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.

Predicting the Extent of Damage in the Humphrey Field Analyzer 24-2 Visual Fields Using 10-2 Test Results in Patients With Advanced Glaucoma.

Purpose: To predict Humphrey Field Analyzer 24-2 test (HFA 24-2) results using 10-2 results. Methods: A total of 175 advanced glaucoma eyes (175 patients) with HFA 24-2 mean deviation (MD24-2) of < -20 dB were prospectively followed up for five years using HFA 10-2 and 24-2 (twice and once in a year, respectively). Using all the HFA 24-2 and 10-2 test result pairs measured within three months (350 pairs from 85 eyes, training dataset), a formula to predict HFA 24-2 result using HFA 10-2 results was constructed using least absolute shrinkage and selection operator regression (LASSO). Using 90 different eyes (testing dataset), the absolute differences between the actual and LASSO-predicted MD24-2 and that between the slopes calculated using five actual and LASSO-predicted MD24-2 values, were adopted as the prediction error. Similar analyses were performed for the mean total deviation values (mTD) of the superior (or inferior) hemifield [hemi-mTDsup.24-2(-hemi-mTDinf.24-2)]. Results: The prediction error for the LASSO-predicted MD24-2 and its slope were 2.98 (standard deviation [SD] = 1.90) dB and 0.32 (0.33) dB/yr, respectively. The LASSO-predicted hemi-mTDsup.24-2 (hemi-mTDinf.24-2), and its slope were 3.02 (2.89) and 3.76 (2.72) dB, and 0.37 (0.41) and 0.44 (0.38) dB/year, respectively. These prediction errors were within two times SD of repeatability of the simulated stable HFA 24-2 VF parameter series. Conclusions: HFA 24-2 results could be predicted using the paired HFA 10-2 results with reasonable accuracy using LASSO in patients with advanced glaucoma. Translational Relevance: It is useful to predict HFA24-2 test from HFA10-2 test, when the former is not available, in advanced glaucoma.

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.

Identifying central 10° visual subfield associated with future worsening of visual acuity in eyes with advanced glaucoma.

BACKGROUND/AIMS: To determine a cluster of test points: visual subfield (VSF) of Humphrey Field Analyzer 10-2 test (HFA 10-2) of which baseline sensitivities were associated with future worsening of visual acuity (VA) in eyes with advanced glaucoma. METHODS: A total of 175 advanced glaucoma eyes of 175 advanced glaucoma patients with well controlled intraocular pressure (IOP), a mean deviation of the Humphrey Field Analyzer 24-2 (HFA 24-2) test ≤ -20 decibels and best corrected VA ≥20/40, were included. At baseline, HFA 24-2 and HFA 10-2 tests were performed along with VA measurements. All patients underwent prospective follow-up of 5 years, and VA was measured every 6 months. The Cox proportional hazards model was used to identify visual field sensitivities associated with deterioration of VA and also blindness. RESULTS: Deterioration of VA and blindness were observed in 15.4% and 3.4% of the eyes, respectively. More negative total deviation (TD) values in the temporal papillomacular bundle VSF were significantly associated with deterioration in VA. Averages of the TD values in this area of the HFA 10-2 test had the most predictive power of future VA deterioration (OR: 0.92, p<0.001). A very similar tendency was observed for blindness. CONCLUSION: In advanced glaucoma eyes with well-controlled IOP, careful attention is needed when the mean TD values in the temporal papillomacular bundle VSF, measured with a HFA 10-2 test is deteriorated. TD values of this VSF indicate higher risks for future deterioration of VA and also blindness.

Factors Threatening Central Visual Function of Patients with Advanced Glaucoma: A Prospective Longitudinal Observational Study.

PURPOSE: To identify risk factors for further deterioration of central visual function in advanced glaucoma eyes. DESIGN: Prospective, observational 5-year study. PARTICIPANTS: Advanced glaucoma patients with well-controlled intraocular pressure (IOP), mean deviation (MD) of the Humphrey Field Analyzer (HFA) 24-2 program ≤-20 dB and best-corrected visual acuity (BCVA) of 20/40. METHODS: The HFA 10-2 test and BCVA examination were performed every 6 months, and the HFA 24-2 test was performed every 12 months for 5 years. The Cox proportional hazards model was used to identify risk factors for deterioration of HFA 10-2 and 24-2 results and BCVA. MAIN OUTCOME MEASURES: Deterioration of HFA 10-2 results was defined by the presence of the same ≥3 points with negative total deviation slope ≤-1 dB/year at P < 0.01 on ≥3 consecutive tests, deterioration of HFA 24-2 results by an increase ≥2 in the Advanced Glaucoma Intervention Study score on ≥2 consecutive tests, and deterioration of BCVA by an increase of ≥0.2 logarithm of the minimum angle of resolution (logMAR) on ≥2 consecutive tests. RESULTS: A total of 175 eyes of 175 patients (mean age, 64.1 years; mean baseline IOP, 13.2 mmHg; mean BCVA, 0.02 logMAR; mean HFA 24-2 and 10-2 MD, -25.9 and -22.9 dB, respectively) were included. The probabilities of deterioration in HFA 10-2 and 24-2 results and BCVA were 0.269 ± 0.043 (standard error), 0.173 ± 0.031, and 0.194 ± 0.033, respectively, at 5 years. Lower BCVA at baseline (P = 0.012) was associated significantly with further deterioration of HFA 10-2 results. Better HFA 24-2 MD (P < 0.001) and use of systemic antihypertensive agents (P = 0.009) were associated significantly with further deterioration of HFA 24-2 results, and a greater ß-peripapillary atrophy area-to-disc area ratio (P < 0.001), use of systemic antihypertensive agents (P = 0.025), and lower BCVA (P = 0.042) were associated significantly with further deterioration of BCVA, respectively. CONCLUSIONS: In advanced glaucoma eyes with well-controlled IOP, BCVA, ß-peripapillary atrophy area-to-disc area ratio, and use of systemic antihypertensive agents were significant prognostic factors for further deterioration of central visual function.

Evaluation of early medication persistence with omidenepag isopropyl, a topical selective prostaglandin EP2 agonist, in patients with glaucoma: a retrospective two-institute study.

OBJECTIVES: We evaluated early medication persistence with new topical antiglaucoma eyedrops, omidenepag isopropyl 0.002% (a selective prostaglandin EP2 agonist). DESIGN AND SETTING: Retrospective two-institute study in Himeji and Akashi in Japan. PARTICIPANTS: We analysed patients with glaucoma who were prescribed topical omidenepag isopropyl from November 2018 to December 2019. From the last outpatient visit of patients until February 2020, 235 patients were prescribed a new solution of omidenepag isopropyl (129 patients in the initial monotherapy group, 85 in the switching group (switched from another topical antiglaucoma eyedrops), 19 added to another topical antiglaucoma eyedrops group, and 2 were lost to follow-up)). Additionally, we recruited 98 patients (3 were lost to follow-up) who received initial latanoprost 0.005% monotherapy during the same period as a control group. OUTCOMES: Medication persistence failure was defined as drug discontinuation due to any adverse effects or change of therapy. Kaplan-Meier survival analysis was performed with a Cox regression analysis. RESULTS: Among 233 patients, 48 (20%) showed failure of treatment; the median persistence time of all patients was 165 days, and the median time until discontinuation of omidenepag isopropyl was 45 days. The total persistence rates were 85%, 80% and 70% at 3, 6 and 12 months, respectively. Risk factors for failure were male gender (HR: 1.45, p=0.023) and monotherapy/switching (HR: 1.715, p=0.002). Comparison between latanoprost and omidenepag isopropyl monotherapy, only male gender (HR: 1.43, p=0.016) was a significant risk factor. Failures associated with omidenepag isopropyl were due to insufficient intraocular pressure-lowering efficiency (n=26, observed during all the period), followed by conjunctival hyperaemia (n=10) and visual acuity disturbance (n=5) in patients who were observed until 3 months. CONCLUSION: Medication persistence with omidenepag isopropyl is mostly positive; however, clinicians should also be cautious of early failure.

Predicting Humphrey 10-2 visual field from 24-2 visual field in eyes with advanced glaucoma.

AIMS: To predict Humphrey Field Analyzer Central 10-2 Swedish Interactive Threshold Algorithm-Standard test (HFA 10-2) results (Carl Zeiss Meditec, San Leandro, CA) from HFA 24-2 results of the same eyes with advanced glaucoma. METHODS: Training and testing HFA 24-2 and 10-2 data sets, respectively, consisted of 175 eyes (175 patients) and 44 eyes (44 patients) with open advanced glaucoma (mean deviation of HFA 24-2 ≤-20 dB). Using the training data set, the 68 total deviation (TD) values of the HFA 10-2 test points were predicted from those of the innermost 16 HFA 24-2 test points in the same eye, using image processing or various machine learning methods including bilinear interpolation (IP) as a standard for comparison. The absolute prediction error (PredError) was calculated by applying each method to the testing data set. RESULTS: The mean (SD) test-retest variability of the HFA 10-2 results in the testing data set was 2.1±1.0 dB, while the IP method yielded a PredError of 5.0±1.7 dB. Among the methods tested, support vector regression (SVR) provided a smallest PredError (4.0±1.5 dB). SVR predicted retinal sensitivity at HFA 10-2 test points in the preserved 'central isle' of advanced glaucoma from HFA 24-2 results of the same eye within an error range of about 25%, while error range was approximately twice of the test-retest variability. CONCLUSION: Applying SVR to HFA 24-2 results allowed us to predict TD values at HFA 10-2 test points of the same eye with advanced glaucoma with an error range of about 25%.

Relationship between Vision-Related Quality of Life and Central 10° of the Binocular Integrated Visual Field in Advanced Glaucoma.

To investigate the relationships between sensitivity loss in various subfields of the central 10° of the binocular integrated visual field (IVF) and vision-related quality of life (VRQoL) in 172 patients with advanced glaucoma. Using the Random Forest algorithm, which controls for inter-correlations among various subfields of the IVF, we analysed the relationships among the Rasch analysis-derived person ability index (RADPAI), age, best-corrected visual acuity (BCVA), mean total deviations (mTDs) of eight quadrant subfields in the IVF measured with the Humphrey Field Analyzer (HFA) 10-2 program (10-2 IVF), and mTDs of the upper/lower hemifields in the IVF measured with the HFA 24-2 program (24-2 IVF). Significant contributors to RADPAIs were as follows: the inner and outer lower-right quadrants of the 10-2 IVF contributed to the dining and total tasks; the lower-left quadrant of the 10-2 IVF contributed to the walking, going out and total tasks; the lower hemifield of the 24-2 IVF contributed to the walking, going out, dining, miscellaneous and total tasks; and BCVA contributed more to the letter, sentence, dressing and miscellaneous tasks than to others. The impact of damage in different 10-2 IVF subfields differed significantly across daily tasks in patients with advanced glaucoma.

Discordance of Disc-Fovea Raphe Angles Determined by Optical Coherence Tomography and MP-3 Microperimetry in Eyes With a Glaucomatous Hemifield Defect.

Purpose: The purpose of this study was to evaluate the concordance of a temporal raphe architecture estimated using optical coherence tomography (OCT) and MP-3 microperimetry. Methods: We enrolled 25 eyes with either an upper or lower glaucomatous hemifield defect, as detected on the Humphrey visual field 30-2 test. A structural temporal raphe was extrapolated from visible end points of retinal nerve fiber bundles present in a perimetrically normal hemiretina on an en face Spectralis OCT image. A functional temporal raphe was drawn as a line from the fovea to the border of at least a 10-dB difference in sensitivity, at vertically adjacent test points, with at least three consecutive pairs among 25 test points placed at 8° to 18° from the fovea (2° intervals) on the MP-3. An angle determined by the optic disc center, the fovea, and the temporal raphe line (the DFR angle) was calculated. Correlations and agreement of the OCT- and MP-3-derived DFR angles and factors affecting discordance of the two estimates were evaluated. Results: Despite no significant demographic differences, the functional DFR angle (mean ± SD, 171.8° ± 3.5°) was significantly larger than that of the structural DFR angle (166.5° ± 3.2°) in 14 eyes with upper hemifield defects and vice versa in 11 eyes with lower hemifield defects (163.4° ± 3.0° vs. 170.5° ± 3.2°). The mean deviation was significantly associated with the functional and structural DFR angle difference in eyes with only upper hemifield defects. Conclusions: The structural temporal raphe was more deviated to the perimetrically normal hemiretina side than to the functional temporal raphe, thereby suggesting that a structural change may precede a functional loss.

Effectiveness and safety of sulcus fixation of Baerveldt glaucoma implants in glaucomatous eyes in patients who underwent multiple intraocular surgeries.

PURPOSE: The purpose of this study was to evaluate the surgical success of sulcus fixation of Baerveldt glaucoma implant (BGIs) in special reference to corneal damage. METHODS: This observational prospective cohort study included 24 patients who underwent a median of 3.0 previous intraocular surgeries and sulcus fixation of BGIs for the first time. The intraocular pressure (IOP), the number of ocular hypotensives used, corneal endothelial cell density (ECD), and logMAR-converted best-corrected visual acuity (VA) of each patient were measured preoperatively and postoperatively until 12 months after surgery. Surgical success was evaluated after 12 months based on the reduction of IOP (5-21 mmHg and > 20% reduction), corneal damage (postoperative development of decompensation, unmeasurable ECD, or ECD reduction of > 20%), loss of light perception, and need for additional surgeries. RESULTS: Surgical success was noted in 16 (66.7%) patients when corneal damage was included as a failure criterion, whereas surgery was successful in 21 (87.5%) patients when solely judged using IOP control similarly as previous clinical trials. The median IOP decreased from 27.5 mmHg preoperatively to 14.5 mmHg postoperatively (P < 0.0001). The number of ocular hypotensives was significantly reduced postoperatively (P < 0.0001). The median postoperative ECD reduction was only 0.15%, although ECD could not be measured during follow-up or it was significantly reduced by > 20% in six patients. VA was not significantly reduced after surgery. Adverse effects were observed in 15 patients (62.5 cumulative %). CONCLUSION: Sulcus fixation of BGIs may be effective and safe in patients with glaucomatous eyes who underwent multiple prior intraocular surgeries.

Excessive scleral shrinkage, rather than choroidal thickening, is a major contributor to the development of hypotony maculopathy after trabeculectomy.

PURPOSE: We previously reported that eyes with hypotony maculopathy (HM) after trabeculectomy (TLE) exhibited more reduction of axial length (AL) than those without HM, suggesting that inward collapse of the scleral wall may contribute to the development of HM after TLE. However, we did not evaluate change in choroidal thickness (CT), which could influence AL measures. We compared the magnitude and rate of AL and CT changes in eyes with and without HM by simultaneously measuring these parameters before and after TLE. METHODS: We enrolled 77 eyes of 77consecutive patients with glaucoma, who underwent TLE between March 2014 and March 2016. Intraocular pressure (IOP), central corneal thickness, keratometry, AL, and CT were measured pre- and postoperatively, up to 6 months. These biometrics were compared in eyes with and without HM. RESULTS: The 14 patients who developed HM were significantly younger than those who did not. The eyes with HM exhibited significantly reduced AL (2.8%) compared to those without HM (0.7%). There was no significant difference in CT change between the two groups. The rate of AL reduction was significantly correlated with age, postoperative IOP, and preoperative AL. Post-adjustment logistic regression analysis revealed that eyes with AL reduction rate ≥ 2% had 11.67 higher risk for developing HM (95% confidence interval, 1.28-106.6; P = 0.03). CONCLUSIONS: AL reduction rates ≥ 2% were significantly associated with HM. Excessive reduction in AL, which was seen in eyes with HM, was not an artificial measure resulting from choroidal thickening but rather reflected reductions in the anterior-posterior diameter of the eyeball. Inward collapse of the scleral wall leads to redundancy of the chorioretinal tissue, contributing to the development of HM after TLE.

Diagnostic utility of combined retinal ganglion cell count estimates in Japanese glaucoma patients.

PURPOSE: To assess the combined estimate of retinal ganglion cell (RGC) count developed by Medeiros et al. as a tool for diagnosis of glaucoma in Japanese patients. STUDY DESIGN: Cross-sectional study. METHODS: Thirty-one eyes of 19 healthy controls and 106 eyes of 70 glaucoma patients underwent standard automated perimetry (SAP) and three types of spectral domain optical coherence tomography (SD-OCT) imaging using the Cirrus, RTVue, and 3D-OCT instruments. RGC counts derived from SAP and SD-OCT data were estimated using the Harwerth model (SAPrgc and OCTrgc, respectively), from which the combined RGC count estimates (CRGC) were calculated using the formula developed by Medeiros et al. Receiver operating characteristic curve (ROC) analyses were conducted for mean deviation (MD), retinal nerve fiber layer thickness (RNFLT), and CRGC. RESULTS: The mean OCTrgc derived from the Cirrus, RTVue, and 3D-OCT instruments were 1150, 1245, and 1316 (× 1000 cells), respectively, for the control group and 463, 519, and 516 (× 1000 cells), respectively, for the patient group. SAPrgc of the controls' group was 1526 and the patients' group, 731 (× 1000 cells), and were consistently greater than OCTrgc in both groups (a generalized estimating equation model, p < 0.001). Partial area under the curve (pAUC) of MD was 0.178, and that of RNFLT and CRGC for the three OCT instruments were 0.185, 0.18, 0.189 and 0.196, 0.196, 0.197, respectively. CRGC had larger pAUC than MD, whereas there was no or marginal difference in pAUC between CRGC and cpRNFLT, irrespective of OCT device used or glaucoma severity. CONCLUSION: CRGC proved well suited to discriminate glaucoma patients from controls. However, its clinical utility did not seem to overwhelm isolated structural measures in the tested Japanese patients.

Impact of the anti-aquaporin-4 autoantibody on inner retinal structure, function and structure-function associations in Japanese patients with optic neuritis.

PURPOSE: An autoantibody against aquaporin-4 (AQP4 Ab) is highly specific for neuromyelitis optica spectrum disorder and plays a pathogenic role in this disease. The purpose of this study was to investigate the impact of AQP4 Ab on inner retinal structure, function, and the structure-function relationships in eyes with optic neuritis. METHODS: Thirty five eyes from 25 cases who had received visual function tests and RTVue optical coherence tomography (OCT) measurement at least six months after the latest episode of optic neuritis were enrolled. Patients with multiple sclerosis were excluded. AQP4 Ab was measured using a cell-based assay. Visual acuity, mean deviation (MD) of the Humphrey visual field SITA standard 30-2 tests, retinal nerve fiber layer (RNFL), ganglion cell complex (GCC) thicknesses, and other clinical variables were compared between the AQP4 Ab-positive and -negative groups. Parameters associated with visual functions were evaluated by generalized estimating equation (GEE) models. RESULTS: The AQP4 Ab-positive group (20 eyes from 12 cases) had a higher proportion of bilateral involvement and longer duration of follow-up than the AQP4 Ab-negative group (15 eyes from 13 cases). Linear mixed effect models revealed worse MD and visual acuity in AQP4 Ab-positive eyes than those in AQP4 Ab-negative eyes after adjusting for within-patient inter-eye dependence, whereas there were no differences in RNFL and GCC thickness between the two groups. In seropositive eyes, GEE regression analyses revealed that depending on age and the number of recurrences of ON episodes, OCT parameters correlated strongly with MD and more weakly with visual acuity. CONCLUSIONS: Reductions in RNFL and GCC thickness were proportional to the visual field defect in eyes with AQP4 Ab but not in eyes without AQP4 Ab. The presence of AQP4 Ab probably plays a critical role in retinal ganglion cell loss in optic neuritis.

Home Monitoring of Intraocular Pressure and it's Diurnal Patterns Using Icare® HOME.

Purpose: To evaluate Icare® HOME for home monitoring of intraocular pressure (IOP) and to observe diurnal IOP patterns for a short term. Patients and methods: Twenty six eyes of 16 patients with open angle glaucoma were included. After instruction and practice in using Icare® HOME, patients were asked to measure their IOP by themselves at home or in a sick room. Patients measured their IOP four times a day with a four hour interval between each measurement for three days. Patients repeated measurements until three successful measurements were obtained at each time. Intra-rater reliability was assessed calculating intraclass correlation coefficient (ICC) of the three measurements. Diurnal IOP patterns were assessed for three days. Results: No adverse events occurred. ICC of three measurements was 0.76 (95% confidence coefficient; 0.71 to 0.81). The median of the difference between the highest and the lowest IOP during a day was 4.26 mmHg (95% CI; 4.06 to 4.67). Repeatable patterns were not found in diurnal IOP for three days. Three out of ten patients who answered the questionnaire after measurements found difficulties in handling the device. Conclusions: Although Icare® HOME is safe and could be used for home monitoring of IOP, some patients had difficulties in using the instrument. Diurnal IOP patterns did not show repeatability during a short term.

Rescue effects of intravenous immunoglobulin on optic nerve degeneration in a rat model of neuromyelitis optica.

PURPOSE: Neuromyelitis optica (NMO) is an autoimmune inflammatory disease that predominantly attacks the optic nerve and spinal cord. This study evaluated the effect of administration of human IgG (hIgG) into the caudal vein on optic nerve degeneration in a rodent model of NMO. METHODS: The optic nerves were exposed to AQP4-Ab-positive sera, and the administration of intravenous immunoglobulin (IVIG) was performed immediately, at 7 days (cohort A) or at 7 days and 10 days (cohort B) after exposure to the sera. A reference group, similarly exposed to the serum, was treated with saline. Retinal ganglion cells (RGCs) labeled by the injection of Fluoro-Gold into the superior colliculus were counted in whole-mounted retina. RGCs labeled by the injection of Fluoro-Gold into the superior colliculus were counted in the whole-mounted retina. RESULTS: The number of RGCs 14 days after optic nerve exposure to sera from patients with NMO was 1455 ± 192/mm(2) (n = 7) in cohort A, 1657 ± 192/mm(2) (n = 4) in cohort B, and 981 ± 182/mm(2) (n = 10) in the saline-treated reference group (p < 0.001). Western blotting revealed that the content of neurofilament in the optic nerve of the hIgG-treated group in cohort A was significantly greater than that in the reference group (p = 0.037). CONCLUSIONS: IVIG administration reduced optic nerve degeneration in a rat model of NMO-optic neuritis. IVIG could be used as a treatment in the acute phase of NMO.

Effects of Axial Length and Age on Circumpapillary Retinal Nerve Fiber Layer and Inner Macular Parameters Measured by 3 Types of SD-OCT Instruments.

PURPOSES: To evaluate the effects of axial length and age on the circumpapillary retinal nerve fiber layer (cpRNFL) and the inner macular parameters measured using 3 spectral-domain optical coherence tomography (OCT) instruments. METHODS: A total of 102 normal eyes (1 eye per subject) were imaged using Cirrus, RTVue, and 3D-OCT. The cpRNFL and the macular retinal nerve fiber layer (mRNFL), the ganglion cell layer+inner plexiform layer (GCLIPL), and the mRNFL+GCLIPL ganglion cell complex, GCC thicknesses were analyzed. The correlations between these values and the axial length or age were evaluated using a partial correlation analysis. These correlations were corrected using the axial length-related magnification effect. RESULTS: All but the nasal quadrant cpRNFL thicknesses and GCC thicknesses obtained using the 3 OCT instruments were significantly correlated with age. The average cpRNFL thickness and GCC thickness measured using the Cirrus and RTVue, but not by the 3D-OCT, had a negative correlation with the axial length. The temporal quadrant cpRNFL thickness measured using the 3 instruments was positively correlated with the axial length. The magnification correction made the most correlations positive. CONCLUSIONS: The average cpRNFL and GCC thicknesses measured using these 3 instruments decreased with age. The axial length affected the cpRNFL and GCC thicknesses as measured using the Cirrus and RTVue; this effect likely depended on the fundus area of analyses.

Trabeculotomy with Schlemm's Canal Endothelium Removal and Deep Sclerectomy.

Purpose: To evaluate the effects of trabeculotomy (TLO) combined with Schlemm's canal endothelium removal (SER) and deep sclerectomy (DS). Method: This retrospective study involved 131 adults eyes, diagnosed with glaucoma that were enrolled with at least 1 year follow-up after TLO. Fifty three eyes received TLO+SER+DS and 78 eyes underwent TLO+DS without SER. SER was performed as peeling of Schlemm's canal endothelium opening under the scleral flap. Surgical success was defined by the need for additional glaucoma surgery, or intraocular pressure (IOP) ≤20 mmHg (criterion A) and ≤16 mmHg (criterion B). Results: The occurrence rate of transient ocular hypertension (≥30 mmHg) was significantly less (p<0.001) in SER (3.8%) compared with Non-SER (21.8%). SER decreased IOP at 3 years without significant efficacy in terms of lowered IOP compared with Non-SER. At 3 years, Kaplan-Meier survival analysis revealed that the success rate of SER was higher than Non-SER for criterion A (p=0.008), but comparable for criterion B (p=0.06). Conclusions: SER was effective for reducing the rate of transient ocular hypertension in TLO and controlling IOP≤20 mmHg in adult eyes.

The Ability of SD-OCT to Differentiate Early Glaucoma With High Myopia From Highly Myopic Controls and Nonhighly Myopic Controls.

PURPOSE: Optical coherence tomography (OCT) instruments do not embed a normative database from highly myopic normal (HMN) eyes. The abilities of three OCT instruments to detect early glaucoma with high myopia were compared using the two controls with or without high myopia. METHODS: A total of 52 early glaucomatous eyes (mean deviation > -6.0 dB) with high myopia (spherical equivalent ≤ -6.0 diopters [HMG]), 54 HMN eyes, and 90 nonhighly myopic normal (NHMN) eyes were enrolled. Each participant was imaged using Cirrus, RTVue, and Topcon 3D OCT to evaluate the thicknesses of the circumpapillary retinal nerve fiber layer (cpRNFL), the macular retinal nerve fiber layer (mRNFL), ganglion cell layer + inner plexiform layer (GCL/IPL), and mRNFL + GCL/IPL (GCC). The covariate-adjusted areas under the receiver operating characteristic curves (AUCs) for detecting HMG were compared among the instruments and between the two normal groups (HMN or NHMN). RESULTS: Highly myopic normal eyes showed higher AUCs for the temporal quadrant cpRNFL thickness but lower AUCs for the superior and inferior RNFL thicknesses compared with NHMN. We found the AUCs for the GCC thickness showed no significant difference between the two control groups, but the GCL/IPL and mRNFL thicknesses had differences. CONCLUSIONS: The abilities of the three OCT instruments to detect early glaucomatous eyes with high myopia were different if the normal eyes were associated with high myopia or not. A normative database that includes data from patients with high myopia should be established for accurate diagnosis of glaucoma with high myopia. (www.umin.ac.jp/ctr number, UMIN000006900.).