Intravitreal bevacizumab combined with infliximab in the treatment of choroidal neovascularization secondary to age-related macular degeneration: case report series

Freitas, Luiz Guilherme Azevedo de; Isaac, David Leonardo Cruvinel; Tannure, William Thomas; Gabriel, Luis Alexandre Rassi; Reis, Ricardo Prado Abreu; Rassi, Alan Ricardo; Freitas, Corina da Costa; Ávila, Marcos Pereira de

doi:10.1590/s0004-27492013000300010

Cited by 11 publications

(6 citation statements)

References 17 publications

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“…There was, however, no placebo group in this trial. Other small studies using intravitreal anti-TNF-α therapy combined with bevacizumab showed beneficial effects [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

The effect of systemic levels of TNF-alpha and complement pathway activity on outcomes of VEGF inhibition in neovascular AMD

Khan

Pierce

Salvo

et al. 2021

Eye

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Background/Objectives Systemic levels of pro-inflammatory cytokines and activated complement components affect the risk and/or progression of neovascular age-related macular degeneration (AMD). This study investigated the effect of serum pro-inflammatory cytokine levels and complement pathway activity on the clinical response to vascular endothelial growth factor (VEGF) inhibition in neovascular AMD. Methods Sixty-five patients with a new diagnosis of neovascular AMD were observed over a six-month period in a single-centre, longitudinal cohort study. At each visit, the visual acuity score (VAS), central macular thickness (CMT), serum levels of CRP, pro-inflammatory cytokines (TNF-α, IL-1β, IL-2, IL-6 and IL-8), and complement pathway activity were measured. Participant DNA samples were sequenced for six complement pathway single nucleotide polymorphisms (SNPs) associated with AMD. Results A statistically significant difference in VAS was observed for serum levels of TNF-α only: there was a gain in VAS (from baseline) of 1.37 for participants below the 1st quartile of mean concentration compared to a reduction of 2.71 for those above the 3rd quartile. Statistical significance was maintained after Bonferroni correction (P value set at <0.006). No significant differences in CMT were observed. In addition, statistically significant differences, maintained after Bonferroni correction, were observed in serum complement activity for participants with the following SNPs: CFH region (rs1061170), SERPING1 (rs2511989) and CFB (rs641153). Serum complement pathway components did not significantly affect VAS. Conclusions Lower serum TNF-α levels were associated with an increase in visual acuity after anti-VEGF therapy. This suggests that targeting pro-inflammatory cytokines may augment treatment for neovascular AMD.

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“…There was, however, no placebo group in this trial. Other small studies using intravitreal anti-TNF-α therapy combined with bevacizumab showed beneficial effects [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

The effect of systemic levels of TNF-alpha and complement pathway activity on outcomes of VEGF inhibition in neovascular AMD

Khan

Pierce

Salvo

et al. 2021

Eye

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“…Besides that, LyeTx I b was administered in a single I.V. application, whereas Freitas et al (2013) [ 29 ] performed a clinical study using multiple intravitreal injections, during which all eyes developed cataract and one patient developed vitritis. One eye had mild persistent submacular fluid without active choroidal neovascularization, whereas the other eye had a persistent amount of intraretinal fluid due to active choroidal neovascularization.…”

Section: Discussionmentioning

confidence: 99%

Intravitreal injection of the synthetic peptide LyeTx I b, derived from a spider toxin, into the rabbit eye is safe and prevents neovascularization in a chorio-allantoic membrane model

Silva

Paiva

Dourado

et al. 2018

J Venom Anim Toxins Incl Trop Dis

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BackgroundThe great diversity of molecules found in spider venoms include amino acids, polyamines, proteins and peptides, among others. Some of these compounds can interact with different neuronal receptors and ion channels including those present in the ocular system. To study potential toxicity and safety of intravitreal injection in rabbits of LyeTx I b, a synthetic peptide derived from the toxin LyeTx I found in venom from the spider Lycosa eritrognatha and to evaluate the angiogenic activity on a CAM model.MethodsARPE-19 cells were treated with LyeTx I b (0.36; 0.54; 0.72; 2.89; 4.34 or 9.06 μM). In this study, New Zealand rabbits were used. LyeTx I b (2.89 μM) labeled with FITC dissolved in PBS, or only PBS, were injected into vitreous humor. Electroretinogram (ERG) was recorded 1 day before injection and at 7, 14 and 28 days post-injection. Clinical examination of the retina was conducted through tonometer and eye fundus after ERG. Eyes were enucleated and retinas were prepared for histology in order to assess retinal structure. CAMs were exposed to LyeTx I b (0.54; 0.72; 2.17 or 2.89 μM).ResultsARPE-19 cells exposed to LyeTx I b showed cell viability at the same levels of the control. The fluorescence of LyeTx I b labeled with FITC indicated its retinal localization. Our findings indicate ERG responses from rats injected in the eye with LyeTx I b were very similar to the corresponding responses of those animals injected only with vehicle. Clinical examination found no alterations of intraocular pressure or retinal integrity. No histological damage in retinal layers was observed. CAM presented reduced neovascularization when exposed to LyeTx I b.ConclusionsIntravitreal injection of LyeTx I b is safe for use in the rabbit eye and prevents neovascularization in the CAM model, at Bevacizumab levels. These findings support intravitreal LyeTx I b as a good candidate to develop future alternative treatment for the retina in neovascularization diseases.

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“…Cataract progressed in four of five patients and one patient developed vasculitis and vitritis 1 month after the second injection. 171…”

Section: Biologicalsmentioning

confidence: 99%

“…Cataract progressed in four of five patients and one patient developed vasculitis and vitritis 1 month after the second injection. 171 Diabetic macular edema. A single retrospective study on the use of intravitreal TNF-alpha inhibitors in refractory DME showed no significant change in BCVA or CMT with the use of intravitreal infliximab.…”

Section: Infliximabmentioning

confidence: 99%

A comprehensive review of intravitreal immunosuppressants and biologicals used in ophthalmology

et al. 2022

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Systemic immunosuppressants and biologicals have been a valuable tool in the treatment of inflammatory diseases and malignancies. The safety profile of these drugs has been debatable, especially in localized systems, such as the eye. This has led to the search for fairly local approaches, such as intravitreal, subconjunctival, and topical route of administration. Immunosuppressants have been used as a second-line drug in patients intolerable to corticosteroids or those who develop multiple recurrences on weaning corticosteroids. Similarly, biologicals have also been used as the next line of therapy, when adequate control of inflammation could not be attained or immunosuppressants were contraindicated to patients. Intravitreal immunosuppressants, such as methotrexate and sirolimus, have been extensively studied in noninfectious posterior uveitis, whereas limited studies have established the efficacy of intravitreal biologicals, such as infliximab and adalimumab. Most of these drugs have shown good safety profile and tolerability in animal studies alone and have not been studied further in human subjects. However, most of the studies in literature are single-case reports or case series which limits the level of evidence. In this comprehensive review, we discuss the mechanism of action, pharmacodynamics, pharmacokinetics, indications, efficacy, and side effects of different intravitreal immunosuppressants and biologicals that have been studied in literature.

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Intravitreal bevacizumab combined with infliximab in the treatment of choroidal neovascularization secondary to age-related macular degeneration: case report series

Cited by 11 publications

References 17 publications

The effect of systemic levels of TNF-alpha and complement pathway activity on outcomes of VEGF inhibition in neovascular AMD

The effect of systemic levels of TNF-alpha and complement pathway activity on outcomes of VEGF inhibition in neovascular AMD

Intravitreal injection of the synthetic peptide LyeTx I b, derived from a spider toxin, into the rabbit eye is safe and prevents neovascularization in a chorio-allantoic membrane model

A comprehensive review of intravitreal immunosuppressants and biologicals used in ophthalmology

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