{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T11:00:25Z","timestamp":1785236425166,"version":"3.55.0"},"reference-count":25,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To examine the safety of intravitreally applied epidermal growth factor (EGF) receptor antibody panitumumab combined with intravitreally injected vascular endothelial growth factor (VEGF) antibody ranibizumab in rabbits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The experimental study included 8 male rabbits (age: 2\u22123 months; weight: 2.5\u20132.6 kg). The right eyes received three intravitreal injections of panitumumab (1 mg in 0.10 mL) combined with intravitreal injections of ranibizumab (0.5 mg in 0.05 mL) in intervals of 4 weeks, while the left eyes received three double intravitreal injections of Ringer\u00b4s solution (0.10 mL and 0.05mL). At baseline, at the time points of the re-injections, and at 2 weeks and at 6 weeks after the last injection, the animals were examined by fundus photography and optical coherence tomography (OCT). At study end at 2 weeks after the last injection for 4 animals (total study duration: 10 weeks) or at 6 weeks after the last injection for the remaining 4 rabbits (total study duration: 14 weeks), the animals were sacrificed and the eyes were histomorphometrically examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The right eyes (study eyes) and left eyes (control eyes) did not differ significantly in cell count of the retinal ganglion cell layer (8.5\u2009\u00b1\u20098.3 cells per 150\u00b5m versus 4.5\u2009\u00b1\u20093.3 cells;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.04), inner nuclear layer (33.1\u2009\u00b1\u200914.0 cells versus 49.0\u2009\u00b1\u200922.3 cells;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.04) and outer nuclear layer (133.7\u2009\u00b1\u200950.0 cells versus 171.3\u2009\u00b1\u200975.3 cells;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.07) nor in mean thickness of the ganglion cell layer (31.8\u2009\u00b1\u200934.4\u00b5m versus 24.3\u2009\u00b1\u200915.2\u00b5m;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.15), inner plexiform layer (32.4\u2009\u00b1\u200948.2\u00b5m versus 25.6\u2009\u00b1\u200911.2\u00b5m;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.22), inner nuclear layer (26.6\u2009\u00b1\u200914.0\u00b5m versus 26.7\u2009\u00b1\u200910.2\u00b5m;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.43), outer plexiform layer (6.6\u2009\u00b1\u20093.7\u00b5m versus 6.8\u2009\u00b1\u20092.0\u00b5m;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.07), outer nuclear layer (32.6\u2009\u00b1\u200916.1\u00b5m versus 30.6\u2009\u00b1\u200911.8 \u00b5m;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.82) and of total retina (157.7\u2009\u00b1\u200999.4\u00b5m versus 152.0\u2009\u00b1\u200960.7\u00b5m;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.34). Apoptotic cells were not detected in either group. Mean IOP did not differ significantly between the right eyes (study eyes) and the left eyes (control eyes). Intravital signs of intraocular toxicity were not detected.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Repeatedly intraocularly applied panitumumab combined with ranibizumab was intraocularly well tolerated and did not differ in the ocular reaction from intravitreal injections of Ringer\u00b4s solution.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0329444","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T18:30:20Z","timestamp":1765909820000},"page":"e0329444","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Safety of \u00edntravitreal panitumumab combined with intravitreal ranibizumab in rabbits"],"prefix":"10.1371","volume":"20","author":[{"given":"Mukharram M.","family":"Bikbov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyulli M.","family":"Kazakbaeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iskander D.","family":"Valishin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aigul M.","family":"Ishbulatova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songhomitra","family":"Panda-Jonas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulshat R.","family":"Mustafina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2972-5227","authenticated-orcid":true,"given":"Jost 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