Toxicological considerations for intravitreal drugs

Penha, Fernando M.; Rodrigues, Eduardo B; Furlani, Bruno; Dib, Eduardo; Melo, Gustavo Barreto; Farah, Michel Eid

doi:10.1517/17425255.2011.585970

Cited by 15 publications

(9 citation statements)

References 91 publications

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“…This includes systemic vascular toxicity such as arterial and venous thromboembolic events and its cardiac complications,66,67 and systemic effects of intraocular administration in one large meta-analysis68 (although not observed in other studies) 69,70. There is also clinical evidence of local toxicity from VEGF blockade,71,72 including acute and chronic elevated intraocular pressure 73,74…”

Section: Discussionmentioning

confidence: 99%

Epithelial Membrane Protein-2 (EMP2) Antibody Blockade Reduces Corneal Neovascularization in an In Vivo Model

Sun

Chan

Law

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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PurposePathologic corneal neovascularization is a major cause of blindness worldwide, and treatment options are currently limited. VEGF is one of the critical mediators of corneal neovascularization but current anti-VEGF therapies have produced limited results in the cornea. Thus, additional therapeutic agents are needed to enhance the antiangiogenic arsenal. Our group previously demonstrated epithelial membrane protein-2 (EMP2) involvement in pathologic angiogenesis in multiple cancer models including breast cancer and glioblastoma. In this paper, we investigate the efficacy of anti-EMP2 immunotherapy in the prevention of corneal neovascularization.MethodsAn in vivo murine cornea alkali burn model was used to study pathologic neovascularization. A unilateral corneal burn was induced using NaOH, and subconjunctival injection of either anti-EMP2 antibody, control antibody, or sterile saline was performed after corneal burn. Neovascularization was clinically scored at 7 days postalkali burn, and eyes were enucleated for histologic analysis and immunostaining including VEGF, CD31, and CD34 expression.ResultsAnti-EMP2 antibody, compared to control antibody or vehicle, significantly reduced neovascularization as measured by clinical score and central cornea thickness, as well as by histologic reduction of neovascularization, decreased CD34 staining, and decreased CD31 staining. Incubation of corneal limbal cells in vitro with anti-EMP2 blocking antibody significantly decreased EMP2 expression, VEGF expression and secretion, and cell migration.ConclusionsThis work demonstrates the effectiveness of EMP2 as a novel target in pathologic corneal neovascularization in an animal model and supports additional investigation into EMP2 antibody blockade as a potential new therapeutic option.

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Section: Discussionmentioning

confidence: 99%

Epithelial Membrane Protein-2 (EMP2) Antibody Blockade Reduces Corneal Neovascularization in an In Vivo Model

Sun

Chan

Law

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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“…Intraocular injection offers the most direct route to attain the high drug concentration bypassing the blood ocular barrier and the blood aqueous barrier, however, the excessive drug concentration may cause retina toxicity and repeated injection is needed due to the rapid drug elimination. Additionally intraocular injections may increase the risks of hemorrhage, endophthalmitis, retinal detachment and cataract (Wu L et al, 2008;Penha et al, 2011;Agard et al, 2015). Periocular drug delivery or transscleral drug delivery containing subconjunctival, subtenon, retrobulbar and peribulbar administration, is relatively less invasive than intraocular injection and considered as a potentially route for the posterior segment drug delivering.…”

Section: Discussionmentioning

confidence: 99%

Research on the comparison of the demethylvancomycin’s diffusion–deposition characteristics in the ocular solid tissues of sustained subtenon drug delivery with subconjunctival injection

et al. 2017

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Purpose: To compare the demethylvancomycin's diffusion-deposition characteristics in the ocular solid tissues of sustained subtenon drug delivery with subconjunctival injection. Method: Sixty adult white rabbits were randomly assigned to the subtenon drug delivery group and the subconjunctival injection group. The subtenon drug delivery group was continuously infused demethylvancomycin to the subtenon of rabbits. The subconjunctival injection group was injected demethylvancomycin to the subconjunctival of rabbits. Cornea, iris and sclera were collected for high-performance liquid chromatography analyses to determine drug concentrations at one hour, three hours, six hours, 12 h and 24 h of drug administration. WinNonlin 6.3 was used to calculate the parameters of cumulative area under the curve (AUC cum ) of demethylvancomycin. Results: The peak levels of demethylvancomycin concentration of the subtenon drug delivery group and the subconjunctival injection group were 92.406 ± 21.555 and 51.778 ± 14.001 mg/g in cornea, 28.451 ± 10.229 mg/g and 42.271 ± 27.291 mg/g in iris, 153.166 ± 51.738 mg/g and 57.423 ± 18.480 mg/g in sclera.

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“…Non-toxic doses of many agents that are used in intravitreal injections were determined in various studies. (13). Clearance of an intravitreal drug takes longer time than intracameral drugs.…”

Section: Discussionmentioning

confidence: 99%