Correlation of Automated Computed Tomography Volumetric Analysis Metrics With Motility Disturbances in Thyroid Eye Disease.

PURPOSE: The authors sought to examine relationships between CT metrics derived via an automated method and clinical parameters of extraocular muscle changes in thyroid eye disease (TED). METHODS: CT images of 204 orbits in the setting of TED were analyzed with an automated segmentation tool developed at the institution. Labels were applied to orbital structures of interest on the study images, which were then registered against a previously established atlas of manually indexed orbits derived from 35 healthy individuals. Point-wise correspondences between study and atlas images were then compared via a fusion algorithm to highlight metrics of interest where TED orbits differed from healthy orbits. RESULTS: Univariate analysis demonstrated several correlations between CT metrics and clinical data. Metrics pertaining to the extraocular muscles-including average diameter, maximum diameter, and muscle volume-were strongly correlated (p < 0.05) with the presence of ocular motility deficits with regards to the superior, inferior, and lateral recti (with exception of superior rectus motility deficits being mildly correlated with muscle volume [p = 0.09]). Motility defects of the medial rectus were strongly correlated with muscle volume, and only weakly correlated with average and maximum muscle diameter. CONCLUSIONS: The novel method of automated imaging metrics may provide objective, rapid clinical information which may have utility in prevention and recognition of visual impairments in TED before they reach an advanced or irreversible stage and while they are able to be improved with immunomodulatory treatments.

Assessment of Orbital Computed Tomography (CT) Imaging Biomarkers in Patients with Thyroid Eye Disease.

To understand potential orbital biomarkers generated from computed tomography (CT) imaging in patients with thyroid eye disease. This is a retrospective cohort study. From a database of an ongoing thyroid eye disease research study at our institution, we identified 85 subjects who had both clinical examination and laboratory records supporting the diagnosis of thyroid eye disease and concurrent imaging prior to any medical or surgical intervention. Patients were excluded if imaging quality or type was not amenable to segmentation. The images of 170 orbits were analyzed with the developed automated segmentation tool. The main outcome measure was to cross 25 CT structural metrics for each eye with nine clinical markers using a Kendall rank correlation test to identify significant relationships. The Kendall rank correlation test between automatically calculated CT metrics and clinical data demonstrated numerous correlations. Extraocular rectus muscle metrics, such as the average diameter of the superior, medial, and lateral rectus muscles, showed a strong correlation (p < 0.05) with loss of visual acuity and presence of ocular motility defects. Hertel measurements demonstrated a strong correlation (p < 0.05) with volumetric measurements of the optic nerve and other orbital metrics such as the crowding index and proptosis. Optic neuropathy was strongly correlated (p < 0.05) with an increase in the maximum diameter of the superior muscle. This novel method of automated imaging metrics may provide objective, rapid clinical information. This data may be useful for appreciation of severity of thyroid eye disease and recognition of risk factors of visual impairment from dysthyroid optic neuropathy from CT imaging.

Imaging biomarkers in thyroid eye disease and their clinical associations.

The purpose of this study is to understand the phenotypes of thyroid eye disease (TED) through data derived from a multiatlas segmentation of computed tomography (CT) imaging. Images of 170 orbits of 85 retrospectively selected TED patients were analyzed with the developed automated segmentation tool. Twenty-five bilateral orbital structural metrics were used to perform principal component analysis (PCA). PCA of the 25 structural metrics identified the two most dominant structural phenotypes or characteristics, the "big volume phenotype" and the "stretched optic nerve phenotype," that accounted for 60% of the variance. Most of the subjects in the study have either of these characteristics or a combination of both. A Kendall rank correlation between the principal components (phenotypes) and clinical data showed that the big volume phenotype was very strongly correlated ( p - value < 0.05 ) with motility defects, and loss of visual acuity. Whereas, the stretched optic nerve phenotype was strongly correlated ( p - value < 0.05 ) with an increased Hertel measurement, relatively better visual acuity, and smoking. Two clinical subtypes of TED, type 1 with enlarged muscles and type 2 with proptosis, are recognizable in CT imaging. Our automated algorithm identifies the phenotypes and finds associations with clinical markers.

Structural Functional Associations of the Orbit in Thyroid Eye Disease: Kalman Filters to Track Extraocular Rectal Muscles.

Pathologies of the optic nerve and orbit impact millions of Americans and quantitative assessment of the orbital structures on 3-D imaging would provide objective markers to enhance diagnostic accuracy, improve timely intervention and eventually preserve visual function. Recent studies have shown that the multi-atlas methodology is suitable for identifying orbital structures, but challenges arise in the identification of the individual extraocular rectus muscles that control eye movement. This is increasingly problematic in diseased eyes, where these muscles often appear to fuse at the back of the orbit (at the resolution of clinical computed tomography imaging) due to inflammation or crowding. We propose the use of Kalman filters to track the muscles in three-dimensions to refine multi-atlas segmentation and resolve ambiguity due to imaging resolution, noise, and artifacts. The purpose of our study is to investigate a method of automatically generating orbital metrics from CT imaging and demonstrate the utility of the approach by correlating structural metrics of the eye orbit with clinical data and visual function measures in subjects with thyroid eye disease. The pilot study demonstrates that automatically calculated orbital metrics are strongly correlated with several clinical characteristics. Moreover, the superior, inferior, medial and lateral rectus muscles obtained using Kalman filters are each correlated with different categories of functional deficit. These findings serve as foundation for further investigation in the use of CT imaging in the study, analysis and diagnosis of ocular diseases, specifically thyroid eye disease.

Socioeconomic Disparities in Cataract Prevalence, Characteristics, and Management.

PURPOSE: To review the current literature on socioeconomic disparities relationship with cataract prevalence, characteristics, and management. SUMMARY: Cataracts are an important cause of preventable visual impairment in both the developing and industrialized world. Cataract surgery is a highly effective operation with an excellent risk profile. Furthermore, cataract surgery has been shown to have significant positive functional, social, and economic implications for patients. Several medical conditions have been shown to have correlation with socioeconomic factors and cataract is among several forms of visual impairment that demonstrate this relationship. Disparities in prevalence, clinical characteristics, and management are documented in the ophthalmic literature. A better understanding of these socioeconomic factors and their clinical relevance is critical to alleviating the burden of cataract-related visual impairment in an aging population.

Suprachoroidal devices in glaucoma surgery.

While conventional glaucoma filtration surgery provides excellent intraocular pressure (IOP) lowering effect, this comes at the expense of significant risks. As the physiology of the suprachoroidal space has become better understood, its potential as a source for aqueous drainage has generated significant interest. This has resulted in the creation of several suprachoroidal glaucoma devices with excellent IOP lowering ability and a much more favorable side effect profile.

The association between glaucomatous and other causes of optic neuropathy and sleep apnea.

PURPOSE: To determine whether an association exists between sleep apnea and open-angle glaucoma, normal-tension glaucoma, nonarteritic ischemic optic neuropathy (NAION), papilledema, or idiopathic intracranial hypertension (IIH) and whether treatment with continuous positive airway pressure affects the development of these conditions. DESIGN: Retrospective, longitudinal cohort study. METHODS: Billing records for beneficiaries 40 years of age and older enrolled in a large United States managed care network from 2001 through 2007 were reviewed. Incidence of open-angle glaucoma, normal-tension glaucoma, NAION, papilledema, and IIH were determined for the beneficiaries and were stratified by sleep apnea status. Cox regression analyses determined the hazard of each of these conditions developing among individuals with and without sleep apnea, with adjustment for sociodemographic, ocular, and medical conditions. RESULTS: Among the 2 259 061 individuals in the study, 156 336 (6.9%) had 1 or more sleep apnea diagnoses. The hazard of open-angle glaucoma was no different among persons with sleep apnea either treated (adjusted hazard ratio [HR], 0.99; 95% confidence interval [CI], 0.82 to 1.18) or untreated with continuous positive airway pressure (HR, 1.01; 95% CI, 0.98 to 1.05) and individuals without sleep apnea. Similar findings were observed when assessing the hazard of normal-tension glaucoma developing (P > .05 for both comparisons). A significantly increased hazard of NAION developing (HR, 1.16; 95% CI, 1.01 to 1.33) and IIH (HR, 2.03; 95% CI, 1.65 to 2.49) was observed among individuals with sleep apnea who were not receiving continuous positive airway pressure therapy as compared with individuals without sleep apnea, although similar increased risks could not be demonstrated among continuous positive airway pressure-treated sleep apnea patients for these conditions (P > .05 for both comparisons). CONCLUSIONS: Patients with untreated sleep apnea are at increased risk for IIH and NAION. Clinicians should consider appropriate screening for these conditions in sleep apnea patients.

Severe adverse events after cataract surgery among medicare beneficiaries.

PURPOSE: To determine rates and risk factors associated with severe postoperative complications after cataract surgery and whether they have been changing over the past decade. DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: A total of 221 594 Medicare beneficiaries who underwent cataract surgery during 1994-2006. METHODS: Beneficiaries were stratified into 3 cohorts: those who underwent initial cataract surgery during 1994-1995, 1999-2000, or 2005-2006. One-year rates of postoperative severe adverse events (endophthalmitis, suprachoroidal hemorrhage, retinal detachment) were determined for each cohort. Cox regression analyses determined the hazard of developing severe adverse events for each cohort with adjustment for demographic factors, ocular and medical conditions, and surgeon case-mix. MAIN OUTCOME MEASURES: Time period rates of development of severe postoperative adverse events. RESULTS: Among the 221 594 individuals who underwent cataract surgery, 0.5% (1086) had at least 1 severe postoperative complication. After adjustment for confounders, individuals who underwent cataract surgery during 1994-1995 had a 21% increased hazard of being diagnosed with a severe postoperative complication (hazard ratio [HR] 1.21; 95% confidence interval [CI], 1.05-1.41) relative to individuals who underwent cataract surgery during 2005-2006. Those who underwent cataract surgery during 1999-2000 had a 20% increased hazard of experiencing a severe complication (HR 1.20; 95% CI, 1.04-1.39) relative to the 2005-2006 cohort. Risk factors associated with severe adverse events include a prior diagnosis of proliferative diabetic retinopathy (HR 1.62; 95% CI, 1.07-2.45) and cataract surgery combined with another intraocular surgical procedure on the same day (HR 2.51; 95% CI, 2.07-3.04). Individuals receiving surgery by surgeons with the case-mix least prone to developing a severe adverse event (HR 0.52; 95% CI, 0.44-0.62) had a 48% reduced hazard of a severe adverse event relative to recipients of cataract surgery performed by surgeons with the case-mix most prone to developing such outcomes. CONCLUSIONS: Rates of sight-threatening adverse events after cataract surgery declined during 1994-2006. Future efforts should be directed to identifying ways to reduce severe adverse events in high-risk groups.

Denervation does not change the ratio of collagen I and collagen III mRNA in the extracellular matrix of muscle.

Denervation or inactivity is known to decrease the mass and alter the phenotype of muscle and the mechanics of tendon. It has been proposed that a shift in the collagen of the extracellular matrix (ECM) of the muscle, increasing type III and decreasing type I collagen, may be partially responsible for the observed changes. We directly investigated this hypothesis using quantitative real-time PCR on muscles and tendons that had been denervated for 5 wk. Five weeks of denervation resulted in a 2.91-fold increase in collagen concentration but no change in the content of collagen in the muscle, whereas in the tendon there was no change in either the concentration or content of collagen. The expression of collagen I, collagen III, and lysyl oxidase mRNA in the ECM of muscle decreased (76 +/- 1.6%, 73 +/- 2.3%, and 83 +/- 3.2%, respectively) after 5 wk of denervation. Staining with picrosirius red confirmed the earlier observation of a change in staining color from red to green. Taken with the observed equivalent decreases in collagen I and III mRNA, this suggests that there was a change in orientation of the ECM of muscle becoming more aligned with the axis of the muscle fibers and no change in collagen type. The change in collagen orientation may serve to protect the smaller muscle fibers from damage by increasing the stiffness of the ECM and may partly explain why the region of the tendon closest to the muscle becomes stiffer after inactivity.

Regional variation of tibialis anterior tendon mechanics is lost following denervation.

Denervation or inactivity is known to decrease the mass and alter the phenotype of muscle. The mechanical response of tendon to inactivity that has been determined experimentally differs from what is reported by patients. We investigated the hypothesis that this difference was the result of artifacts of the testing process and did not represent what occurred in vivo. To test this hypothesis, a novel approach was used to determine the mechanical properties of the tibialis anterior (TA) tendon by optically measuring the end-to-end mechanical strains as well as the local strains at specific regions of excised TA tendon units. When the end-to-end strain of normal TA tendon is determined, stress-strain response curves show considerably more extensibility than when strain is measured across only the midsection of the tendon (mid-tendon). The strain experienced by the region close to the muscle (muscle tendon) is five times greater than the strain in either the mid-tendon or near the bone (bone-tendon). Five weeks of denervation decreased muscle mass by 67%; increased tendon mass by 10%; and changed the entire shape of the nonlinear response curve, including a loss in regional variation in strain, a 3.9-fold increase in end-to-end tangent modulus, and a 70% reduction in the toe region, as a result of a drastic reduction of the extensibility in the muscle-tendon region. The stress-strain response in the mid-tendon region of a normal TA tendon is therefore not indicative of its overall ability to deform in vivo as it transmits forces from muscle to bone.