Outcomes of intravitreal anti-VEGF therapy in eyes with both neovascular age-related macular degeneration and diabetic retinopathy

Bandello, Francesco; Corvi, Federico; Spina, Carlo La; Benatti, Lucia; Querques, Giuseppe; Capuano, Vittorio; Naysan, Jonathan; Chen, Xuejing; Sarraf, David; Parodi, Maurizio Battaglia; Souied, Eric H.; Freund, K. Bailey

doi:10.1136/bjophthalmol-2016-308400

Cited by 8 publications

(4 citation statements)

References 31 publications

(17 reference statements)

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“…VEGF has long been known to contribute to angiogenesis and increase the permeability of the vascular endothelium. Anti-VEGF therapy aimed at preventing macular oedema and retinal neovascularisation has been widely used, and it has produced satisfactory results [48–51]. EPO is still being considered a “two-faced Janus” factor in the retina where it acts by binding to a trans-membrane receptor (EPOR).…”

Section: Discussionmentioning

confidence: 99%

Time-dependent changes in hypoxia- and gliosis-related factors in experimental diabetic retinopathy

Zhang

et al. 2018

Eye

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Diabetes causes various biochemical changes in the retina; long-term changes in the factors associated with hypoxia and gliosis have rarely been reported. The present study was conducted to explore the changes in these factors in a time-dependent manner in experimental diabetic retinopathy (DR). Diabetes was induced in Sprague–Dawley rats by intraperitoneal injection of streptozotocin. The expression of the following factors was examined using immunofluorescence and western blot analysis at 0.5, 1, 2, 4 and 6 months after diabetes onset: hypoxia-inducible factor-1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF), erythropoietin (EPO), erythropoietin receptor (EPOR), glial fibrillary acidic protein (GFAP), vimentin, glutamate-aspartate transporter (GLAST) and glutamine synthase (GS). The expression of factors such as HIF-1alpha, VEGF, EPO, EPOR, GFAP and vimentin, was up-regulated with the progression of diabetes in the diabetic rat retinas compared to the expression in normal control retinas, whereas the expression of GS and GLAST was down-regulated. Changes in EPO and EPOR appeared 2 weeks after diabetes onset. HIF-1alpha, VEGF and GFAP started to increase at 1 month and vimentin at 4 months after diabetes onset. GS and GLAST started to decrease at 1 month after diabetes onset. The expression of these factors, which are involved in the processes of hypoxia and gliosis, varied at different stages of DR. The time-course change may be helpful in the evaluation of the progression of DR, and it may indicate the optimal intervention time points for DR.

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Section: Discussionmentioning

confidence: 99%

Time-dependent changes in hypoxia- and gliosis-related factors in experimental diabetic retinopathy

Zhang

et al. 2018

Eye

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“…Although this route of administration is a common clinical practice in several diseases, like age-related macular degeneration (AMD) and diabetic retinopathy, 18 easier administration routes would be very important from the clinical point-of-view. Topical administration (eye drops) provides a suitable noninvasive method for treating ophthalmic diseases.…”

Section: Methodsmentioning

confidence: 99%

Ocular Delivery of PACAP1-27 Protects the Retina From Ischemic Damage in Rodents

Werling

Reglődi

Banks

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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Citation: Werling D, Reglodi D, Banks WA, et al. Ocular delivery of PACAP1-27 protects the retina from ischemic damage in rodents. Invest Ophthalmol Vis Sci. 2016;57:6683-6691. DOI: 10.1167/iovs.16-20630 PURPOSE. Pituitary adenylate cyclase activating polypeptide (PACAP) is neuroprotective in neuronal injuries. Bilateral common carotid artery occlusion (BCCAO) causes chronic hypoperfusion-induced degeneration in the rat retina, where we proved the retinoprotective effect of intravitreal PACAP. Although this route of administration is a common clinical practice in several diseases, easier routes are clinically important. Our aim was to investigate the potential retinoprotective effects of PACAP eye drops in BCCAO-induced ischemic retinopathy.METHODS. After performing BCCAO in rats, the right eyes were treated with PACAP1-27 eye drops (1 lg/drop, 2 3 1 drops/day for 5 days), containing different vehicles: saline, water for injections, thiomersal or benzalkonium solution for ophthalmic use (SOCB). Histology and immunohistochemistry were performed 2 weeks after surgery, while molecular analysis was performed 24 hours after BCCAO. Passage of PACAP1-27 through the ocular layers was tested with radioactive PACAP-SOCB in mice.RESULTS. Bilateral common carotid artery occlusion led to a severe degeneration of all retinal layers. Solution for ophthalmic use was the most effective vehicle for delivering PACAP (PACAP-SOCB), significantly ameliorating BCCAO-induced damage. The massive upregulation of GFAP was not observed in retinas treated with PACAP-SOCB eye drops. PACAP-SOCB treatment also increased activation of the protective Akt and ERK1/2 in hypoperfused retinas. The cytokine profile showing upregulation in different cytokines was attenuated by PACAP-SOCB. Radioactive PACAP reached the retina when delivered in SOCB-containing eye drops.CONCLUSIONS. PACAP1-27, delivered in the SOCB vehicle as eye drops, was retinoprotective in ischemic retinopathy, providing the basis for future therapeutic administration.

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“…Thus, although screening programs have been established and early diagnoses and treatments have been made for the disease, DR still remains the most common cause of visual impairment and blindness [23]. In recent studies, inhibitors of vascular endothelial growth factor (VEGF) have been found to revolutionize the management and treatment of DR and possess special efficacy on diabetic macular edema [24]. However, anti-VEGF agents are not effective in all patients, reinforcing and confirming the fact that DR is a multi-factorial disease which needs to be further elucidated [25].…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin E2 Activates NLRP3 Inflammasome in Endothelial Cells to Promote Diabetic Retinopathy

2018

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Proliferative diabetic retinopathy (PDR) is the leading cause of blindness and accounts for approximately 12% of all new cases of blindness. Prostaglandin E (PGE) and nucleotide-binding domain and Leucine-rich repeat Receptor containing a Pyrin domain 3 (NLRP3) inﬂammasomes have been long considered to be associated with PDR. Levels of pro-inflammatory mediators were examined by Enzyme-linked immunosorbent assay (ELISA) measurements. PGE levels were analyzed by using the Prostaglandin E Monoclonal EIA Kit. Human retinal microvascular endothelial cells (HRMECs) were stained with Annexin V/propidium iodide and analyzed by ﬂow cytometry for testing the apoptosis. Expression levels of NLRP3 inflammasome components under various conditions were detected by Western blot and real-time PCR. Inﬂammasome markers and PGE were highly expressed in the vitreous of PDR patients. PGE and NLRP3 induced apoptosis of HRMECs. PGE upregulated the expression of NLRP3 inﬂammasome components and inﬂammatory chemokines. Knockdown of NLRP3 attenuated the expression of NLRP3 inﬂammasome components and inhibited the effect of PGE. Our results suggest that PGE levels and NLRP3 inﬂammasome activation are closely related to the pathogenesis of PDR and nonsteroidal anti-inﬂammatory drugs may have a potential therapeutic effect on PDR.

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Outcomes of intravitreal anti-VEGF therapy in eyes with both neovascular age-related macular degeneration and diabetic retinopathy

Abstract: Outcomes analysis of intravitreal anti-VEGF therapy for eyes with both neovascular AMD and DR showed stabilisation of BCVA and reduction of CMT, along with stable or improved DR stage throughout follow-up.

Cited by 8 publications

References 31 publications

Time-dependent changes in hypoxia- and gliosis-related factors in experimental diabetic retinopathy

Time-dependent changes in hypoxia- and gliosis-related factors in experimental diabetic retinopathy

Ocular Delivery of PACAP1-27 Protects the Retina From Ischemic Damage in Rodents

Prostaglandin E2 Activates NLRP3 Inflammasome in Endothelial Cells to Promote Diabetic Retinopathy

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