarithm for the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) at 1 week after the last SES will be measured as the primary outcome. LogMAR BCVA will be measured at four and 8 weeks after the last SES treatment. The Humphrey visual field sensitivity test using size V stimulation and critical fusion frequency at 1, 4 and 8 weeks after the last SES session will be secondary outcome measurements. Slit-lamp examination, optical coherence tomography and specular microscopy will also be performed to verify the safety of SES. ETHICS AND DISSEMINATION: The protocol was approved by the Institutional Review Board at Kobe University, Japan (Approval No.C190030). This study is in progress and deserves Pre-result. All documents communicating with the ethics committee will be reposited by the researcher. Modifications to the protocol will be reviewed by the ethics committee and implemented after approval. Data monitoring will be performed by a researcher who is not involved in the study every 6 months after approval. The research summary results will be registered in the Japan Registry of Clinical Trials (jRCTs) and made available to participants in accordance with the terms described in the documents. In addition, the results of this study will be presented at domestic and international meetings and published in peer-reviewed journals within a year after data is fixed. TRIAL REGISTRATION NUMBER: jRCTs052200033.

Three-year outcome of sulcus fixation of Baerveldt glaucoma implant surgery.

PURPOSE: The purpose of this study was to evaluate the 3-year surgical outcome of the sulcus fixation of Baerveldt glaucoma implant (BGI), focusing on corneal damage. METHODS: This prospective observational study included 37 patients who underwent a median of two previous glaucoma surgeries and sulcus fixation of BGI for the first time. Each patient's intraocular pressure (IOP), glaucoma drug score, corneal endothelial cell density (ECD), and logMAR-converted best-corrected visual acuity (VA) were measured preoperatively and postoperatively until 36 months after surgery. Complete success was defined as reduced IOP (5-21 mmHg and >20% rate), without corneal damage (postoperative development of decompensation, unmeasurable ECD, or reduction in ECD of >20%), without loss of light perception, and without additional surgery requirement. Qualified success was defined by excluding the corneal criteria from complete success. RESULTS: A total of 51% (19/37) patients experienced complete treatment success, whereas 86% (32/37) had qualified success. The median IOP (glaucoma drug score) decreased from 26 mmHg (5) to 15 mmHg (2) at three years postoperatively. The median postoperative ECD (reduction rate) decreased from 1838 cells/cm2 preoperatively to 1587 cells/mm2 (14%) at one year, 1358 cells/mm2 (26%) at two years, and 1228 cells/mm2 (33%) at three years postoperatively. One month after surgery, the VA was significantly reduced from preoperative values but did not decline after that. CONCLUSION: Sulcus fixation of BGI was effective for IOP reduction. However, ECD decreased over time.

Comparison of efficacy and early surgery-related complications between one-quadrant and two-quadrant microhook ab interno trabeculotomy: a propensity score matched study.

PURPOSE: We compared the 1-year outcomes and early surgery-related complications between 1-quadrant and 2-quadrant microhook ab interno trabeculotomy (TLO). METHODS: Medical chart extraction was performed on 47 consecutive patients with 1-quadrant incision and 37 consecutive patients with 2-quadrant incision of trabecular meshwork. Logistic regression analysis was conducted to calculate the propensity score to create a 1:1 match for a comparative analysis of 1-year postoperative success. Success was defined as postoperative intraocular pressure (IOP) between 5-21 mmHg, >20% IOP reduction from baseline, and no additional glaucoma surgery. Outcome-related covariates were age, glaucoma type, mean deviation of visual field tests, preoperative IOP, the number of preoperative glaucoma eye drops and the presence of combined cataract surgery. Thirty eyes from each group were compared. RESULTS: The median preoperative IOP was not different between the 1-quadrant and 2-quadrant groups (28.5 mmHg, quartile range 23-33.5 versus 27 mmHg, 23.3-30.0, p = 0.47). There was no difference in median postoperative IOP at 1 year (15 mmHg versus 16 mmHg, p = 0.80). The success rate was 73% in the 1-quadrant group versus 70% in the 2-quadrant group (p = 1.00). The 2-quadrant group had a significantly higher proportion of patients with transiently elevated IOP (47%) than the 1-quadrant (17%; Fisher's exact test, p = 0.02). There was no difference of hyphema formation (Fisher's exact test, p = 0.18). CONCLUSION: The 1-year success rate was not significantly different between 1- and 2-quadrant incisions of microhook TLO. However, the 2-quadrant TLO showed significantly higher proportion of post-surgical transient IOP elevation.

Granulomatosis with Polyangiitis Presenting with Bilateral Orbital Apex Syndrome.

We report a rare case of granulomatosis with polyangiitis (GPA) presenting with bilateral orbital apex syndrome (OAS). A 73-year-old woman with a history of endoscopic sinus surgery for ethmoidal sinusitis experienced a sudden decrease in visual acuity (VA) of both eyes. At the initial examination, her VA had decreased to 0.01 in the right eye and 0.03 in the left eye, and eye movement in both eyes was mildly limited in all directions. Visual field tests of both eyes showed a large central scotoma. Laboratory tests revealed an elevation of myeloperoxidase-anti-neutrophil cytoplasmic antibody. Facial computed tomography demonstrated a thickened mucosal membrane in the entire ethmoidal sinus, and the posterosuperior walls of Onodi cells filled with infiltrative lesions had thinned. Orbital magnetic resonance imaging showed severe inflammation in the orbital apex. From these clinical findings, the patient was diagnosed with GPA presenting with OAS associated with ethmoid sinusitis. Emergent endoscopic sinus surgery was performed for biopsy and debridement of the ethmoidal and sphenoid sinusitis to decompress the optic nerve. One day after endoscopic sinus surgery, the patient's VA and visual field were improved, and steroid pulse therapy was commenced postoperatively. Four days later, VA had recovered to 1.0 in both eyes, and eye movement and visual field had were improved. Although OAS is a rare manifestation, early surgical treatment should be considered when the orbital lesion presents as risk of rapid deterioration of visual function in patients with GPA.

A case of neurosarcoidosis presenting with multiple cranial neuropathies.

PURPOSE: We report a case of neurosarcoidosis that presented simultaneously with oculomotor nerve palsy, contralateral abducens nerve palsy, and paresthesia of both lower limbs. OBSERVATIONS: A 69-year-old Japanese woman who suffered from repeated diplopia and lower-limb paresthesia was referred to our hospital. Ophthalmic findings included oculomotor nerve and contralateral abducens nerve palsies. No remarkable abnormalities were detected via enhanced brain magnetic resonance imaging (MRI), chest X-ray, and cerebrospinal fluid analysis. Chest computed tomography (CT) was performed to exclude neoplastic lesions; this revealed right hilar lymphadenopathy, and positron emission tomography MRI showed strong 18-F fluorodeoxyglucose uptake in the hilar lymph node. Biopsy of the lymph node showed non-caseating epithelioid granulomatous tissue, leading to a diagnosis of probable neurosarcoidosis. After the initiation of oral prednisolone treatment, the patient experienced complete remission without any recurrence. CONCLUSIONS AND IMPORTANCE: When examining a patient presenting with multiple cranial neuropathies of unknown cause, neurosarcoidosis should be considered as a differential diagnosis and chest CT should be performed even when the chest X-ray and angiotensin-converting enzyme appears normal.

A Single-Arm, Prospective, Exploratory Study to Preliminarily Test Effectiveness and Safety of Skin Electrical Stimulation for Leber Hereditary Optic Neuropathy.

Leber hereditary optic neuropathy (LHON) is an intractable disease associated with mitochondrial DNA (mtDNA) mutations. In this preliminary, single-arm, prospective, open-label exploratory trial, we investigated the effectiveness and safety of skin electrical stimulation (SES) for cases of LHON harboring the mtDNA 11,778 mutation. Of the 11 enrolled patients, 10 completed six sessions of SES once every two weeks over a 10-week period. The primary outcome measure was the change in logarithm of the minimum angle of resolution (logMAR)-converted best-corrected visual acuity (BCVA) at one week after the last session of SES. The main secondary outcome measures were the logMAR BCVA at four and eight weeks and Humphrey visual field test sensitivities at one, four, and eight weeks. At all follow-up points, the logMAR BCVA had improved significantly from baseline [1.80 (1.70­1.80) at baseline, 1.75 (1.52­1.80) at one week, 1.75 (1.50­1.80) at four weeks, and 1.75 (1.52­1.80) at eight weeks; p < 0.05]. At eight weeks of follow-up, five patients showed >2-fold increase in the summed sensitivity at 52 measurement points from baseline. No adverse effects were observed. In conclusion, SES could be a viable treatment option for patients with LHON in the chronic phase harboring the mtDNA 11,778 mutation.

A comparison of the 1-year surgical outcomes of ab externo trabeculotomy and microhook ab interno trabeculotomy using propensity score analysis.

OBJECTIVE: To compare the 1-year outcomes of trabeculotomy ab externo (ab externo TLO) and trabeculotomy ab interno using a microhook (ab interno TLO) for glaucoma patients using propensity score analysis. METHODS AND ANALYSIS: The medical charts of 65 consecutive patients who underwent ab externo TLO and those of 69 patients who underwent ab interno TLO were reviewed. Logistic regression analysis was conducted to calculate the propensity score using 1:1 matched analysis, which indicates the likelihood of surgical success at 12 months. We set the outcome-related covariates as age, glaucoma type, mean deviation, preoperative intraocular pressure (IOP), the number of preoperative glaucoma eye drops and the presence or absence of combined cataract surgery. Fifty eyes per each surgery group were subsequently compared. RESULTS: The mean preoperative IOP was 32.5±11.2 mm Hg in the ab externo TLO group and 28.4±7.8 mm Hg in the ab interno TLO group (p=0.08). The mean postoperative IOP at 12 months was 18.3±7.4 mm Hg in the former group and 17.8±6.3 mm Hg in the latter (p=0.91). When surgical success was defined as a postoperative IOP of between 5 and 21 mm Hg with a more than 20% IOP reduction from baseline and no additional glaucoma surgery, the rate at 12 months was 78% in the ab externo TLO group and 74% in the ab interno TLO group (p=1.00). CONCLUSION: The 1-year success rate was not significantly different between ab externo and ab interno TLO.

Efficacy for the Annual Relapse Rate after the Immunosuppressive Therapy in Patients Associated with Anti-AQP4 or Anti-MOG Antibody-Positive Optic Neuritis.

PURPOSE: Although oral prednisolone is the first-line treatment for preventing recurrent optic neuritis (ON) after the completion of acute-phase treatment, especially anti-aquaporin 4 (AQP4) antibody-positive ON, and anti-myelin oligodendrocyte glycoprotein (MOG) antibody-positive ON, some patients experience relapses. Immunosuppressants could be effective in reducing the recurrence rate for neuromyelitis optica spectrum disorder and MOG antibody-related diseases, but there have been few studies addressing this issue focusing on the changes in ophthalmic parameters. The objective of the study was to analyze the impact of off-label uses of immunosuppressants to reduce recurrent ON. DESIGN: Retrospective observational study, clinical case series. METHODS: We reviewed the medical charts of 11 cases (22 eyes) who underwent immunosuppressive therapy in Kobe University Hospital and compared the annualized relapse rate (ARR) before and after immunosuppressive therapy. We also evaluated the dosage of prednisolone, complications of immunosuppressants, and other visual functional ophthalmologic parameters. RESULTS: Eleven cases in total had AQP4 antibody (9 cases) and/or MOG antibody (3 cases). One case was double positive for these antibodies. Nine patients received azathioprine and two received mycophenolate mofetil as an initial immunosuppressive therapy. The median duration of immunosuppressant treatment was 2.8 years. The median ON ARR before immunosuppressive therapy was 0.33, and this decreased significantly to 0 after the therapy (p = 0.02). The dose of prednisolone was reduced from 17.8 ± 7.1 mg/day before to 5.8 ± 2.2 mg/day after immunosuppressive therapy (p < 0.01). Although two patients presented with mild elevation of liver enzymes and nausea, all patients were able to continue taking the immunosuppressants. CONCLUSIONS: Immunosuppressants can potentially decrease relapses and steroid dosage in patients with anti-AQP4 or MOG antibody-positive ON without severe adverse events and the exacerbation of visual acuities.

A Case of Multi-System Langerhans Cell Histiocytosis with Local Invasion of the Orbital Apex.

Langerhans cell histiocytosis (LCH) is characterised by tissue destruction caused by the abnormal proliferation of pathogenic dendritic cells. We report a rare case of multi-system LCH with local invasion of the orbital apex. A 56-year-old woman suffered from a decrease of visual acuity in the left eye caused by central scotoma and the limitation of eye movement in all directions. Magnetic resonance imaging revealed an enhanced lesion in the left orbital apex, suggesting optic nerve compression. She had been diagnosed with eosinophilic granuloma 24 years previously. Two weeks after the current presentation, we admitted the patient for optic canal and orbital apex decompression and subtotal tumour resection. Histopathological analysis confirmed the diagnosis of LCH. Post-surgical treatment with low-dose cytarabine was initiated for the residual tumour. However, it was ceased because of myelosuppression-induced pyelonephritis. After surgery, the central scotoma disappeared on day 5 and eye movement palsy resolved by 6 months. After the cessation of cytarabine, she has received low-dose steroid therapy for 2 years with no recurrence. Early surgical intervention with low-dose steroid therapy can lead to recovery of visual acuity and resolve eye movement palsy in patients with lesions of the orbital apex caused by multi-system LCH.

En Face Slab Images Visualize Nerve Fibers With Residual Visual Sensitivity in Significantly Thinned Macular Areas of Advanced Glaucomatous Eyes.

Purpose: The present study aimed to assess the ability of en face slab images of maculae to detect residual nerve fiber bundles in eyes with advanced glaucoma. Methods: This study included 36 eyes with diffuse thinning of the ganglion cell and inner plexiform layers (GCL+IPL). Inclusion criterion was GCL+IPL thickness of <1% of the normative database level as detected using optical coherence tomography (OCT). En face slab images (50-µm thickness) were reconstructed from the macular cube scan data using advanced visualization settings. Thereafter, we assessed the agreement of the locations between hyperreflective nerve fiber bundles and normal points in the Humphrey visual field test 10-2 pattern deviation (PD) plots. Additionally, total deviation (TD) corresponding to hyperreflective and hyporeflective areas was compared. Results: Hyperreflective areas were detected in 31 out of 36 eyes; all 31 eyes exhibited at least one normal PD point despite the substantial GCL+IPL thinning in the macular region. Two eyes with abnormalities in all PD points showed no hyperreflective area. The remaining three eyes had normal PD points despite the lack of high reflectivity areas in the slab images. Therefore, 91.7% of eyes showed agreement between en face slab images and PD plots. Moreover, hyperreflective areas demonstrated significantly better TD than hyporeflective areas. Conclusions: En face slab images of maculae were able to reveal the residual nerve fiber bundles in the eyes with advanced glaucoma despite the GCL+IPL thickness in the maculae being diffusely and substantially reduced.

A study protocol for evaluating the efficacy and safety of skin electrical stimulation for Leber hereditary optic neuropathy: a single-arm, open-label, non-randomized prospective exploratory study.

Background: Leber hereditary optic neuropathy (LHON) is a maternally inherited disease caused by three missense mutations of mitochondrial (mt) DNA, ie, m 3460 G>A, m 11778 G>A, or m 14484 T>C in the greater portion of LHON. m 11778 G>A mutation is especially observed in >90% of the cases in Japanese families. Although spontaneous remission of visual function infrequently occurs, effective treatment for LHON remains unestablished. Transcorneal electrical stimulation has been shown to be efficacious in individuals with optic neuropathy. However, due to potential risk of corneal damage, repeated treatments are not permissible. In this exploratory study, we will be conducting skin electrical stimulation (SES) as an intervention for patients with LHON having 11778 missense mutation and investigate effectiveness and safety of SES. Methods: This is a single-arm, prospective, open-label exploratory trial focused on patients with LHON having 11778 missense mutation. Eleven patients will be enrolled and receive six consecutive SES once every 2 weeks up to 10 weeks. The safety of the SES will be monitored with specular microscopy, slit-lamp biomicroscopy, fundus examinations, and the observation of facial skin. The primary outcome measure will be the averaged l ogarithm of minimum angle resolution (logMAR) converted visual acuity 1 week after the last SES. Secondary outcome measures include changes, in logMAR at 4 and 8 weeks after the last SES, such as visual field indices measured using Humphrey visual field and microperimetry-3, the thickness of peripapillary retinal fiber and macular ganglion cell complex, multifocal visual evoked potentials, critical flicker frequency, and color vision. Discussion: The results of this proposed proof-of-concept feasibility trial will help plan and execute a larger definitive trial to test SES as an effective strategy for LHON and related optic neuropathies and help establish a beneficial treatment for LHON.