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   <ref-type name="Journal Article">17</ref-type>
   <contributors>
    <authors>
     <author>Bikbov, M.M.</author>
     <author>Kazakbaeva, G.M.</author>
     <author>Valishin, I.D.</author>
     <author>Ishbulatova, A.M.</author>
     <author>Panda-Jonas, S.</author>
     <author>Mustafina, G.R.</author>
     <author>Jonas,  J.B.</author>
    </authors>
   </contributors>
   <titles>
    <title>SAFETY OF ÍNTRAVITREAL PANITUMUMAB COMBINED WITH INTRAVITREAL RANIBIZUMAB IN RABBITS</title>
   </titles>
   <keywords>
    <keyword>Scopus</keyword>
    <keyword>Web of Science</keyword>
    <keyword>Белый список</keyword>
   </keywords>
   <dates>
    <year>2025</year>
    <pub-dates>
     <date>2026-05-02</date>
    </pub-dates>
   </dates>
   <doi>10.1371/journal.pone.0329444</doi>
   <journal>PLOS ONE</journal>
   <abstract>Purpose&#13;
To examine the safety of intravitreally applied epidermal growth factor (EGF) receptor antibody panitumumab combined with intravitreally injected vascular endothelial&#13;
growth factor (VEGF) antibody ranibizumab in rabbits.&#13;
Methods&#13;
The experimental study included 8 male rabbits (age: 2−3 months; weight: 2.5–2.6&#13;
kg). The right eyes received three intravitreal injections of panitumumab (1 mg in&#13;
0.10 mL) combined with intravitreal injections of ranibizumab (0.5 mg in 0.05 mL) in&#13;
intervals of 4 weeks, while the left eyes received three double intravitreal injections&#13;
of Ringer´s solution (0.10 mL and 0.05mL). At baseline, at the time points of the&#13;
re-injections, and at 2 weeks and at 6 weeks after the last injection, the animals were&#13;
examined by fundus photography and optical coherence tomography (OCT). At study&#13;
end at 2 weeks after the last injection for 4 animals (total study duration: 10 weeks)&#13;
or at 6 weeks after the last injection for the remaining 4 rabbits (total study duration:&#13;
14 weeks), the animals were sacrificed and the eyes were histomorphometrically&#13;
examined.&#13;
Results&#13;
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±8.3 cells per 150µm versus 4.5±3.3 cells;P=0.04), inner nuclear layer (33.1±14.0 cells versus 49.0±22.3 cells;P=0.04) and outer nuclear layer (133.7±50.0 cells versus 171.3±75.3 cells;P=0.07) nor in mean thickness of the ganglion cell&#13;
layer (31.8±34.4µm versus 24.3±15.2µm;P=0.15), inner plexiform layer&#13;
(32.4±48.2µm versus 25.6±11.2µm;P=0.22), inner nuclear layer (26.6±14.0µm&#13;
versus 26.7±10.2µm;P=0.43), outer plexiform layer (6.6±3.7µm versus&#13;
6.8±2.0µm;P=0.07), outer nuclear layer (32.6±16.1µm versus 30.6±11.8&#13;
µm;P=0.82) and of total retina (157.7±99.4µm versus 152.0±60.7µm;P=0.34).&#13;
Apoptotic cells were not detected in either group. Mean IOP did not differ significantly&#13;
between the right eyes (study eyes) and the left eyes (control eyes). Intravital signs of&#13;
intraocular toxicity were not detected.&#13;
Conclusions&#13;
Repeatedly intraocularly applied panitumumab combined with ranibizumab was&#13;
intraocularly well tolerated and did not differ in the ocular reaction from intravitreal&#13;
injections of Ringer´s solution.</abstract>
   <urls>
    <web-urls>
     <url>https://repo.bashgmu.ru/publication/5212</url>
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    <pdf-urls>
     <url>https://repo.bashgmu.ru/files/5405</url>
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