Richard K. Lee

Cochlin induced TREK-1 co-expression and annexin A2 secretion: role in trabecular meshwork cell elongation and motility.

Fluid flow through large interstitial spaces is sensed at the cellular level, and mechanistic responses to flow changes enables expansion or contraction of the cells modulating the surrounding area and brings about changes in fluid flow. In the anterior eye chamber, aqueous humor, a clear fluid, flows through trabecular meshwork (TM), a filter like region. Cochlin, a secreted protein in the extracellular matrix, was identified in the TM of glaucomatous patients but not controls by mass spectrometry. Cochlin undergoes shear induced multimerization and plays a role in mechanosensing of fluid shear. Cytoskeletal changes in response to mechanosensing in the ECM by cochlin will necessitate transduction of mechanosensing. TREK-1, a stretch activated outward rectifying potassium channel protein known to act as mechanotransducer was found to be expressed in TM. Cochlin expression results in co-expression of TREK-1 and filopodia formation. Prolonged cochlin expression results in expression and subsequent secretion of annexin A2, a protein known to play a role in cytoskeletal remodeling. Cochlin interacts with TREK-1 and annexin A2. Cochlin-TREK-1 interaction has functional consequences and results in changes in cell shape and motility. Annexin A2 expression and secretion follows cochlin-TREK-1 syn-expression and correlates with cell elongation. Thus cytoskeleton changes in response to fluid shear sensed by cochlin are further mediated by TREK-1 and annexin A2.

Residual and Dynamic Range of Retinal Nerve Fiber Layer Thickness in Glaucoma: Comparison of Three OCT Platforms.

PURPOSEnTo estimate visual field (VF) sensitivity at which retinal nerve fiber layer (RNFL) thinning reaches the measurement floor and at which RNFL stops thinning (change points), the dynamic range of RNFL thickness, and the number of steps from normal to RNFL floor among three optical coherence tomography (OCT) devices.nnnMETHODSnGlaucomatous patients (n = 58) and healthy subjects (n = 55-60) prospectively underwent VF testing and RNFL thickness measurement with Cirrus, Spectralis, and RTVue. Change points and corresponding RNFL thicknesses were estimated with simple linear regression (SLR) and Bayesian change point (BCP) analyses. The dynamic range and number of steps to RNFL floor were determined.nnnRESULTSnThe average VF change points and corresponding residual thickness at the time RNFL stopped thinning were -22.2 dB and 57.0 μm (Cirrus), -25.3 dB and 49.2 μm (Spectralis), and -24.6 dB and 64.7 μm (RTVue). The RNFL dynamic ranges derived from SLR values were wider on Spectralis (52.6 μm) than on Cirrus (35.4 μm) and RTVue (35.5 μm); the corresponding number of steps to reach the RNFL floor were 9.0 on Cirrus, 10.6 on Spectralis, and 8.3 on RTVue.nnnCONCLUSIONSnThe relative VF sensitivity at which average RNFL thickness reaches the measurement floor, the residual layer thickness, and RNFL dynamic measurement range differ among the three devices. However, the number of steps from normal to the RNFL thickness floor is comparable.

Molecular Biomarkers in Glaucoma

The seventh annual ARVO/Pfizer Ophthalmic Research Institute conference was held Friday and Saturday, April 29 and 30, 2011, at the Fort Lauderdale Hyatt Regency Pier 66, Fort Lauderdale, Florida. The conference, funded by The ARVO Foundation for Eye Research through a grant from Pfizer Ophthalmics, provided an opportunity to gather experts from within and outside ophthalmology to determine the state of knowledge pertaining to molecular biomarkers associated with glaucoma, as well as the methods to identify and validate them to predict (a) those who would be susceptible to development of glaucoma; (b) markers that will enable prediction of glaucoma progression; and (c) markers that will predict efficacy of treatment of glaucoma. Identification of such biomarkers will aid in prevention of glaucoma-related vision loss and blindness. The conference focused on an evaluation of glaucoma molecular biomarkers and progress needed for future validation of glaucoma biomarkers. n nA working group of 21 glaucoma researchers, 7 scientists focused on diseases other than glaucoma and with expertise in areas such as proteomic biomarkers or molecular mechanisms for neurodegeneration, and 60 observers from ARVO, Pfizer, and clinical and basic ophthalmic research convened to evaluate current understanding of the molecular biomarkers of glaucoma. The meeting format emphasized discussion and concentrated on questions within areas of glaucoma molecular biomarker research: n n nSession I: How to define a biomarker in medicine? Current knowledge about biomarkers in human health and in glaucoma n n nSession II: Genetic biomarkers in glaucoma n n nSession III: Proteomic biomarkers in glaucoma n n nSession IV: Pre-immune and immune events: Immunoproteomics and its possible applications in glaucoma n n nSession V: From bench to bedside: How can a translational approach be successful? n n n nEach session began with a 10-minute overview by a glaucoma researcher followed by a 30-minute presentation by an outside expert, with parallels between their fields of expertise and the eye included. Invited outside experts covered several areas of research, including proteomic biomarker discovery in cancer (Emanuel Petricoin, PhD, George Mason University, Maryland; and Akhilesh Pandey, MD, PhD, Johns Hopkins University, Maryland) and astroglial cells in neurodegeneration (Stephen D. Miller, PhD, Northwestern University, Illinois).

Cholesterol and Glycosphingolipids of Human Trabecular Meshwork and Aqueous Humor: Comparative Profiles from Control and Glaucomatous Donors

Abstract Purpose: To determine the differential profiles of cholesterol and glycosphingolipid species and their quantitative differences between control and glaucomatous aqueous humor (AQH) and the trabecular meshwork (TM) derived from human donors. Methods: Control TM and selected primary open angle glaucoma (POAG) TM samples were collected from cadaveric donors. Other TM samples, glaucomatous AQH and control AQH were procured during intraocular surgery. Lipid extraction was performed using modifications of the Bligh and Dyer method. Protein concentration was estimated using the Bradford colorimetric assay. Cholesterol and glycosphingolipids were identified and subjected to ratiometric quantification utilizing precursor ion scan and neutral ion loss scan in positive ion mode using appropriate class specific lipid standards (Cholesterol and Psychosine) on a TSQ Quantum Access Max mass spectrometer. Results: Control and glaucomatous AQH demonstrated 7 and 4 unique cholesterol species, whereas the TM demonstrated 7 and 12 unique species, respectively. The control and POAG AQH showed 6 and 0 whereas TM samples showed 5 and 1 unique glycosphingolipids, respectively. A total of 65 and 62 common cholesterol species and 59 and 58 common glycosphingolipids were found in AQH and TM, respectively. Increased zymosterol and glucopyranosyl cholesterol levels were found in glaucomatous AQH. Significantly decreased levels of galactosylceramide, glucosylceramide in glaucomatous TM were found compared to control TM. Conclusion: A high percentage of cholesterol and glycosphingolipid species was found to be common between control and POAG AQH and TM. Several cholesterol and glycosphingolipid species was found to be unique in a subset of POAG or controls. Glaucomatous aqueous humor and TM showed relatively higher levels of zymosterol (an intermediate precursor of cholesterol) and decreased glycoceramide levels, respectively.

Combined central retinal vein and central retinal artery occlusions and neovascular glaucoma associated with interferon treatment.

Purpose Interferon (IFN) is a mainstay medication used for treatment of chronic hepatitis C, as well as for treatment of certain neoplastic and autoimmune conditions. We present a case of a 50-year-old man who, while on IFN treatment, developed central retinal vein and artery occlusions complicated by the development of neovascular glaucoma secondary to severe retinal ischemia. Interferon retinopathy is associated with ischemic retinal cotton-wool spots. This case illustrates how IFN can lead to severe and sight-threatening retinal ischemia. Methods Case report. Results A 50-year-old man with previously good vision presented with decreased vision in the right eye while being treated with IFN therapy for chronic hepatitis C. He was diagnosed with central retinal vein occlusion and 2 weeks later also developed a central retinal artery occlusion. His course was complicated by the development of neovascular glaucoma. The final visual acuity was ultimately light perception. Conclusions Interferon therapy is commonly utilized for chronic hepatitis C, neoplastic conditions, and multiple sclerosis. Clinicians should be aware of the sight-threatening complications of IFN therapy, especially with regard to ocular vaso-occlusive disease and severe retinal ischemia.

Treating uncorrected refractive error in adults in the developing world with autorefractors and ready-made spectacles

Background:u2002 To evaluate a method for treating uncorrected refractive error in adults in the developing world.

Prevalence and risk factors of primary open-angle glaucoma in a city of Eastern China: a population-based study in Pudong New District, Shanghai

BackgroundThe aim of the present study was to investigate the prevalence and characteristics of primary open-angle glaucoma among the urban population of Pudong New District, Shanghai.MethodsThree residents’ committees were randomly selected from Pudong New District, and residents aged 50 and older were screened for primary open-angle glaucoma (POAG) from March to April 2011. In remote screening, the tests on visual acuity, refraction, intraocular pressure (IOP), and the photographs of anterior segment and fundus were used to identify POAG suspect. The suspected subjects were then reexamined with the tests on IOP, gonioscopy, Humphrey visual field test, and retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT). POAG was diagnosed according to the criteria defined by International Society for Geographic and Epidemiological Ophthalmology (ISGEO). Finally, POAG risk factors were evaluated using logistic regression analysis.ResultsA total of 2528 citizens out of 3,146 eligible residents (80.36xa0%) participated in this study. Among the citizens, 72 were diagnosed to have POAG, giving the crude prevalence rate of 2.85xa0% (95xa0% CI:2.20xa0%–3.50xa0%) in general and age- and gender-adjusted prevalence rate of 2.8xa0% (95xa0% CI: 2.78xa0%–2.83xa0%). Among the 72 POAG patients, only 22 cases had IOP exceeding 21xa0mmHg while other 50 cases had IOP of 21xa0mmHg or less; nine cases had one eye blind (12.5xa0%). Intriguingly, only eight cases (11.11xa0%) had been diagnosed with POAG before this screening.ConclusionsMore efforts are required for early screening and education on POAG in communities, especially in a POAG high-risk population.

RESOLUTION OF CONJUNCTIVAL SESSILE HEMANGIOMA WITH TOPICAL TIMOLOL

Purpose: To report a single case of acquired sessile hemangioma of the conjunctiva which resolved after treatment with topical timolol. Methods: Case report and literature review. Results: A 77-year-old African American woman developed an acquired sessile hemangioma of the conjunctiva of the right eye. She was followed for primary open-angle glaucoma, and the lesion was monitored for 12 months without change. Topical timolol-dorzolamide was then added to her glaucoma medication regimen twice daily. On follow-up examination 6 months later, the lesion had completely resolved. Conclusions: In this case report, an acquired sessile hemangioma of the conjunctiva resolved with topical timolol therapy.

Low-cost, smartphone based frequency doubling technology visual field testing using virtual reality (Conference Presentation)

Glaucoma is the leading cause of irreversible blindness worldwide. Due to its wide prevalence, effective screening tools are necessary. The purpose of this project is to design and evaluate a system that enables portable, cost effective, smartphone based visual field screening based on frequency doubling technology. The system is comprised of an Android smartphone to display frequency doubling stimuli and handle processing, a Bluetooth remote for user input, and a virtual reality headset to simulate the exam. The LG Nexus 5 smartphone and BoboVR Z3 virtual reality headset were used for their screen size and lens configuration, respectively. The system is capable of running the C-20, N-30, 24-2, and 30-2 testing patterns. Unlike the existing system, the smartphone FDT tests both eyes concurrently by showing the same background to both eyes but only displaying the stimulus to one eye at a time. Both the Humphrey Zeiss FDT and the smartphone FDT were tested on five subjects without a history of ocular disease with the C-20 testing pattern. The smartphone FDT successfully produced frequency doubling stimuli at the correct spatial and temporal frequency. Subjects could not tell which eye was being tested. All five subjects preferred the smartphone FDT to the Humphrey Zeiss FDT due to comfort and ease of use. The smartphone FDT is a low-cost, portable visual field screening device that can be used as a screening tool for glaucoma.

Differences in Optical Coherence Tomography Assessment of Bruch Membrane Opening Compared to Stereoscopic Photography for Estimating Cup-to-Disc Ratio

PURPOSEnTo compare the vertical and horizontal cup-to-disc ratio (VCDR, HCDR) by an updated optical coherence tomography (OCT) Bruch membrane opening (BMO) algorithm and stereoscopic optic disc photograph readings by glaucoma specialists.nnnDESIGNnReliability analysis.nnnMETHODSnA total of 195 eyes (116 glaucoma and 79 glaucoma suspect) of 99 patients with stereoscopic photographs and OCT scans of the optic discs taken during the same visit were compared. Optic disc photographs were read by 2 masked glaucoma specialists for VCDR and HCDR estimation. Intraclass correlation coefficient (ICC) and Bland-Altman plots were used to assess the agreement between photograph reading and OCT in estimating CDR.nnnRESULTSnOCT images computed significantly larger VCDR and HCDR than photograph reading before and after stratifying eyes based on disc size (P < .001). The difference in CDR estimates between the 2 methods was equal to or greater than 0.2 in 29% and 35% of the eyes for VCDR and HCDR, respectively, with a mean difference of 0.3 in each case. The ICCs between the readers and OCT ranged between 0.50 and 0.63. The size of disagreement in VCDR correlated weakly with cup area in eyes with medium (r2xa0= 0.10, Pxa0= .008) and large (r2xa0= 0.09, Pxa0= .007) discs.nnnCONCLUSIONSnOCT and photograph reading by clinicians agree poorly in CDR assessment. The difference in VCDR between the 2 methods was depended on cup area in medium and large discs. These differences should be considered when making conclusions regarding CDRs in clinical practice.