Eyeworld

EW IN OTHER NEWS 84 November 2018 New finding in pediatric retinoblastoma pathogenesis Research published in the Proceed- ings of the National Academy of Sci- ences identifies the stage in human retina development at which reti- noblastoma could begin to develop. This finding could ultimately lead to better prevention and intervention efforts. The research from investiga- tors at Children's Hospital Los Ange- les found that when cone precursor cells enter the cell cycle, due to inactivation of RB1 tumor suppres- sor gene and loss of RB protein, they could begin dividing and growing out of control. "Given the current state of genomic analyses, we can look forward to a time when we will be able to test for mutations in RB1, as well as other disease-associated genes, and provide disease-prevent- ing interventions," David Cobrinik, MD, PhD, said in a press release. Reference Singh H, et al. Development stage-specific proliferation and retinoblastoma genesis in RB-deficient human but not mouse cone pre- cursors. PNAS. 2018. Epub ahead of press. Possible alternative to anti-VEGF therapy While anti-VEGF injections have become a mainstay of therapy for several retinal diseases, new research suggests that an alternative mol- ecule—atypical protein kinase C (aPKC)—could be targeted to block inflammation and protect vision in patients with these potentially blinding diseases. "Our data re- veal aPKC as an interesting target both for vascular permeability and inflammation and developing aPKC inhibitors may provide a new therapeutic option for blinding eye diseases," lead investigator David Antonetti, PhD, said in a press release. "Our research may help patients with diabetic retinopathy, the leading cause of blindness in working age adults in the United States, and may also lead to new treatments for uveitis, a spectrum of diseases that leads to inflammation of the eye, as well as for retinal vein and artery occlusions." EW Reference Lin CM et al. Inhibition of atypical protein kinase C reduces inflammation-induced retinal vascular permeability. Am J Pathol. 2018;188:2392–2405. light in the procedure was pulsed, increasing oxygen levels and thus the crosslinking effect; and prior to light exposure, the riboflavin was rinsed from the surface of the eye. "Although it is not clear what role each of these protocol components played in producing the clinical out- comes we observed, the effect is un- deniable," Stulting et al. wrote. No eyes showed progression and there was no loss of the crosslinking's strengthening effect up to 2 years postop. Uncorrected distance visual acuity and corrected distance visual acuity improvement was compara- ble to epi-off crosslinking. Pain from the procedure, study authors report- ed, lasted less than 24 hours postop, and preop visual acuity levels were regained 1 to 2 days postop. Reference Stulting RD, et al. Corneal crosslinking without epithelial removal. J Cataract Refract Surg. 2018. Epub ahead of print. Therapy for genetic "day blindness" moves to human clinical trials A herd sheep suffering from "day blindness" or achromatopsia, a disorder caused by a missing gene, showed long-term daytime visual recovery after gene therapy, which led to recent approval from the U.S. Food and Drug Administration for this research to move to human trials for patients suffering from a similar genetic condition. The gene therapy involves a single treatment with the functional CNGA3 gene in a viral vector. The nine sheep from the initial study that were available for long-term follow-up showed sig- nificant cone function up to 6 years after the gene therapy injection. "Less than 10 years after we first discovered the vision-impaired herd, we began human clinical trials. This marks a wonderful feat in ovine-to- human and research-to-cure efforts," lead author Ron Ofri, PhD, said in a press release. Reference Ofri R, et al. Six years and counting: resto- ration of photopic retinal function and visual behavior following gene augmentation therapy in a sheep model of CNGA3 achromatopsia. Hum Gene Ther. 2018. Epub ahead of print. AI brings "specialty-level diagnostics to a primary care setting" The U.S. Food and Drug Adminis- tration approved IDx-DR as the first artificial intelligence (AI) device used to detect diabetic retinopathy in April. More recently, data from its pivotal trial published in Nature Digital Medicine revealed the tech- nology's ability to diagnose diabetic retinopathy with such accuracy that it brings "specialty-level diagnos- tics to a primary care setting, with the potential to increase access and lower cost," Michael Abramoff, MD, PhD, said in a press release. The device showed a sensitivity of 87.2%, specificity of 90.7%, and an imageability rate of 96.1%, accord- ing to the trial. Reference Abramoff MD, et al. Pivotal trial of an autonomous AI-based diagnostic system for detection of diabetic retinopathy in primary care offices. Nature Digital Medicine. 2018. Epub ahead of print. Safety, efficacy, and long- term stability seen in epi- on crosslinking protocol A prospective observational study of 512 eyes of 308 patients with kerato- conus or forme fruste keratoconus and 80 eyes of 55 patients with post- LASIK ectasia were treated with an epithelium-on crosslinking protocol, deviating from the standard Dres- den, epithelium-off protocol. The epi-on technique involved confirma- tion of riboflavin concentration of at least 15 μg/g of stromal tissue; UV Possible new method for pseudophakic bullous keratopathy prevention Corneal endothelial cell loss after phacoemulsification could be reduced with a prophylactic rho-ki- nase (ROCK) inhibitor, according to research published by Achiron et al. in the Journal of Cataract and Refractive Surgery. At this point, the research with a prophylactic ROCK inhibitor for this purpose was performed ex vivo in human donor corneolimbal rings. Fragments of these rings were stored in a com- mercial media for 1 week, some with 10 mM ROCK inhibitor, and were then exposed to phacoemulsifica- tion. Those that were exposed to a ROCK inhibitor showed a 37.06% reduction in their early corneal endothelial cell apoptosis rate and a 45.27% reduction in their late apop- tosis rate. With these early findings, researchers think a prophylactic ROCK inhibitor could limit or slow endothelial cell loss, which could be especially useful in at-risk eyes and "might be a promising new method for preventing pseudophakic bullous keratopathy," Achiron et al. wrote. The researchers are planning further studies to evaluate prophylactic ROCK inhibitor use to simulate that of an eye drop vs. continuous expo- sure as in this study, as well as other refinements to their study design. Reference Achiron A, et al. Prophylactic exposure of human corneal endothelial cells to Rho-as- sociated kinase inhibitor reduced apoptosis rate after phacoemulsification: ex vivo study. J Cataract Refract Surg. 2018;44:1261–1266. News in brief

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