Worldwide Argus II implantation: recommendations to optimize patient outcomes

Abstract Background A position paper based on the collective experiences of Argus II Retinal Prosthesis System investigators to review strategies to optimize outcomes in patients with retinitis pigmentosa undergoing retinal prosthesis implantation. Methods Retinal surgeons, device programmers, and rehabilitation specialists from Europe, Canada, Middle East, and the United States were convened to the first international Argus II Investigator Meeting held in Ann Arbor, MI in March 2015. The recommendations from the collective experiences were collected. Factors associated with successful outcomes were determined. Results Factors leading to successful outcomes begin with appropriate patient selection, expectation counseling, and preoperative retinal assessment. Challenges to surgical implantation include presence of staphyloma and inadequate Tenon’s capsule or conjunctiva. Modified surgical technique may reduce risks of complications such as hypotony and conjunctival erosion. Rehabilitation efforts and correlation with validated outcome measures following implantation are critical. Conclusions Bringing together Argus II investigators allowed the identification of strategies to optimize patient outcomes. Establishing an on-line collaborative network will foster coordinated research efforts to advance outcome assessment and rehabilitation strategies.http://deepblue.lib.umich.edu/bitstream/2027.42/134581/1/12886_2016_Article_225.pd

Spatial Distribution of the Pathways of Cholesterol Homeostasis in Human Retina

The retina is a light-sensitive tissue lining the inner surface of the eye and one of the few human organs whose cholesterol maintenance is still poorly understood. Challenges in studies of the retina include its complex multicellular and multilayered structure; unique cell types and functions; and specific physico-chemical environment.We isolated specimens of the neural retina (NR) and underlying retinal pigment epithelium (RPE)/choroid from six deceased human donors and evaluated them for expression of genes and proteins representing the major pathways of cholesterol input, output and regulation. Eighty-four genes were studied by PCR array, 16 genes were assessed by quantitative real time PCR, and 13 proteins were characterized by immunohistochemistry. Cholesterol distribution among different retinal layers was analyzed as well by histochemical staining with filipin. Our major findings pertain to two adjacent retinal layers: the photoreceptor outer segments of NR and the RPE. We demonstrate that in the photoreceptor outer segments, cholesterol biosynthesis, catabolism and regulation via LXR and SREBP are weak or absent and cholesterol content is the lowest of all retinal layers. Cholesterol maintenance in the RPE is different, yet the gene expression also does not appear to be regulated by the SREBPs and varies significantly among different individuals.This comprehensive investigation provides important insights into the relationship and spatial distribution of different pathways of cholesterol input, output and regulation in the NR-RPE region. The data obtained are important for deciphering the putative link between cholesterol and age-related macular degeneration, a major cause of irreversible vision loss in the elderly

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Management of Endophthalmitis While Preserving the Uninvolved Crystalline Lens

Twelve phakic eyes (11 patients) with culture-positive endophthalmitis were treated without removal of the uninvolved crystalline lens. Eight eyes were treated by pars plana vitrectomy and intraocular injection of antibiotics. Four eyes were treated with intraocular antibiotic injection alone. The clinical infection was successfully eradicated in all patients, including one patient treated with reinjection of antibiotics. During follow-up after successful treatment, eight eyes had progression of a preexisting lens opacification, two eyes had stable lens opacification, and two eyes maintained clear lenses. Six of 12 eyes achieved 20/80 or better visual acuity with an average follow-up time of 13 months. Six of eight eyes treated with pars plana vitrectomy and intraocular antibiotic injection achieved this level of visual acuity in contrast to none of four eyes treated with only intraocular antibiotic injection. These results indicated that endophthalmitis in phakic eyes can be successfully treated while preserving a clear, uninvolved crystalline lens by the use of pars plana vitrectomy and intraocular administration of appropriate antibiotics

Implanting the Argus(R) II Retinal Prosthesis System in a patient with dry AMD

The following is an edited movie of a previously live-streamed surgical video featuring renowned Consultant Ophthalmologist and Vitreoretinal surgeon Professor Paulo E. Stanga, MD, implanting the Argus® II Retinal Prosthesis System in a patient with dry Age Related Macular Degeneration (AMD). To date, June 2016, over 180 Argus® II devices have been implanted worldwide, and are used routinely in advanced Retinitis Pigmentosa patients. This video, recorded at Manchester Royal Eye Hospital, UK, in April 2016, shows Prof. Stanga performing the procedure on a dry AMD patient as part of an investigational study of the Argus® II system in dry AMD (clinicaltrials.gov #NCT02227498 (https://urldefense.proofpoint.com/v2/url?u=http-3A__clinicaltrials.gov_&d=BQMFaQ&c=bMxC-A1upgdsx4J2OmDkk2Eep4PyO1BA6pjHrrW-ii0&r=7eyJJ8AWeg0LAg2jsrUotjxJxMXx-Ph-SVfpXeotLmg&m=gd8KSZ2q-0EknjXm4AycD2Fus7vBLej2uxBB1IdPpXo&s=WwGP-DH6EXzK_4VV6UBiNh0OQf6B571LE559LnerqVQ&e=), being conducted under an approval from MHRA and the Ethics Committee at Manchester Royal Eye Hospital). The trial patients are the first in history to combine artificial vision provided by the Argus® II with their remaining natural peripheral sight. The surgery is commentated by Dr. Suber Huang, of University Hospitals Case Medical Center, Cleveland, Ohio and Francesco Merlini of Second Sight Medical Products Inc

Retinal Pericytes Inhibit Activated T Cell Proliferation

The role of retinal pericytes in diabetic retinopathy was not clear. This study demonstrated a novel role of retinal pericytes, suggesting that their immunoregulatory activity could contribute to the pathogenesis of diabetic retinopathy

Cholestenoic Acid Is an Important Elimination Product of Cholesterol in the Retina: Comparison of Retinal Cholesterol Metabolism with That in the Brain

This is the first comprehensive investigation of oxysterol levels in the human retina and retinal pigment epithelium that establishes the major mechanism for enzymatic cholesterol elimination from the posterior part of the eye