Divakar Gupta

Gsα deficiency in skeletal muscle leads to reduced muscle mass, fiber-type switching, and glucose intolerance without insulin resistance or deficiency

The ubiquitously expressed G protein alpha-subunit G(s)alpha is required for receptor-stimulated intracellular cAMP responses and is an important regulator of energy and glucose metabolism. We have generated skeletal muscle-specific G(s)alpha-knockout (KO) mice (MGsKO) by mating G(s)alpha-floxed mice with muscle creatine kinase-cre transgenic mice. MGsKO mice had normal body weight and composition, and their serum glucose, insulin, free fatty acid, and triglyceride levels were similar to that of controls. However, MGsKO mice were glucose intolerant despite the fact that insulin sensitivity and glucose-stimulated insulin secretion were normal, suggesting an insulin-independent mechanism. Isolated muscles from MGsKO mice had increased basal glucose uptake and normal responses to a stimulator of AMP-activated protein kinase (AMPK), which indicates that AMPK and its downstream pathways are intact. Compared with control mice, MGsKO mice had reduced muscle mass with decreased cross-sectional area and force production. In addition, adult MGsKO mice showed an increased proportion of type I (slow-twitch, oxidative) fibers based on kinetic properties and myosin heavy chain isoforms, despite the fact that these muscles had reduced expression of peroxisome proliferator-activated receptor coactivator protein-1alpha (PGC-1alpha) and reduced mitochondrial content and oxidative capacity. Therefore G(s)alpha deficiency led to fast-to-slow fiber-type switching, which appeared to be dissociated from the expected change in oxidative capacity. MGsKO mice are a valuable model for future studies of the role of G(s)alpha signaling pathways in skeletal muscle adaptation and their effects on whole body metabolism.

Optic nerve head perfusion in normal eyes and eyes with glaucoma using optical coherence tomography-based microangiography.

BACKGROUND To investigate the differences of perfusion in the optic nerve head (ONH) between normal and glaucomatous eyes using optical microangiography (OMAG) based optical coherence tomography (OCT) angiography technique. METHODS One eye from each subject was scanned with a 68 kHz Cirrus 5000 HD-OCT-based OMAG prototype system centered at the ONH (Carl Zeiss Meditec Inc, Dublin, CA, USA). Microvascular images were generated from the OMAG dataset by detecting the differences in OCT signal between consecutive B-scans. The pre-laminar layer (preLC) was isolated by a semi-automatic segmentation program. En face OMAG images for preLC were generated using signals with highest blood flow signal intensity. ONH perfusion was quantified as flux, vessel area density, and normalized flux within the ONH. Standard t-tests were performed to analyze the ONH perfusion differences between normal and glaucomatous eyes. Linear regression models were constructed to analyze the correlation between ONH perfusion and other clinical measurements. RESULTS Twenty normal and 21 glaucoma subjects were enrolled. Glaucomatous eyes had significantly lower ONH perfusion in preLC in all three perfusion metrics compared to normal eyes (P≤0.0003). Significant correlations between ONH perfusion and disease severity as well as structural changes were detected in glaucomatous eyes (P≤0.012). CONCLUSIONS ONH perfusion detected by OMAG showed significant differences between glaucoma and normal controls and was significantly correlated with disease severity and structural defects in glaucomatous eyes. ONH perfusion measurement using OMAG may provide useful information for detection and monitoring of glaucoma.

Comparison of complication rates of porous anophthalmic orbital implants.

BACKGROUND AND OBJECTIVE Porous anophthalmic orbital implants are used widely. This study evaluates risk factors for porous anophthalmic orbital implant complications and compares complication rates of hydroxyapatite, porous polyethylene, and polyglactin mesh-wrapped aluminum oxide implants. PATIENTS AND METHODS The records of 105 patients (110 eyes) who received porous anophthalmic orbital implants for any indication were reviewed retrospectively. Complications were recorded and correlated with potential risk factors, including implant material. All patient records were de-identified to protect privacy. RESULTS Porous polyethylene and aluminum oxide implants were associated with higher exposure rates (porous polyethylene: odds ratio 6.1 [1.29, 29.1]; aluminum oxide: odds ratio 6.0 [1.58, 23.1]; P = .004) and higher overall complication rates compared to hydroxyapatite implants. CONCLUSION Implant material may be a risk factor for several anophthalmic clinical outcomes.

Repeatability and reproducibility of optic nerve head perfusion measurements using optical coherence tomography angiography

Abstract. Optical coherence tomography angiography (OCTA) has increasingly become a clinically useful technique in ophthalmic imaging. We evaluate the repeatability and reproducibility of blood perfusion in the optic nerve head (ONH) measured using optical microangiography (OMAG)-based OCTA. Ten eyes from 10 healthy volunteers are recruited and scanned three times with a 68-kHz Cirrus HD-OCT 5000-based OMAG prototype system (Carl Zeiss Meditec Inc., Dublin, California) centered at the ONH involving two separate visits within six weeks. Vascular images are generated with OMAG processing by detecting the differences in OCT signals between consecutive B-scans acquired at the same retina location. ONH perfusion is quantified as flux, vessel area density, and normalized flux within the ONH for the prelaminar, lamina cribrosa, and the full ONH. Coefficient of variation (CV) and intraclass correlation coefficient (ICC) are used to evaluate intravisit and intervisit repeatability, and interobserver reproducibility. ONH perfusion measurements show high repeatability [CV≤3.7% (intravisit) and ≤5.2% (intervisit)] and interobserver reproducibility (ICC≤0.966) in all three layers by three metrics. OCTA provides a noninvasive method to visualize and quantify ONH perfusion in human eyes with excellent repeatability and reproducibility, which may add additional insight into ONH perfusion in clinical practice.

Orbital peripheral nerve sheath tumors.

Peripheral nerve sheath tumors of the orbit and ocular adnexa are a rare group of neoplasms hallmarked by nonspecific clinical presentations, variable tumor locations, challenging therapeutic efforts, and occasional diagnostic dilemmas. We review these tumor types and provide an updated summary on their clinical, histopathologic, radiological, and emerging molecular features.

Malignant Peripheral Nerve Sheath Tumor of the Lower Eyelid: Case Presentation and Literature Review

Solitary benign neurogenic tumors are common in the orbit, but only rarely arise from peripheral nerves in the eyelids. In contrast, malignant tumors of neural or nerve sheath elements are exceedingly rare in the orbit and, to date, have never been reported in the lower eyelid. The authors report a 55-year-old man with multiple recurrent lower eyelid masses initially treated as chalazia then misdiagnosed as neurotropic malignant melanoma on pathology. Diagnosis of malignant peripheral nerve sheath tumor was ultimately confirmed histopathologically after surgical resection. The patient has since undergone multiple resections and adjuvant radiotherapy. Twenty-two months since the last procedure, the patient remains disease-free.

Cytokine biomarkers in tear film for primary open-angle glaucoma.

Purpose To determine the utility of tear film cytokines as biomarkers for early primary open-angle glaucoma (POAG). Methods Patients without POAG and eye drop-naïve patients with newly diagnosed POAG were recruited from an academic hospital-based glaucoma practice. Tear films of recruited patients were obtained and analyzed using a multiplex, high-sensitivity electrochemiluminescent enzyme-linked immunosorbent assay for proinflammatory cytokines (IFNγ, IL-10, IL-12p70, IL-13, IL-1β, IL-2, IL-4, IL-6, IL-8, and TNFα). Results Mean concentrations of tear film cytokines were lower in the glaucoma group for 8 of 10 cytokines tested. IL-12p70 (3.94±2.19 pg/mL in control vs 2.31±1.156 pg/mL in POAG; P=0.035) was significantly lower in the tear film of patients with newly diagnosed POAG. Conclusion Proinflammatory cytokines were lower in eye drop-naïve newly diagnosed glaucoma patients. Tear film cytokine profiles may be used as biomarkers of early POAG.

Macular thickness analysis for glaucoma diagnosis and management

There is increasing literature regarding the role of macular imaging by optical coherence tomography (OCT) in glaucoma care. Spectral domain OCT (SD-OCT) has allowed for high resolution imaging of the total macula and macular segments. With the use of asymmetry analysis, macular thickness is a measurement that can be used for the detection and progression of glaucoma. Some artifacts seen on retinal nerve fiber layer (rNFL) scans may be overcome by macular SD-OCT imaging. Also, nonglaucomatous optic neuropathies may be more easily identified on macular thickness plots than rNFL scans. Special populations, such as children or myopes, may also have improved glaucoma surveillance using macular SD-OCT. In this review we explore the advantages and pitfalls of macular OCT in glaucoma care and offer an approach on how to use macular thickness scans in clinical practice.

Effect of surgical case order on cataract surgery complication rates and procedure time

Purpose To determine whether surgical warm‐up affects cataract surgery complication rates and surgical case times. Setting University of Washington Medicine Eye Institute, Harborview, Seattle, Washington, USA. Design Retrospective case‐control study. Methods Patients who had phacoemulsification from June 2010 to December 2011 were consecutively reviewed. Case order for each surgeon was evaluated, comparing intraoperative complication rates and case times for attending and resident surgeons for the first case of the day (considered the warm‐up case) versus subsequent cases. Simple (AMA Current Procedural Terminology code 66984) and complex (code 66982) phacoemulsification surgeries were included. Excluded were patients who had cataract surgery combined with another surgery. Pearson chi‐square tests and 2‐tailed independent‐sample t tests were used to analyze data. Results The study reviewed 1424 patients. Cataract surgery complication rates were not statistically different between the first cases of the day and subsequent cases (3.3% versus 4.0%) (P = .552). There was, however, a significant difference in mean case time between these groups. The mean case time for simple phacoemulsification by resident physicians was 49.45 minutes ± 19.38 (SD) for first cases and 42.27 ± 15.78 minutes for subsequent cases (P = .021) and by attending physicians, 32.54 ± 12.91 minutes and 26.69 ± 9.17 minutes, respectively (P <. 0001). Conclusion Surgical case order might not affect complication rates of cataract surgery; however, the first case of the day was longer than subsequent cases, suggesting that a preoperative warm‐up exercise might decrease cataract surgery time. Financial Disclosure Neither author has a financial or proprietary interest in any material or method mentioned.

Optic Disc Hemorrhages in Glaucoma

Optic disc hemorrhages are a significant clinical sign seen in patients with glaucoma and often herald glaucomatous progression. Longitudinal and population-based studies have shown that disc hemorrhages are most commonly seen in glaucoma, particularly normal tension glaucoma patients. The exact pathophysiology of an optic disc hemorrhage is not completely understood, but both mechanical rupture and vascular dysregulation theories have been proposed. Recent studies using spectral domain optic coherence tomography and visual field progression analysis have highlighted that structural and functional loss both precede and follow detection of an optic disc hemorrhage. The relationship between intraocular pressure and disc hemorrhages is not completely understood as some patients with disc hemorrhages may progress independent of intraocular pressure lowering therapy.