Safety and tolerability of intravitreal cetuximab in young and adult rabbits
To assess safety and tolerability of intraocularly applied cetuximab as epidermal growth factor receptor antibody, we conducted the experimental study which consisted of groups of adult rabbits (body weight: 2.4 kg) and young rabbits (body weight: 1.6 kg). All animals received three intravitreal inj...
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| Vydané v: | Scientific reports Ročník 12; číslo 1; s. 11454 - 6 |
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Nature Publishing Group UK
06.07.2022
Nature Publishing Group Nature Portfolio |
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| Abstract | To assess safety and tolerability of intraocularly applied cetuximab as epidermal growth factor receptor antibody, we conducted the experimental study which consisted of groups of adult rabbits (body weight: 2.4 kg) and young rabbits (body weight: 1.6 kg). All animals received three intravitreal injections of 0.5 mg cetuximab (Erbitux) (0.10 mL; 5 mg cetuximab/mL) into their right eyes in 4-week intervals, while the contralateral eyes received intravitreal injections of Ringer's solution. All animals underwent regular ophthalmological examinations at baseline and two-week intervals. Four weeks after the last injection, the animals were sacrificed, and the eyes were enucleated, fixed and examined by light microscopy. The study included 10 adult rabbits (age: 18 weeks; range: 17–19 weeks) and 8 young rabbits (age: 8 weeks; range: 7–10 weeks). Biometric measurements of axial length, anterior chamber depth and lens thickness and intraocular pressure readings did not differ significantly (all
P
> 0.05, Bonferroni corrected) between the right (study) eyes and the left (control) eyes, neither in the young nor in the adult rabbit group. Signs of intraocular inflammation or fundus peculiarities were not detected. Thickness of the outer nuclear layer, inner nuclear layer, combined outer and inner nuclear layer and outer plexiform layer, and total retina, measured at the posterior pole, posterior pole/equator midpoint, equator, and ora serrata region, did not vary significantly between study eyes and control eyes (all
P
> 0.05, Bonferroni corrected). The results suggest that repeated intravitreal application of cetuximab did not result in any detected intraocular toxic or destructive effect in young and adult rabbits, concurring with the notion of an intraocular tolerability of cetuximab. |
|---|---|
| AbstractList | To assess safety and tolerability of intraocularly applied cetuximab as epidermal growth factor receptor antibody, we conducted the experimental study which consisted of groups of adult rabbits (body weight: 2.4 kg) and young rabbits (body weight: 1.6 kg). All animals received three intravitreal injections of 0.5 mg cetuximab (Erbitux) (0.10 mL; 5 mg cetuximab/mL) into their right eyes in 4-week intervals, while the contralateral eyes received intravitreal injections of Ringer's solution. All animals underwent regular ophthalmological examinations at baseline and two-week intervals. Four weeks after the last injection, the animals were sacrificed, and the eyes were enucleated, fixed and examined by light microscopy. The study included 10 adult rabbits (age: 18 weeks; range: 17–19 weeks) and 8 young rabbits (age: 8 weeks; range: 7–10 weeks). Biometric measurements of axial length, anterior chamber depth and lens thickness and intraocular pressure readings did not differ significantly (all
P
> 0.05, Bonferroni corrected) between the right (study) eyes and the left (control) eyes, neither in the young nor in the adult rabbit group. Signs of intraocular inflammation or fundus peculiarities were not detected. Thickness of the outer nuclear layer, inner nuclear layer, combined outer and inner nuclear layer and outer plexiform layer, and total retina, measured at the posterior pole, posterior pole/equator midpoint, equator, and ora serrata region, did not vary significantly between study eyes and control eyes (all
P
> 0.05, Bonferroni corrected). The results suggest that repeated intravitreal application of cetuximab did not result in any detected intraocular toxic or destructive effect in young and adult rabbits, concurring with the notion of an intraocular tolerability of cetuximab. To assess safety and tolerability of intraocularly applied cetuximab as epidermal growth factor receptor antibody, we conducted the experimental study which consisted of groups of adult rabbits (body weight: 2.4 kg) and young rabbits (body weight: 1.6 kg). All animals received three intravitreal injections of 0.5 mg cetuximab (Erbitux) (0.10 mL; 5 mg cetuximab/mL) into their right eyes in 4-week intervals, while the contralateral eyes received intravitreal injections of Ringer's solution. All animals underwent regular ophthalmological examinations at baseline and two-week intervals. Four weeks after the last injection, the animals were sacrificed, and the eyes were enucleated, fixed and examined by light microscopy. The study included 10 adult rabbits (age: 18 weeks; range: 17-19 weeks) and 8 young rabbits (age: 8 weeks; range: 7-10 weeks). Biometric measurements of axial length, anterior chamber depth and lens thickness and intraocular pressure readings did not differ significantly (all P > 0.05, Bonferroni corrected) between the right (study) eyes and the left (control) eyes, neither in the young nor in the adult rabbit group. Signs of intraocular inflammation or fundus peculiarities were not detected. Thickness of the outer nuclear layer, inner nuclear layer, combined outer and inner nuclear layer and outer plexiform layer, and total retina, measured at the posterior pole, posterior pole/equator midpoint, equator, and ora serrata region, did not vary significantly between study eyes and control eyes (all P > 0.05, Bonferroni corrected). The results suggest that repeated intravitreal application of cetuximab did not result in any detected intraocular toxic or destructive effect in young and adult rabbits, concurring with the notion of an intraocular tolerability of cetuximab.To assess safety and tolerability of intraocularly applied cetuximab as epidermal growth factor receptor antibody, we conducted the experimental study which consisted of groups of adult rabbits (body weight: 2.4 kg) and young rabbits (body weight: 1.6 kg). All animals received three intravitreal injections of 0.5 mg cetuximab (Erbitux) (0.10 mL; 5 mg cetuximab/mL) into their right eyes in 4-week intervals, while the contralateral eyes received intravitreal injections of Ringer's solution. All animals underwent regular ophthalmological examinations at baseline and two-week intervals. Four weeks after the last injection, the animals were sacrificed, and the eyes were enucleated, fixed and examined by light microscopy. The study included 10 adult rabbits (age: 18 weeks; range: 17-19 weeks) and 8 young rabbits (age: 8 weeks; range: 7-10 weeks). Biometric measurements of axial length, anterior chamber depth and lens thickness and intraocular pressure readings did not differ significantly (all P > 0.05, Bonferroni corrected) between the right (study) eyes and the left (control) eyes, neither in the young nor in the adult rabbit group. Signs of intraocular inflammation or fundus peculiarities were not detected. Thickness of the outer nuclear layer, inner nuclear layer, combined outer and inner nuclear layer and outer plexiform layer, and total retina, measured at the posterior pole, posterior pole/equator midpoint, equator, and ora serrata region, did not vary significantly between study eyes and control eyes (all P > 0.05, Bonferroni corrected). The results suggest that repeated intravitreal application of cetuximab did not result in any detected intraocular toxic or destructive effect in young and adult rabbits, concurring with the notion of an intraocular tolerability of cetuximab. To assess safety and tolerability of intraocularly applied cetuximab as epidermal growth factor receptor antibody, we conducted the experimental study which consisted of groups of adult rabbits (body weight: 2.4 kg) and young rabbits (body weight: 1.6 kg). All animals received three intravitreal injections of 0.5 mg cetuximab (Erbitux) (0.10 mL; 5 mg cetuximab/mL) into their right eyes in 4-week intervals, while the contralateral eyes received intravitreal injections of Ringer's solution. All animals underwent regular ophthalmological examinations at baseline and two-week intervals. Four weeks after the last injection, the animals were sacrificed, and the eyes were enucleated, fixed and examined by light microscopy. The study included 10 adult rabbits (age: 18 weeks; range: 17–19 weeks) and 8 young rabbits (age: 8 weeks; range: 7–10 weeks). Biometric measurements of axial length, anterior chamber depth and lens thickness and intraocular pressure readings did not differ significantly (all P > 0.05, Bonferroni corrected) between the right (study) eyes and the left (control) eyes, neither in the young nor in the adult rabbit group. Signs of intraocular inflammation or fundus peculiarities were not detected. Thickness of the outer nuclear layer, inner nuclear layer, combined outer and inner nuclear layer and outer plexiform layer, and total retina, measured at the posterior pole, posterior pole/equator midpoint, equator, and ora serrata region, did not vary significantly between study eyes and control eyes (all P > 0.05, Bonferroni corrected). The results suggest that repeated intravitreal application of cetuximab did not result in any detected intraocular toxic or destructive effect in young and adult rabbits, concurring with the notion of an intraocular tolerability of cetuximab. Abstract To assess safety and tolerability of intraocularly applied cetuximab as epidermal growth factor receptor antibody, we conducted the experimental study which consisted of groups of adult rabbits (body weight: 2.4 kg) and young rabbits (body weight: 1.6 kg). All animals received three intravitreal injections of 0.5 mg cetuximab (Erbitux) (0.10 mL; 5 mg cetuximab/mL) into their right eyes in 4-week intervals, while the contralateral eyes received intravitreal injections of Ringer's solution. All animals underwent regular ophthalmological examinations at baseline and two-week intervals. Four weeks after the last injection, the animals were sacrificed, and the eyes were enucleated, fixed and examined by light microscopy. The study included 10 adult rabbits (age: 18 weeks; range: 17–19 weeks) and 8 young rabbits (age: 8 weeks; range: 7–10 weeks). Biometric measurements of axial length, anterior chamber depth and lens thickness and intraocular pressure readings did not differ significantly (all P > 0.05, Bonferroni corrected) between the right (study) eyes and the left (control) eyes, neither in the young nor in the adult rabbit group. Signs of intraocular inflammation or fundus peculiarities were not detected. Thickness of the outer nuclear layer, inner nuclear layer, combined outer and inner nuclear layer and outer plexiform layer, and total retina, measured at the posterior pole, posterior pole/equator midpoint, equator, and ora serrata region, did not vary significantly between study eyes and control eyes (all P > 0.05, Bonferroni corrected). The results suggest that repeated intravitreal application of cetuximab did not result in any detected intraocular toxic or destructive effect in young and adult rabbits, concurring with the notion of an intraocular tolerability of cetuximab. To assess safety and tolerability of intraocularly applied cetuximab as epidermal growth factor receptor antibody, we conducted the experimental study which consisted of groups of adult rabbits (body weight: 2.4 kg) and young rabbits (body weight: 1.6 kg). All animals received three intravitreal injections of 0.5 mg cetuximab (Erbitux) (0.10 mL; 5 mg cetuximab/mL) into their right eyes in 4-week intervals, while the contralateral eyes received intravitreal injections of Ringer's solution. All animals underwent regular ophthalmological examinations at baseline and two-week intervals. Four weeks after the last injection, the animals were sacrificed, and the eyes were enucleated, fixed and examined by light microscopy. The study included 10 adult rabbits (age: 18 weeks; range: 17–19 weeks) and 8 young rabbits (age: 8 weeks; range: 7–10 weeks). Biometric measurements of axial length, anterior chamber depth and lens thickness and intraocular pressure readings did not differ significantly (all P > 0.05, Bonferroni corrected) between the right (study) eyes and the left (control) eyes, neither in the young nor in the adult rabbit group. Signs of intraocular inflammation or fundus peculiarities were not detected. Thickness of the outer nuclear layer, inner nuclear layer, combined outer and inner nuclear layer and outer plexiform layer, and total retina, measured at the posterior pole, posterior pole/equator midpoint, equator, and ora serrata region, did not vary significantly between study eyes and control eyes (all P > 0.05, Bonferroni corrected). The results suggest that repeated intravitreal application of cetuximab did not result in any detected intraocular toxic or destructive effect in young and adult rabbits, concurring with the notion of an intraocular tolerability of cetuximab. |
| ArticleNumber | 11454 |
| Author | Kazakbaev, Renat A. Khakimov, Dinar A. Kazakbaeva, Gyulli M. Tuliakova, Azaliia M. Nuriev, Ildar F. Miniazeva, Liana A. Jonas, Jost B. Bikbov, Mukharram M. Panda-Jonas, Songhomitra Gilemzianova, Leisan I. Fakhretdinova, Albina A. |
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| Cites_doi | 10.1016/j.ophtha.2017.12.005 10.1111/aos.14080 10.1096/fj.202001095RR 10.1016/j.ebiom.2017.02.021 10.1007/s10792-021-01761-w 10.1007/s00417-021-05200-5 10.1056/NEJMoa033025 10.1016/j.ajo.2010.05.009 10.1056/NEJMoa0805019 10.1001/jamaophthalmol.2021.3303 10.1136/bjophthalmol-2019-314619 10.1093/annonc/mdi279 10.1053/j.seminoncol.2006.04.003 10.1097/IAE.0000000000001464 |
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| References | Cunningham (CR10) 2004; 351 Saka (CR1) 2010; 150 Fang (CR2) 2018; 125 CR15 Mendelsohn, Baselga (CR13) 2006; 33 Dong (CR7) 2019; 97 Dong (CR8) 2020; 34 Bikbov, Khalimov, Cerrada-Gimenez, Ragauskas, Kalesnykas, Jonas (CR12) 2021; 41 Jiang (CR6) 2017; 17 Van Cutsem (CR11) 2009; 360 Jonas, Ohno-Matsui, Jiang, Panda-Jonas (CR5) 2017; 37 Segaert, Van Cutsem (CR14) 2005; 16 Du (CR4) 2021; 139 Jonas (CR9) 2021; 259 Lee, Lee, Lim, Kim (CR3) 2020; 104 MW Lee (15642_CR3) 2020; 104 WJ Jiang (15642_CR6) 2017; 17 L Dong (15642_CR8) 2020; 34 L Dong (15642_CR7) 2019; 97 Y Fang (15642_CR2) 2018; 125 JB Jonas (15642_CR5) 2017; 37 R Du (15642_CR4) 2021; 139 E Van Cutsem (15642_CR11) 2009; 360 MM Bikbov (15642_CR12) 2021; 41 JB Jonas (15642_CR9) 2021; 259 15642_CR15 S Segaert (15642_CR14) 2005; 16 N Saka (15642_CR1) 2010; 150 J Mendelsohn (15642_CR13) 2006; 33 D Cunningham (15642_CR10) 2004; 351 |
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