Dexamethasone intravitreal implant as adjunct therapy for patients with wet age-related macular degeneration with incomplete response to ranibizumab

Purpose: To evaluate the efficacy of a dexamethasone intravitreal implant in combination with intravitreal anti-vascular endothelial growth factor (VEGF) agents for treatment-resistant neovascular age-related macular degeneration (nvAMD). Methods: This study was designed as a single-center, retrospective interventional case series. Consecutive patients with treatment-resistant nvAMD underwent simultaneous combined injection of anti-VEGF agent and dexamethasone intravitreal implant. Eighteen patients with mean age of 81.5 years were included. Patients received an average of 26.3 anti-VEGF injections before dual therapy, with a mean follow-up of 8.2 months after dual therapy. Results: Dual therapy produced a significant mean decrease in central foveal thickness (126.3 μm), compared to a mean increase in 29.9 μm when treated with anti-VEGF monotherapy ( P = .0017). Patients also had a mean decrease in macular cube volume of −0.85 mm3 with dual therapy compared to anti-VEGF monotherapy ( P = .0014). There was a moderate correlation between the number of prior anti-VEGF injections and the magnitude of anatomic response, suggesting that shorter disease duration may positively influence response to combined treatment. Although there was a slight trend toward improved mean visual acuity after dual therapy, these differences did not reach statistical significance. Nevertheless, with combination treatment, 33% of patients gained 1 or more lines of vision. Dual therapy resulted in a significantly lower number of required anti-VEGF injections (4.25 vs 5.33) and an increase in the anti-VEGF injection-free interval to 1.41 months from 1.12 months during the 6 months following dual therapy compared to the same interval before dual therapy. Dual therapy was well tolerated; 2 eyes developed mild intraocular pressure elevation effectively managed with topical therapy and 1 patient developed worsening cataract. Conclusions: Combined treatment of anti-VEGF with dexamethasone intravitreal implant is a viable alternative for treatment-resistant nvAMD and may reduce treatment burden. Earlier treatment with dual therapy may be beneficial to maximize anatomic and visual outcomes in these patients.

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Dexamethasone Intravitreal Implant as Adjunctive Therapy to Ranibizumab in Neovascular Age-Related Macular Degeneration: A Multicenter Randomized Controlled Trial

Ophthalmologica ◽

10.1159/000381865 ◽

2015 ◽

Vol 234 (1) ◽

pp. 40-54 ◽

Cited By ~ 14

Author(s):

Baruch D. Kuppermann ◽

Michaella Goldstein ◽

Raj K. Maturi ◽

Ayala Pollack ◽

Michael Singer ◽

...

Keyword(s):

Macular Degeneration ◽

Adjunctive Therapy ◽

Controlled Trial ◽

Age Related Macular Degeneration ◽

Intravitreal Ranibizumab ◽

Dexamethasone Intravitreal Implant ◽

Free Interval ◽

Intravitreal Implant

Purpose: To evaluate the efficacy and safety of dexamethasone intravitreal implant 0.7 mg (DEX) as adjunctive therapy to ranibizumab in neovascular age-related macular degeneration (nvAMD). Procedures: This was a 6-month, single-masked, multicenter study. Patients were randomized to DEX implant (n = 123) or sham procedure (n = 120) and received 2 protocol-mandated intravitreal ranibizumab injections. The main outcome measure was injection-free interval to first as-needed ranibizumab injection. Results: DEX increased the injection-free interval versus sham (50th percentile, 34 vs. 29 days; 75th percentile, 85 vs. 56 days; p = 0.016). 8.3% of DEX versus 2.5% of sham-treated patients did not require rescue ranibizumab (p = 0.048). Visual acuity and retinal thickness outcomes were similar in DEX and sham-treated patients. Only reports of conjunctival hemorrhage (18.2 vs. 8.5%) and intraocular pressure elevation (13.2 vs. 4.2%) were significantly different in the DEX versus the sham treatment groups. Conclusion: DEX reduced the need for adjunctive ranibizumab treatment and showed acceptable tolerability in nvAMD patients.

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Molecular Biomarkers of Neovascular Age-Related Macular Degeneration With Incomplete Response to Anti-Vascular Endothelial Growth Factor Treatment

Frontiers in Pharmacology ◽

10.3389/fphar.2020.594087 ◽

2020 ◽

Vol 11 ◽

Author(s):

Irmela Mantel ◽

Angelica Borgo ◽

Jacopo Guidotti ◽

Edwige Forestier ◽

Olga Kirsch ◽

...

Keyword(s):

Growth Factor ◽

Macular Degeneration ◽

Inflammatory Responses ◽

Molecular Biomarkers ◽

Age Related Macular Degeneration ◽

Interleukin 12 ◽

Vascular Endothelial ◽

Incomplete Response ◽

Anti Vegf ◽

Age Related

The standard treatment for neovascular age-related macular degeneration (nAMD) consists of intravitreal anti-vascular endothelial growth factors (VEGF). However, for some patients, even maximal anti-VEGF treatment does not entirely suppress exudative activity. The goal of this study was to identify molecular biomarkers in nAMD with incomplete response to anti-VEGF treatment. Aqueous humor (AH) samples were collected from three groups of patients: 17 patients with nAMD responding incompletely to anti-VEGF (18 eyes), 17 patients affected by nAMD with normal treatment response (21 eyes), and 16 control patients without any retinopathy (16 eyes). Proteomic and multiplex analyses were performed on these samples. Proteomic analyses showed that nAMD patients with incomplete anti-VEGF response displayed an increased inflammatory response, complement activation, cytolysis, protein-lipid complex, and vasculature development pathways. Multiplex analyses revealed a significant increase of soluble vascular cell adhesion molecule-1 (sVCAM-1) [ p = 0.001], interleukin-6 (IL-6) [ p = 0.009], bioactive interleukin-12 (IL-12p40) [ p = 0.03], plasminogen activator inhibitor type 1 (PAI-1) [ p = 0.004], and hepatocyte growth factor (HGF) [ p = 0.004] levels in incomplete responders in comparison to normal responders. Interestingly, the same biomarkers showed a high intercorrelation with r2 values between 0.58 and 0.94. In addition, we confirmed by AlphaLISA the increase of sVCAM-1 [ p < 0.0001] and IL-6 [ p = 0.043] in the incomplete responder group. Incomplete responders in nAMD are associated with activated angiogenic and inflammatory pathways. The residual exudative activity of nAMD despite maximal anti-VEGF treatment may be related to both angiogenic and inflammatory responses requiring specific adjuvant therapy. Data are available via ProteomeXchange with identifier PXD02247

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Age related macular degeneration (ARMD) – pathophysiological and clinical features and therapeutic concepts

Therapeutische Umschau ◽

10.1024/0040-5930.58.1.28 ◽

2001 ◽

Vol 58 (1) ◽

pp. 28-35 ◽

Cited By ~ 1

Author(s):

Ursula Körner-Stiefbold

Keyword(s):

Macular Degeneration ◽

Clinical Features ◽

Altersbedingte Makuladegeneration ◽

Age Related Macular Degeneration ◽

Genetische Faktoren ◽

Age Related ◽

Therapeutic Concepts

Die altersbedingte Makuladegeneration (AMD) ist eine der häufigsten Ursachen für einen irreversiblen Visusverlust bei Patienten über 65 Jahre. Nahezu 30% der über 75-Jährigen sind von einer AMD betroffen. Trotz neuer Erkenntnisse in der Grundlagenforschung ist die Ätiologie, zu der auch genetische Faktoren gehören, noch nicht völlig geklärt. Aus diesem Grund sind die Behandlungsmöglichkeiten zum jetzigen Zeitpunkt noch limitiert, so dass man lediglich von Therapieansätzen sprechen kann. Die derzeit zur Verfügung stehenden Möglichkeiten wie medikamentöse, chirurgische und laser- und strahlentherapeutische Maßnahmen werden beschrieben.

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