PMID- 36753186 OWN - NLM STAT- MEDLINE DCOM- 20230210 LR - 20230328 IS - 2164-2591 (Electronic) IS - 2164-2591 (Linking) VI - 12 IP - 2 DP - 2023 Feb 1 TI - Inner Retinal Changes in Acute Experimental BRVO Treated With Bevacizumab or Triamcinolone Acetonide. PG - 11 LID - 10.1167/tvst.12.2.11 [doi] LID - 11 AB - PURPOSE: Apoptosis is a key process in neural degeneration associated with retinal vascular diseases. Vascular endothelial growth factor (VEGF) antagonists, including bevacizumab, are used to treat macular edema in these diseases. As VEGF has a critical role in the preservation of retinal neuronal cells, this study investigates the effects of bevacizumab on neural damage in a pig model of branch retinal vein occlusion (BRVO) and compares it with triamcinolone acetonide (TA) which is reported to possess neuroprotective properties. METHODS: Thirty-six pigs had a photothrombotic BRVO in both eyes. Six pigs were injected with bevacizumab in one eye and TA in the fellow eye, then they were sacrificed, the eyes enucleated, and retinas processed at 2, 6, 10, and 20 days, respectively, together with three pigs (six eyes) BRVO only and three normal pigs (six eyes). Neuronal degeneration (apoptosis) and associated inner retinal changes were determined by terminal deoxyynuclotidyl transferase dUTP nick-end labeling (TUNEL), histology, and immunohistochemistry for macrophages. RESULTS: TUNEL labeling showed significantly higher apoptosis rates in the ganglion cell layer (GCL) and the inner nuclear layer (INL) in the bevacizumab-treated compared with the TA-treated retinas at 2, 10, and 20 day time points after occlusion (P < 0.05). Pyknotic cells were significantly higher in the GCL in bevacizumab-treated eyes at 6, 10, and 20 days and in the INL at 2 days compared to TA-treated retinas (P < 0.05). Macrophage infiltration was seen at all time points in both untreated and treated retinas with an absence of significance between bevacizumab- and TA-treated retinas (P > 0.05). CONCLUSIONS: Neurodegeneration in the BRVO acute phase is exacerbated by current standard treatments for BRVO. These results may have implications for the timing and treatment type. TRANSLATIONAL RELEVANCE: In the acute phase of BRVO, VEGF suppression with bevacizumab and to a lesser extent with triamcinolone exacerbates apoptosis in the inner retinal layers, which has implications for both the timing and choice of treatment. FAU - McAllister, Ian L AU - McAllister IL AD - Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Australia. AD - Lions Eye Institute, The University of Western Australia, Perth, Australia. AD - Department of Ophthalmology, Royal Perth Hospital, Perth, Australia. FAU - Vijayasekaran, Sarojini AU - Vijayasekaran S AD - Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Australia. AD - Lions Eye Institute, The University of Western Australia, Perth, Australia. FAU - Bhikoo, Riyaz AU - Bhikoo R AD - Lions Eye Institute, The University of Western Australia, Perth, Australia. AD - Department of Ophthalmology, Royal Perth Hospital, Perth, Australia. FAU - Chen, Fred K AU - Chen FK AD - Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Australia. AD - Lions Eye Institute, The University of Western Australia, Perth, Australia. AD - Department of Ophthalmology, Royal Perth Hospital, Perth, Australia. AD - Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, Australia. FAU - Zhang, Dan AU - Zhang D AD - Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Australia. AD - Lions Eye Institute, The University of Western Australia, Perth, Australia. FAU - Kanagalingam, Emily AU - Kanagalingam E AD - Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Australia. AD - Lions Eye Institute, The University of Western Australia, Perth, Australia. FAU - McLenachan, Samuel AU - McLenachan S AD - Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Australia. AD - Lions Eye Institute, The University of Western Australia, Perth, Australia. FAU - Yu, Dao-Yi AU - Yu DY AD - Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Australia. AD - Lions Eye Institute, The University of Western Australia, Perth, Australia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Transl Vis Sci Technol JT - Translational vision science & technology JID - 101595919 RN - F446C597KA (Triamcinolone Acetonide) RN - 2S9ZZM9Q9V (Bevacizumab) RN - 0 (Vascular Endothelial Growth Factor A) SB - IM MH - Swine MH - Animals MH - *Triamcinolone Acetonide/pharmacology/therapeutic use MH - Bevacizumab/pharmacology/therapeutic use MH - *Retinal Vein Occlusion/drug therapy MH - Vascular Endothelial Growth Factor A MH - Retina/metabolism PMC - PMC9919627 COIS- Disclosure: I.L. McAllister, None; S. Vijayasekaran, None; R. Bhikoo, None; F.K. Chen, None; D. Zhang, None; E. Kanagalingam, None; S. McLenachan, None; D.-Y. Yu, None EDAT- 2023/02/09 06:00 MHDA- 2023/02/11 06:00 PMCR- 2023/02/08 CRDT- 2023/02/08 11:34 PHST- 2023/02/08 11:34 [entrez] PHST- 2023/02/09 06:00 [pubmed] PHST- 2023/02/11 06:00 [medline] PHST- 2023/02/08 00:00 [pmc-release] AID - 2785351 [pii] AID - TVST-22-4912 [pii] AID - 10.1167/tvst.12.2.11 [doi] PST - ppublish SO - Transl Vis Sci Technol. 2023 Feb 1;12(2):11. doi: 10.1167/tvst.12.2.11.