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.

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.

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.

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.

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.

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

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

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.

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.

What Are the Factors Associated with the Structural Damage Differences in Open-Angle Glaucoma? RNFL- and GCIPL-Dominant Progression.

We sought to analyze the parameters associated with retinal nerve fiber layer (RNFL)-dominant progression or ganglion cell-inner plexiform layer (GCIPL)-dominant progression in patients with open-angle glaucoma. A prospective observational study was conducted. Overall, 58 eyes from 33 patients with open-angle glaucoma were categorized into the following two groups: patients with RNFL- and GCIPL-dominant progression, and the primary outcome was the difference in associated factors between two groups. Higher pre-treatment and mean IOP, greater lamina cribrosa curvature index (LCCI), and younger age were more significantly associated with the RNFL-dominant progression group than the GCIPL-dominant progression group. When adjusting for mean IOP, age, LCCI, and microvascular dropout (MVD), only pre-treatment IOP was significantly associated with the RNFL-dominant progression group. However, when adjusting for pre-treatment IOP, age, LCCI, and MVD, both higher mean IOP and greater LCCI were significantly associated with RNFL-dominant progression. In conclusion, pre-treatment and mean IOP and LCCI were more strongly associated with the RNFL-dominant progression group than the GCIPL-dominant progression group. In contrast, age, peripapillary choroidal microvascular dropout, and systolic and diastolic blood pressures tended to damage the GCIPL predominantly rather than the RNFL. Therefore, our findings suggest the potential to set different treatment targets and identify various treatment methods for each group.

Increased risk of open-angle glaucoma in non-smoking women with obstructive pattern of spirometric tests.

To investigate differences in the prevalence of open-angle glaucoma (OAG) between different pulmonary function types. A population-based, cross-sectional analysis was conducted using Korean National Health and Nutrition Examination Surveys from 2008 to 2011. A total of 8941 subjects ≥ 40 years of age were analyzed. Chronic obstructive pulmonary disease (COPD) was defined as the ratio between first second of forced expiration (FEV1) and forced vital capacity (FVC) below 70%. The prevalence of glaucoma, as defined by the International Society of Geographical and Epidemiological Ophthalmology, was the main outcome. OAG was more prevalent in women with COPD (8.0% vs. 4.8% normal, P = 0.001) compared to women with normal pulmonary function. Intraocular pressure (IOP) of women with COPD were 13.3 (0.2) mmHg (13.9 (0.1) mmHg for normal function, P = 0.182). Never-smokers were more prevalent in women with COPD and glaucoma (92.9% vs. 52.4% normal function; P < 0.001). COPD was found to increase the risk of glaucoma in women (OR 2.077, P = 0.017) and even further in non-smoking women (OR 2.711, P = 0.003). Women with COPD showed a higher glaucoma prevalence despite similar IOP in comparison to women with normal pulmonary function. Non-smoking COPD is significantly associated with open-angle glaucoma in women.

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.

Long-term Intraocular Pressure Fluctuation Is a Risk Factor for Visual Field Progression in Advanced Glaucoma.

PRCIS: Intraocular pressure (IOP) fluctuations increase the risk of visual field progression of primary open-angle glaucoma (POAG) in the advanced stage even when IOP is maintained low on average. PURPOSE: The purpose of this study was to identify risk factors associated with the progression of visual field defect in patients with advanced POAG. MATERIALS AND METHODS: A retrospective review of medical records was conducted to identify patients who met the Hodapp-Parrish-Anderson criteria for advanced POAG. A total of 122 eyes of 122 patients had undergone IOP measurement with Goldmann applanation tonometer, standard automated perimetry, Cirrus optical coherence tomography, and fundus photography at 6-month intervals. Visual field progression was defined as the deterioration of a minimum of 3 visual field locations more than baseline at 5% levels in 4 consecutive visual fields with 24-2 SITA testing. RESULTS: Thirty-six eyes of 122 eyes (29.5%, 51.9±13.9 y old) showed visual field progression during 100.7±44.2 months of follow-up. The progression group showed greater long-term IOP fluctuations (2.6±1.4 mm Hg) than the no progression group (53.5±13.5 y; 2.0±1.0 mm Hg, P=0.008). Disc hemorrhage was detected more frequently in the progression group (40.5% vs. 17.4%, P=0.005). Multivariate Cox regression analysis revealed long-term IOP fluctuations [hazard ratio (HR)=2.567, 95% confidence interval (CI): 1.327-5.370, P=0.012] and disc hemorrhage (HR=2.351, 95% CI: 1.120-4.931, P=0.024) to be independent risk factors of visual field progression. Patients who showed both disc hemorrhage and long-term IOP fluctuations were at greater risks of progression (HR=2.675, 95% CI: 1.072-6.457, P=0.035). CONCLUSIONS: Long-term IOP fluctuations and disc hemorrhage are independent and additive risk factors of visual field progression in advanced glaucoma even at low IOPs. Patients in whom these risk factors are identified require close monitoring and vigorous treatment.

Eyedrop vaccination: an immunization route with promises for effective responses to pandemics.

INTRODUCTION: Mucosal vaccines have several advantages over parenteral vaccines. They induce both systemic and mucosal antigen-specific immune responses, allow easy administration, and bypass the need for trained medical personnel. AREAS COVERED: Eye mucosa is a novel route of mucosal vaccine administration. Eyedrop vaccination induces systemic and mucosal immune responses similar to other forms of mucosal vaccines such as oral and intranasal vaccines. EXPERT OPINION: Eyedrop vaccines are free of serious adverse side effects like the infiltration of CNS by pathogens. Studies over the years have shown promising results for eye drop vaccines against infectious agents like the influenza virus, Salmonella typhi, and Escherichia coli in animal models. Such efficacy and safety of eyedrop vaccination enable the application of eyedrop vaccines against other infectious diseases as well as chronic diseases. In this review of published literature, we examine the mechanism, efficacy, and safety of eyedrop vaccines and contemplate their role in times of a pandemic.

Corneal endothelial cell changes and surgical results after Ahmed glaucoma valve implantation: ciliary sulcus versus anterior chamber tube placement.

We compared the changes in corneal endothelial cells and surgical outcomes after Ahmed glaucoma valve (AGV) implantation with the valve tip inserted either into ciliary sulcus (CS) or anterior chamber (AC). We retrospectively reviewed the medical records of patients treated with CS AGV (n = 24) and AC AGV (n = 38). We compared the preoperative and postoperative central corneal endothelial cell density (ECD), endothelial cell coefficient of variation (CV), best-corrected visual acuity, intraocular pressure (IOP), number of glaucoma medications, and postoperative complications in the two groups. Both groups had similar baseline characteristics and follow-up period. At the last follow-up, the AC AGV group had significantly higher mean monthly ECD loss (17.47 ± 11.50 cells/mm2 vs. 6.40 ± 7.69 cells/mm2, p < 0.0001) and greater proportion of mean monthly ECD loss than the CS AGV group (0.84 ± 0.53 vs. 0.36 ± 0.39%, p < 0.0001). Both groups had similar mean monthly CV changes. The qualified success rates at 2 years were 83.3% and 76.3% for the CS AGV and AC AGV groups, respectively. Although similar surgical outcomes including visual acuity, IOP, number of glaucoma medications, and postoperative complications were obtained following CS AGV and AC AGV, corneal ECD loss was higher in the AC AGV group. Thus, CS AGV may be a better surgical option than AC AGV.

Serial Detection of MYD88 L265P Mutation in the Aqueous Humor of a Patient with Vitreoretinal Lymphoma for Disease Monitoring.

PURPOSE: To report a case of a patient whose MYD88 mutation disappeared from the aqueous humor following treatment with intravitreal methotrexate. METHODS: A retrospective review of clinical, histopathological and imaging records. RESULTS: A 49-year-old woman presented with bilateral primary vitreoretinal lymphoma confirmed by molecular and next-generation sequencing studies on vitreous biopsy samples. Initially, the MYD88 L265P mutation was detected in aqueous samples of both eyes. Serial testing for MYD88 L265P mutations performed on aqueous samples collected at the time of the weekly intravitreal methotrexate injections showed the mutation ceased to be detected after four weekly injections in the non-vitrectomized right eye and after two weekly injections in the vitrectomized left eye. Clinical improvement accompanied the negativization of the mutation in both eyes. CONCLUSION: We present a case that demonstrates the possible utilization of serial testing for the MYD88 L265P mutation as a tool for monitoring disease course in vitreoretinal lymphoma.

Clinical Predictors of the Region of First Structural Progression in Early Normal-tension Glaucoma.

PURPOSE: This study aimed to compare the clinical characteristics of patients who showed structural progression in the peripapillary retinal nerve fiber layer (RNFL) first against those who showed progression in the macular ganglion cell-inner plexiform layer (GCIPL) first and to investigate clinical parameters that help determine whether a patient exhibits RNFL or GCIPL damage first. METHODS: A retrospective review of medical records of patients diagnosed with early-stage normal-tension glaucoma was performed. All eyes underwent intraocular pressure measurement with Goldmann applanation tonometer, standard automated perimetry, and Cirrus optical coherence tomography at 6-month intervals. Structural progression was determined using the Guided Progression Analysis software. Blood pressure was measured at each visit. RESULTS: Forty-one eyes of 41 patients (mean age, 52.6 ± 16.7 years) were included in the study. In 21 eyes, structural progression was first detected in the RNFL at 54.2 ± 14.8 months, while structural progression was first observed at the macular GCIPL at 40.5 ± 11.0 months in 20 eyes. The mean intraocular pressure following treatment was 13.1 ± 1.8 mmHg for the RNFL progression first group and 13.4 ± 1.8 mmHg for the GCIPL progression first group (p = 0.514). The GCIPL progression first group was older (p = 0.008) and had thinner RNFL at baseline (p = 0.001). The logistic regression analyses indicated that both age and follow-up duration until first progression predicted the region of structural progression (odds ratio, 1.051; 95% confidence interval, 1.001-1.105; p = 0.046 for age; odds ratio, 0.912; 95% confidence interval, 0.840-0.991; p = 0.029 for time until progression). CONCLUSIONS: Age of glaucoma patients and time until progression are associated with the region of the first structural progression in normal-tension glaucoma. Further studies exploring the association between glaucomatous progression and the location of damage are needed.

Glycogen Synthase Kinase-3ß Mediates Proinflammatory Cytokine Secretion and Adipogenesis in Orbital Fibroblasts from Patients with Graves' Orbitopathy.

Purpose: We sought to determine the role of glycogen synthase kinase-3ß (GSK-3ß) in the pathogenesis of Graves' orbitopathy(GO). Methods: Expression of the GSK-3ß gene in whole orbital tissue explants was compared between GO and non-GO donors using quantitative real-time PCR (RT-PCR). The expression of proinflammatory molecules in the presence of the GSK-3ß inhibitor CHIR 99021 was analyzed using RT-PCR, western blot, and ELISA. Adipogenic differentiation was identified using Oil Red O staining, and the levels of peroxisome proliferator activator gamma (PPARγ) and CCAAT-enhancer-binding proteins (C/EBPs) α and ß were determined by western blot. Results: The expression of GSK-3ß was significantly higher in GO tissues than in control tissues. The addition of CHIR 99021 led to a decrease in the active form of the kinase in which the Y216 residue is phosphorylated. When GO and non-GO fibroblasts were stimulated with IL-1ß or TNF-α, IL-6, IL-8, intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-1 (COX-1), and monocyte chemoattractant protein 1 (MCP-1) showed increased production, which was blunted when CHIR 99021 was added. The activation of Akt, PI3K, nuclear factor (NF)-κB, Erk, Jnk, and p38 kinase by IL-1ß and TNF-α was diminished with CHIR 99021 in GO cells. A decrease in lipid droplets and expression of PPARγ and c/EBPα and -ß was noted in fibroblasts treated with CHIR 99021 during adipocyte differentiation. The inhibition of Wnt and ß-catenin in adipogenesis was reversed by CHIR 99021. Conclusions: GSK-3ß plays a significant role in GO pathogenesis. The inhibition of the kinase attenuated the proinflammatory cytokines production and fibroblast differentiation into adipocytes. GSK-3ß may be a potential target for anti-inflammatory and anti-adipogenic treatment of GO.