EyeWorld Weekly Update, March 31, 2017

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March 31, 2017
Volume 22 , Number 13

NIH-funded study to explore development of ophthalmic probe for Alzheimer's disease

A $1.8 million Phase 2 SBIR grant award from the National Institute on Aging of the National Institutes of Health (NIH) will help researchers at Amydis Diagnostics (San Diego) develop an ophthalmic diagnostic probe for Alzheimer's disease. The buildup of amyloid-beta plaques in the brain are a hallmark sign of Alzheimer's disease, and many researchers are interested in early detection of this plaque, according to a company press release. Plaque buildup is thought to occur before clinical signs of cognitive decline. Although detection of amyloid-beta is currently done through brain imaging techniques or biochemical assays, Amydis plans to develop a noninvasive diagnostic method based on ophthalmologic procedures. The company previously received a Phase 1 grant from the NIH.

Company receives $1 million in NEI funding for treatment geared toward retinal disease

The National Eye Institute (NEI) has awarded approximately $1 million for ONL Therapeutics (Ann Arbor, Michigan) to continue the advancement of ONL1204, a small molecule Fas inhibitor designed to protect retinal cells, including photoreceptors, from cell death occurring in various retinal diseases and conditions. "Death of these retinal cells, both direct and via inflammatory signaling, is the root cause of vision loss and the leading cause of blindness," according to a company press release. The company will use the funding to support remaining preclinical activities required for submission of an investigational New Drug Application to the U.S. Food and Drug Administration (FDA). Use of ONL1204 is being initially developed to treat retinal detachment; the FDA has granted the compound an orphan drug designation. However, preclinical data and other research indicate the compound may be used in other ocular diseases, including age-related macular degeneration, the company reported.

Topical ocular formulation using cannabinoids for glaucoma under development

A topical ocular formulation of tetrahydrocannabinol-valine-hemisuccinate (THCVHS), a prodrug of THC, will be further developed in an agreement between Nanomerics (London) and NEMUS Bioscience (Costa Mesa, California). Tetrahydrocannabinol-valine-hemisuccinate is an active component of the drug candidate NB1111 (NEMUS Bioscience), which is under development for glaucoma treatment. The companies plan to conduct initial studies to assess the preparation of clinical-grade eye drops using a patented approach called Molecular Envelope Technology, which is developed by Nanomerics. "Historically, it has been challenging to formulate hydrophobic, or fat-soluble, cannabinoid molecules for efficient and predictable entry into the body, especially the eye," said Brian Murphy, MD, MBA, Nemus CEO and chief medical officer, in a press release. The collaboration between the companies is an important step before human studies begin, he said.

NEI study pinpoints molecular cause of posterior capsule opacification

A molecular cause for posterior capsule opacification (PCO) has been possibly identified by Bruce A. Bowell, and fellow investigators, in a recent study. It is already known that PCO is caused by residual lens cells that transdifferentiate into myofibroblasts or that mature into lens fiber cells. Transforming growth factor (TGF)-beta has been implicated in lens cell fibrosis, according to investigators, but they showed for the first time that TGF-beta can induce purified primary lens epithelial cells within the same culture to undergo differentiation into lens fiber cells or myofibroblasts. An analysis of markers confirmed that the two cell phenotypes were mutually exclusive. "Blocking the p38 kinase pathway, either with direct inhibitors of the p38 MAP kinase or with a small molecule therapeutic that also inhibits the activation of p38, prevented TGF-beta from inducing epithelial-to-myofibroblast transition and cell migration but did not prevent fiber cell differentiation," they wrote. "Rapamycin had the converse effect, linking MTOR signaling to induction of fiber cell differentiation by TGF-beta." The findings provide potential therapeutic strategies for PCO and help extend the TGF-beta paradox, in which the later can induce two disparate cell fates to a new epithelial disease fate, they concluded. The study was funded by the NEI. The findings can be found in Molecular Biology of the Cell.

RESEARCH BRIEFS

  • Residents in today's ophthalmology residency training programs often begin surgical training with phacoemulsification rather than extracapsular cataract extraction, and residents perform a higher number of phacoemulsification cases than is required by the American Council of Graduate Medical Education, according to Mona Lotfipour, MS, and co-investigators. Their focus was to evaluate trends in cataract surgery training curricula and factors that affect timing of resident participation as a primary surgeon. Forty-four percent of the 116 ophthalmology residency program directors around the U.S. completed the survey sent by investigators. At 91% of programs, clear corneal phacoemulsification was the first technique taught to trainees. Seventy-one percent of program directors responded that their program had a cataract surgery curriculum geared toward gradually transitioning residents to the operating room. Many residents begin to perform phacoemulsification as early as the first or second year of residency. However, 29% of respondents reported that they did not have a formal cataract surgery training program. The study is published in the Journal of Cataract & Refractive Surgery.
  • Use of the Sjö test (Bausch + Lomb, Bridgewater, New Jersey), a commercially available diagnostic panel that tests for traditional Sjögren's syndrome (SS) biomarkers and more recently identified early biomarkers could help rheumatologists, ophthalmologists, and dentists screen for SS, according to Kenneth A. Beckman, MD, and co-investigators. "Data suggest that these novel biomarkers may appear earlier in the course of disease and are often identified in cases that test negative to traditional biomarkers," the investigators wrote. Biomarkers for SS used traditionally, such as anti-Sjögren's syndrome-related antigen A (SS-A/Ro), anti-Sjögren's syndrome-related antigen B (SS-B/La), antinuclear antibody (ANA) titers, and rheumatoid factor (RF), have low specificity for SS and are not always positive, the investigators reported. The newer biomarkers include autoantibodies to proteins specific to the salivary and lacrimal glands (SP-1 [salivary gland protein-1]), PSP (parotid secretory protein), and CA-6 (carbonic anhydrase VI)]. Ophthalmologists and dentists are often the first point of diagnosis of SS because of the common symptoms of dry eye and dry mouth. The study is published in Advanced Therapeutics.
  • The use of an artificial intelligence-based grading system could one day be used to review fundus photographs from patients with diabetes and to help identify which patients should receive further evaluation for possible diabetic retinopathy, according to Rishab Gargeva, and co-investigators. A data-driven deep learning algorithm was developed that processed color fundus images and categorized them as healthy or having diabetic retinopathy. More than 75,000 publicly available fundus images were used to test the artificial intelligence model. A panel of retinal specialists and the MESSIDOR 2 and E-Ophtha databases were also used for external validation. "Our model achieved a 0.97 [area under the receiver operating characteristic curve] with a 94% and 98% sensitivity and specificity, respectively, on 5-fold cross-validation using our local data set. Testing against the independent MESSIDOR 2 and E-Ophtha databases achieved a 0.94 and 0.95 AUC score, respectively," the investigators wrote. The study appears in Ophthalmology.

PRODUCT NEWS

  • The FDA has approved the Icare HOME tonometer (Icare USA, Raleigh, North Carolina) for the monitoring of IOP. The device previously received a CE Mark in 2014.
  • The FDA has approved the AcrySof IQ ReSTOR +2.5 multifocal IOL with ACTIVEFOCUS optical design (Alcon, Fort Worth, Texas). The IOL designed to address both astigmatism and presbyopia.

This issue of EyeWorld Weekly Update was edited by Amy Goldenberg and Vanessa Caceres.

EyeWorld Weekly Update (ISSN 1089-0319), a digital publication of the American Society of Cataract and Refractive Surgery and the American Society of Ophthalmic Administrators, is published every Friday, distributed by email, and posted live on Friday.

Medical Editors: Eric Donnenfeld, MD, chief medical editor; Rosa Braga-Mele, MD, cataract editor; Clara Chan, MD, cornea editor; Nathan Radcliffe, MD, glaucoma editor; and Vance Thompson, MD, refractive editor.

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