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Glaucoma structure function

Xiao-Ling Yang, Yolandi van der Merwe, Jeffrey Sims, Carlos Parra, Leon C Ho, Joel S Schuman, Gadi Wollstein, Kira L Lathrop, Kevin C Chan
Although elevated intraocular pressure (IOP) and age are major risk factors for glaucoma, their effects on glaucoma pathogenesis remain unclear. This study examined the onset and progression of glaucomatous changes to ocular anatomy and physiology, structural and physiological brain integrity, and visuomotor behavior in the DBA/2J mice via non-invasive tonometry, multi-parametric magnetic resonance imaging (MRI) and optokinetic assessments from 5 to 12 months of age. Using T2-weighted MRI, diffusion tensor MRI, and manganese-enhanced MRI, increasing IOP elevation at 9 and 12 months old coincided with anterior chamber deepening, altered fractional anisotropy and radial diffusivity of the optic nerve and optic tract, as well as reduced anterograde manganese transport along the visual pathway respectively in the DBA/2J mice...
March 15, 2018: Scientific Reports
Mihaela-Roxana Mănoiu, Jade Amine Amri, Alexandra Țicle, Cristina Stan
Optic nerve head drusen is an incidental finding in current ophthalmological practice. Although patients rarely display symptoms, structural, and functional defects, there are exceptional cases when clinical appearance can make it difficult to diagnose underlying or coexisting conditions, such as glaucoma. The following case report demonstrates how overlapping optic nerve pathologies can interfere in clinical judgement and therapeutic decision making in a young male patient, with relevant family history for both glaucoma and bilateral optic nerve head drusen...
October 2017: Romanian Journal of Ophthalmology
A Popa-Cherechenau, D Schmidl, G Garhöfer, L Schmetterer
BACKGROUND: Structural endpoints have been discussed as surrogate endpoints for the approval of neuroprotective drugs in glaucoma. OBJECTIVE: Is the evidence strong enough to establish structural endpoints as surrogate endpoints? MATERIAL AND METHODS: Review of current understanding between structure and function in glaucoma. RESULTS: The introduction of optical coherence tomography has revolutionized imaging in glaucoma patients...
March 6, 2018: Der Ophthalmologe: Zeitschrift der Deutschen Ophthalmologischen Gesellschaft
William Fusi-Rubiano, Chandoshi Mukherjee, Mark Lane, Marie D Tsaloumas, Nicholas Glover, Andrej Kidess, Alastair K Denniston, Helen E Palmer, Avinash Manna, Rupal Morjaria
BACKGROUND: To compare visual function and structural improvements in pseudophakic eyes with diabetic macular oedema (DMO) treated with the 0.19mg Fluocinolone Acetonide (FAc) intravitreal implant (IluvienTM ) in a 'real world' setting. METHODS: A single centre retrospective evaluation of patients with DMO unresponsive to conventional treatment treated with the FAc implant according to UK guidelines. Primary efficacy endpoint was best corrected visual acuity (BCVA); secondary endpoints included optical coherence tomography evaluations of the macula (a) central retinal and (b) peak macular thickness collected at annual time points...
February 27, 2018: BMC Ophthalmology
Mohsin H Ali, Mark S Dikopf, Anthony G Finder, Ahmad A Aref, Thasarat Vajaranant, Jose de la Cruz, Maria Soledad Cortina
PURPOSE: To investigate glaucomatous damage in Boston keratoprosthesis type I (KPro) patients through structural analysis of the optic nerve head and digital planimetric quantification of Goldmann visual fields, a novel method of monitoring perimetric changes in KPro patients. METHODS: Records of patients undergoing KPro implantation from 2007 to 2015 at a single institution were reviewed. Parameters related to glaucoma status and KPro outcomes were analyzed. RESULTS: Twenty-two eyes from 21 patients met inclusion criteria, with mean follow-up of 49...
February 22, 2018: Cornea
Myoung Sup Shim, Keun-Young Kim, Jung Hyun Bu, Hye Seung Nam, Seung Won Jeong, Tae Lim Park, Mark H Ellisman, Robert N Weinreb, Won-Kyu Ju
Glaucoma is characterized by a progressive loss of retinal ganglion cells and their axons, but the underlying biological basis for the accompanying neurodegeneration is not known. Accumulating evidence indicates that structural and functional abnormalities of astrocytes within the optic nerve head (ONH) have a role. However, whether the activation of cyclic adenosine 3',5'-monophosphate (cAMP) signaling pathway is associated with astrocyte dysfunction in the ONH remains unknown. We report here that the cAMP/protein kinase A (PKA) pathway is critical to ONH astrocyte dysfunction, leading to caspase-3 activation and cell death via the AKT/Bim/Bax signaling pathway...
February 19, 2018: Cell Death & Disease
Xi Han, Yang Liu, Wendy R Kam, David A Sullivan
We recently discovered that the anti-glaucoma pharmaceuticals timolol, a β adrenergic antagonist, and pilocarpine, a cholinergic compound, negatively influence the morphology, proliferative capacity and survival of human meibomian gland epithelial cells (HMGECs). We hypothesize that another class of anti-glaucoma drugs, the α2 adrenergic agonists, also acts directly on HMGECs to affect their structure and function. We tested this hypothesis. Immortalized (i) HMGECs were cultured with brimonidine, as well as clonidine (α2 agonist), phenylephrine (α1 agonist), RX821002 (inverse α2 agonist) and MK912 (neutral α2 agonist) for up to 7 days...
February 13, 2018: Experimental Eye Research
Da Zhao, Christine T O Nguyen, Zheng He, Vickie H Y Wong, Anna K van Koeverden, Algis J Vingrys, Bang V Bui
Age-related changes to the balance between the pressure inside the eye (intraocular pressure, IOP) and the pressure inside the brain (intracranial pressure, ICP) can modify the risk of glaucoma. In this study, we consider whether the optic nerve in older rat eyes is more susceptible to acute IOP and ICP modification. We systematically manipulate both ICP and IOP and quantify their effects on ganglion cell function (electroretinography, ERG), optic nerve structure (optical coherence tomography, OCT) and retinal blood flow (Doppler OCT)...
February 13, 2018: Scientific Reports
Mineo Ozaki
The most important characteristic of exfoliation syndrome (XFS) is that it involves a greater risk of developing glaucoma. In comparison with other forms of open-angle glaucoma, exfoliation glaucoma (XFG) is more resistant to medical therapy and progresses faster. Possible pathological mechanisms of glaucoma development in XFS comprise: (1) elevated intraocular pressure (IOP) caused by functional impairment of aqueous humor outflow due to deposition of exfoliation material (XFM) in the trabecular meshwork and trabecular cell dysfunction, (2) XFS-associated connective tissue elastosis leading to structural and functional alterations of the lamina cribrosa which increases the vulnerability toward elevated IOP and development of glaucomatous optic neuropathy, (3) elevated IOP due to closure of the anterior chamber angle accompanied by forward displacement of the crystalline lens due to zonular weakness, (4) presumable primary functional impairment of retinal ganglion cells...
February 9, 2018: Journal of Glaucoma
Fabio Lavinsky, Camila Zanella Benfica, Nédio Castoldi, Anne Elise Cruz do Carmo Chaves, Paulo Augusto de Arruda Mello
Purpose: To evaluate the hypotenuse of the vertical optic nerve head cup (HVOC), measured using the length and depth of the cup obtained with enhanced depth imaging spectral-domain optic coherence tomography (SD-OCT), as a biomarker for glaucoma diagnosis. Methods: This was a prospective cross-sectional study of patients with glaucoma and controls. SD-OCT was performed in all participants to assess average circumpapillary retinal nerve fiber layer (RNFL) thickness...
2018: Clinical Ophthalmology
Kuldeep Mohanty, Rima Dada, Tanuj Dada
BACKGROUND: Recently SIX1 and SIX6 genes have been associated with primary open angle glaucoma (POAG). This study was planned to do mutation screening in SIX1 and SIX6 genes in North Indian POAG patients and correlate with clinical phenotypes. MATERIALS AND METHODS: SIX1 and SIX6 genes were amplified by PCR and sequenced in 115 POAG cases and 105 controls. Four pathogenecity prediction tools (MutationTaster, PolyPhen-2 HumDiv, PolyPhen-2 HumVar and SIFT) were used to predict the pathogenicity of the missense mutations...
February 6, 2018: Ophthalmic Genetics
Dustin Je Huard, Vincent M Crowley, Yuhong Du, Ricardo A Cordova, Zheying Sun, Moya O Tomlin, Chad A Dickey, John Koren, Laura Blair, Haian Fu, Brian S J Blagg, Raquel L Lieberman
Gain-of-function mutations within the olfactomedin (OLF) domain of myocilin result in its toxic intracellular accumulation and hastens the onset of open-angle glaucoma. The absence of myocilin does not cause disease; therefore, strategies aimed at eliminating myocilin could lead to a successful glaucoma treatment. The endoplasmic reticulum Hsp90 paralog Grp94 accelerates OLF aggregation. Knockdown or pharmacological inhibition of Grp94 in cells facilitates clearance of mutant myocilin via a non-proteasomal pathway...
February 5, 2018: ACS Chemical Biology
Qi N Cui, Scott J Fudemberg, Arthur F Resende, Thuy-Anh Vu, Chen Zhou, Kamran Rahmatnejad, Lisa A Hark, Jonathan S Myers, L Jay Katz, Michael Waisbourd
PURPOSE: To compare the diagnostic assessment of glaucoma specialists with an automated structure-function correlation report combining visual field (VF) and spectral-domain optical coherence tomography (SD-OCT) imagining in subjects with glaucoma. METHODS: This prospective, cross-sectional study was conducted at Wills Eye Hospital, Philadelphia, PA, USA. Subjects with glaucoma received ophthalmic examination, VF testing, and SD-OCT imaging. An automated report was generated describing structure-function correlations between the two structural elements [retinal nerve fiber layer (RNFL) and Bruch's membrane opening-minimum rim width (MRW)] and VF sectors...
February 2, 2018: International Ophthalmology
Grace M Richter, Ingy Madi, Zhongdi Chu, Bruce Burkemper, Ryuna Chang, Arman Zaman, Beau Sylvester, Alena Reznik, Amir Kashani, Ruikang K Wang, Rohit Varma
PURPOSE: To quantify retinal microvasculature within the macular ganglion cell-inner plexiform layer (GCIPL) in primary open angle glaucoma (POAG) and normal eyes, determine association of vessel parameters with structural and functional measures, and report diagnostic accuracy of vessel parameters. METHODS: POAG and normal patients underwent 6▒mm×6▒mm macula scans (Angioplex optical coherence tomography angiography [OCTA]; Cirrus HD-OCT 5000); and Humphrey Field Analyzer II-i 24-2 visual field (VF) (Zeiss, Dublin, CA)...
February 1, 2018: Journal of Glaucoma
Faxiang Li, Daichao Xu, Yingli Wang, Zixuan Zhou, Jianping Liu, Shichen Hu, Yukang Gong, Junying Yuan, Lifeng Pan
OPTN (optineurin), a ubiquitin-binding scaffold protein, functions as an important macroautophagy/autophagy receptor in selective autophagy processes. Mutations in OPTN have been linked with human neurodegenerative diseases including ALS and glaucoma. However, the mechanistic basis underlying the recognition of ubiquitin by OPTN and its regulation by TBK1-mediated phosphorylation are still elusive. Here, we demonstrate that the UBAN domain of OPTN preferentially recognizes linear ubiquitin chain and forms an asymmetric 2:1 stoichiometry complex with the linear diubiquitin...
February 2, 2018: Autophagy
Donald C Hood, Carlos Gustavo De Moraes
The most common clinical paradigm (CCP) for diagnosing glaucoma includes a visual field (VF) with a 6° test grid (e.g., the 24-2 or 30-2 test pattern) and an optical coherence tomography (OCT) scan of the optic disc. Furthermore, these tests are assessed based upon quantitative metrics (e.g., the pattern standard deviation [PSD] of the VF and the global retinal nerve fiber thickness of the OCT disc scan). This CCP is facing three challenges. First, the macular region (i.e., ±8° from fixation) is affected early in the glaucomatous process, and the CCP can miss and/or underestimate the damage...
February 1, 2018: Investigative Ophthalmology & Visual Science
Maria A Mavrommatis, Zhichao Wu, Saskia I Naegele, Jason Nunez, Gustavo C de Moraes, Robert Ritch, Donald C Hood
Purpose: To examine the structure-function relationship in glaucoma between deep defects on visual fields (VF) and deep losses in the circumpapillary retinal nerve fiber layer (cpRNFL) on optical coherence tomography (OCT) circle scans. Methods: Thirty two glaucomatous eyes with deep VF defects, as defined by at least one test location worse than ≤ -15 dB on the 10-2 and/or 24-2 VF pattern deviation (PD) plots, were included from 87 eyes with "early" glaucoma (i...
February 1, 2018: Investigative Ophthalmology & Visual Science
P Enders, F Schaub, W Adler, M M Hermann, T S Dietlein, C Cursiefen, L M Heindl
PurposeTo compare Bruch's membrane opening (BMO)-based spectral domain optical coherence tomography (SD-OCT) and margin based confocal scanning laser tomography (CSLT) of the optic nerve head (ONH) to visual field function in large optic discs (macrodiscs) and to assess performance for glaucoma detection.MethodsIn a case-control, cross-sectional study, 125 eyes of 125 patients with disc size >2.45 mm2 , thereof 44 glaucoma and 11 ocular hypertension (OHT) patients and 70 healthy controls underwent SD-OCT and CSLT examination, visual field testing and clinical evaluation...
February 2018: Eye
Xiang-Ji Li, Lin Xie, Fu-Sheng Pan, Yong Wang, Hong Liu, Yu-Rong Tang, Cindy Ml Hutnik
Technological advances in glaucoma have challenged the traditional treatment paradigm. Historically incisional surgery has been used in cases of advanced disease and/or uncontrolled intraocular pressures resistant to medical or laser interventions. More recently, perhaps due to advancements in imaging, surgery has been suggested to be beneficial earlier in the treatment paradigm. Despite these trends, surgical manipulation of the tissues and unpredictability of wound healing continue to result in surgical failure...
2018: International Journal of Ophthalmology
Rebecca King, Felix L Struebing, Ying Li, Jiaxing Wang, Allison Ashley Koch, Jessica N Cooke Bailey, Puya Gharahkhani, Stuart MacGregor, R Rand Allingham, Michael A Hauser, Janey L Wiggs, Eldon E Geisert
Central corneal thickness (CCT) is one of the most heritable ocular traits and it is also a phenotypic risk factor for primary open angle glaucoma (POAG). The present study uses the BXD Recombinant Inbred (RI) strains to identify novel quantitative trait loci (QTLs) modulating CCT in the mouse with the potential of identifying a molecular link between CCT and risk of developing POAG. The BXD RI strain set was used to define mammalian genomic loci modulating CCT, with a total of 818 corneas measured from 61 BXD RI strains (between 60-100 days of age)...
January 2018: PLoS Genetics
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