Glaucoma progression due to refraining examination amid the pandemic of COVID-19.

PURPOSE: Some patients refrained from seeking an ophthalmologist due to the anxiety and morbidity associated with the coronavirus disease (COVID-19) pandemic. We investigated progressive visual field defects in patients with glaucoma who refrained from ophthalmological examinations. METHODS: This was a retrospective study. We 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. CONCLUSION: Patients with glaucoma with visit interruptions due to the pandemic should be monitored for the progression of visual field impairment.

Three-year efficacy and safety of omidenepag isopropyl in patients with normal tension glaucoma.

PURPOSE: To retrospectively evaluate the 3-year efficacy and safety of single-agent omidenepag isopropyl in patients with normal tension glaucoma (NTG). STUDY DESIGN: Retrospective. METHODS: One hundred patients (100 eyes) who had newly been administered omidenepag isopropyl were enrolled in this study. Intraocular pressure (IOP) was compared at baseline and 6, 9, 12, 18, 24, 30, and 36 months after administration. The mean deviation values at baseline and 12, 24, and 36 months measured using the Humphrey visual field test (30-2 Swedish Interactive Threshold Algorithm standard) were compared. Adverse reactions and dropouts were assessed. RESULTS: IOP significantly decreased from 15.5±2.7 mmHg at baseline to 13.8 ±2.3 mmHg after 6 months, 13.9± 2.3 mmHg after 12 months, 13.9±2.3 mmHg after 18 months, 13.8±2.1 mmHg after 24 months, 13.9±2.0 mmHg after 30 months, and 13.6±1.7 mmHg after 36 months (P < 0.0001). There was no significant difference in the mean deviation values at baseline (-3.66±3.49 dB), 12 months (-3.41±3.80 dB), 24 months (-3.13±3.81 dB), and 36 months (-3.06±3.30 dB). Adverse reactions occurred in 11 patients (11.0%), including conjunctival hyperemia in 6 patients. Fifty-two patients (52.0%) were excluded from the analysis because they discontinued treatment either due to IOP measurement by NCT or the use of additional drugs. CONCLUSION: After the administration of omidenepag isopropyl, IOP in patients with NTG decreased within 3 years, visual fields were maintained, and safety was satisfactory. Thus, omidenepag isopropyl can be used as the first-line treatment for patients with NTG.

Effects of Deep Optic Nerve Head Structures on Bruch's Membrane Opening- Minimum Rim Width and Peripapillary Retinal Nerve Fiber Layer.

PURPOSE: To explore the effects of deep optic nerve head (ONH) structures on Bruch's membrane opening (BMO)-minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness (pRNFLT) in healthy eyes. DESIGN: Prospective cross-sectional study. METHODS: Two hundred five healthy eyes of 141 subjects (mean ± standard deviation of age and axial length (AXL): 46.9 ± 10.0 years and 24.79 ± 1.15 mm) were enrolled. Best fit multivariable linear mixed models identified factors associated with BMO-MRW and pRNFLT. Explanatory variables included age, gender, AXL, BMO and anterior scleral canal opening (ASCO) area and ovality, magnitude of BMO and ASCO shift, peripapillary choroidal thickness, lamina cribrosa (LC) parameters, prelaminar thickness, and peripapillary scleral (PPS) angle. RESULTS: Thinner BMO-MRW was associated with older age, smaller ASCO/BMO offset magnitude, larger BMO area, thinner prelaminar thickness, deeper LC, and thinner pRNFLT (P = .011, <.001, .004, <.001, <.001, <.001 respectively). Thinner pRNFLT was associated with shorter AXL, smaller ASCO area, a more posteriorly bowed PPS, shallower LC and thinner BMO-MRW. (P = .030, .002, .035, .012, <.001 respectively) CONCLUSIONS: BMO-MRW and pRNFLT were influenced by several deep ONH structures such as BMO and ASCO position shift, BMO or ASCO area, prelaminar thickness, PPS bowing and LC depth in addition to patient characteristics such as age and AXL. The degree and/or direction of associations varied between deep ONH structures and BMO-MRW or pRNFLT. Despite both BMO-MRW and pRNFLT being surrogate parameters for RGC loss, a complex relationship with ONH deep-layer morphology was indicated.

Switching to Brimonidine/Ripasudil Fixed Combination from Brimonidine + Ripasudil.

Purpose: A fixed-combination eye drop has several advantages over combination therapy, however, the intraocular pressure (IOP)-lowering efficacy and safety of the newly available brimonidine + ripasudil fixed-combination (BRFC) eye drops after switching from brimonidine + ripasudil is yet to be established. Therefore, this study aimed to retrospectively investigate the 6-month safety, usability, and IOP-lowering efficacy of BRFC switched from brimonidine and ripasudil. Patients and Methods: Overall, 69 patients with primary open-angle glaucoma (69 eyes) receiving brimonidine + ripasudil were enrolled in this study. Brimonidine + ripasudil was discontinued, and treatment was switched to BRFC without a washout period. The IOP was compared before and at 3 and 6 months after switching to BRFC. The side effects, discontinued cases, and usability (a questionnaire survey) were also investigated. Results: The IOP was not significantly different after switching to BRFC (15.1 ± 3.3 mmHg at baseline, 15.9 ± 3.6 mmHg after 3 months, and 14.6 ± 3.3 mmHg after 6 months). Adverse reactions occurred in four patients (5.8%): allergic conjunctivitis, two patients; irritation, one patient; and blurred vision, one patient. Treatment was discontinued in five (7.2%) patients owing to allergic conjunctivitis, two patients; increased IOP, two patients; and blurred vision, one patient. In the questionnaire survey, 68 patients with eye pain, 67 with itching, 64 with conjunctival hyperemia, 64 with irritation, and 62 with blurred vision reported no change or improved conditions. Additionally, in response to the question regarding preferences for pre-treatment and fixed combinations, 14 participants (20.2%) favored pre-treatment, while 53 (76.8%) preferred fixed combinations. Conclusion: The IOP was maintained for 6 months, with satisfactory safety and comfort of use, with BRFC switched from brimonidine and ripasudil.

Association of Bergmeister Papilla and Deep Optic Nerve Head Structures With Prelaminar Schisis of Normal and Glaucomatous Eyes.

PURPOSE: To investigate factors associated with the severity of prelaminar schisis (PLS) in heathy subjects and glaucoma patients. DESIGN: Prospective cross-sectional study. METHODS: A total of 217 eyes of 217 subjects (110 normal eyes and 107 open angle glaucoma eyes) were studied. Frequency and severity of PLS were compared between normal and glaucomatous eyes. Multivariate logistic models were used to assess factors associated with the severity of PLS. Factors considered were age, axial length, glaucomatous damage indices, Bruch membrane opening (BMO) and anterior scleral canal opening parameters, tractional forces (posterior vitreous staging and presence of Bergmeister papilla), circumpapillary choroidal thickness, lamina cribrosa (LC) parameters, and peripapillary scleral (PPS) angle. RESULTS: The frequency of PLS was 70.9% in normal eyes and 72.0% in glaucomatous eyes. There was no difference in frequency and severity between the groups. The presence of Bergmeister papilla was the strongest predictor of a more severe PLS in both normal and glaucomatous eyes (odds ratio [OR] + 9.78, 12.5; both P < .001). A larger PPS angle in normal eyes (OR = 1.19; P = .003) and a larger BMO area and a deeper LC depth in glaucomatous eyes (OR = 1.08, 1.05; both P = .038) were associated with severity of PLS. CONCLUSIONS: The severity of PLS was strongly associated with the presence of Bergmeister papilla, suggesting a traction-related phenomenon. Correlation of PLS severity with larger BMO area and deeper LC depth, which are optic nerve head structures associated with glaucoma, suggested its possible relationship with glaucomatous damage.

Deep Optic Nerve Head Structures Associated With Increasing Axial Length in Healthy Myopic Eyes of Moderate Axial Length.

PURPOSE: To elucidate which swept-source optical coherence tomography (OCT)-derived optic nerve head (ONH) parameters are associated with longer axial length (AXL) in healthy myopic eyes. DESIGN: Prospective cross-sectional observational study. METHODS: Two hundred eleven healthy eyes of 140 participants (96 emmetropic-mild myopic [AXL: 22.2-24.5 mm], 83 moderately myopic [24.5-26.0 mm], and 32 highly myopic [26.0-27.4 mm] eyes) were enrolled. Bruch membrane opening (BMO), anterior scleral canal opening (ASCO) area and ovality, minimum rim width, parameters defining misalignment between the BMO and ASCO planes, OCT-defined region of perineural canal retinal epithelium atrophy and externally oblique choroidal border tissue, circumpapillary retinal nerve fiber layer thickness (cpRNFLT), circumpapillary choroidal thickness (cpChT), lamina cribrosa parameters, and peripapillary scleral (PPS) angle were calculated from BMO-centered radial scans reconstructed from 3D raster scans. Multivariate linear mixed models were used to elucidate ONH parameters that are independently associated with AXL. RESULTS: Longer AXL was associated with a greater misalignment between ASCO and BMO planes, larger region of externally oblique choroidal border tissue, thinner cpChT, larger PPS angle, larger ASCO area, and thicker cpRNFLT (all P < .040 after Bonferroni's correction for number of included explanatory variables). CONCLUSIONS: A greater misalignment between BMO and ASCO planes, thinner choroid, a more posteriorly bowed PPS, an enlargement of ASCO, and thicker cpRNFLT were each associated with longer AXL. An enhanced understanding of these AXL-associated configurations should provide essential information to improve our ability to detect glaucoma-induced ONH morphology in myopic eyes.

Intraocular pressure-lowering effects and safety of brimonidine/brinzolamide fixed combination after switching from other medications.

PURPOSE: To investigate the effects of switching to brimonidine/brinzolamide fixed combination (BBFC) eye drops on intraocular pressure (IOP) and safety. STUDY DESIGN: A retrospective observational study. METHODS: 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. RESULTS: 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; P < 0.0001). 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; P < 0.01). 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%). CONCLUSION: BBFC had satisfactory IOP-lowering effects without serious adverse reactions in patients who switched medications.

One-Year Efficacy and Safety of Omidenepag Isopropyl in Patients with Normal-Tension Glaucoma.

Purpose: To retrospectively evaluate the 1-year efficacy and safety of single-agent of omidenepag isopropyl in patients with normal-tension glaucoma (NTG). Methods: One hundred patients (100 eyes) newly administered omidenepag isopropyl were enrolled. Intraocular pressure (IOP) was compared at baseline and 3, 6, 9, and 12 months after administration. The mean deviation values at baseline and 12 months measured using the Humphrey visual field test (30-2 Swedish Interactive Threshold Algorithm standard) were compared. Adverse reactions and dropouts were observed. Results: IOP significantly decreased from 15.5 ± 2.7 mmHg at baseline to 13.3 ± 2.5 mmHg after 3 months, 13.7 ± 2.3 mmHg after 6 months, 13.9 ± 2.4 mmHg after 9 months, and 13.7 ± 2.3 mmHg after 12 months (P < 0.0001). There was no significant difference in the mean deviation values at baseline (-3.66 ± 3.49 dB) and after 12 months (-3.41 ± 3.80 dB). Adverse reactions occurred in 9 patients (9.0%): conjunctival hyperemia (n = 6), eye pain (n = 1), iritis (n = 1), and blepharitis (n = 1). Twenty-one patients (21.0%) discontinued administration because of changes in medication (n = 7), interruption of visits (n = 5), adverse reactions (n = 4), and others. Conclusions: After administering omidenepag isopropyl, the IOP in patients with NTG decreased within 1 year, visual fields were maintained, and safety was satisfactory. Omidenepag isopropyl can be used as the first-line medication for patients with NTG.

Frequency of Use of Fixed-Combination Eye Drops by Patients with Glaucoma at Multiple Private Practices in Japan.

Purpose: 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 χ 2 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/ß-blocker (PG/ß), carbonic anhydrase inhibitor/ß-blocker (CAI/ß), and α-2-adrenergic agonist/ß-blocker (α2/ß) 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/ß in the two-medications group and CAI/ß 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/ß 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/ß fixed-combination medication. There was little use of α2/ß 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.

The second Japanese family with Malattia Leventinese/Doyne honeycomb retinal dystrophy.

PURPOSE: To describe the clinical and genetic findings of patients in the second Japanese family with Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Periocular Adverse Reactions to Omidenepag Isopropyl.

PURPOSE: To investigate the periocular adverse reactions to omidenepag isopropyl (OMDI). DESIGN: Nonrandomized comparative clinical study. METHODS: 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. RESULTS: 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). CONCLUSIONS: The frequencies of periocular adverse reactions to OMDI, ranging from 0% to 2.0%, were lower than those to tafluprost.

Characterization of laser speckle flowgraphy pulse waveform parameters for the evaluation of the optic nerve head and retinal circulation.

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 ß-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 ß-PPA area (P = 0.026); MT- and MV-flow acceleration index positively correlated with CRAE, MT, and MV (P = 0.041-< 0.001), compatible with these parameters' observed correlations to systemic factors. Significantly negative correlations of the blowout score and acceleration time index to CRAE partly conflicted with their correlations to systemic factors, and other waveform parameters showed little correlation to ocular factors. Thus, Skew and flow acceleration index assisted the in vivo ocular circulation characterization.

Ocular and Systemic Factors Affecting Laser Speckle Flowgraphy Measurements in the Optic Nerve Head.

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 ß-peripapillary atrophy (ß-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 ß-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 ß-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.

Evaluation of the relationship between glaucomatous disc subtypes and occurrence of disc hemorrhage and glaucoma progression in open angle glaucoma.

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 < 0.0220). The central corneal thickness (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.

Short-Term Efficacy and Safety of Omidenepag Isopropyl in Patients with Normal-Tension Glaucoma.

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<0.0001). Eleven patients (22.4%) were non-responders. Adverse reactions occurred in 4 patients (7.4%), including conjunctival hyperemia in 3 patients (after 1 week, 2 weeks, and 1 month, respectively) and eye pain in 1 patient (after 1 month). Five patients (9.3%) dropped out of the study because of an adverse reaction in 3 patients, insufficient IOP reduction in 1 patient, and discontinuation of follow-up of 1 patient at our institution. CONCLUSION: After administration of omidenepag isopropyl, IOP in patients with NTG was significantly decreased. However, adverse reactions occurred in 7.4% of patients.

Spatial and Temporal Relationship between Structural Progression and Disc Hemorrhage in Glaucoma in a 3-Year Prospective Study.

PURPOSE: 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. DESIGN: Prospective cohort study. PARTICIPANTS: Patients with POAG and intraocular pressure of ≤18 mmHg on monotherapy with prostaglandin analogs. METHODS: 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. MAIN OUTCOME MEASURES: Relationship between DH and structural progression at the same site. RESULTS: 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%, P < 0.0001). 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; P < 0.0001). 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. CONCLUSIONS: 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.

One-Year Efficacy and Safety Assessment of Ripasudil, a Rho Kinase Inhibitor, in an Addition to or Replacing Existing Treatment Regimens: A Retrospective Study.

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 128 glaucoma patients who were prescribed ripasudil as an addition to or a switch from their preexisting antiglaucoma instillations. We investigated the rate and factors for discontinuation and intraocular pressure (IOP) reduction. Results: Almost half of the patients (60 eyes) discontinued ripasudil treatment before the 1 year mark, while remaining patients completed the treatment. The lack of efficacy and development of adverse effects were significantly correlated with discontinuation (P < 0.001) in the Cox proportional hazards model. In the Kaplan-Meier curve, adverse effects occurred in earlier phase and almost 60% dropped out within 3 months after ripasudil administration. However, adverse effects also occurred randomly throughout the study period. In patients who continued ripasudil, the mean IOPs (mmHg) at baseline, 6 and 12 months after treatment were 17.7 ± 5.1, 14.6 ± 5.0, and 14.8 ± 3.8 in the Addition group, and 17.8 ± 4.1, 15.4 ± 3.2, and 15.4 ± 5.0 in the Switch group, respectively (all P values <0.05). Conclusions: Almost half of the patients discontinued ripasudil owing to the lack of efficacy and the generation of adverse effects within the 1 year. In the remaining half, the addition and switching of ripasudil to the existing glaucoma treatment effectively reduced IOP for 1 year.

Short-Term Efficacy and Safety of Switching from a Latanoprost/Timolol Fixed Combination to a Latanoprost/Carteolol Fixed Combination.

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<0.01 and p<0.0001, respectively). There was a significant decrease in systolic blood pressure after 1 month and diastolic pressure after 3 months (p<0.05). There was no significant change in pulse rate during the study. Adverse reactions (blurred vision, blepharitis, and conjunctival hyperemia) occurred in 3 patients (10.0%). Four patients (13.3%) discontinued treatment during the 3-month study period. CONCLUSION: A switch from a fixed combination of latanoprost/timolol to that of latanoprost/carteolol can maintain intraocular pressure and adherence with once-daily administration while improving tear film break-up time and corneal epithelial defects.

Incidence and Risk Factors of Iatrogenic Retinal Breaks: 20-Gauge versus 25-Gauge Vitrectomy for Idiopathic Macular Hole Repair.

PURPOSE: We compared the incidences of iatrogenic retinal breaks and postoperative retinal detachment between eyes that underwent 20-gauge vitrectomy and those that underwent 25-gauge vitrectomy for idiopathic macular hole repair. METHODS: This retrospective nonrandomized consecutive observational case series included 185 eyes of 183 patients (130 eyes of 129 patients and 55 eyes of 54 patients in the 20- and 25-gauge groups, respectively). We assessed the relationship between the incidence of retinal breaks and postoperative retinal detachment and related this to posterior vitreous detachment and lattice degeneration. RESULTS: The incidences of iatrogenic retinal breaks were 36.9% and 12.7% in the 20-gauge and 25-gauge groups, respectively. These groups did not differ in their respective frequencies of posterior vitreous detachment (the 20-gauge group: 31.5% and the 25-gauge group: 27.3%) and lattice degeneration (the 20-gauge group: 14.6% and the 25-gauge group: 7.3%). Among eyes without lattice degeneration, the 20-gauge group showed a higher incidence of iatrogenic retinal breaks than the 25-gauge group. However, among the eyes with lattice degeneration, the frequency of retinal breaks did not differ between the two surgery types, and four cases of postoperative retinal detachment were reported in both groups. CONCLUSIONS: The incidence of retinal breaks related to idiopathic macular hole surgery is higher among patients undergoing 20-gauge vitrectomy than among those undergoing 25-gauge vitrectomy. Posterior vitreous detachment and lattice degeneration are associated with considerably increased incidences of retinal break.

A scoping review and network meta-analysis for efficacy and safety of glaucoma medication in Japanese patients.

PURPOSE: 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. STUDY DESIGN: Scoping network meta-analysis. METHODS: 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%. RESULTS: Eleven multicenter trials of ten medications in total, (five prostaglandin (PG) analogs, three ß-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. CONCLUSION: 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.