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Induced Pluripotent Stem Cells: A Research Tool and a Potential Therapy for RPE-Associated Blinding Eye Diseases
Published in Deepak A. Lamba, Patient-Specific Stem Cells, 2017
Ruchi Sharma, Balendu Shekhar Jha, Kapil Bharti
AMD is the leading cause of irreversible blindness in developed countries. More than nine million individuals are affected with this disease in the Unites States (Rein et al., 2009). AMD is a complex disease that has been linked to a number of genetic loci and to different signaling and metabolic pathways, suggesting the possibility of an integration of multiple diseases into one clinical phenotype (Swaroop et al., 2009; van Lookeren Campagne et al., 2014). It is thought that AMD disease processes originate in the RPE–choroidal complex, and they severely compromise RPE health and functions (Ambati and Fowler, 2012). The disease has two main subtypes based on clinical presentation: (a) “dry” AMD is characterized by the accumulation of proteinaceous deposits called drusen underneath the RPE. The advanced stage of dry AMD is called geographic atrophy (GA), when RPE cells die off in the macular region of the eye leading to photoreceptor cell death and vision loss; (b) “wet” AMD or neovascular AMD is also an advanced disease stage when choroidal blood vessels start to abnormally proliferate, penetrate through the RPE blood–retina barrier, and leak fluid or blood in the subretinal space leading to vision loss (Swaroop et al., 2009; Ambati and Fowler, 2012). Although AMD is clinically well characterized, little is presently known about the molecular mechanisms that are responsible for its initiation (Zarbin and Rosenfeld, 2010). Several major roadblocks have precluded the study of disease initiation: (a) lack of any detectable clinical symptoms in patients until well past the middle age; (b) native RPE tissue supply from AMD cadavers is limited and is often disrupted and damaged by the end stage disease; (c) genetic complexity and aspects of disease pathology are not fully represented in animal models. iPSCs allow the possibility of addressing all these roadblocks. RPE derived from AMD patient iPSCs can be potentially used to discover disease-initiating events; iPSC-derived RPE are potentially available as an unlimited supply of fresh human material, and iPSCs derived from patients with different AMD risk alleles allow the possibility of linking patients’ genetics with cellular endophenotypes of disease. Thus, iPSC technology is ideally suited to address the challenges of discovering potential drugs for AMD.
Swept-source optical coherence tomography imaging of the retinochoroid and beyond
Published in Expert Review of Medical Devices, 2020
Jayesh Vira, Alessandro Marchese, Rohan Bir Singh, Aniruddha Agarwal
de Oliveira Dias et al. studied the natural history of subclinical neovascularization in non-exudative AMD in 160 eyes of which 110 eyes were diagnosed with intermediate AMD and 50 eyes with geographic atrophy. Kaplan–Meier cumulative estimates of exudation at 1 year were evaluated. The prevalence of subclinical neovascularization at the time of initial imaging was 14.4% (23 eyes). Thirteen of the 134 eyes with follow-up showed exudation and conversion to neovascular AMD on subsequent visits. By 12 months, the Kaplan–Meier cumulative incidence of exudation for all 134 eyes was 6.8%. For eyes with subclinical CNV at the time of the initial SS-OCTA, the incidence was 21.1%, and for eyes without subclinical CNV, the incidence was 3.6%. There was no difference in the cumulative incidence of exudation from preexisting MNV in eyes with intermediate AMD or geographic atrophy (P = 0.847, log-rank test) [16]. This study concludes that SS-OCTA is an invaluable tool in identifying and following-up patients with intermediate AMD, as well as geographic atrophy.
Optical coherence tomography angiography (OCTA) flow speed mapping technology for retinal diseases
Published in Expert Review of Medical Devices, 2018
Malvika Arya, Ramy Rashad, Osama Sorour, Eric M. Moult, James G. Fujimoto, Nadia K. Waheed
Optical coherence tomography angiography (OCTA) is a noninvasive imaging technique that allows for depth-resolved, high-resolution imaging of retinal and choroidal vasculature. Qualitative and quantitative analysis using OCTA has been essential in further understanding the pathogenesis and progression of various vascular pathologies, such as diabetic retinopathy.A limitation of OCTA is that it offers an image depicting either the presence or absence of flow, without information about flow velocities.Variable interscan time analysis (VISTA) overcomes the grayscale limitation of OCTA and provides a color-coded map of relative retinal blood flow speeds. VISTA has been used to further analyze retinal vascular diseases, such as age-related macular degeneration, including choroidal neovascularization and geographic atrophy, diabetic retinopathy, and aneurysmal type 1 neovascularization.Further development of VISTA and its flow speed mapping capabilities may allow OCTA to become an essential tool for screening purposes.
The effect of visually significant dermatochalasis and blepharoptosis on driving safety
Published in Traffic Injury Prevention, 2021
Suzanne W. van Landingham, Katherine M. Lucarelli, Kyle McDaniel, Cat N. Burkat, Mark J. Lucarelli
Exclusion criteria included lack of Wisconsin state driving record or licensure, unilateral surgery, age less than 18, and visual acuity that failed to meet the criteria for unrestricted licensure in the State of Wisconsin (worse than 20/40 in either eye). Patients with ophthalmic comorbidities of glaucoma (other than early or mild), geographic atrophy, exudative age-related macular degeneration, or proliferative diabetic retinopathy were also excluded. While data regarding the impact of these diseases on driving is mixed, they are relatively common and can cause visual deficits that are not captured by visual acuity (such as visual field or contrast sensitivity defects) and that may influence driving (A1). (van Landingham et al. 2012, 2013; Sengupta et al. 2014)