Abstract

Purpose: To observe the effect of subconjunctival (SC) approach for the treatment of retinopathy of prematurity (ROP) in an experimental rat model.

Methods: We used 4 groups (G) comprising 18 new-born rats in each. G1: healthy control, G2: untreated oxygen induced retinopathy (OIR) control, G3: SC rat anti vascular endothelial growth factor antibody (antiVEGFab) injected and G4: Intravitreal (IVT) antiVEGFab injected. G2, G3 and G4 were exposed to oxygen fluctuations alternating between 50% and 10% every 24 hours until postnatal day (p) 14 at which time the groups were placed into room air for 4 days. At p18; OIR was observed through fluorescein angiography (FA). G3 and G4 were treated immediately 1 µg/10 µl and 50 ng/2 µl respectively. FAs repeated at p19, p25 and p30. To evaluate OIR; modified retinopathy scoring system (MRSS) was calculated according to the FA images, including retinal vascular development, vascular tuft formation, extraretinal neovascularization, vascular tortuosity and retinal haemorrhage. Blood analysis was performed on the same three days for the measurement of serum VEGF levels. Histopathological evaluation was performed with haematoxylin & eosin staining for the vascular lumen quantification on the retinal specimens of the enucleated eyes on the same days.

Results: There was no significant difference between the G3 and G4 at the end of the study according to the MRSS values (p: 0,101), systemic VEGF levels (p: 0,796) and vascular lumen counts of histopathological specimens (p: 0,359).

Conclusion: The therapeutic effect of SC and IVT on OIR were similar. SC anti VEGF treatment may be a safer and effective alternative to IVT injection for the treatment of ROP.

Keywords: Subconjunctival; Retinopathy of Prematurity; Vascular Endothelial Growth Factor; Oxygen Induced Retinopathy

References

1. Pozarowska D and Pozarowski P. “The era of anti-vascular endothelial growth factor (VEGF) drugs in ophthalmology, VEGF and anti-VEGF therapy”. Central-European Journal of Immunology 41 (2016): 311-316.
2. Connolly BP MJ., et al. “A comparison of laser photocoagulation with trans-scleral cryotherapy in the treatment of threshold retinopathy of prematurity”. Ophthalmology 105 (1998): 1628-1631.
3. Jandeck C. “[New therapeutic approaches in the treatment of retinopathy of prematurity]”. Klinische Monatsblatter Fur Augenheilkunde 226 (2009): 914-920.
4. Karkhaneh R., et al. “Efficacy of intravitreal bevacizumab for zone-II retinopathy of prematurity”. Acta Ophthalmology 94 (2016): 417-420.
5. Geloneck MM CA., et al. “Refractive outcomes following bevacizumab monotherapy compared with conventional laser treatment: a randomized clinical trial”. JAMA Ophthalmology 132 (2014): 1327-1333.
6. O'Keeffe N., et al. “Bevacizumab compared with diode laser in stage 3 posterior retinopathy of prematurity: A 5 year follow up”. Irish Medical Journal 109 (2016): 355.
7. Larranaga-Fragoso P., et al. “Intravitreal Bevacizumab for Zone II Retinopathy of Prematurity”. Journal Of Pediatric Ophthalmology And Strabismus 53 (2016): 375-382.
8. Mintz-Hittner HA., et al. “Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity”. The New England Journal of Medicine 364 (2011): 603-615.
9. Xu Y and Tan CS. “Safety and complications of intravitreal injections performed in an Asian population in Singapore”. International Ophthalmology (2016).
10. Penn JS HM and Tolman BL. “Exposure to alternating hypoxia and hyperoxia causes severe proliferative retinopathy in the newborn rat”. Pediatric Research 36 (1994): 724-731.
11. Liu K., et al. “The retinal vasculature and function of the neural retina in a rat model of retinopathy of prematurity”. Investigative Ophthalmology and Visual Science 47 (2006): 2639-2647.
12. Hartnett ME., et al. “Neutralizing VEGF decreases tortuosity and alters endothelial cell division orientation in arterioles and veins in a rat model of ROP: relevance to plus disease”. Investigative Ophthalmology and Visual Science 49 (2008): 3107-3114.
13. Werdich XQ and Penn JS. “Specific involvement of SRC family kinase activation in the pathogenesis of retinal neovascularization”. Investigative Ophthalmology and Visual Science 47 (2006): 5047-5056.
14. Akula JD., et al. “The anatomy of the rat eye with oxygen-induced retinopathy”. Documenta Ophthalmologica Advances In Ophthalmology 120 (2010): 41-50.
15. Geisen P PL., et al. “Neutralizing antibody to VEGF reduces intravitreous neovascularization and does not interfere with vascularization of avascular retina in an ROP model”. Molecular Vision 14 (2008): 718-727.
16. Zhao Y and Lei W. “[Retina penetration of subconjunctival ranibizumab injection in the rabbit eye]”. [Zhonghua Yan Ke Za Zhi] Chinese Journal Of Ophthalmology 51 (2015): 356-359.

Citation

Citation: Tuncay Topal., et al. “Evaluation of the Efficacy of Subconjunctival Anti Vascular Endothelial Growth Factor İnjection in the Treatment of Retinopathy of Prematurity in an Experimental Rat Model". Acta Scientific Ophthalmology 3.11 (2020): 19-26.

Copyright

Copyright: © 2020 Tuncay Topal., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.