New Drugs in the Pipeline for the Management of AMD

Anti-vascular endothelial growth factor (anti-VEGF) therapies have revolutionized the care of patients with retinal diseases. In the 1990s, it was observed that anti-VEGF antibodies reduced tumor angiogenesis, and consequently, these antibodies started to be used off-label in the exudative form of age-related macular degeneration (AMD). In the 2000s, research was directed towards the development of anti-VEGF therapies for retinal disease management. Several anti-VEGF therapies were approved: pegaptanib, an RNA aptamer, in 2004; ranibizumab, an anti-VEGF Fab, in 2008; aflibercept, a humanized IgG Fc, in 2011; and brolucizumab, an scFv, in 2019. Currently, new therapeutic options are emerging, and approval is expected soon. These new therapies aim to increase treatment durability and thus reduce treatment burden and improve real-world outcomes. In this chapter, the mechanisms of action and the preliminary trial results of these potential new therapies will be described

Real-world retrospective comparison of 0.19 mg fluocinolone acetonide and 0.7 mg dexamethasone intravitreal implants for the treatment of diabetic macular edema in vitrectomized eyes

Purpose: The aim of this study was to evaluate the long-term real-world effectiveness of FAc and DEX implants in vitrectomized DME eyes in a real-world setting. Methods: This was a non-interventional, retrospective, comparative study of 46 vitrectomized eyes in 33 patients with persistent or recurrent DME quantified best-corrected visual acuity (BCVA), central foveal thickness (CFT) and intraocular pressure (IOP) over up to 37 months. Results: Both FAc and DEX treatment led to statistically and clinically significant improvements in BCVA and CFT. FAc >10-letter improvement on the Early Treatment Diabetic Retinopathy Study [ETDRS] chart over months 3-24 and a sustained ~200 µm CFT reduction over months 1-24; DEX: >5-letter improvement on the ETDRS chart at months 1 and 3 and >100 µm CFT reduction at month 1. FAc demonstrated sustained, stable and predictable effects on BCVA and CFT over 24 months and also improved BCVA and decreased CFT in a cohort of DME eyes that was refractory to DEX over 6 months. Conclusion: This real-world study demonstrates long-term effectiveness of FAc in vitrectomized DME eyes and sustained effectiveness in DME eyes that did not respond to DEX therapy.Writing support was provided by Hayward Medical Communications and funded by Alimera Sciences Ltd. This paper was funded by Alimera Sciences Ltd.info:eu-repo/semantics/publishedVersio

Aqueous humor erythropoietin levels in open-angle glaucoma patients with and without TTR V30M familial amyloid polyneuropathy

Purpose: Glaucoma is the leading cause of irreversible blindness in familial amyloidotic polyneuropathy (FAP) patients. Erythropoietin (EPO) is a cytokine that has been shown to play a role in neuroprotection and is endogenously produced in the eye. EPO levels in the aqueous humor are increased in eyes with glaucoma. In this study, we evaluated the EPO concentration in the aqueous humor of FAP and non-FAP patients, with and without glaucoma. Methods: Undiluted aqueous humor samples were obtained from 42 eyes that underwent glaucoma surgery, phacoemulsification, or vitrectomy. EPO concentration in the aqueous humor and blood were measured using the Immulite 2000 Xpi using an automatic analyzer (Siemens Healthcare Diagnostics). Results: The mean EPO concentration in the aqueous humor of non-FAP glaucoma eyes group 2 (75.73±13.25 mU/ml) was significantly higher than non-FAP cataract eyes (17.22±5.33 mU/ml; p<0.001), FAP glaucoma eyes (18.82±10.16 mU/ml; p<0.001), and FAP nonglaucoma eyes (20.62±6.22 mU/ml; p<0.001). There was no statistically significant difference between FAP nonglaucoma eyes versus non-FAP cataract eyes (p = 0.23) and FAP glaucoma eyes versus FAP nonglaucoma eyes (p = 0.29). In the glaucoma groups, there was no correlation between the aqueous humor EPO concentration and the ocular pressure (p = 0.95) and mean deviation (p = 0.41). There was no correlation between the EPO serum concentration and EPO aqueous humor concentration in our patients (p = 0.77). Conclusions: Unlike other glaucomatous patients, FAP patients with glaucoma do not show increased and potentially neuroprotective endocular EPO production in the aqueous humor and may need more aggressive glaucoma management

Enzymatic vitreolysis for the treatment of tractional diabetic macular edema

© The Author(s), 2019. Article reuse guidelines: sagepub.com/journalspermissionsBackground: A new approach to address focal vitreomacular adhesion in patients with diabetic macular edema may control and stabilize diabetic macular edema with fewer antivascular endothelial growth factor injections. Objectives: The aim of this study was to demonstrate that diabetic macular edema can be improved by inducing the release of a vitreomacular adhesion, with less than 2500μm, with enzymatic vitreolysis. Methods: From a retrospective analysis of clinical records from patients with diabetic retinopathy, patients with diabetic macular edema and vitreomacular adhesion <2500μm were selected for a single-arm prospective study. The primary endpoint was to control diabetic macular edema with fewer anti-vascular endothelial growth factor injections after an observed vitreomacular adhesion release. A statistical subanalysis was performed for the following two groups: the group with vitreomacular adhesion release (group 1) and the group without vitreomacular adhesion release (group 2). Results: A total of 23 eyes from 19 patients were included. A reduction of the median number of injections was achieved in group 1 (p=0.006). Adverse events were mild and transitory. Conclusion: Release of vitreomacular adhesion <2500μm through enzymatic vitreolysis contributed to the control and stabilization of diabetic macular edema with fewer anti-vascular endothelial growth factor injections, reducing the burden and the risks related to these invasive and frequently chronic treatments.info:eu-repo/semantics/publishedVersio

Challenging Clinical Cases – A Walk Through Supplemental Therapy with Intravitreal Ranibizumab Therapy Following Treatment of Diabetic Macular Edema with the 0.19 mg Fluocinolone Acetonide Implant (ILUVIEN®)

Purpose: There are limited published data regarding the use of supplemental intravitreal therapies in patients with diabetic macular edema (DME) following treatment with the 0.19 mg fluocinolone acetonide (FAc; ILUVIEN®) intravitreal implant. The aim of this report was to analyze five challenging eyes that required supplemental therapies after treatment with the FAc implant. Methods: This is a retrospective case series conducted at the Centro Hospitalar Universitário do Porto in Porto, Portugal, between 2015 and 2019. It aimed to assess the patient background, treatment history and patient outcomes in challenging clinical cases in which intravitreal injections (IVI) of ranibizumab had been given pro re nata following treatment with the FAc implant (with a minimum follow-up of 33 months). Parameters measured included best-corrected visual acuity in early treatment diabetic retinopathy scale, central macular thickness and intraocular pressure. Patients: Five eyes (three patients) diagnosed with persistent or recurrent DME and suitable for treatment with the FAc implant according to its licensed indication in Europe. Results: In the first 2 patients, one bilateral, DME was refractory to IVI of short-acting corticosteroids and anti-VEGF. Following FAc therapy, there was a favorable evolution and a clear regression of diabetic retinopathy (DR) severity. Supplemental treatments were adopted, but a reduced number of treatments were needed beyond three years in these cases. The third case had bilateral DME. One eye had been vitrectomized and FAc therapy led to resolution of DME within 6 months. In the contralateral eye, the control of DME was dependent on anti-VEGF supplemental treatments until a pars plana vitrectomy was performed. Conclusion: The multifactorial nature of DME means there is a need for an individualized treatment approach to the management of DME. It also explains why some patients need a combined or a more aggressive approach to therapy in order to achieve successful outcomes for the patient.info:eu-repo/semantics/publishedVersio

Long-term management of non-ischemic central retinal vein occlusion with fluocinolone acetonide intravitreal implant 190 μg (ILUVIEN®)

Introduction: Macular edema after central retinal vein occlusion is a common cause of vision loss. Upregulation of vascular endothelial growth factor and higher levels of inflammatory mediators have been involved in the pathogeny of the macular edema in central retinal vein occlusion. Case report: The authors report a case with non-ischemic central retinal vein occlusion that was successfully treated with a single sustained-release fluocinolone acetonide intravitreal implant. After a course of repeated injections of shorter-acting corticosteroid, the affected eye presented a visual acuity of 20/200 and a central subfield foveal thickness of 587 µm. After fluocinolone acetonide in intravitreal implant and during a follow-up period of 12 months, a continuous and sustained increase in visual acuity until 20/25 with significant anatomical improvements and an acceptable safety profile was observed. Conclusion: These results, demonstrate that fluocinolone acetonide intravitreal implant might be an effective treatment option in macular edema secondary to non-ischemic central retinal vein occlusion

Fluocinolone Acetonide 0.19 mg Implant in Patients with Cystoid Macular Edema Due To Irvine–Gass Syndrome

Background: Cystoid macular edema (CME) due to Irvine-Gass syndrome (IGS) is one of the common causes of painless visual impairment post-cataract extraction. The treatment of recurrent cases remains unstandardized. Objective: To evaluate the effectiveness and safety of fluocinolone acetonide intravitreal implant (0.2 µg/day; ILUVIEN®) in the off-label treatment of recurrent CME due to IGS. Methods: Retrospective 36-month case series in the Ophthalmology Department of Centro Hospitalar Universitário do Porto, Portugal. Consecutive eyes of patients with recurrent cystoid macular edema due to Irvine-Gass syndrome who underwent a single intravitreal injection of fluocinolone acetonide intravitreal implant were included. Best-corrected visual acuity (logMAR), central macular thickness (µm) and safety (intraocular pressure, mmHg) at baseline and at 6, 12, 24 and 36 months post-administration of the fluocinolone acetonide intravitreal implant were recorded. Results: Five eyes from three patients were included. The duration of cystoid macular edema was 67.8±25.9 months and all five eyes received more than 2 intravitreal injections of a corticosteroid (triamcinolone and/or dexamethasone implant) prior to fluocinolone acetonide intravitreal implantation. At baseline (median - interquartile range), best-corrected visual acuity was 0.3-0.3; central macular thickness was 492.0-38.0; and intraocular pressure was 16.0-0. By Month 36, best-corrected visual acuity was 0.4 -0.3; central macular thickness was reduced to 369.0-324.0 and intraocular pressure was 17.0-3.0. Four of five eyes had increased intraocular pressure and were managed with intraocular pressure-lowering eye drops. Conclusion: We report improved functional and anatomical outcomes after treatment with fluocinolone acetonide intravitreal implant, indicating its use as a therapeutic alternative in recurrent cases of cystoid macular edema due to Irvine-Gass syndrome. Additionally, in eyes with suboptimal response to intravitreal therapies, fluocinolone acetonide intravitreal implant may provide longer recurrence-free periods with reduced treatment burden.info:eu-repo/semantics/publishedVersio