A Bayesian Hierarchical Spatial Longitudinal Model Improves Estimation of Local Macular Rates of Change in Glaucomatous Eyes.

Purpose: Demonstrate that a novel Bayesian hierarchical spatial longitudinal (HSL) model improves estimation of local macular ganglion cell complex (GCC) rates of change compared to simple linear regression (SLR) and a conditional autoregressive (CAR) model. Methods: We analyzed GCC thickness measurements within 49 macular superpixels in 111 eyes (111 patients) with four or more macular optical coherence tomography scans and two or more years of follow-up. We compared superpixel-patient-specific estimates and their posterior variances derived from the latest version of a recently developed Bayesian HSL model, CAR, and SLR. We performed a simulation study to compare the accuracy of intercept and slope estimates in individual superpixels. Results: HSL identified a significantly higher proportion of significant negative slopes in 13/49 superpixels and a significantly lower proportion of significant positive slopes in 21/49 superpixels than SLR. In the simulation study, the median (tenth, ninetieth percentile) ratio of mean squared error of SLR [CAR] over HSL for intercepts and slopes were 1.91 (1.23, 2.75) [1.51 (1.05, 2.20)] and 3.25 (1.40, 10.14) [2.36 (1.17, 5.56)], respectively. Conclusions: A novel Bayesian HSL model improves estimation accuracy of patient-specific local GCC rates of change. The proposed model is more than twice as efficient as SLR for estimating superpixel-patient slopes and identifies a higher proportion of deteriorating superpixels than SLR while minimizing false-positive detection rates. Translational Relevance: The proposed HSL model can be used to model macular structural measurements to detect individual glaucoma progression earlier and more efficiently in clinical and research settings.

Epidemiology of Consumer-Product-Related Ocular Injuries in the Geriatric Population in the United States.

INTRODUCTION: The purpose of this study was to assess trends in consumer-product-related geriatric ocular injuries using National Electronic Injury Surveillance System (NEISS) data. Understanding the specific consumer products and settings coded in the NEISS dictionary that contribute to geriatric (≥ 65 years) ocular injuries, along with changing patterns during events like the COVID-19 pandemic, provides crucial insights for tailoring therapy and preventative strategies. This ultimately may reduce the burden of eye injuries on both older adults and healthcare systems. METHODS: This was a retrospective population-based cohort study. The NEISS database was used to study eye injuries in geriatric adults from 2010 to 2021. Patients were categorized by age groups (65-74, 75-84, 85-94, ≥ 95 years), and data on demographics, injury types, product categories, and COVID-19 impact were collected. Pearson's chi-squared test (with p < 0.001 taken to indicate significance) was used to assess differences in expected ratios between age groups. RESULTS: A total of 168,685 eye injury cases in adults aged 65 years and older were analyzed. Household items, tools, and gardening products accounted for over 75% of injuries. Most injuries occurred at home (65.3%). Contusions/abrasions (40.3%) and a foreign body (19.3%) were common diagnoses. Females had more household-item-related injuries, while males had more foreign body injuries. Regarding therapeutic disposition, 93.7% of all injuries were treated/examined and released, which showed a decreasing trend as age increased, while hospital admission/transfer rates increased with age. Compared to before COVID-19, the percentage of injuries during COVID-19 due to tools decreased (from 22.5% to 18.3%), while injuries due to gardening/lawn/landscaping/patio products increased (from 13.8% to 15.3%). CONCLUSIONS: Our study characterizes geriatric ocular injuries and COVID-19 impact, highlighting common products and locations. Different age groups showed different injury patterns. Understanding these trends can aid injury prevention strategies for consumers and healthcare providers. Demographics and injury frequencies differed based on age and sex. Future research should further explore post-COVID-19 trends.

Association of Blood Pressure With Rates of Macular Ganglion Cell Complex Thinning in Patients With Glaucoma.

Importance: There are scarce data on the association of blood pressure measures with subsequent macular structural rates of change in patients with glaucoma. Objective: To investigate the association of baseline blood pressure measures with rates of change of the macular ganglion cell complex in patients with central or moderate to advanced glaucoma damage at baseline. Design, Setting, and Participants: This prospective cohort study, conducted from August 2021 to August 2022, used data from patients in the Advanced Glaucoma Progression Study at the University of California, Los Angeles. Participants were between 39 and 80 years of age and had more than 4 macular imaging tests and 2 or more years of follow-up. Exposures: A diagnosis of glaucoma with either central damage or a visual field mean deviation worse than -6 dB. Main Outcomes and Measures: The main outcome was the association of blood pressure measures with ganglion cell complex rates of change. Macular ganglion cell complex thickness rates of change were estimated with a bayesian hierarchical model. This model included relevant demographic and clinical factors. Blood pressure measures, intraocular pressure, and their interactions were added to the model to assess the association of baseline blood pressure measures with global ganglion cell complex rates of change. Results: The cohort included 105 eyes from 105 participants. The mean (SD) age, 10-2 visual field mean deviation, and follow-up time were 66.9 (8.5) years, -8.3 (5.3) dB, and 3.6 (0.4) years, respectively, and 67 patients (63.8%) were female. The racial and ethnic makeup of the cohort was 15 African American (14.3%), 23 Asian (21.9%), 12 Hispanic (11.4%), and 55 White (52.4%) individuals based on patient self-report. In multivariable analyses, female sex, history of taking blood pressure medications, higher intraocular pressure, thicker central corneal thickness, shorter axial length, higher contrast sensitivity at 12 cycles per degree, and higher baseline 10-2 visual field mean deviation were associated with faster ganglion cell complex thinning. Lower diastolic blood pressure was associated with faster rates of ganglion cell complex thinning at higher intraocular pressures. For intraocular pressures of 8 and of 16 mm Hg (10% and 90% quantiles, respectively), every 10 mm Hg-lower increment of diastolic blood pressure was associated with 0.011 µm/y slower and -0.130 µm/y faster rates of ganglion cell complex thinning, respectively. Conclusions and Relevance: In this cohort study, a combination of lower diastolic blood pressure and higher intraocular pressure at baseline was associated with faster rates of ganglion cell complex thinning. These findings support consideration of evaluating and addressing diastolic blood pressure as a therapeutic measure in patients with glaucoma if supported by appropriate clinical trials.

Multivariate Longitudinal Modeling of Macular Ganglion Cell Complex: Spatiotemporal Correlations and Patterns of Longitudinal Change.

Purpose: To investigate spatiotemporal correlations among ganglion cell complex (GCC) superpixel thickness measurements and explore underlying patterns of longitudinal change across the macular region. Design: Longitudinal cohort study. Subjects: One hundred eleven eyes from 111 subjects from the Advanced Glaucoma Progression Study with ≥ 4 visits and ≥ 2 years of follow-up. Methods: We further developed our proposed Bayesian hierarchical model for studying longitudinal GCC thickness changes across macular superpixels in a cohort of glaucoma patients. Global priors were introduced for macular superpixel parameters to combine data across superpixels and better estimate population slopes and intercepts. Main Outcome Measures: Bayesian residual analysis to inspect cross-superpixel correlations for subject random effects and residuals. Principal component analysis (PCA) to explore underlying patterns of longitudinal macular change. Results: Average (standard deviation [SD]) follow-up and baseline 10-2 visual field mean deviation were 3.6 (0.4) years and -8.9 (5.9) dB, respectively. Superpixel-level random effects and residuals had the greatest correlations with nearest neighbors; correlations were higher in the superior than in the inferior region and strongest among random intercepts, followed by random slopes, residuals, and residual SDs. PCA of random intercepts showed a first large principal component (PC) across superpixels that approximated a global intercept, a second PC that contrasted the superior and inferior macula, and a third PC, contrasting inner and nasal superpixels with temporal and peripheral superpixels. PCs for slopes, residual SDs, and residuals were remarkably similar to those of random intercepts. Conclusions: Introduction of cross-superpixel random intercepts and slopes is expected to improve estimation of population and subject parameters. Further model enhancement may be possible by including cross-superpixel random effects and correlations to address spatiotemporal relationships in longitudinal data sets.

Effectiveness of Topical ρ-Kinase Inhibitors in Veterans with Severe Glaucoma on Maximally Tolerated Medical Therapy.

SIGNIFICANCE: The real-world pharmacological use of netarsudil shows that it can produce a clinically significant decrease in intraocular pressure for a small group of patients, even if they are already taking three or four other hypotensive glaucoma medication classes. PURPOSE: This study aimed to assess the effectiveness of netarsudil in reducing intraocular pressure among veterans with advanced glaucoma on maximally tolerated medical therapy. METHODS: All patients with glaucoma who received netarsudil between June 2018 and April 2020 from the West Los Angeles Veterans Administration Medical Center were reviewed. Inclusion criteria included a minimum of one intraocular pressure measurement in each of two time windows (within and after 4 months of netarsudil use). Exclusion criteria included medication nonadherence, change in treatment plan before post-treatment intraocular pressure could be obtained, corneal disease precluding reliable measurement, outside follow-up, and loss to follow-up. Intraocular pressure at baseline and that at two time windows were compared using analyses of variance. Relationships between intraocular pressure and number of baseline medications and concurrent statin therapy were evaluated. Netarsudil tolerability was reported. RESULTS: Of 200 patients prescribed netarsudil, 42 patients (eyes) met the enrollment criteria. The mean age of these patients was 75.7 years (95% confidence interval [CI], 73.0 to 78.4 years), 64% were of African descent, 79% had open-angle glaucoma, and the mean number of baseline medications was 3.7 (95% CI, 3.5 to 3.9). Baseline intraocular pressure of 17.2 mmHg (95% CI, 16.1 to 18.2 mmHg) decreased to 15.1 mmHg (95% CI, 14.0 to 16.2 mmHg; P < .001), and a reduction of >20% was seen in 30.9% of patient after 4 months of netarsudil therapy. Intraocular pressure reduction was not associated with number of baseline medications or systemic statin use. CONCLUSIONS: Netarsudil may produce a clinically significant intraocular pressure reduction in up to a third of the patients with advanced glaucoma already on maximally tolerated medical therapy.

Ganglion Cell Complex: The Optimal Measure for Detection of Structural Progression in the Macula.

PURPOSE: To test the hypothesis that macular ganglion cell complex (GCC) thickness from optical coherence tomography (OCT) provides a stronger change signal regardless of glaucoma severity compared with other macular measures. DESIGN: Prospective cohort study. METHODS: Eyes were from 112 patients with moderate to severe glaucoma at baseline from a tertiary glaucoma center. In each 3° × 3° macular superpixel, a hierarchical Bayesian random intercept and slope model with random residual variance was fit to longitudinal full macular thickness (FMT), outer retina layers, GCC, ganglion cell-inner plexiform layer (GCIPL), and ganglion cell layer (GCL) measurements. We estimated population- and individual-level slopes and intercepts. Proportions of substantial worsening and improving superpixel slopes were compared between layers and in superpixels with mild to moderate vs severe damage (total deviation of corresponding visual field location ≥ -8 vs < -8 dB). RESULTS: Mean (SD) follow-up time and baseline 10-2 visual field mean deviation were 3.6 (0.4) years and -8.9 (5.9) dB, respectively. FMT displayed the highest proportion of significant negative slopes (1932/3519 [54.9%]), followed by GCC (1286/3519 [36.5%]), outer retina layers (1254/3519 [35.6%]), (GCIPL) (1075/3518 [30.6%]), and (GCL) (698/3518 [19.8%]). Inner macular measures detected less worsening in the severe glaucoma group; yet GCC (223/985 [22.6%]) identified the highest proportion (GCIPL: 183/985 [18.6%]; GCL: 106/985 [10.8%]). Proportions of positive rates were small and comparable among all measures. CONCLUSIONS: GCC is the optimal macular measure for detection of structural change in eyes with moderate to severe glaucoma. Although a higher proportion of worsening superpixels was observed for FMT, a large portion of FMT change could be attributed to changes in outer retina layers.

Detection of Longitudinal Ganglion Cell/Inner Plexiform Layer Change: Comparison of Two Spectral-Domain Optical Coherence Tomography Devices.

PURPOSE: We compared rates of change of macular ganglion cell/inner plexiform (GCIPL) thickness and proportion of worsening and improving rates from 2 optical coherence tomography (OCT) devices in a cohort of eyes with glaucoma. DESIGN: Longitudinal cohort study. METHODS: In a tertiary glaucoma clinic we evaluated 68 glaucoma eyes with ≥2 years of follow-up and ≥4 OCT images. Macular volume scans from 2 OCT devices were exported, coregistered, and segmented. Global and sectoral GCIPL data from the central 4.8 × 4.0-mm region were extracted. GCIPL rates of change were estimated with linear regression. Permutation analyses were used to control specificity with the 2.5 percentile cutoff point used to define "true" worsening. Main outcome measures included differences in global/sectoral GCIPL rates of change between 2 OCT devices and the proportion of negative vs positive rates of change (P < .05). RESULTS: Average (standard deviation) 24-2 visual field mean deviation, median (interquartile range) follow-up time, and number of OCT images were -9.4 (6.1) dB, 3.8 (3.3-4.2) years, and 6 (5-8), respectively. GCIPL rates of thinning from Spectralis OCT were faster (more negative) compared with Cirrus OCT; differences were significant in superonasal (P = .03) and superotemporal (P = .04) sectors. A higher proportion of significant negative rates was observed with Spectralis OCT both globally and in inferotemporal/superotemporal sectors (P < .04). Permutation analyses confirmed the higher proportion of global and sectoral negative rates of change with Spectralis OCT (P < .001). CONCLUSIONS: Changes in macular GCIPL were detected more frequently on Spectralis' longitudinal volume scans than those of Cirrus OCT. OCT devices are not interchangeable with regard to detection of macular structural progression.

Estimating Ganglion Cell Complex Rates of Change With Bayesian Hierarchical Models.

Purpose: Develop a hierarchical longitudinal regression model for estimating local rates of change of macular ganglion cell complex (GCC) measurements with optical coherence tomography (OCT). Methods: We enrolled 112 eyes with four or more macular OCT images and ≥2 years of follow-up. GCC thickness measurements within central 6 × 6 superpixels were extracted from macular volume scans. We fit data from each superpixel separately with several hierarchical Bayesian random-effects models. Models were compared with the Watanabe-Akaike information criterion. For our preferred model, we estimated population and individual slopes and intercepts (baseline thickness) and their correlation. Results: Mean (SD) follow-up time and median (interquartile range) baseline 24-2 visual field mean deviation were 3.6 (0.4) years and -6.8 (-12.2 to -4.3) dB, respectively. The random intercepts and slopes model with random residual variance was the preferred model. While more individual and population negative slopes were observed in the paracentral and papillomacular superpixels, superpixels in the superotemporal and inferior regions displayed the highest correlation between baseline thickness and rates of change (r = -0.43 to -0.50 for the top five correlations). Conclusions: A Bayesian linear hierarchical model with random intercepts/slopes and random variances is an optimal initial model for estimating GCC slopes at population and individual levels. This novel model is an efficient method for estimating macular rates of change and probability of glaucoma progression locally. Translational Relevance: The proposed Bayesian hierarchical model can be applied to various macular outcomes from different OCT devices and to superpixels of variable sizes to estimate local rates of change and progression probability.

Strabismus After Ahmed Glaucoma Valve Implantation.

PURPOSE: Most reports of strabismus after glaucoma drainage device implantation study larger devices and rarely note the incidence of strabismus after Ahmed glaucoma valve (AGV) implantation. It is unknown if the pattern of strabismus is similar with smaller devices. We investigated characteristics of strabismus after AGV implantation. DESIGN: Retrospective review. METHODS: Institutional study of 732 patients at our institution undergoing AGV implantation between 2013 and 2018. Rate and characteristics of strabismus were the primary outcome; age, gender, and location of AGVs were also analyzed. RESULTS: We identified 29 patients who developed new-onset strabismus postoperatively after initial AGV implantation, for 4% incidence of strabismus. Twenty-one (72%) of these had diplopia. AGVs were implanted superotemporally in 21, superonasally in 5, inferotemporally in 1, and inferonasally in 2. Three patients were esotropic, 11 were exotropic, 4 had hypertropia, 2 had hypotropia, and 9 patients had combined horizontal/vertical strabismus (esotropia/hypotropia [n = 1] or exotropia/hypertropias [n = 8]). Exotropia was the most common type of strabismus in both the superotemporal and superonasal (60%) AGV groups. Superotemporal AGVs were more commonly associated with ipsilateral hypertropia (43%) than superonasal AGVs. Treatments included strabismus surgery (n = 14), prisms (n = 6), or an occlusive lens (n = 1). DISCUSSION: In the largest single-center series of patients undergoing initial AGV implantation, the overall incidence of postoperative strabismus was 4%. This is comparable to strabismus incidence following implantation of other types of glaucoma drainage devices, even larger devices. The possibility of this complication should be discussed with patients prior to surgery.

Adduction-Induced Strain on the Optic Nerve in Primary Open Angle Glaucoma at Normal Intraocular Pressure.

PURPOSE/AIM: The optic nerve (ON) becomes taut during adduction beyond ~26° in healthy people and patients with primary open angle glaucoma (POAG), but only retracts the globe in POAG. We used magnetic resonance imaging (MRI) to investigate this difference. MATERIALS AND METHODS: MRI was obtained in 2-mm quasi-coronal planes in central gaze, and smaller (~23-25°) and larger (~30-31°) adduction and abduction in 21 controls and 12 POAG subjects whose intraocular pressure never exceeded 21 mmHg. ON cross-sections were analyzed from the globe to 10 mm posteriorly. Area centroids were used to calculate ON path lengths and changes in cross-sections to calculate elongation assuming volume conservation. RESULTS: For both groups, ON path was nearly straight (<102.5% of minimum path) in smaller adduction, with minimal further straightening in larger adduction. ON length was redundant in abduction, exceeding 103% of minimum path for both groups. For normals, the ON elongated 0.4 ± 0.5 mm from central gaze to smaller adduction, and 0.4 ± 0.5 mm further from smaller to larger adduction. For POAG subjects, the ON did not elongate on average from central gaze to smaller adduction and only 0.2 ± 0.4 mm from smaller to larger adduction (P = .045 vs normals). Both groups demonstrated minimal ON elongation not exceeding 0.25 mm from central gaze to smaller and larger abduction. The globe retracted significantly more during large adduction in POAG subjects than normals (0.6 ± 0.7 mm vs 0.2 ± 0.5 mm, P = .027), without appreciable retraction in abduction. For each mm increase in globe axial length, ON elongation in large adduction similarly increased by 0.2 mm in each group. CONCLUSIONS: The normal ON stretches to absorb force and avert globe retraction in adduction. In POAG with mild to severe visual field loss, the relatively inelastic ON tethers and retracts the globe during adduction beyond ~26°, transfering stress to the optic disc that could contribute to progressive neuropathy during repeated eye movements.

Comparison of Rates of Progression of Macular OCT Measures in Glaucoma.

Purpose: The purpose of this study was to compare rates of change of various macular thickness measures and evaluate the influence of baseline damage on macular rates of change. Methods: One hundred twelve eyes (112 patients) with ≥ 2 years of follow-up and ≥ 5 macular optical coherence tomography (OCT) images and 10-2 visual field (VF) tests were included. OCT measures of interests were full macular thickness (FMT), ganglion cell complex (GCC), ganglion cell/inner plexiform layer (GCIPL), ganglion cell layer (GCL), and outer retinal layer (ORL) thickness in 3° × 3° superpixels. Rates of change were estimated with linear regression and normalized by dividing rates by the average normative superpixel thickness. We compared rates of change and proportion of significantly worsening superpixels (detection rate) and improving superpixels (false discovery rate [FDR]) among macular measures as a function of baseline thickness and 10-2 VF status. Results: Median (interquartile range [IQR]) baseline VF mean deviation, follow-up time, and number of VFs/OCTs were -7.6 dB (-11.8 to -3.8 dB), 4.5 years (4.0-5.0 years), and 9 (8-10), respectively. Normalized FMT and GCC rates of change were faster and detection rates were higher than GCIPL and GCL (P < 0.001), but FMT had lower FDR than GCC (P = 0.02); faster FMT rates were partially explained by ORL rates of change. GCC detection rates were less likely than GCIPL and GCL rates to decrease with diminishing baseline thickness or worse VF damage. In eyes with 10-2 VF worsening, GCC and GCL demonstrated the fastest rates of change. Conclusions: GCC measurements are most likely to detect structural worsening along the spectrum of glaucoma severity. Although FMT rates of change are least influenced by baseline thickness, they partially reflect likely age-related ORL changes. Translational Relevance: GCC thickness measurements seem to be the optimal macular outcome measure for detection of glaucoma deterioration.

Long-Term Outcomes of Descemet Membrane Endothelial Keratoplasty in Eyes with Prior Glaucoma Surgery.

PURPOSE: The purpose of this study was to evaluate the long-term outcomes of Descemet membrane endothelial keratoplasty (DMEK) in eyes that had previously undergone trabeculectomy and/or drainage device implantation. DESIGN: Retrospective, noncomparative case series. METHODS: Medical records of 251 consecutive DMEK procedures performed by 1 surgeon (S.X.D.) from 2013 to 2017 were reviewed. Patients with ≥2 years of follow-up were divided into 3 groups: eyes with prior glaucoma surgery (ST), eyes with medically treated glaucoma (MT), and eyes without glaucoma (NG). Main outcomes measured were visual acuity, endothelial cell count (ECC), rates of secondary graft failure (SGF), and postoperative complications. RESULTS: Ninety procedures (87 eyes) met inclusion criteria. The mean follow-up period of all eyes was 38.4 ± 11.2 months (range, 24.2-64.4 months). At last follow-up, the proportion of eyes reaching a vision of ≥20/40 was higher than that before the DMEK procedure in each group (all P < .05). The rate of ECC loss was the highest in the ST group compared to that in the MT and NG groups (63.8% vs 47.6% vs 44.0%, respectively; P < .05) as well as the rate of SGF (41.6% vs 0% vs 2.4%, respectively; P < .05). The rate of SGF of repeat DMEK was higher than that of primary DMEK (P < .05). The rates of postoperative complications were similar among all groups (all P > .05). CONCLUSIONS: In eyes with prior glaucoma surgery, DMEK achieved good long-term visual outcomes but experienced a higher rate of SGF than eyes without such comorbidity.

Efficacy of Combined Suprachoroidal Stent and Cataract Surgery in Patients With Glaucoma.

PURPOSE: The purpose of this study was to evaluate the efficacy of intraocular pressure (IOP) control after combined CyPass Micro-Stent implantation and cataract surgery (combined surgery). METHODS: All cases of combined surgery performed from February 2017 to July 2018 at Stein and Doheny Eye Institutes were reviewed. The primary outcome was a qualified success with stratified IOP targets based on criteria: final IOP (A) ≤18 mm Hg and reduction of 20%, (B) ≤15 mm Hg and reduction of 25%, (C) ≤12 mm Hg and reduction of 30%. Secondary outcome measures included postoperative IOP and number of medications, complications, additional glaucoma surgery, and postoperative refractive error. Predictive factors for failure were investigated. IOP spike was defined as a postoperative IOP ≥30 or >10 mm Hg increase from preoperative IOP. RESULTS: One hundred forty-one eyes (107 patients) were included. Mean (±SD) preoperative IOP was 15.4±3.4 mm Hg on an average of 2.2±1.1 medications. A statistically significant reduction in IOP and number of medications was seen at 12 months (13.8±4.2 mm Hg, 1.3±1.3 medications, P<0.001). Fifteen eyes (10.6%) had a postoperative IOP spike. Thirteen eyes (9.2%) experienced 17 complications (12.1%). Additional glaucoma surgery was performed in 3 eyes (2 patients). Cumulative success rates at 1 year based on criteria A, B, and C were 42%, 33%, and 28%, respectively. Lower preoperative IOP, greater preoperative medication number, the occurrence of postoperative IOP spike, and non-Caucasian ethnicity were associated with failure. CONCLUSION: Combined CyPass Micro-Stent implantation and cataract surgery may reduce glaucoma medication burden with a success rate of 28% to 42% at 1 year.

Orbital Fat Volume After Treatment with Topical Prostaglandin Agonists.

Purpose: Topical prostaglandin analogs (PGAs) are common treatment for primary open-angle glaucoma (POAG) but reportedly may cause adnexal fat atrophy. We asked if patients with POAG treated with PGAs have abnormalities in orbital fat volume (OFV). Methods: We studied 23 subjects with POAG who had never experienced intraocular pressure (IOP) exceeding 21 mm Hg and were treated long term with PGAs, in comparison with 21 age-matched controls. Orbital volume, non-fat orbital tissue volume, and OFV were measured using high-resolution magnetic resonance imaging. Results: Subjects with POAG had been treated with PGAs for 39 ± 19 months (SD) and were all treated within the 4 months preceding study. In the region from trochlea to orbital apex, OFV in POAG was significantly less at 9.8 ± 1.9 mL than in the control subjects at 11.1 ± 1.3 mL (P = 0.019). However, between the globe-optic nerve junction (GONJ) and trochlea, OFV was similar in both groups. Width and cross sectional area of the bony orbit were significantly smaller in POAG than in controls (P < 0.0001). Posterior to the GONJ, the average orbital cross-sectional area was 68.2 mm2 smaller, and the orbital width averaged 1.5 mm smaller throughout the orbit, in patients with POAG than in controls. Conclusions: Patients with POAG who have been treated with PGAs have lower overall OFV than controls, but OFV in the anterior orbit is similar in both groups. Lower overall OFV in POAG may be a primary association of this disorder with a horizontally narrower bony orbit, which may be a risk factor for POAG at nonelevated IOPs.

Longitudinal Macular Structure-Function Relationships in Glaucoma.

PURPOSE: To investigate the relationship between longitudinal changes in macular thickness measurements from OCT and changes in central visual field (VF) in patients with glaucoma with central or advanced damage at baseline. DESIGN: Longitudinal cohort study. PARTICIPANTS: A total of 116 eyes with ≥3 years of follow-up and ≥5 macular OCT images and central 10° VF tests were selected. METHODS: OCT superpixels and VF locations were matched correcting for retinal ganglion cell (RGC) displacement. Superpixel thickness and VF total deviation (TD) values, in both logarithmic and linear scales, were averaged within 3 eccentricities (3.4°, 5.6°, and 6.8°) and superior and inferior hemiretinas and hemifields. We estimated pointwise TD rates of change and rates of change at superpixels for full macular thickness (FMT), ganglion cell complex (GCC), ganglion cell inner plexiform layer (GCIPL), and ganglion cell layer (GCL). Correlation of structure-function (SF) rates of change was investigated with parametric tests. We compared the proportion of worsening and positive slopes for superpixels and VF test locations (negative vs. positive rates of change with P < 0.05) throughout the follow-up period. Permutation analyses were used to control specificity. MAIN OUTCOME MEASURES: Magnitude of correlation between structural and functional rates of change and proportion of worsening and positive slopes as a function of follow-up time. RESULTS: The median (interquartile range) follow-up and number of exams were 4.2 (3.7-4.6) years and 8 (7-9), respectively. The highest correlation of change rates was observed at 3.4° and 5.6° eccentricities (r = 0.24, 0.41, 0.40, and 0.40 for FMT, GCC, GCIPL, and GCL for 3.4° eccentricity and r = 0.28, 0.32, 0.31, and 0.32 for FMT, GCC, GCIPL, and GCL for 5.6° eccentricity, respectively). Although GCC measures demonstrated the highest overall longitudinal SF correlations, the differences were not statistically significant. Significant structural worsening was more frequently detected than functional deterioration at 3- and 5-year time points (P < 0.025). Permutation analyses also confirmed this finding. CONCLUSIONS: Correlations between central structural and functional rates of change were weak to fair in this cohort. Structural changes were detected more frequently than functional changes. Measurements of both structure and function are required for optimal detection of central progression.

Acupuncture for glaucoma.

BACKGROUND: Glaucoma is a multi-factorial optic neuropathy characterized by an acquired loss of retinal ganglion cells at levels beyond normal age-related loss and corresponding atrophy of the optic nerve. Although many treatments are available to manage glaucoma, patients may seek complementary or alternative medicine approaches such as acupuncture to supplement their regular treatment. The underlying plausibility of acupuncture is that disorders related to the flow of Chi (traditional Chinese concept of vital force or energy) can be managed by stimulating relevant points on the body surface. OBJECTIVES: To assess the effectiveness and safety of acupuncture compared with other treatments, no treatment, or placebo in patients with glaucoma. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Trials Register (2018, Issue 11); Ovid MEDLINE; Embase.com; the Cumulative Index to Nursing and Allied Health Literature (CINAHL); the Allied and Complementary Medicine Database (AMED); PubMed; Latin American and Caribbean Literature on Health Sciences (LILACS); ZETOC; the metaRegister of Controlled Trials (mRCT); ClinicalTrials.gov; the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP); and the National Center for Complementary and Alternative Medicine (NCCAM) website. We did not use any language or date restrictions in the search for trials. We last searched electronic databases on November 16, 2018, with the exception of NCCAM, which we last searched on July 14, 2010, and the metaRegister of Controlled Trials (mRCT), which we last searched on January 8, 2013. We handsearched Chinese medical journals at Peking Union Medical College Library in April 2007. We searched the Chinese Acupuncture Trials Register, the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS), the Chinese Biological Database (CBM), and the China National Knowledge Infrastructure (CNKI). We last searched Chinese electronic databases on November 19, 2018. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in which one arm involved acupuncture treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently screened results, then extracted the data and assessed risk of bias for eligible trials. MAIN RESULTS: We included three completed trials and one ongoing trial in the 2019 update of this review. The three completed trials, conducted in Taiwan and the United States, included participants with glaucoma or intraocular hypertension. The interventions investigated varied across trials. One trial compared auricular acupressure－a non-standard acupuncture technique－with the sham procedure in 33 patients. Another trial compared transcutaneous electrical nerve stimulation (TENS) with a sham procedure in 82 patients. The third trial compared 12 sessions of acupuncture on eye-points versus on non-eye-points in 22 patients. All three trials were rated at high risk of bias for at least one domain. The certainty of evidence across all outcomes was very low due to high risk of bias in at least one contributing study; substantial clinical heterogeneity and methodological heterogeneity; and imprecision of results. One trial reported change in the visual field from baseline without any between-group comparison. Because of the quantity of missing data (50%), we did not calculate a between-group comparison, as the quantitative results are difficult to interpret. All three trials reported data for estimation of reduction of intraocular pressure (IOP). However, time points of IOP measurement varied. For the trial comparing acupressure to a sham procedure, the difference in IOP reduction (measured in mm Hg) is estimated to be -3.70 (95% confidence interval [CI] -7.11 to -0.29) for the right eye and -4.90 (95% CI -8.08 to -1.72) for the left eye at four weeks, and -1.30 mm Hg (95% CI -4.78 to 2.18) for the right eye and -2.30 mm Hg (95% CI -5.73 to 1.13) for the left eye at eight weeks. For the trial comparing TENS to sham treatment, the difference reduction is estimated to be -2.81 (95% CI -3.8 to -1.84) for the right eye and -2.58 (95% CI -3.36 to -1.80) for the left eye immediately after treatment, -2.93 (95% CI -3.72 to -2.13) for the right eye and -3.56 (95% CI -4.35 to 2.78) for the left eye 30 minutes after treatment, and finally -3.61 (95% CI -4.47 to -2.75) for the right eye and -3.61 (95% -4.47 to -2.74) for the left eye. For the trial that compared acupuncture on eye-points versus non-eye-points, 11 out of 22 (50%) participants did not complete the treatment. One trial reported data for estimation of visual acuity. When acupressure is compared to sham treatment, the difference in uncorrected visual acuity (UCVA, measured in logMAR) is estimated to be -0.01 (95% CI -0.24 to 0.22) for the right eye and -0.04 (95% CI -0.27 to 0.19) for the left eye at four months, and -0.03 logMAR (95% CI -0.27 to 0.21) for the right eye and -0.16 logMAR (95% CI -0.43 to 0.11) for the left eye at eight months. The difference in best corrected visual acuity (BCVA) is estimated to be 0.10 (95% CI -0.06 to 0.26) for the right eye and 0 (95% CI -0.14 to 0.14) for the left eye at four months, and -0.04 logMAR (95% CI -0.09 to 0.17) for the right eye and -0.04 logMAR (95% CI -0.18 to 0.10) for the left eye at eight months. One trial reported progression of optic disc damage or nerve fiber layer loss without any between-group comparison. Because of the quantity of missing data (50%), we did not calculate a between-group comparison, as the quantitative results are difficult to interpret. One trial reported adverse events in two patients (out of 22) who experienced needle sensitivity. However, the study did not report between-group comparisons. Because of the quantity of missing data (50%), we did not calculate a between-group comparison, as the quantitative results are difficult to interpret. AUTHORS' CONCLUSIONS: At this time, it is impossible to draw reliable conclusions from available data to support the use of acupuncture for treatment of patients with glaucoma. Because of ethical considerations, RCTs comparing acupuncture alone with standard glaucoma treatment or placebo are unlikely to be justified in countries where the standard of care has already been established.

Optic Nerve Traction During Adduction in Open Angle Glaucoma with Normal versus Elevated Intraocular Pressure.

Purpose/Aim: We used magnetic resonance imaging (MRI) to investigate effects of intraocular pressure (IOP), race, and other factors on optic nerve (ON) traction in adduction, a phenomenon proposed as neuropathic in open angle glaucoma (OAG).Materials and Methods: Thirty-five patients with OAG (26 with maximal untreated IOP ≤21 mmHg, 9 with IOP >21mmHg) and 48 controls underwent axial and quasi-coronal MRI in central gaze and large (27-33°) abduction and adduction. Some underwent MRI at smaller ductions (21-28°). Effects of presence vs. absence of OAG; within OAG whether maximum IOP level was ≤21 mmHg vs. >21 mmHg; adduction angle; race; age; and gender on ON path length and globe translation were analyzed using generalized estimating equations to account for possible intereye correlations of individual subjects.Results: Average visual field mean deviation (±standard error of mean, SEM) was -8.2 ± 1.2 dB in OAG with normal IOP, and -6.1 ± 1.4 in high IOP. In central gaze, ON path in OAG was significantly more redundant than in controls but in both groups the ON became significantly and almost equally straighter in small (~21°) or large (~27°) adduction than in central gaze. With progressive adduction only, globes retracted in OAG (P < 0.005) but not in controls; this was only weakly related to globe size and not to IOP elevation. Globe retraction in adduction was significant only in OAG, and in that group was significantly greater in Asian than white patients (P < 0.02).Conclusions: Although ON tethering in adduction is normal, progressive adduction is associated with abnormal globe retraction in OAG regardless of IOP level. This phenomenon is more prominent in Asians who have OAG. Traction in adduction may cause repetitive strain injury to the ON and peripapillary sclera, thus contributing to the optic neuropathy of glaucoma independent of IOP.

Geleophysic dysplasia: novel missense variants and insights into ADAMTSL2 intracellular trafficking.

Geleophysic dysplasia (GPHYSD1, MIM231050; GPHYSD2, MIM614185; GPHYSD3, MIM617809) is an autosomal disorder characterized by short-limb dwarfism, brachydactyly, cardiac valvular disease, and laryngotracheal stenosis. Mutations in ADAMTSL2, FBN1, and LTBP3 genes are responsible for this condition. We found that three previously described cases of GPHYSD diagnosed clinically were homozygote or compound heterozygotes for five ADAMTSL2 variants, four of which not being previously reported. By electron microscopy, skin fibroblasts available in one case homozygote for an ADAMTSL2 variant showed a defective intracellular localization of mutant ADAMTSL2 protein that did not accumulate within lysosome-like intra-cytoplasmic inclusions. Moreover, this mutant ADAMTSL2 protein was less secreted in medium and resulted in increased SMAD2 phosphorylation in transfected HEK293 cells.