{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T18:08:25Z","timestamp":1781114905259,"version":"3.54.1"},"reference-count":28,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Recensa Medical"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background\/Objective<\/jats:title>\n                    <jats:p>To evaluate the safety and effectiveness of a medical device providing cooling anesthesia to the eye as local anesthesia for intravitreal (IVT) injections.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Subjects\/Methods<\/jats:title>\n                    <jats:p>As a multicenter, open label, dose escalation clinical trial, subjects receiving at least 3 IVT injections in the study eye were recruited to participate. All patients received subconjunctival lidocaine as their anesthesia for previous IVT injections. Subjects receiving IVT injections were assigned (non-randomized) to four groups in which the cooling device was applied to the conjunctiva at the location of the intravitreal injection: Group 1: \u221210\u02daC for 20 seconds; Group 2: \u221215\u02daC for 10 seconds; Group 3: \u221215\u02daC for 15 seconds; and Group 4: \u221215\u02daC for 20 seconds. The primary outcome was pain during IVT injection assessed by a visual analog scale (0\u201310).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eighty subjects were enrolled at 2 sites. The mean number of prior IVT injections was 20.3 for Group 2 and 15.0 for Group 3. Pain was significantly less for the 10 second vs the 15 second application (2.2 vs 3.6, p\u2009=\u20090.0255). The mean pain score was lower for Group 2 (\u221215\u00b0C for 10 seconds) ranging a score of 1.0 to 2.9 across the study visits, compared with Group 3 (\u221215\u00b0C for 15 seconds) with a mean range of 3.2 to 5.2 across the study visits. Treatment order (visit) significantly decreased by 0.10 pain units per visit (p\u2009=\u20090.0002). Punctate epithelial erosions (PEE) were reported in 20 of 56 eyes (35.7%) in Group 2, none were reported in Group 3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Cooling anesthesia device reduced the severity of pain associated with IVT injection during the procedure, although mild and transient PEE may be associated with treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov identifier,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03956797\" xlink:type=\"simple\">NCT03956797<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                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