A central tenet in understanding the biological effects of ionizing radiation has been that the initially affected cells were directly damaged by the radiation. By contrast, evidence has emerged concerning ''bystander'' responses involving damage to nearby cells that were not themselves directly traversed by the radiation. These long-range effects are of interest both mechanistically and for assessing risks from low-dose exposures, where only a small proportion of cells are directly hit. Bystander effects have been observed largely by using single-cell in vitro systems that do not have realistic multicellular morphology; no studies have as yet been reported in three-dimensional, normal human tissue. Given that the bystander phenomenon must involve cell-to-cell interactions, the relevance of such single-cell in vitro studies is questionable, and thus the significance of bystander responses for human health has remained unclear. Here, we describe bystander responses in a three-dimensional, normal human-tissue system. Endpoints were induction of micronucleated and apoptotic cells. A charged-particle microbeam was used, allowing irradiation of cells in defined locations in the tissue yet guaranteeing that no cells located more than a few micrometers away receive any radiation exposure. Unirradiated cells up to 1 mm distant from irradiated cells showed a significant enhancement in effect over background, with an average increase in effect of 1.7-fold for micronuclei and 2.8-fold for apoptosis. The surprisingly long range of bystander signals in human tissue suggests that bystander responses may be important in extrapolating radiation risk estimates from epidemiologically accessible doses down to very low doses where nonhit bystander cells will predominate.bystander ͉ normal human tissue ͉ radiological risk

Telemedicine is the provision of healthcare-related services from a distance and is poised to move healthcare from the physician's office back into the patient's home. The field of ophthalmology is often at the forefront of technological advances in medicine including telemedicine and the use of artificial intelligence. Multiple studies have demonstrated the reliability of tele-ophthalmology for use in screening and diagnostics and have demonstrated benefits to patients, physicians, as well as payors. There remain obstacles to widespread implementation, but recent legislation and regulation passed due to the devastating COVID-19 pandemic have helped to reduce some of these barriers. This review describes the current status of tele-ophthalmology in the United States including benefits, hurdles, current programs, technology, and developments in artificial intelligence. With ongoing advances patients may benefit from improved detection and earlier treatment of eye diseases, resulting in better care and improved visual outcomes.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.