The potential of anti-VEGF (Vasotide) by eye drops to treat proliferative retinopathies

Purpose: Choroidal neovascularization (CNV) associated with punctate inner choroidopathy (PIC) is a rare clinical entity, yet still a challenge for medical treatment. A case of a young myopic woman developing CNV secondary to unilateral PIC is presented. Clinical morphology, diagnostic procedure and follow-up are reported. Case Report: A 29-year-old woman presented with multiple yellowish dots at the posterior pole. No other signs of inflammation could be seen. Angiography with fluorescein yielded hyperfluorescent signals in the affected areas with a diffuse leak, and SD-OCT showed a slightly elevated retinal pigment epithelial layer, consistent with the diagnosis of PIC. Additionally a classic CNV was observed. Results: Anti-inflammatory therapy with local prednisolone acetate eye drops in combination with intravitreal injection of anti-vascular endothelial growth factor (VEGF, bevacizumab) yielded an increased best-corrected visual acuity. As CNV reappeared, systemic medication with prednisone and azathioprine in combination with two further intravitreal injections of anti-VEGF stabilized CNV and increased visual acuity again. Conclusion: Combined therapy of immunosuppression with intravitreal anti-VEGF injections can be considered as therapeutic strategy in the management of recurrent CNV associated with PIC.

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Galectin-1 expression imprints a neurovascular phenotype in proliferative retinopathies and delineates responses to anti-VEGF

Oncotarget ◽

10.18632/oncotarget.17129 ◽

2017 ◽

Vol 8 (20) ◽

pp. 32505-32522 ◽

Cited By ~ 14

Author(s):

Magali E. Ridano ◽

Paula V. Subirada ◽

María C. Paz ◽

Valeria E. Lorenc ◽

Juan C. Stupirski ◽

...

Keyword(s):

Anti Vegf ◽

Proliferative Retinopathies

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Gaining insight on mitigation of rubeosis iridis by UPARANT in a mouse model associated with proliferative retinopathy

Journal of Molecular Medicine ◽

10.1007/s00109-020-01979-8 ◽

2020 ◽

Vol 98 (11) ◽

pp. 1629-1638

Author(s):

Filippo Locri ◽

Noemi A. Pesce ◽

Monica Aronsson ◽

Maurizio Cammalleri ◽

Mario De Rosa ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Proliferative Retinopathy ◽

Vascular Endothelial ◽

Urokinase Plasminogen Activator Receptor ◽

Rubeosis Iridis ◽

Anti Vegf ◽

Iris Neovascularization ◽

Proliferative Retinopathies ◽

Endothelial Growth Factor

Abstract Proliferative retinopathies (PR) lead to an increase in neovascularization and inflammation factors, at times culminating in pathologic rubeosis iridis (RI). In mice, uveal puncture combined with injection of hypoxia-conditioned media mimics RI associated with proliferative retinopathies. Here, we investigated the effects of the urokinase plasminogen activator receptor (uPAR) antagonist—UPARANT—on the angiogenic and inflammatory processes that are dysregulated in this model. In addition, the effects of UPARANT were compared with those of anti-vascular endothelial growth factor (VEGF) therapies. Administration of UPARANT promptly decreased iris vasculature, while anti-VEGF effects were slower and less pronounced. Immunoblot and qPCR analysis suggested that UPARANT acts predominantly by reducing the upregulated inflammatory and extracellular matrix degradation responses. UPARANT appears to be more effective in comparison to anti-VEGF in the treatment of RI associated with PR in the murine model, by modulating multiple uPAR-associated signaling pathways. Furthermore, UPARANT effectiveness was maintained when systemically administered, which could open to novel improved therapies for proliferative ocular diseases, particularly those associated with PR. Key messages • Further evidence of UPARANT effectiveness in normalizing pathological iris neovascularization. • Both systemic and local administration of UPARANT reduce iris neovascularization in a model associated with proliferative retinopathies. • In the mouse models of rubeosis iridis associated with proliferative retinopathy, UPARANT displays stronger effects when compared with anti-vascular endothelial growth factor regimen.

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Treatment of Corneal Neovascularization Using Anti-VEGF Bevacizumab

Journal of Ophthalmology ◽

10.1155/2014/178132 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 16

Author(s):

Deli Krizova ◽

Magdalena Vokrojova ◽

Katerina Liehneova ◽

Pavel Studeny

Keyword(s):

Corneal Neovascularization ◽

Eye Drops ◽

Percentage Reduction ◽

Application Form ◽

Antiangiogenic Effect ◽

Anti Vegf ◽

Group A ◽

Group B ◽

Local Use

Purpose. To evaluate antiangiogenic effect of local use of bevacizumab (anti-VEGF antibody) in patients with corneal neovascularization.Methods. Patients were divided into two groups. All patients suffered from some form of corneal neovascularization (NV). Patients in group A received 0.2–0.5 mL of bevacizumab solution subconjunctivally (concentration 25 mg/mL) in a single dose. Group A included 28 eyes from 27. Patients in group B applied bevacizumab eye drops twice daily (concentration 2.5 mg/mL) for two weeks. Group B included 38 eyes from 35 patients. We evaluated the number of corneal segments affected by NV, CDVA, and the incidence of complications and subjective complaints related to the treatment. The minimum follow-up period was six months.Results. By the 6-month follow-up, in group A the percentage reduction of the affected peripheral segments was 21.6% and of the central segments was 9.6%; in group B the percentage reduction of the central segments was 22.7% and of the central segments was 38.04%. In both groups we noticed a statistically significant reduction in the extent of NV.Conclusion. The use of bevacizumab seems to be an effective and safe method in the treatment of corneal neovascularization, either in the subconjunctival or topical application form.

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Assessment of a New Nanostructured Microemulsion System for Ocular Delivery of Sorafenib to Posterior Segment of the Eye

International Journal of Molecular Sciences ◽

10.3390/ijms22094404 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4404

Author(s):

Manuela Santonocito ◽

Cristina Zappulla ◽

Santa Viola ◽

Luca Rosario La Rosa ◽

Elena Solfato ◽

...

Keyword(s):

Growth Factor ◽

Therapeutic Potential ◽

Ischemia Reperfusion ◽

Growth Factor Receptor ◽

Diabetic Rats ◽

Microemulsion System ◽

Eye Drops ◽

Necrosis Factor Alpha ◽

Proliferative Retinopathies

Eye drop formulations allowing topical treatment of retinal pathologies have long been sought as alternatives to intravitreal administration. This study aimed to assess whether a novel nanostructured microemulsions system (NaMESys) could be usefully employed to deliver sorafenib to the retina following topical instillation. NaMESys carrying 0.3% sorafenib (NaMESys-SOR) proved to be cytocompatible in vitro on rabbit corneal cells, and well-tolerated following b.i.d. ocular administration to rabbits during a 3-month study. In rats subject to retinal ischemia-reperfusion, NaMESys-SOR significantly inhibited retinal expression of tumor necrosis factor-alpha (TNFα, 20.7%) and inducible nitric oxide synthase (iNos, 87.3%) mRNAs in comparison to controls. Similarly, in streptozotocin-induced diabetic rats, NaMESys-SOR inhibited retinal expression of nuclear factor kappa B (NFκB), TNFα, insulin like growth factor 1 (IGF1), IGF1 receptor (IGF1R), vascular endothelial growth factor receptor 1 (VEGFR1) and 2 (VEGFR2) mRNAs by three-fold on average compared to controls. Furthermore, a reduction in TNFα, VEGFR1 and VEGFR2 protein expression was observed by western blot. Moreover, in mice subject to laser-induced choroidal neovascularization, NaMESys-SOR significantly inhibited neovascular lesions by 54%. In conclusion, NaMESys-SOR was shown to be a well-tolerated ophthalmic formulation able to deliver effective amounts of sorafenib to the retina, reducing proinflammatory and pro-angiogenic mediators in reliable models of proliferative retinopathies. These findings warrant further investigations on the full therapeutic potential of NaMESys-SOR eye drops, aiming to address unmet needs in the pharmacotherapy of retinal neovascular diseases.

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