Factors associated with ocular adverse event after immune checkpoint inhibitor treatment.

Ocular adverse events (OAEs) including vision-threatening intraocular inflammation after immune checkpoint inhibitor (ICI) treatment have been increasingly reported; however, the risk factors associated with OAEs remain elusive. Here, we determined the factors associated with OAEs after ICI treatment. We analyzed 40 consecutive patients who experienced OAEs after ICI treatments. The OAEs included anterior uveitis, chorioretinitis, papillitis, foveal interdigitation zone thickening/serous retinal detachment (IZT/SRD), retinal vascular occlusion, and strabismus and ptosis. Of 40 patients, 18 (45%) were treated with atezolizumab, 13 (33%) with pembrolizumab, 7 (18%) with nivolumab, 1 (3%) with ipilimumab/nivolumab, and the other 1 (3%) with durvalumab/tremelimumab. BRAF/MEK inhibitors were concurrently used in 19 (48%) patients. Occurrence of intraocular inflammation was significantly associated with previous ocular surgery and trauma history (P = 0.015) and pembrolizumab use (P = 0.031). Neuro-ophthalmic complications and IZT/SRD were associated with brain metastasis (P = 0.005) and treatment with BRAF/MEK inhibitor (P < 0.001), respectively. In extensive literature review for clinical cases, we identified seven cases with intraocular inflammation, which were not observed with ipilimumab treatment, that occurred after a change of the drug to pembrolizumab. Collectively, these findings provide better understandings of OAEs after ICI treatment.

Risk factors associated with poor outcome after medial rectus resection for recurrent intermittent exotropia.

PURPOSE: To describe characteristics of recurrent intermittent exotropia after bilateral lateral rectus (BLR) recession, and identify factors associated with poor outcome after unilateral medial rectus (MR) resection for recurrent intermittent exotropia. METHODS: We retrospectively reviewed 124 patients who have undergone unilateral MR resection for recurrent intermittent exotropia after BLR recession. Patients were followed for at least 2 years after MR resection. Clinical characteristics and risk factors associated with poor outcome after unilateral MR resection were evaluated. Successful outcome was defined as distant deviation within the range of 4 prism diopters (PD) esotropia and 10 PD exotropia at last visit after MR resection. RESULTS: Among 124 patients, 50 patients (41.1%) were male, and the mean age at the time of MR resection was 9.5 ± 3.1 years. The average follow-up period after MR resection was 43.8 ± 23.7 months. Forty-seven patients (37.9%) were classified to have poor outcome at last visit, and 29 patients (23.4%) underwent third operation. None of the patients was overcorrected after MR resection. Multiple logistic regression analyses showed that distant deviation at post-operative 3 months and male gender were associated with poor outcome (OR 1.49; 95% CI 1.27-1.73; P < 0.001, and OR 5.19; 95% CI 1.42-18.98; P = 0.013, respectively). CONCLUSION: Ocular deviation at 3 months after unilateral MR resection for recurrent intermittent exotropia may play a valuable role in anticipating poor outcome. Patients whose exotropia exceeded 9 PD at distance at 3 months' follow-up tended to recur while those whose exotropia remained below 9 PD at distance showed a stable disease course.

SURGICAL OUTCOMES OF MYOPIC TRACTION MACULOPATHY ACCORDING TO THE INTERNATIONAL PHOTOGRAPHIC CLASSIFICATION FOR MYOPIC MACULOPATHY.

PURPOSE: To compare treatment results of myopic traction maculopathy according to the international photographic classification for myopic maculopathy. METHODS: This was a retrospective, single-surgeon-based, observational case series of 35 consecutive eyes that underwent vitrectomy for myopic traction maculopathy. Eyes were classified into nonpathologic myopia (PM) (n = 15) and PM (n = 20) groups. Main outcome measures constituted best-corrected visual acuity (BCVA) and anatomical change. RESULTS: The mean follow-up was 32.03 ± 6.85 months. Axial length correlated with myopic maculopathy category (rho = 0.6836, P < 0.001). In the total group, BCVA improved from 20/61 to 20/36 (P = 0.001). In the subgroup, BCVA improved from 20/41 to 20/22 in the non-PM group (P = 0.002), whereas from 20/82 to 20/52 in the PM group (P = 0.048). Postoperative BCVA of the PM group was inferior to that of the non-PM group (P = 0.002) and the PM group was more likely to have postoperative BCVA <20/30 (odds ratio, 17.3; 95% CI, 2.6-325.0; P = 0.012). Two cases of macular hole retinal detachment occurred after surgery in the PM group. CONCLUSION: Because there are limited benefits of vitrectomy in myopic traction maculopathy accompanied by PM, careful consideration would be necessary when determining surgery. Optical coherence tomography should not be used alone in determining vitrectomy because myopic traction maculopathy can also have PM defined mainly by fundus photographs.

Long-Term Regular Use of Low-Dose Aspirin and Neovascular Age-Related Macular Degeneration: National Sample Cohort 2010-2015.

PURPOSE: The association between long-term cardioprotective aspirin use and neovascular age-related macular degeneration (AMD) is controversial. This study was undertaken to estimate the risk of neovascular AMD with long-term regular use of low-dose aspirin. DESIGN: Retrospective population-based study, using a nationwide cohort from a variety of clinics and hospitals in South Korea. PARTICIPANTS: Nonregular aspirin users and regular aspirin users under national health insurance, aged ≥45 years, who were followed from 2010 to 2015, were identified. METHODS: Incidence per 10 000 person-years for neovascular AMD was estimated. Long-term regular use of low-dose aspirin was defined as sustained intake of ≤100 mg aspirin with ≥1044 days prescription between 2005 and 2009. Nonregular aspirin users included occasional users or nonusers. The analyses included a propensity score-adjusted analysis in a large, randomly selected, unmatched whole cohort (n = 482 613); propensity score-matched analysis in a matched cohort (n = 74 196); and maximally adjusted analysis in the unmatched whole cohort (n = 482 613). MAIN OUTCOME MEASURES: Incidence of newly developed neovascular AMD using the registration code for intractable disease under national health insurance. RESULTS: Incidence of neovascular AMD was 3.5 among nonregular aspirin users and 7.2 among regular aspirin users per 10 000 person-years in the unmatched whole cohort. However, propensity score-adjusted analyses revealed no association between aspirin use and neovascular AMD (adjusted hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.73-1.30). Likewise, propensity score-matched analyses showed no association; incidences of neovascular AMD were 7.5 and 7.1 among nonregular aspirin users and regular aspirin users (crude HR, 0.94; 95% CI, 0.70-1.28), respectively. A maximally adjusted model, including age, sex, income, residential area, and history of 100 randomly selected types of generic drugs, showed no association (adjusted HR, 0.95; 95% CI, 0.71-1.28). CONCLUSIONS: We found no association between long-term regular use of low-dose aspirin for 5 years and future incidence of neovascular AMD. Thus, this large-scale study suggests that regular, long-term use of low-dose aspirin appears to be safe with respect to the new development of neovascular AMD.

High circulating adiponectin level is associated with poor clinical outcome after catheter ablation for paroxysmal atrial fibrillation.

Aims: Circulating adiponectin is known to have anti-diabetic, anti-atherogenic, and anti-inflammatory properties. However, the predictive value of adiponectin in cardiovascular disease has been reported to be contradictory ('adiponectin paradox') and its relationship with atrial fibrillation (AF) is controversial. We hypothesized that pre-procedural plasma level of adiponectin would have prognostic value in patients who underwent AF catheter ablation. Methods and results: This observational cohort study included 874 patients with paroxysmal AF (PAF) (73.0% male, mean age 57.6 ± 11.2 years) who underwent catheter ablation. Quartile analyses of plasma level of adiponectin were performed to determine AF-related clinical factors. Patients in the highest quartile of plasma adiponectin were more likely to be older (P < 0.001), female (P < 0.001), and have a higher CHA2DS2-VASc score (P < 0.001) than patients in the other three quartiles. Plasma level of adiponectin was independently associated with female gender (B 2.92 [1.84∼4.00], P < 0.001), older age (B 0.06 [0.03∼0.10], P < 0.001), lower body mass index (B - 0.22 [-0.42∼-0.03], P = 0.025), and greater LA volume index (B 0.05 [0.01∼0.08], P = 0.005). During the 29.9 ± 18.0 months of follow-up, plasma adiponectin level (HR 1.17 [1.02∼1.35], P = 0.022) was independently associated with clinical recurrence of AF, and the clinical recurrence rate was significantly higher in the highest quartile of adiponectin group than the others (log rank P = 0.029), especially in age <65 years (log rank P = 0.038), but not in age ≥65. Conclusion: High circulating adiponectin is independently associated with AF recurrence after catheter ablation for PAF, especially younger than 65 years old.

Blunted rate-dependent left atrial pressure response during isoproterenol infusion in atrial fibrillation patients with impaired left ventricular diastolic function: a comparison to pacing.

AIMS: A heart rate (HR)-dependent haemodynamic linkage between peak left atrial (LA) pressure during sinus rhythm (LAPpeak) and estimated left ventricular (LV) filling pressure (E/Em) has not yet been explored. We hypothesized that rate-dependent LAPpeak response differs depending on E/Em in patients with atrial fibrillation (AF). METHODS AND RESULTS: A total of 331 patients (68.0% male, 59.8 ± 10.8 years old) undergoing radiofrequency catheter ablation (RFCA) for AF were included, and their LAPpeak in sinus rhythm was recorded at the beginning of the procedure and at the HRs of 90, 100, 110, and 120 b.p.m. during right atrial pacing and isoproterenol (ISO-stress) infusion. We compared LAPpeak changes between patients with E/Em ≥ 15 (n = 58) and those with <15 (n = 273). (i) The patterns of pacing rate-dependent LAPpeak increase were similar in both the E/Em < 15 (P < 0.001) and E/Em ≥ 15 groups (P = 0.002). (ii) The ISO-stress reduced LAPpeak in patients with E/Em < 15 (P = 0.015), but not in those with E/Em ≥ 15 (P = 0.582). (iii) Paradoxical ISO-stress LAP elevation in patients with E/Em ≥ 15 was independently associated with 1-year follow-up E/Em reduction (B = -4.07, 95% CI -5.41 to -2.72, P < 0.001). Coexistence of E/Em ≥ 15 and ISO-stress LAP elevation increased specificity in predicting 1-year follow-up E/Em reduction after AF ablation than E/Em alone. CONCLUSION: Isoproterenol LAPpeak reduction was blunted in patients with impaired LV diastolic function estimated by E/Em ≥ 15. The improvement of LV diastolic dysfunction 1 year after AF ablation was independently associated with both paradoxical ISO-stress LAP elevation and E/Em ≥ 15 at the time of procedure. CLINICALTRIALSGOV: NCT02138695.

Systemic Arterial Stiffness and Choroidal Microvascular Insufficiency on the Structural Progression of Normal Tension Glaucoma.

PURPOSE: To identify the role of systemic arterial stiffness and choroidal microvascular insufficiency on structural progression of normal-tension glaucoma (NTG). DESIGN: Retrospective cohort study. METHODS: A total of 107 early NTG eyes of 88 patients, who underwent pulse wave velocity (PWV) measurements and optical coherence tomography (OCT) angiography (OCT-A) at baseline, were categorized depending on the presence of peripapillary choroidal microvasculature dropout (MvD) and PWV. Differences in glaucomatous progression were analyzed. Structural progression rates were determined using the trend-based analysis of cirrus OCT. RESULTS: Thirty-two eyes displayed choroidal MvD (62.7 (95% CI 58.4-67.0) years old, 53.6% males), and 70 eyes did not show any MvD (59.9 (95% CI 57.1-62.6) years old, 53.3% males) at baseline. Patients were followed for 48.4 (95% CI 40.0-56.8) months. When they were further divided based on PWV (high PWV≥1400cm/sec), those with choroidal MvD and high PWV showed significantly faster thinning in macular ganglion cell-inner plexiform layer (GCIPL; P=0.023). In comparison to those with low PWV and no MvD, eyes with high PWV and MvD in the peripapillary area were likely to show fast structural progression (≤-1.2 µm/year) in the macular GCIPL by odds of 6.019 (95% CI 1.619-38.531, P=0.025). CONCLUSIONS: In NTG eyes, GCIPL thinning was faster when choroidal MvD and high systemic arterial stiffness were present. The simultaneous presence of regional and systemic vascular insufficiency may be associated with rapid glaucoma structural progression in eyes with low baseline intraocular pressure.

Clinical characteristics of open-angle glaucoma progression with peripapillary microvasculature dropout in different locations.

OBJECTIVE: The study attempted to identify clinical characteristics associated with structural progression in open-angle glaucoma (OAG) in the presence of MvD in different locations. METHODS: A total of 181 consecutive OAG eyes (follow-up 7.3 ± 4.0 years), which demonstrated peripapillary choroidal MvD (defined as a focal capillary loss with no visible microvascular network in choroidal layer) on optical coherence tomography (OCT) angiography (OCTA), were divided based on the location of MvD. Structural progression was determined using trend-based analysis of the Guided Progression Analysis software of Cirrus OCT. RESULTS: MvD was identified in the temporal quadrant in 110 eyes (temporal MvD; 60.5 ± 12.6 years), and in the inferior quadrant in 71 eyes (inferior MvD; 60.3 ± 11.1 years). After adjusting for age, average intraocular pressure (IOP) and baseline retinal nerve fibre layer (RNFL) thickness and visual field mean deviation, inferior MvD eyes showed faster rates of thinning in the inferior RNFL (mean (95% CI); -0.833 (-1.298 to -0.367)) compared to temporal MvD eyes (-0.144 (-0.496 to 0.207)) when long-term IOP fluctuation was larger than the median value (1.7 mmHg; P = 0.022). Long-term IOP fluctuations were independently associated with inferior RNFL thinning in eyes with inferior MvD (P = 0.002) but not in eyes with temporal MvD. CONCLUSIONS: In OAG eyes, the rates of RNFL and GCIPL thinning were comparable regardless of MvD locations. However, inferior MvD is associated with faster RNFL and GCIPL thinning in the same quadrant when long-term IOP fluctuation is present. Structural progression in the presence of temporal MvD was less associated with IOP fluctuation.

Left ventricular diastolic function is closely associated with mechanical function of the left atrium in patients with paroxysmal atrial fibrillation.

BACKGROUND: Left ventricular (LV) diastolic dysfunction may be a mechanism of left atrial (LA) electroanatomical remodeling in atrial fibrillation (AF). We evaluated the association between LV diastolic function and LA mechanical function in non-valvular paroxysmal AF (PAF). METHODS AND RESULTS: In 286 patients with PAF (males 73%, 57 ± 11 years), LA size, indexed LA volume, LV diastolic function, and LA appendage flow velocity (LAA-FV) in sinus rhythm were measured using transthoracic echocardiography, transesophageal echocardiography and cardiac computed tomography. The LA voltage map was obtained using NavX contact mapping. Patients with impaired LA mechanical function (LAA-FV <58 cm/s, n=142) showed a higher E/Em ratio (10.3 vs. 9.2, P=0.034) and lower Em velocity (6.8 vs. 7.7 cm/s, P=0.004) than those with preserved function (LAA-FV ≥ 58 cm/s, n=144). The patient population displayed weak correlations of E/Em with LAA-FV (r=-0.19, P=0.003) and LA voltage (r=-0.23, P=0.004), but more significant association of E/Em and LAA-FV (r=-0.39, P<0.001) for age ≥ 55 years and LA diameter ≥ 40 mm. E/Em was an independent predictor of LAA mechanical function (ß=-0.20, P=0.013) even after age, sex, LA size and comorbidities were controlled for. CONCLUSIONS: In patients with non-valvular PAF, LA mechanical function is closely related to the degree of LA remodeling and LV diastolic function. Impaired LV diastolic function significantly contributes to LA electoanatomical remodeling in older patients with a larger LA.

Retraction: Serological Predictors for the Recurrence of Atrial Fibrillation After Electrical Cardioversion.

This corrects the article on p.185 in vol.40, PMID: 20421959.

Alterations of Macular Structure in Non-Glaucomatous Subjects With Obstructive Pulmonary Function.

Purpose: The purpose of this study was to identify possible associations between obstructive pulmonary function and macular structure parameters on optical coherence tomography (OCT) and angiography in subjects without glaucomatous optic neuropathy. Methods: A total of 70 patients were prospectively enrolled from June to December 2021 as a part of All About Life Yongin-Pulmonary/Psychiatry, Rehabilitation, Eye (AALY PRE) cohort in Yongin Severance Hospital. Patients underwent intraocular pressure (IOP), visual acuity measurements, cirrus OCT, OCT angiography, and pulmonary function testing (PFT) on the same day. Subjects with glaucomatous optic nerve damage were excluded. Those whose first second of forced expiration (FEV1) to forced vital capacity (FVC) ratio was below 70% were diagnosed with obstructive pulmonary function. Vessel densities (VDs) of retinal superficial vascular plexus were compared. Results: Patients with obstructive function (n = 30) were significantly older than those with normal pulmonary function (n = 40, P < 0.001). After adjusting for age, IOP, and average ganglion cell-inner plexiform layer (GCIPL) thickness, macular VD was significantly decreased in all sectors except for the nasal sector in subjects with obstructive pulmonary function in comparison to those with normal function (P = 0.006). Multivariate regression analysis demonstrated that macular VD was linearly associated with FEV1/FVC (ß = 0.102, P = 0.031). In subjects with obstructive function, the severity of pulmonary obstruction, FEV1, was linearly associated with GCIPLT (ß = 0.302, P = 0.017). Conclusions: Obstructive pulmonary function is associated with reduced macular VD in subjects without glaucoma. Among subjects with obstructive pulmonary function, the severity of pulmonary obstruction is associated with GCIPL thickness in the macular region. Further studies are needed on the relationship between pulmonary function and macular disease.

Effectiveness and safety of injectable human papilloma virus vaccine administered as eyedrops.

Mucosal vaccines have the advantages of ease of administration and the induction of strong mucosal immunity and a systemic immune response. Recently, the eye mucosa has been shown to be an effective and safe alternative vaccination route against influenza, Toxoplasma gondii infection, and hemolytic uremic syndrome in mice. In this study, we showed that the commercially available human papilloma virus (HPV) vaccine, Cervarix, induced significant immune reactions in terms of anti-HPV antigen (Ag)-specific immunoglobulin G (IgG) and IgA antibody production following eyedrop (ED) vaccination in mice. The HPV ED vaccines (EDV) provoked no signs of inflammation within 24 h, as indicated by the inflammatory cytokine mRNA levels and infiltration of mononuclear cells in inoculation sites. Moreover, the morphology of the cornea and retina and intraocular pressure of mice did not change after the HPV EDV. The functions of photoreceptor cells, including rod and cone cells, were normal following the HPV EDV inoculation in mice. These results suggest that Cervarix EDV could be a potent, safe, and effective mucosal vaccine against HPV-associated cancers.

Effect of Intraoperative Mitomycin C on the Surgical Outcomes of Ahmed Glaucoma Valve Implantation with Ciliary Sulcus Tube Placement.

PURPOSE: To evaluate the effect of intraoperative mitomycin C (MMC) on the surgical outcomes of ciliary sulcus (CS) Ahmed glaucoma valve (AGV) tube placement. METHODS: A retrospective review of medical records of 54 consecutive patients who underwent AGV implantation with tube placed in CS was performed. Consecutive cases operated without the use of intraoperative MMC from 2017 to 2019 were compared with consecutive cases operated with MMC from 2019 to 2021. Surgical failure was defined as intraocular pressure (IOP) exceeding 21 mmHg in two consecutive visits after postoperative 3 months or ≤30% IOP reduction, IOP ≤5 mmHg in two consecutive visits, or loss of light perception. Kaplan-Meier survival analysis and log-rank test were performed to compare the surgical failure rates. RESULTS: A total of 54 eyes of 54 patients were investigated. Mean follow-up period after AGV implantation was 1.4 ± 0.8 years. The MMC group showed significantly lower IOP during the 1st postoperative month (20.5 ± 8.6 mmHg vs. 15.8 ± 6.4 mmHg, p = 0.027), but the difference did not persist 6 months after the surgery (p = 0.805). The mean number of postoperative antiglaucoma medications was significantly lower in the MMC group in the 1st postoperative month (p = 0.047) but no difference was found at 6 months. No statistical difference was noted in the rates of postoperative complications. Kaplan-Meier survival analysis showed comparable survival rates between MMC group and no MMC group (p = 0.356). CONCLUSIONS: The intraoperative use of MMC significantly lowered IOP in the 1st postoperative month but did not increase 6 months success rates in patients receiving AGV tube placement in CS.

Peripapillary choroidal microvasculature dropout is associated with poor prognosis in optic neuritis.

PURPOSE: To identify peripapillary choroidal microvasculature dropout (MvD) in eyes with optic neuritis and its association with longitudinal changes in retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIP) thicknesses following diagnosis. METHODS: A total of 48 eyes with optic neuritis was evaluated to identify the presence of peripapillary choroidal MvD, defined as a focal capillary loss with no visible microvascular network in choroidal layer, using optical coherence tomography (OCT) angiography (OCTA). Patients were divided based on the presence of MvD. OCT and standard automated perimetry (SAP) conducted at 1, 3 and 6 months follow-up were analyzed. RESULTS: MvD was identified in 20 of 48 eyes (41.7%) with optic neuritis. MvD was most commonly found in the temporal quadrant (85.0%), and peripapillary retinal vessel density in the temporal quadrant was significantly lower in eyes with MvD (P = 0.012). At 6 months follow-up, optic neuritis eyes with MvD showed significantly thinner GCIP in superior, superotemporal, inferior and inferotemporal sectors (P<0.05). No significant difference was noted in SAP parameters. The presence of MvD was significantly associated with thinner global GCIP thickness at 6 months follow-up (OR 0.909, 95% CI 0.833-0.992, P = 0.032). CONCLUSION: Optic neuritis showed peripapillary choroidal microvascular impairment in the form of MvD. MvD was associated with structural deterioration at macular GCIP. Further studies are necessary to identify the causal relationship between microvascular impairment and retinal nerve fiber layer damage in optic neuritis.

Effect of antihypertensive medications on the risk of open-angle glaucoma.

The purpose of this study was to identify the effect of antihypertensive medication on risks of open-angle glaucoma (OAG) among patients diagnosed with hypertension (HTN). A total of 5,195 patients, who were diagnosed with HTN between January 1, 2006 and December 31, 2015, and subsequently diagnosed with OAG, were selected for analysis. For each OAG patient, 5 non-glaucomatous, hypertensive controls were matched (n = 25,975) in hypertension diagnosis date, residential area, insurance type and economic status. Antihypertensive medications were stratified into 5 types: angiotensin converting enzyme inhibitor (ACEi), angiotensin receptor blockers (ARB), calcium channel blockers (CCB), ß-blockers and diuretics. Relative risks were calculated. After adjusting for age, sex, body mass index, lifestyle, comorbidities, blood pressure (BP), follow-up duration, and use of other types of antihypertensive drugs, ARB and CCB were found to slightly increase OAG risks (RR 1.1087 (95% CI 1.0293-1.1942); 1.0694 (1.0077-1.1349), respectively). Combinations of ARB with diuretics (1.0893 (1.0349-1.1466)) and CCB (1.0548 (1.0122-1.0991)) also increased OAG risks. The risks for OAG were found to increase by antihypertensive medication use, but the effects appeared to be small. Further studies are necessary to identify the associations of increased BP, medication and therapeutic effect with OAG.

Increased Risks of Open-Angle Glaucoma in Untreated Hypertension.

PURPOSE: Hypertension (HTN) has been associated with open-angle glaucoma (OAG), but whether elevated blood pressure (BP) alone is associated with OAG is unknown. Whether stage 1 hypertension, as per the 2017 American College of Cardiology/American Heart Association (ACC/AHA) BP guidelines, increases the risk of the disease is uncertain. DESIGN: Retrospective, observational, cohort study. METHODS: A total of 360,330 subjects who were ≥40 years of age and not taking antihypertensive or antiglaucoma drugs at the time of health examinations between January 1, 2002, and December 31, 2003, were included. Subjects were categorized based on their untreated BP, into normal BP (systolic BP [SBP] <120 and diastolic BP [DBP] <80 mm Hg; n = 104,304), elevated BP (SBP 120-129 and DBP <80 mm Hg; n = 33,139), stage 1 HTN (SBP 130-139 or DBP 80-89 mm Hg; n = 122,534), or stage 2 HTN (SBP ≥140 or DBP ≥90mm Hg; n = 100,353). Cox regression analysis was performed to calculate hazard ratios (HR) of OAG risk. RESULTS: The mean age of the subjects was 51.17 ± 8.97 years, and 56.2% were male. During a mean follow-up period of 11.76 ± 1.37 years, 12,841 subjects (3.56%) were diagnosed with OAG. Multivariable-adjusted HRs (95% CIs) were 1.056 (0.985-1.132) for elevated BP, 1.101(1.050-1.155) for stage 1 HTN, and 1.114(1.060-1.170) for stage 2 HTN with normal BP as the reference. CONCLUSIONS: The risk for OAG becomes greater with increases in untreated BP. Stage 1 HTN per the 2017 ACC/AHA BP guidelines is a significant risk factor for OAG.

Automatic measurement of mouse visual acuity based on optomotor response: SKY optomotry.

In the field of visual science study using rodents, several assessment methods have been developed for measuring visual function. However, methods such as electroretinograms tests, visual evoked potentials tests and maze tests have limitations in that they measure function of only a specific type of cells, are difficult to quantify or require sufficient training time. The method which uses an optokinetic reflex and optomotor response, a compensatory eye and head movement in response to changes in the visual scene, became the most widely used method. However, this method requires highly trained experimenters and is time consuming. We showed that measured visual acuity values are significantly different between beginner and expert. Here we suggest an automated optometry program, 'SKY optomotry', which automatically tracks rodents' optomotor response to overcome subjectivity and the lengthy scoring procedure of the existing method. To evaluate the performance of SKY optomotry using 8-12-week-old C57BL/6 mice we compared the binomial decision of SKY optomotry with a skilled expert, and the area under the curve of SKY optomotry was 0.845. Comparing the final visual acuity, the intraclass correlation coefficient value between SKY optomotry and an expert was 0.860 (95% confidence interval (CI) 0.709-0.928), whereas that between an expert and a beginner was 0.642 (95% CI 0.292-0.811). SKY optomotry showed an excellent level of performance with good inter-rater agreements based on the visual acuity measured by an expert. With the use of our application, researchers will be able to test an experimental animal's eyesight more accurately while saving time on specialized training.

Significant reduction of atrial defibrillation threshold and inducibility by catheter ablation of atrial fibrillation.

BACKGROUND: Radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) has antiarrhythmic effects by multiple mechanisms. We hypothesized that RFCA curtails atrial defibrillation threshold (A-DFT) and postablation induction pacing cycle length (iPCL), making critical mass reduction one potential mechanism by which antiarrhythmic effect is achieved. METHODS: We included 289 patients with AF (male 77.9%, 55.7 ± 10.8 years old; 197 paroxysmal AF: 92 persistent AF) who underwent RFCA. A-DFT (serial internal cardioversion 2, 3, 5, 7, and 10 J) and iPCL (serial 10 mA 10-second atrial pacing with pacing cycle length 250, 200, 190, 180, 170, 160, and 150 ms) were evaluated before and after RFCA. RESULTS: (1) RFCA of AF reduced the A-DFT from 6.7 ± 3.7 J to 3.0 ± 3.0 J (P < 0.001). (2) AF ablation reduced AF inducibility from 95.4% before the procedure to 56.3% after the procedure (P < 0.001), and the iPCL from 194.8 ± 32.6 to 160.9 ± 26.2 ms (P < 0.001). (3) In patients who underwent a greater number of ablation lines, the post-RFCA A-DFT (P < 0.001) was lower, and %ΔA-DFT (P = 0.003) and proportion of atrial tachycardia (P = 0.022) were higher than those with a lower number of ablation lines. CONCLUSION: AF ablation significantly reduced A-DFT, AF inducibility, and iPCL, and the degree of their reduction was related to the number of ablation lines. (PACE 2012;35:1428-1435).

Brimonidine tartrate ophthalmic solution 0.025% for redness relief: an overview of safety and efficacy.

INTRODUCTION: Ocular redness, or conjunctival hyperemia, is a common ophthalmic sign associated with reduced quality of life. For redness without apparent underlying pathology, topical ophthalmic decongestants have been widely used. AREAS COVERED: Brimonidine tartrate was approved in 2017 as a topical vasoconstrictor at a 0.025% concentration for relief of ocular redness. Since then, investigators have reported on efficacy and safety findings from studies evaluating low-dose brimonidine for reducing ocular redness. EXPERT OPINION: Brimonidine is highly selective for α2-adrenergic receptors. Clinical trials have so far shown that the drug in low doses significantly reduces ocular redness in comparison to vehicle for up to 8 hours. Brimonidine-treated eyes did not present side effects of other vasoconstrictors, such as hypotension, cardiac arrhythmia, or drowsiness. Ocular adverse events, such as allergic reactions and redness rebound, were also minimal. In this review, we examine in detail published literature on the mechanism of brimonidine tartrate and its efficacy and safety in relieving conjunctival hyperemia.

Systemic Arterial Stiffness Is Associated With Structural Progression in Early Open-Angle Glaucoma.

Purpose: The purpose was to identify association between systemic arterial stiffness predicted by brachial-ankle pulse wave velocity (PWV) and initial location of structural progression in early open-angle glaucoma. Methods: Patients with early open-angle glaucoma who underwent PWV measurements were subjected to a retrospective review of medical records. A total of 160 eyes of 160 patients were subjected to analyses. Patients were categorized into three PWV groups. Structural progression was determined using event-based analysis of the Guided Progression Analysis software of Cirrus optical coherence tomography. Results: Thirty-eight patients had a PWV of 1400 cm/s or less on both the left and right sides (low PWV, 39.5% females, 53.9 ± 8.8 years old), and 46 patients showed a PWV of 1800 cm/s or more on either side (high PWV; 54.3% females, 71.3 ± 5.8 years old). The rest of the patients had an intermediate PWV (n = 76, 50.0% females, 59.8 ± 8.6 years old). Among patients who showed progression in 69.3 ± 41.5 months, macular ganglion cell-inner plexiform layer (mGCIPL) loss preceded peripapillary retinal nerve fiber layer (ppRNFL) loss in 86.7% of high PWV group (n = 15, 60.0% females, 70.0 ± 6.0 years old) in comparison with 26.7% of the low PWV group (P = 0.002). The PWV was significantly higher in patients whose structural progression was first observed at mGCIPL (1744.1 ± 347.7 cm/s) than patients whose initial location was ppRNFL (1452.0 ± 201.0 cm/s; P = 0.012). A high PWV was associated with increased likelihood of structural progression at mGCIPL (odds ratio, 7.484; 95% confidence interval, 1.212-49.196; P = 0.030) among patients who showed progression. Conclusions: PWV is a significant predictor of the location of structural progression in open-angle glaucoma. Vascular insufficiency may be an important aspect in the pathogenesis of glaucoma.