Volume 20, Number 37Monday, August 31, 2020AUGUST IS CHILDREN’S EYE HEALTH AND SAFETY MONTH
In this issue: (click heading to view article)
Progression of Photoreceptor Degeneration in GA Secondary to AMDResearchers wrote that sensitive outcome measures for disease progression are needed for treatment trials in geographic atrophy secondary to age-related macular degeneration. Toward that end, they quantified photoreceptor degeneration outside regions of GA in eyes with nonexudative AMD, evaluated its association with future GA progression and characterized its spatio-temporal progression. In the monocenter cohort study (“Directional Spread in Geographic Atrophy”) and analysis of data from a normative data study at a tertiary referral center, 158 eyes of 89 individuals (51 women and 38 men) with a mean (SD) age of 77.7 (7.1) years (median area of GA of 8.87 mm2 [IQR, 4.09 to 15.60]; median follow-up of 1.1 years [IQR, 0.52 to 1.7 years]) were included, as well as 93 normal eyes from 93 participants. Researchers segmented longitudinal spectral-domain optical coherence tomography volume scans (121 B-scans across 30 × 25 degrees) with a deep learning pipeline and standardized them in a pointwise manner with age-adjusted normal data (z scores). They quantified the outer nuclear layer (ONL), photoreceptor inner segment (IS) and outer segment (OS) thickness along evenly spaced contour lines surrounding GA lesions. In addition, they applied linear mixed models to assess the association between photoreceptor-related imaging features and GA progression rates, and characterized the pattern of photoreceptor degeneration over time. The main outcome measure was association of ONL thinning with follow-up time (after adjusting for age, retinal topography [z score] and distance to the GA boundary). Here are some of the findings:
Researchers found that distinct and progressive alterations of photoreceptor laminae (exceeding GA spatially) were detectable and quantifiable. The degree of photoreceptor degeneration outside of regions of retinal pigment epithelium atrophy varied markedly between eyes and was associated with future GA progression. Researchers concluded that macula-wide photoreceptor laminae thinning represents a potential candidate endpoint for monitoring treatment effects, beyond GA lesion size progression. SOURCE: Pfau M, von der Emde L, de Sisternes L, et al. Progression of photoreceptor degeneration in geographic atrophy secondary to age-related macular degeneration. JAMA Ophthalmol. 2020; Aug. 13. [Epub ahead of print].IOP Agreement Between Icare ic200 and GAT in Adult Eyes with Normal CorneasInvestigators studied the agreement between the Icare ic200 and the Goldmann Applanation tonometer in the measurement of intraocular pressure in adult eyes, as part of a non-interventional, cross-sectional study. A total of 156 eyes of 156 individuals with clear corneas were included. IOP measurements with Icare ic200 (ICare Finland Oy) were obtained by one observer, followed by GAT readings by a second masked observer. The central corneal thickness and biometry of all subjects were recorded. Main outcome measures included agreement between the Icare ic200 and GAT, measured using the Bland Altman plot. The mean age ± standard deviation of subjects was 55.3 ±13.7 years. Investigators reported that the Icare ic200 overestimated IOP, although the mean disagreement between the IOP measurement by GAT and Icare ic200 was <2 mmHg at all ranges of IOP. (The overestimation increased as the baseline IOP increased.) Other findings included:
The investigators added that the narrow limits of agreement between the tonometers for IOPs <21 mmHg make the Icare ic200 device a useful alternative to GAT in this pressure range. SOURCE: Badakere SV, Chary R, Choudhari NS, et al. Agreement of intraocular pressure measurement of Icare ic200 with Goldmann Applanation Tonometer in adult eyes with normal cornea. Ophthalmol Glaucoma 2020; Aug 12. [Epub ahead of print]. A Clinical Metabolite of AZT Inhibits Experimental CNV & RPE DegenerationScientists wrote that azidothymidine (AZT), a nucleoside reverse transcriptase inhibitor, possesses anti-inflammatory and anti-angiogenic activity independent of its ability to inhibit reverse transcriptase. The aim of this study was to evaluate the efficacy of 5′-glucuronyl azidothymidine (GAZT)—an antiretrovirally inert hepatic clinical metabolite of AZT—in mouse models of retinal pigment epithelium degeneration (a hallmark feature of dry age-related macular degeneration) and choroidal neovascularization (a hallmark feature of wet AMD). Scientists induced RPE degeneration in wild-type (WT) C57BL/6J mice by subretinal injection of Alu RNA. They assessed RPE degeneration by fundus photography and confocal microscopy of zonula occludens-1-stained RPE flat mounts. They induced CNV by laser injury in WT mice, and measured CNV volume by confocal microscopy. Scientists delivered AZT and GAZT by intravitreous injections. They monitored inflammasome activation by western blotting for caspase-1 and by ELISA for IL-1β in Alu RNA-treated bone marrow-derived macrophages (BMDMs). Scientists reported that GAZT inhibited Alu RNA-induced RPE degeneration and laser-induced CNV. They wrote further that GAZT also reduced Alu RNA-induced caspase-1 activation and IL-1β release in BMDMs. Scientists concluded that GAZT possesses dual anti-inflammatory and anti-angiogenic properties, and could be a viable treatment option for both forms of AMD. SOURCE: Narendran S, Pereira F, Yerramothu P, et al. A clinical metabolite of azidothymidine inhibits experimental choroidal neovascularization and retinal pigmented epithelium degeneration. Invest Ophthalmol Vis Sci. 2020;61(10):4. Ex Vivo Safety & Efficacy of Using Paired Peripheral Incisions in DMEK Grafts to Facilitate UnscrollingResearchers evaluated the ex vivo safety and efficacy of using paired peripheral incisions to achieve a triple scroll conformation that facilitates unscrolling in Descemet’s membrane endothelial keratoplasty. They evaluated the safety of adding paired peripheral incisions to DMEK grafts by assessing endothelial cell loss (ECL) and risk of tearing. They measured ECL using calcein-AM staining after incisions, and evaluated risk of tearing by comparing incision lengths before and after simulated DMEK surgery using cadaveric eyes. Efficacy was evaluated by comparing the scrolling pattern and the width of grafts with different incision lengths (0.0, 0.5 and 1 mm). Researchers also evaluated surgical unscrolling times in simulated DMEK surgery performed by a novice DMEK surgeon, to determine whether the incisions facilitated unscrolling in DMEK surgery. Findings included:
Researchers concluded that paired peripheral incisions were safe and effective for inducing a triple scroll in DMEK grafts if the donor age was ≤65 years. They wrote further that adding incisions may facilitate unscrolling for inexperienced DMEK surgeons. Source: de la Presa M, Bedard P, Justin JJ, et al. Ex vivo safety and efficacy of using paired peripheral incisions in Descemet membrane endothelial keratoplasty grafts to facilitate unscrolling. Cornea 2020; Aug 4. [Epub ahead of print].BRIEFLY Kubota Gets Orphan Products Clinical Trial Grant for Emixustat, Completes Study Using Wearable Myopia Control Device Gyroscope Gets FDA Nod for Orbit Subretinal Delivery System, Initiates Phase II Program Evaluating Gene Therapy for Dry AMD 4DMT’s First Patient Dosed in Phase I/II Trial of 4D-125 4D Molecular Therapeutics announced the first patient was dosed in a Phase I/II clinical trial of 4D-125 for x-linked retinitis pigmentosa. 4D-125 is an AAV gene therapy with a proprietary vector designed to deliver a functional copy of the RPGR gene to photoreceptors in the retina. The open-label, dose-exploration and -expansion study is expected to enroll approximately 18 male patients with x-linked retinitis pigmentosa, and assess the preliminary safety, tolerability and biological activity of a single intravitreal injection of 4D-125, in addition to the effect of 4D-125 on visual function and retinal degeneration. Read more.
AGTC Announces Publication of Preclinical Data that Support Clinical Development of Gene Therapy Program Applied Genetic Technologies Corporation announced that preclinical data validating the transgene (hRPGRco) being evaluated in the company’s ongoing Phase I/II clinical trial in individuals with x-linked retinitis pigmentosa were published in the July 15, print issue of Human Gene Therapy. The studies, which evaluated the safety and efficacy of hRPGRco and another XLRP transgene in a canine model of XLRP, demonstrated higher RPGR gene expression than the other transgene at all dose levels evaluated. Following subretinal administration using AGTC’s proprietary AAV2tYF vector, each of the XLRP transgenes corrected rod-cone opsin mislocalization, but the hRPGRco transgene demonstrated a broader therapeutic index. Read more. Foundation Fighting Blindness Commits $6.5 Million for Research Grants The Foundation Fighting Blindness, an organization committed to finding treatments and cures for blinding retinal diseases, announced $6.5 million in funding for 15 new grants, bringing its research portfolio to a total of 84 grants. The submissions were rigorously evaluated and scored by the Foundation’s Scientific Advisory Board. Read summaries of newly funded grants. Review of Ophthalmology® Online is published by the Review Group, a Division of Jobson Medical Information LLC (JMI), 11 Campus Boulevard, Newtown Square, PA 19073. |