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Purpose Some patients refrain from seeking an ophthalmologist due to the anxiety and morbidity associated with the coronavirus disease 2019 (COVID-19) pandemic. We investigated progressive visual field defects in patients with glaucoma who refrained from ophthalmological examinations. Methods We retrospectively analyzed data from 886 patients with glaucoma who visited Inouye Eye Hospital in June 2022 and were followed-up prior to January 2020. We examined the number of times patients canceled visits between January 2020 and May 2022 due to coronavirus concerns. We assessed the mean deviation (MD) values of the Humphrey Visual Field Assessment (HFA) program 30 − 2 SITA Standard values after visit interruptions for worsening beyond the MD values predicted by the MD slope. Factors influencing this difference were analyzed using logistic regression analysis. Results The study included 374 men and 512 women. The mean age was 68.7 ± 12.0 years. Visit interruptions occurred in 146 patients (16.5%), with 95 (65.1%) rescheduling once, 27 (18.5%) twice, and 24 (16.4%) three or more times. Among 90 patients who underwent HFA regularly, 50 (55.6%) experienced worse-than-expected MD values and 12 (13.3%) deteriorated by 2 dB or more. Longer interruptions and high intraocular pressure before interruption worsened the MD values by 2 dB or more. Conclusions Patients with glaucoma with visit interruptions due to the pandemic should be monitored for the progression of visual field impairment.

To investigate the periocular adverse reactions to omidenepag isopropyl (OMDI).Nonrandomized comparative clinical study.We enrolled 100 patients (100 eyes) with primary open-angle glaucoma or ocular hypertension who received initial treatment with OMDI or tafluprost in only 1 eye for ≥6 months. Photographs of the eyelids were taken on the day of the participants' visit after ≥6 months of prescription. Subsequently, 3 ophthalmologists individually determined the occurrence of eyelid pigmentation, eyelash growth, and deepening of the upper eyelid sulcus (DUES). Additionally, a questionnaire on the subjective symptoms was administered. Multivariate analysis of baseline data was performed to investigate the factors involved in adverse reactions.The mean duration of drug administration was 10.2 ± 3.8 and 10.8 ± 4.1 months in the OMDI and tafluprost groups, respectively. The frequencies of eyelid pigmentation, eyelash growth, and DUES were 0.0%, 0.0%, and 2.0%, respectively, in the OMDI group, whereas the corresponding values in the tafluprost group were 4.0%, 32.0%, and 12.0%. The only significant difference was that the OMDI group showed fewer patients with eyelash growth than in the tafluprost group (P.0001). In the questionnaire, the subjective symptoms of eyelid pigmentation, eyelash growth, and DUES were 8.0%, 2.0%, and 4.0%, respectively, in the OMDI group, whereas the corresponding values in the tafluprost group were 12.0%, 40.0%, and 4.0%, respectively. Multivariate analysis revealed a correlation between the type of drug administered and these adverse reactions (R = 0.38, P = .005).The frequencies of periocular adverse reactions to OMDI, ranging from 0% to 2.0%, were lower than those to tafluprost.

To describe the clinical and genetic findings of patients in the second Japanese family with Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD). Two patients (a 41-year-old male proband and his third son) underwent comprehensive ophthalmic examinations, including full-field and multifocal electroretinography (ERG). Sanger sequencing was performed to detect an EFEMP1 gene variant (p.Arg345Trp), which was identified as the only causative pathogenic variant. Genetic analysis revealed that both patients carried the heterozygous variant, but the other unaffected family members did not. Although the proband exhibited innumerable radially distributed drusen in both the posterior poles and good visual acuity at initial presentation, bilateral choroidal neovascularization (CNV) developed during the 15-year follow-up. The proband received 15 intravitreal anti-vascular endothelial growth factor (VEGF) injections in the left eye (LE) and two injections in the right eye (RE). At 56 years of age, his decimal best-corrected visual acuity was 0.1 and 1.2 in the LE and RE, respectively. Full-field ERG showed that while the rod and combined responses were within normal amplitudes, the cone and 30-Hz flicker responses had slightly decreased amplitudes. Multifocal ERG revealed attenuated central responses in the LE and decreased temporal responses in the RE. In the 20-year-old son, multifocal ERG showed normal responses in both eyes. This is the first report of ML/DHRD in a patient who developed bilateral CNV and received anti-VEGF treatment in both eyes. Although multifocal ERG exhibited worsening of macular function, the generalized photoreceptor function was preserved until middle age.

To characterize laser speckle flowgraphy (LSFG) pulse waveform parameters for ocular circulation evaluation, a multicenter, prospective, cross-sectional study was conducted in 111 eyes of 86 healthy Japanese individuals. Optic nerve head (ONH) tissue-area, vessel-area mean blur rate (MT and MV, respectively), and MT and MV pulse waveform parameters were obtained using LSFG and ONH structural parameters using planimetry. Multivariate linear mixed-effects modeled regression analysis identified factors contributing to MT- or MV-waveforms using age, gender, smoking history, body mass index, systolic and diastolic blood pressure, heart rate, intraocular pressure, axial length, disc, rim, and β-peripapillary atrophy areas, MT or MV, central retinal artery, and vein equivalents (CRAE and CRVE) as explanatory variables. MT- and MV-waveforms significantly correlated with one or more systemic factors, consistent with previous studies. Following confounding factor adjustment, MT-Skew significantly negatively correlated with β-PPA area (P = 0.026); MT- and MV-flow acceleration index positively correlated with CRAE, MT, and MV (P = 0.041–

Purpose: To evaluate efficacy and safety of ripasudil for 1 year in addition to or replacing existing treatment regimens. Methods: We retrospectively reviewed the medical records for 128 eyes of 12...

Purpose To retrospectively evaluate the short-term efficacy of omidenepag isopropyl (EYBELIS 0.002%) by assessing its intraocular pressure (IOP)-lowering capability and safety in patients with normal-tension glaucoma (NTG). Patients and Methods Fifty-four NTG patients (54 eyes) who were newly administrated with omidenepag isopropyl were enrolled in the study. The subjects comprised 22 men and 32 women, and the mean age of the subjects was 55.0 ± 14.1 years. The mean deviation value using the Humphrey visual field test program (30-2 SITA Standard) was -5.03 ± 3.38 dB. The following data were retrieved from the medical records and used for retrospective analyses: IOP at baseline 1-2 months and 3-4 months after administration. The frequency of non-responder patients who had less than 10% IOP reduction was evaluated. Patients were observed for adverse reactions and dropouts at each time point. Results IOP at baseline, after 1-2 months and after 3-4 months was 15.7 ± 2.6 mmHg, 13.5 ± 2.3 mmHg, and 13.6 ± 2.4 mmHg, respectively. There was a significant decrease in IOP after administration (p

Purpose To investigate the short-term intraocular pressure-lowering efficacy and safety of switching from a fixed combination of latanoprost/timolol to a fixed combination of latanoprost/carteolol. Patients and Methods The subjects were 30 eyes of 30 adult patients with primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension who were using a latanoprost-/timolol-fixed combination with insufficient intraocular pressure-lowering efficacy or adverse reactions. The subjects were switched from once-daily latanoprost/timolol to once-daily latanoprost/carteolol with no washout interval. Intraocular pressure, tear film break-up time, corneal epithelial defects, conjunctival hyperemia, blood pressure, and pulse rate were measured and compared before and 1 and 3 months after switching. Patients were monitored for adverse reactions at each visit, and dropouts were recorded. Results The mean intraocular pressure at 1 month (15.9±3.1 mmHg) and 3 months (16.3±3.8 mmHg) was not significantly different from that at baseline (16.1±3.1 mmHg). The tear film break-up time and corneal epithelial defects were significantly improved after switching (p

To investigate the efficacy and safety of glaucoma medication in Japanese patients, network meta-analysis (NMA) of an intraocular pressure(IOP) reduction, adverse reaction rates and conjunctival congestion rates of major glaucoma drugs used in clinical practice in Japan were conducted using the new drug application (NDA) data. Scoping network meta-analysis. Out of all clinical trials in the interview forms of major glaucoma drugs approved in Japan as of July 2015, active-control clinical trials with Japanese patients were identified through screening with specific criteria. The details of IOP reduction, adverse reaction rates and conjunctival hyperemia rates of the trials were collected from published articles, package inserts, interview forms and Summary basis of approval made by Japan Pharmaceutical and Medical Devices Agency (PMDA). The mean difference in IOP reduction, adverse reaction rates, and conjunctival hyperemia rates of eligible trials were assessed using NMA as referenced to those of timolol maleate 0.5%. Eleven multicenter trials of ten medications in total, (five prostaglandin (PG) analogs, three β-blockers, one α-1 blocker, and one α-2 stimulator) were selected. The mean difference in IOP reduction in mmHg with 95% confidence intervals were as follows: bimatoprost −3.00 (−3.71; −2.29), tafluprost −2.45 (−3.65; −1.25), travoprost −2.35 (−3.41; −1.29), and latanoprost −2.05 (−2.72; −1.38). The highest IOP reduction was achieved by PG analogs. Adverse reaction rates and conjunctival hyperemia rates were significantly larger with PG analogs than with other medications. The efficacy and safety of glaucoma medications were assessed by NMA as reference to those of timolol maleate 0.5% in Japanese patients. PG analogs were the most efficacious in reducing IOP. However, PG analogs were also associated with higher rates of adverse reactions and conjunctival hyperemia.

Kenji Inoue,1 Ryoko Komori,1 Shiho Kunimatsu-Sanuki,2 Kyoko Ishida,3 Goji Tomita1,3 1Inouye Eye Hospital, Tokyo, Japan; 2Nishikasai Inouye Eye Hospital, Tokyo, Japan; 3Department of Ophthalmology, Toho University Ohashi Medical Center, Tokyo, JapanCorrespondence: Kenji Inoue, Inouye Eye Hospital, 4-3 Kanda-surugadai, Chiyoda-ku, Tokyo, 101-0062, Japan, Tel +813-3295-0911, Fax +813-3295-0917, Email 2inoue-k@inouye-eye.or.jpPurpose: To investigate the current use of fixed-combination eye drops by patients with glaucoma in Japan.Patients and Methods: A total of 5303 outpatients (5303 eyes) with glaucoma or ocular hypertension were enrolled in the survey at 78 private practices from March 8 to 14, 2020. The medications they used were investigated. The use of fixed-combination medications was analyzed, stratified by the number of medications used. The results were compared to those of the survey performed in 2016 via χ2 tests.Results: Fixed-combination medications were used by 55.6%, 79.8%, 84.9%, 91.3%, and 94.1% of patients in the two-, three-, four-, five, and six-medications groups. The use of prostaglandin analog/β-blocker (PG/β), carbonic anhydrase inhibitor/β-blocker (CAI/β), and α-2-adrenergic agonist/β-blocker (α 2/β) fixed-combination medications were 42.8%, 12.0%, and 0.8% in the two-medications group; 36.2%, 41.6%, and 2.0% in the three-medications group; and 23.5%, 60.1%, and 1.3% in the four-medications group, respectively. The most commonly used fixed-combination medications were PG/β in the two-medications group and CAI/β in the groups using three or more medications. Compared to those in the survey performed in 2016, there were increases (both P < 0.0001) in the use of PG/β fixed-combination medication in the two- (28.7% to 42.8%) and three-medications (21.7% to 36.2%) groups, and none in the use of CAI/β fixed-combination medication. There was little use of α 2/β fixed-combination medication, probably because it was launched only three months before the survey.Conclusion: The proportion of fixed-combination medications increased as the number of medications per patient increased.Keywords: intraocular pressure, PG/β fixed combination, CAI/β fixed combination, α 2/β fixed combination, multicenter

To investigate the effects of switching to brimonidine/brinzolamide fixed combination (BBFC) eye drops on intraocular pressure (IOP) and safety.A retrospective observational study.We enrolled 238 patients with primary open-angle glaucoma or ocular hypertension who were switched to BBFC eye drops, from June 2020 to March 2021 from their previous medications without a washout period. Patients were divided into 3 groups based on previous medications: Group A, brimonidine and brinzolamide concomitantly; Group B, brinzolamide; and Group C, brimonidine. IOP at baseline, after 3 months, and after 6 months in each group were compared.In Group A (n = 102), there was no difference in IOP at baseline (14.4 ± 3.0 mmHg), 3 months (14.1 ± 3.1 mmHg), and 6 months (13.9 ± 2.8 mmHg). In Group B (n = 104), IOP significantly decreased at 3 months and 6 months (baseline, 14.8 ± 3.0 mmHg; 3 months, 13.1±2.6 mmHg; 6 months 13.8±2.9 mmHg; P0.0001). In Group C (n = 32), IOP significantly decreased at 3 months and 6 months (baseline, 16.2 ± 3.5 mmHg; 3 months, 15.2 ± 3.5 mmHg; 6 months, 14.6 ± 3.2 mmHg; P0.01). Adverse reactions occurred in 6.9%, 18.3%, and 15.6% in Groups A, B, and C, respectively. The frequent adverse reactions in all patients were conjunctival hyperemia (3.4%), conjunctivitis (2.9%), blepharitis (2.9%), and itching (2.5%).BBFC had satisfactory IOP-lowering effects without serious adverse reactions in patients who switched medications.

To determine the relationship between the subfoveal choroidal thickness (SCT) and intraocular pressure (IOP) following 25-gauge (25G) and 23-gauge (23G) vitrectomy for idiopathic epiretinal membrane (ERM). Retrospective, consecutive, interventional case series. Sixty-two patients undergoing 25G vitrectomy and 56 patients undergoing 23G vitrectomy for ERM participated. SCT was measured using enhanced depth imaging optical coherence tomography and IOP were measured both at baseline and postoperatively. In both groups, the IOPs on day one and one week after surgery were significantly lower than at baseline (P < 0.001 for both). The rates of changes of IOP were significantly greater in 23G compared to 25G on day one (P = 0.026). In 23G the SCTs on day one and one week after surgery were significantly thicker (P < 0.001) than baseline. The rates of changes in SCT between baseline and day one negatively correlated with those of IOP in 23G (r = −0.559, P < 0.001) but no correlation was observed with 25G (r = −0.129, P = 0.316). Choroidal thickness increases soon after 23G vitrectomy for ERM which is probably due to the transient hypotony, however, early SCT change does not appear in 25G vitrectomy. Twenty-five-gauge vitrectomy may have an advantage in minimizing postoperative choroidal changes.

We performed an investigation of the temporal impact on corneal endothelial cell (CEC) shape after ophthalmic instillation of one drop of the ROCK inhibitor, ripasudil. Subjects comprised 32 healthy adult volunteers, each of whom instilled ripasudil in the right eye. CEC shape [defined as CEC density (CECD), coefficient of variation (CV), and hexagonal cell rate (6A)], central corneal thickness (CCT), intraocular pressure (IOP), and conjunctival hyperemia were evaluated before instillation (baseline) and at 15 min, 1 h, 2 h, and 4–6 h after instillation by non-contact specular microscopy and slit-lamp microscopy. The incidence of pseudo gutta was also assessed. The CECD (cells/mm2) significantly decreased after instillation as follows: 2661 cells/mm2 at baseline, 2578 cells/mm2 at 15 min, 2527 cells/mm2 at 1 h, 2575 cells/mm2 at 2 h, and 2613 cells/mm2 at 4–6 h. After instillation, CV significantly increased and 6A significantly decreased. Pseudo gutta appeared in 18 subjects (56.3%) after instillation. There was no difference in CCT before and after instillation. IOP significantly decreased after instillation. The most severe conjunctival hyperemia was observed at 15 min after instillation, but had nearly disappeared within 2 h. Pseudo gutta appeared in more than half of the subjects, and the CEC shape changed upon instillation of one drop of ripasudil; however, it recovered at 4–6 h after instillation. Therefore, these changes would not greatly impact clinical treatment. Similar to the presence of conjunctival hyperemia, changes in CEC shape occur at early stages after instillation of ripasudil.

To investigate macular vessel density (MVD) and structural alterations in untreated normal tension glaucoma (NTG) with a hemifield defect (HFD) and to compare these with the findings in healthy eyes. Case series with a healthy group for comparison. Thirty-four eyes of 34 untreated NTG patients with HFD and 28 eyes of 28 healthy subjects were enrolled. RTVue-XR AvantiTM (Optovue, Inc.), a combined OCT-A and SD-OCT system, was used to determine MVD and inner macular thickness (IMT) measurements. Mean circumpapillary retinal nerve fiber (cpRNFL) and macular ganglion cell complex (mGCC) thicknesses were measured with the RTVue-100TM (Optovue, Inc.). Wilcoxon signed-rank test was used to evaluate differences between defective and normal hemifields in NTG eyes and Mann–Whitney U test to evaluate differences between normal hemifields in NTG eyes and healthy eyes. In comparison with healthy eyes, the normal hemifields of NTG eyes showed significantly reduced MVD, as well as cpRNFL and mGCC thicknesses, although IMT did not differ between the two groups. The defective hemifield in NTG eyes showed significantly reduced IMT, as well as cpRNFL and mGCC thicknesses, compared with the normal hemifield, although MVD did not differ between the two hemifields. Hemodynamic deficiencies and structural damage might have already begun in the perimetrically normal hemifields of NTG eyes. Further studies are needed to elucidate whether the reduction in MVD may precede structural changes or the reduction in vasculature and structural loss may vary with disease severity in at least in some cases.

Purpose: To evaluate the relationship between the macular vessel density and photopic negative response (PhNR) amplitude of focal electroretinograms (ERGs) in patients with early-stage normal tension glaucoma (NTG). Materials and Methods: This prospective cross-sectional study included a total of 42 subjects with early-stage NTG. Optical coherence tomography angiography was used to measure macular vessel density, and focal ERGs were elicited by a white light stimulus (30 cd/m2) with background light (1.5 cd/m2). The amplitude of the PhNR was measured from the peak of the b-wave to the PhNR trough. Mean visual field sensitivity was measured by the Humphrey Field Analyzer (HFA) program central 10-2. Spearman's coefficients were used to evaluate the correlation between the macular vessel density, PhNR amplitude, mean deviation (MD) of the HFA 10-2, retinal nerve fiber layer (RNFL) thickness, and ganglion cell complex (GCC) thickness measured by spectral domain-optical coherence tomography. Results: The mean MD of the HFA 10-2 was -2.0 ± 3.2 dB. The PhNR amplitude significantly correlated with the macular vessel density (r = 0.420, P = 0.006), but not with the MD, GCC thickness, or RNFL thickness. The macular vessel density significantly correlated with the MD (r = 0.364, P = 0.018) and RNFL thickness (r = 0.369, P = 0.016), but not with GCC thickness (r = 0.266, P = 0.089). Conclusions: Macular vessel density significantly correlated with PhNR amplitude in patients with early-stage NTG, suggesting that microvascular alterations are associated with functional changes recorded by focal ERG in very early-stage glaucoma.

Purpose To investigate the ocular and systemic factors related to glaucoma and to be adjusted for interindividual comparison of ocular blood flow measurement results by laser speckle flowgraphy (LSFG) obtained from the optic nerve head (ONH) in normal Japanese individuals. Methods A multicenter, prospective cross-sectional study was conducted. The ONH tissue-area and vessel-area mean blur rate (MT and MV) were evaluated using LSFG and ONH structural parameters using planimetric methods. Multivariate linear mixed-effects modeled regression analysis was used to identify the contributing factors to the MT and MV. The explanatory variables were age; gender; smoking history; body mass index; mean arterial pressure (MAP); heart rate; intraocular pressure; axial length (AL); disc, rim, cup, and β-peripapillary atrophy (β-PPA) areas; and central retinal artery and vein equivalents. Results In total, 195 eyes of 126 healthy individuals with an average age of 48.1 years were included. Multivariate analysis showed that MAP and disc area had a negative (P < 0.001) correlation, whereas β-PPA area had a positive correlation with MT (P = 0.010). Age and AL had a negative correlation (P = 0.001 and P = 0.011, respectively), whereas cup area had a positive correlation (P = 0.012) with MV. Conclusions Interindividual comparison of MT or MV must be adjusted for both systemic factors (blood pressure or age) and local ocular factors (AL and disc, cup, or β-PPA area). Translational Relevance Our results provided reference data on the LSFG measurement and are important in comparing ocular blood flow between individuals using LSFG.

Purpose To retrospectively evaluate the short-term efficacy of omidenepag isopropyl (EYBELIS 0.002%) by assessing its intraocular pressure (IOP)-lowering capability and safety in patients with normal-tension glaucoma (NTG). Patients and Methods Fifty-four NTG patients (54 eyes) who were newly administrated with omidenepag isopropyl were enrolled in the study. The subjects comprised 22 men and 32 women, and the mean age of the subjects was 55.0 ± 14.1 years. The mean deviation value using the Humphrey visual field test program (30–2 SITA Standard) was −5.03 ± 3.38 dB. The following data were retrieved from the medical records and used for retrospective analyses: IOP at baseline 1–2 months and 3–4 months after administration. The frequency of non-responder patients who had less than 10% IOP reduction was evaluated. Patients were observed for adverse reactions and dropouts at each time point. Results IOP at baseline, after 1–2 months and after 3–4 months was 15.7 ± 2.6 mmHg, 13.5 ± 2.3 mmHg, and 13.6 ± 2.4 mmHg, respectively. There was a significant decrease in IOP after administration (p

To investigate the spatial and temporal relationship between disc hemorrhage (DH) and structural progression in patients with primary open-angle glaucoma (POAG) in a 3-year prospective study.Prospective cohort study.Patients with POAG and intraocular pressure of ≤18 mmHg on monotherapy with prostaglandin analogs.Fundus photographs were taken at baseline and every 3 months for 3 years. Disc hemorrhage and structural progression were detected independently by flicker chronoscopy. If present, clock-hour disc locations in the right eye format and colocalization were determined. Statistical comparisons were based on mixed-effects models accounting for the correlation between different disc sites within the same eye and between fellow eyes in the same patient.Relationship between DH and structural progression at the same site.Among 195 eyes of 115 patients, DH appeared in 85 sites in 65 eyes (33.3%) and was most frequently at the 7 o'clock disc location (29.4%, P0.0001). Structural progression occurred at 63 sites of 52 eyes (26.7%) comparably in both superior and inferior hemidiscs, which was mostly detected as widening of the retinal nerve fiber layer defects (RNFLDs). Temporal RNFLD widening was common, whereas nasal widening occurred exclusively in the vertical quadrants (P = 0.035). Of 41 progression sites in eyes with DH, 28 sites (68.2%) had both DH and progression. Progression sites with DH were less common in the superior quadrant than in the inferior and temporal quadrants (P = 0.011). Eyes with DH had a significantly higher risk of progression than eyes without DH (hazard ratio, 3.72; P0.0001). For 63 progression sites, DH recurrence and more visits with DH at the progression site were significantly associated with shorter time to progression from baseline (P = 0.021, P = 0.017, respectively), whereas colocalization of DH and progression were not.In a 3-year prospective study with a Japanese POAG cohort, the relationship between DH and RNFLD and the pattern of RNFLD progression differed by disc location. The association between more frequent DH at the progression site and shorter time to progression indicates that DH may reflect vulnerability to same-site structural deterioration.

To compare the occurrence of disc hemorrhages (DH) and glaucoma progression in open-angle glaucoma (OAG) patients with different glaucomatous disc types. Prospective, hospital-based, observational cohort study. OAG patients examined between 2000 and 2005, whose discs were classified as typical myopic glaucomatous (MG), generalized enlargement of cup (GE), or focal glaucomatous (FG) disc type were included and followed for 5 years. The first occurrence of DH during follow-up was analyzed using Kaplan–Meier analysis and difference in DH occurrence based on glaucomatous disc type using the Cox proportional-hazards model to adjust for effects of confounding factors. For inter-group comparison of glaucoma progression, the change rate of the mean deviation, Collaborative Initial Glaucoma Treatment Study scores, and fundus photographs were used. Thirty-nine patients with MG-, 18 with FG-, and 17 with GE-disc types were included. No significant inter-group difference was seen in the rate of glaucoma progression. The five-year probability of DH occurrence was much lower with MG- than with FG- or GE-disc types (P P = 0.0024) and mean intraocular pressure and its variations (P = 0.0450, 0.0219) contributed to DH occurrence. The MG-disc type demonstrated a much lower DH occurrence during follow-up than other disc types.

We prospectively investigated the efficacy and safety of switching from concomitant latanoprost and carteolol hydrochloride (CH) to a latanoprost/carteolol fixed combination (LCFC) in patients with primary open-angle glaucoma or ocular hypertension.A total of 43 patients (43 eyes) who were using latanoprost (once daily in the evening) and CH (once daily in the morning) concomitantly were switched to LCFC (once daily in the morning) with no washout interval. The primary efficacy endpoint was change in intraocular pressure (IOP) between baseline (before switching) and 1 and 3 months after switching. Systemic blood pressure and pulse rate, corneal epithelial defects, and tear film break-up time (TBUT) were also compared before and 1 and 3 months after switching. A questionnaire was administered 1 month after switching to investigate ocular comfort and treatment preferences. Adverse reactions and dropouts were recorded.There was no significant difference in IOP after switching to LCFC (15.0±2.6, 15.1±2.4, and 15.0±2.4 mm Hg at baseline and at 1 and 3 months, respectively). There was a significant decrease in corneal epithelial defects and significant increase in TBUT, without significant changes in systemic blood pressure or pulse rate. Three patients (7.3%) preferred concomitant latanoprost and CH; 33 (80.5%) preferred the LCFC. One patient each (9.3%) discontinued treatment because of foreign body sensation, blepharitis, increased IOP, or loss to follow-up.Switching from concomitant latanoprost and CH to LCFC led to similar IOP control with good safety and patient acceptance, at least in the short term.

ORIGINAL ARTICLE, Introduction: To evaluate relationships between the area and extent of peripapillary atrophy (PPA) and optic nerve head (ONH) blood flow and between PPA parameters and structural and functional damage in eyes with untreated normal-tension glaucoma (NTG). Methods: Thirty-six eyes (36 subjects) with newly diagnosed, untreated NTG were included. Correlations between PPA and ONH blood flow were examined. The PPA was examined using confocal scanning laser ophthalmoscopy, ONH was examined using laser speckle flowgraphy, and circumpapillary retinal nerve fiber layer thickness was measured using spectral-domain optical coherence tomography. Retinal function was examined using standard automated perimetry mean deviation (MD). Results: The PPA area was significantly correlated with the refractive spherical equivalent (r = -0.418, P = 0.010), mean blur rate (MBR) inside the ONH (MBRA; r = -0.394, P = 0.016), and MBR of ONH tissue (MBRT; r = -0.328, P = 0.048). Total angular extent around the ONH of PPA was significantly correlated with MD (r = -0.344, P = 0.037), MBRA (r = -0.360, P = 0.029), and MBRT (r = -0.368, P = 0.025). Multiple regression analyses revealed that PPA area significantly contributed to changes in MBRA. Total angular extent of PPA significantly contributed to changes in MBRT. Conclusions: Significant relationships between PPA and ONH blood flow parameters were identified in eyes with untreated NTG.

Background: The Tafluprost/Timolol Fixed Combination (TTFC) has demonstrated efficacy and safety in reducing Intraocular Pressure (IOP). However, direct comparisons of switching from tafluprost to TTFC are limited. Objective: To investigate the efficacy and safety of switching from tafluprost to TTFC in patients with Primary Open-Angle Glaucoma (POAG). Methods: Thirty-four eyes (34 patients) with POAG that did not achieve adequate IOP reduction on tafluprost were switched to TTFC with no washout period. IOP, systolic/diastolic blood pressure and pulse rate were measured 1 and 3 months later and compared with baseline values. All participants were asked about specific adverse reactions after 1 and 3 months of treatment. Patients also completed a questionnaire about preference and adherence after 1 month of treatment. Results: Mean IOP after 1 and 3 months was significantly lower than at baseline (14.2 ± 2.1 mmHg and 14.1 ± 2.3 mmHg, respectively, vs 16.0 ± 2.0 mmHg, P < 0.0001). Systolic/diastolic blood pressure and pulse rate were not significantly different from baseline after 1 and 3 months. The questionnaire indicated that the frequency of missing a dose was not different before (27.3%) or after (18.2%) switching to TTFC (P = 0.2371). There were five reports of adverse reactions (14.7%), including a corneal epithelium disorder, ocular irritation, skin irritation at the wrist, and chest pain. Two patients (5.9%) withdrew because of adverse reactions. Conclusion: Switching from tafluprost to TTFC achieved IOP control safely and was well accepted by patients.

PurposeTo determine the frequency with which retinal tissues other than the nerve fibre layer, hereafter referred to as protruded retinal layers (PRL), are a component of optical coherence tomography (OCT) neuroretinal rim measurements.MethodsNinety healthy (30 White, Black and Japanese, respectively) subjects were included in the study. A radial scan pattern (24 B-scans centred on Bruch's membrane opening [BMO]) was used. For each of the 48 minimum rim width (MRW) measurement points, we determined whether PRL were present, absent or indeterminate. When present, the proportion of PRL within the MRW was quantified.ResultsProtruded retinal layers were present in 503 (11.6%), absent in 3805 (88.1%) and indeterminate in 12 (0.3%) measurement points. Overall, 69 (76.6%) subjects had ≥1 points with PRL, with White subjects having the highest frequency and Japanese the lowest (29 [97%] and 18 [60%], respectively; p&nbsp

A shift or displacement of the retinal blood vessels (RBVs) with neuroretinal rim thinning indicates the progression of glaucomatous optic neuropathy. In chronic open angle glaucoma, individuals with RBV positional shifts exhibit more rapid visual field loss than those without RBV shifts. The retinal vessels reportedly move onto the optic nerve head (ONH) in response to glaucoma damage, suggesting that RBVs are pulled toward the ONH in response to increased cupping. Whether this phenomenon only applies to RVBs located in the vicinity or inside the ONH or, more generally, to RBVs also located far from the ONH, however, is unclear. The aim of this study was to evaluate the movement of RBVs located relatively far from the ONH edge after increasing intraocular pressure (IOP) in an experimental monkey model of glaucoma. Fundus photographs were obtained in 17 monkeys. High IOP was induced in the monkeys by laser photocoagulation burns applied uniformly with 360° irradiation around the trabecular meshwork of the left eye. The right eye was left intact and used as a non-treated control. Considering the circadian rhythm of IOP, it was measured in both eyes of each animal at around the same time-points. Then, fundus photographs were obtained. Using Image J image analysis software, an examiner (N.E.) measured the fundus photographs at two time-points, i.e. before laser treatment (time 1) and the last fundus photography after IOP elevation (time 2). The following parameters were measured (in pixels): 1) vertical diameter of the ONH (DD), 2) distance from the ONH edge to the first bifurcation point of the superior branch of the central retinal vein (UV), 3) distance from the ONH edge to the first bifurcation point of the inferior branch of the central retinal vein (LV), 4) ONH area, and 5) surface area of the cup of the ONH. We calculated the ratios of UV to DD (UV/DD), LV to DD (LV/DD), and the cup area to disc area ratio (C/D). The mean UV/DD at time 1 (0.656 ± 0.233) was decreased at time 2 (0.542 ± 0.192) (p 0.01), and the mean LV/DD at time 1 (0.642 ± 0.151) was decreased at time 2 (0.534 ± 0.171) (p 0.01). The mean C/D at time 1 (0.303 ± 0.035) was increased at time 2 (0.556 ± 0.110) (p 0.01). The mean IOP at time 1 was 19.8 ± 2.5 and that at time 2 was 54.2 ± 15.8. The amount and rate of the change in LV/DD and C/D between time 1 and time 2 were significantly correlated (r = -0.654 and -0.536, p = 0.004 and 0.026, respectively). Therefore, in an experimental monkey model of glaucoma, RBVs located relatively far from the ONH were pulled toward the ONH as cupping increased.

Seiji Takagi,1–3 Michiko Mandai,1,4 Noriko Miyamoto,1,2 Akihiro Nishida,1,2 Yasuhiko Hirami,1,2 Hirofumi Uyama,1,2 Midori Yamamoto,1,2 Masayo Takahashi,1,2,4 Goji Tomita,3 Yasuo Kurimoto1,2 1Department of Ophthalmology, Kobe City Medical Center General Hospital, 2Department of Translational Research, Division of Ophthalmology, Institute of Biomedical Research and Innovation, Kobe, Hyogo, 3Department of Ophthalmology, Toho University Ohashi Medical Center, Meguro-ku, Tokyo, 4RIKEN Center for Developmental Biology, Kobe, Hyogo, Japan Purpose: The purpose of this study was to investigate the occurrence of outer retinal tubulation (ORT) among patients with different types of choroidal neovascularization (CNV) over time. Materials and methods: In this retrospective chart review, disease type was classified as typical age-related macular degeneration (t-AMD), polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP), or myopic CNV (mCNV). Spectral domain-optical coherence tomography (SD-OCT) images were evaluated for the appearance of ORT and subretinal fibrosis and fluid. Furthermore, the association of the presence of ORT with clinical data and OCT findings was investigated. Results: Among the 136 eyes studied, the overall rates of occurrence of ORT were 7.8%, 18.8%, and 31.6% after 12, 24, and 36months from baseline, respectively. Among patients with t-AMD, RAP, and mCNV, the occurrence of ORT increased soon after the initial visit. Incontrast, among patients with PCV, the occurrence of ORT increased slowly over time. Patients with and without ORT – ORT(+) and ORT(-) groups, respectively – differed significantly in terms of sex ratio and presence of intraretinal fluid at the initial visit and presence of subretinal fibrosis at 3years from baseline. The ORT(+) group exhibited lower visual acuity (VA; 0.67±0.43) than that of the ORT(-) group (0.41±0.36; P

Purpose To investigate the short-term intraocular pressure-lowering efficacy and safety of switching from a fixed combination of latanoprost/timolol to a fixed combination of latanoprost/carteolol. Patients and Methods The subjects were 30 eyes of 30 adult patients with primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension who were using a latanoprost-/timolol-fixed combination with insufficient intraocular pressure-lowering efficacy or adverse reactions. The subjects were switched from once-daily latanoprost/timolol to once-daily latanoprost/carteolol with no washout interval. Intraocular pressure, tear film break-up time, corneal epithelial defects, conjunctival hyperemia, blood pressure, and pulse rate were measured and compared before and 1 and 3 months after switching. Patients were monitored for adverse reactions at each visit, and dropouts were recorded. Results The mean intraocular pressure at 1 month (15.9±3.1 mmHg) and 3 months (16.3±3.8 mmHg) was not significantly different from that at baseline (16.1±3.1 mmHg). The tear film break-up time and corneal epithelial defects were significantly improved after switching (p

Although reduction in intraocular pressure (IOP) is the principle of glaucoma treatment, impaired ocular blood flow is believed to play a role in the progression of glaucoma. This study evaluated the effect of glaucoma treatment on pulse waveforms for optic nerve head (ONH) microcirculation in patients with glaucoma. Fifty-one subjects were included on the basis of the glaucoma treatment administered, which involved instillation of prostaglandin (PG) analogs (PG group; n = 28) or trabeculectomy (trabeculectomy group; n = 23). ONH blood flow, represented by the mean blur rate (MBRT) and pulse waveforms, was measured using laser speckle flowgraphy before and 1 and 3 months after treatment. Three months after treatment, IOP exhibited a significant decrease (p<0.05). Although there was no significant change in MBRT after treatment, the acceleration time index (ATI) significantly decreased (p=0.034) in the PG group. In the trabeculectomy group, there was no significant change in the MBRT after treatment, while fluctuation (p=0.019) and blowout score (BOS) (p=0.036) exhibited significant decrease and increase, respectively. Multiple regression analysis showed that mean deviation was significantly associated with the rate of change in the BOS (p=0.013), age was a significant contributing factor for the rate of change in fluctuation in the trabeculectomy group, reflection was significantly associated with the ATI (p=0.037) in the in the PG group. Both glaucoma treatments can change the pulse waveforms, with MBRT remaining unchanged, and IOP reduction owing to the treatment may contribute to stable blood flow in the tissue area of the ONH. As impaired ocular blood flow plays a role in the progression of glaucomatous damage, it would be beneficial if glaucoma treatment could improve the stability of ONH microcirculation.

To investigate patients whose intraocular pressure (IOP) did not decrease after treatment using a prostaglandin analog (nonresponders).This was an open-label, retrospective, case series study from a single institution. We retrospectively investigated the mean IOP reduction rates, and the proportions of nonresponders, among normal tension glaucoma (NTG) patients (209 cases, 209 eyes) treated using 1 of 4 prostaglandin analogs: latanoprost (40 patients), travoprost (64 patients), tafluprost (52 patients), or bimatoprost (53 patients). Absolute IOP was compared with pretreatment values for all 4 groups at the first and second visits after commencement of prostaglandin analog monotherapy. The IOP reduction rate was compared between groups. The proportion of nonresponders, defined as patients with IOP reduction rate10% at both visits, was calculated in each group.The average IOP had significantly decreased from the pretreatment value at the first visit after treatment; the average IOP reduction rate ranged from 15.3% to 22.6%. The IOP reduction rate in the bimatoprost group was significantly higher than those in the travoprost and tafluprost groups (P 0.001). We identified 6 nonresponders (15.0%) in the latanoprost group, 9 (14.1%) in the travoprost group, 4 (7.7%) in the tafluprost group, and none (0.0%) in the bimatoprost group; nonresponse rates were significantly lower in the bimatoprost group than in the other groups (P ≤ 0.05).Among NTG patients treated using prostaglandin analogs, from 0% to 15% were classified as nonresponders, depending on the prostaglandin analog used. The proportion of nonresponders was significantly lower in the bimatoprost group.

Background: OCT angiography (OCTA) and laser speckle flowgraphy (LSFG) are novel and noninvasive imaging modalities which could evaluate fundus blood flow quantitatively. However, the role of OCTA and LSFG as diagnostic tools has not been widely investigated. Previous reports indicated that NO, reduced by hyperglycemia, exerts a key role for the autoregulation of retinal blood flow. We designed this study to evaluate the retinal blood flow by OCTA and LSFG in hyperglycemic DM. Method: 10 patients with extreme hyperglycemia at our outpatient clinic (FPG>250mg/dL, or casual PG>350mg/dL, age 58±5, 7 males, HbA1c 11.1±0.5%) and 32 healthy volunteers (age 48±2, 17 males) were included. Vascular density was calculated using OCTA. LSFG measured relative blood velocity (mean blur rate: MBR) in the optic nerve head (ONH). MBR-A (the mean of all area), MBR-V (the vessel mean) and MBR-T (the tissue mean) were analyzed. Result: OCTA revealed no difference between two groups in the vascular density at macula (47.37±1.14% for DM and 47.44±0.67% for NDM) and a tendency of decrease in the diabetic vascular density at ONH (40.14±3.56% for DM and 42.48±1.25% for NDM) without statistical significance. With LSFG, MBR-A and MBR-T did not exhibit significant differences, while MBR-V significantly decreased in DM compared to the healthy (42.85±2.05% for DM, 49.25±1.34% for NDM, p = 0.025). Discussion: Our results demonstrated that vascular hypoperfusion at ONH was associated with extreme hyperglycemia in DM with tendency to decrease in vascular density. It is generally supposed that the retinal blood flow decreases in DM and acute hyperglycemia. In DM actually presented physiological changes in the retina. Besides, there is a report that autoregulation of blood flow in the ONH is disrupted in diabetic rabbits, as well as in healthy ones with uncoupled gap junctions. It is possible that the similar mechanisms are involved in ONH blood flow decrease observed in this study. Disclosure T. Mitsumatsu: None. F. Yagi: None. Y. Kondo: None. A. Anraku: None. S. Okahata: None. K. Sakamoto: None. G. Tomita: None. T. Shiba: Speaker's Bureau; Self; Shionogi & Co., Ltd., Pfizer Inc., Merck Sharp & Dohme Corp., Kowa Company, Ltd., Daiichi Sankyo Company, Limited.

To compare the effectiveness and safety of either switching from topical prostaglandin (PG) analog monotherapy to topical PG/timolol fixed combination therapy or adding topical ripasudil therapy. An open-label, prospective, randomized, parallel group, comparative study Fifty-one patients (51 eyes) with primary open-angle glaucoma who experienced insufficient intraocular pressure (IOP) control while taking a PG analog were enrolled. The participants were divided into the following treatment groups: PG/timolol fixed combination (switched group) or ripasudil therapy addition (added group). Blood pressure, IOP, and pulse rate were measured at baseline and after 1 and 3 months of study treatment. Adverse reactions and decreased effectiveness were examined. The mean IOP after 3 months of therapy was 14.3 ± 2.2 mmHg in the switched group and 14.7 ± 3.0 mmHg in the added group, both of which were significantly lower than those at baseline (switched, 16.3 ± 3.0 mmHg; added, 16.6 ± 2.8 mmHg; both P < .001). At 3 months, the IOP was reduced by 2.0 ± 1.7 mmHg (11.7 ± 9.6%) in the switched group and by 1.8 ± 2.1 mmHg (10.7 ± 12.5%) in the added group. In the added group, the diastolic blood pressure after 1 month of therapy was significantly lower than that at baseline (P < .05). In the switched group, 10 (40.0%) and 2 (8.0%) participants experienced adverse reactions at 1 and 3 months, respectively. In the added group, 6 (23.1%) and 4 (15.4%) participants experienced adverse reactions at 1 and 3 months, respectively. Treatment was discontinued in 4 participants (16.0%) in the switched group and in 1 participant (3.8%) in the added group. Treatment changes involving either switching from a PG analog to PG/timolol fixed combination eye drops or adding ripasudil to PG analog therapy were equally safe and effective in reducing IOP.

Purpose To identify determinants of Bruch's membrane opening (BMO), and BMO-minimum rim width (BMO-MRW) and circumpapillary retinal nerve fiber layer thickness (RNFLT) centered on BMO center and characterize these parameters in a normal Japanese population. Methods Spectral-domain optical coherence tomography images of optic nerve head and circumpapillary and macular retina were obtained in 258 eyes of 258 normal Japanese with mean (standard deviation) age of 51.7 (18.2) years. BMO area, BMO-MRW, RNFLT (measured with a 3.5-mm-diameter circle scan) were all acquired and analyzed relative to the eye-specific fovea to BMO (FoBMO) axis. One randomly selected eye of each subject was analyzed. Multiple regression analysis was used to identify determinants to the parameters. Results BMO area, global BMO-MRW, RNFLT, and FoBMO angle averaged 2.06 (0.45) mm2, 305.5 (50.0) μm, 101.8 (9.6) μm, and -7.8° (3.8°), respectively. There was a modest correlation between global BMO-MRW and RNFLT (r = 0.337; P < 0.001), while the sectorwise correlations were highest in the superior-temporal sector (r = 0.500; P < 0.001) and lowest in the nasal sector (r = 0.117; P = 0.063). Global BMO-MRW and RNFLT declined with age at -1.04 μm/y (P < 0.001) and -0.12 μm/y (P = 0.001), and the former correlated negatively (P = 0.001) and the latter positively (P < 0.001) with BMO area after adjustment for other factors (R2 = 0.191 and 0.272, respectively). BMO area correlated positively with axial length (P = 0.023) and negatively with age (P < 0.001) (R2 = 0.157). Conclusions BMO-MRW and RNFLT declined with age with a difference between them in their relationship to BMO area. BMO area positively correlated with axial length and negatively with age.