Antibody therapies and their challenges in the treatment of age-related macular degeneration

Volz, Cornelia; Pauly, Diana

doi:10.1016/j.ejpb.2015.02.020

Cited by 57 publications

(47 citation statements)

References 121 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While various novel approaches to treat these diseases are currently under investigation, such as molecular targeting of complement regulators in the innate immune system or visual cycle modulation for geographic atrophy in dry AMD and gene therapy or modified vitamin A derivatives for SMD, direct replacement of the damaged or absent RPE with healthy tissue is an attractive paradigm potentially applicable to both patient populations. [1][2][3][4] In order to regenerate or create healthy RPE, the identity of RPE must be defined structurally and functionally. As a monolayer of polarized columnar epithelial cells with its basal surface resting on Bruch's membrane and its apical microvilli in contact with photoreceptors, critical RPE functions include maintenance of the blood-retina barrier via intercellular tight junctions, phagocytosis of outer segment discs shed by the photoreceptors, metabolic regeneration of 11 cisretinal during the visual cycle, and secretion of growth factors.…”

Section: Introductionmentioning

confidence: 99%

Stem Cell-Based Therapy for Diseases of the Retinal Pigment Epithelium: From Bench to Bedside

Sachdeva

Eliott

2016

Seminars in Ophthalmology

View full text Add to dashboard Cite

Age-related macular degeneration (AMD) represents a leading cause of blindness in the elderly, and Stargardt's macular dystrophy (SMD) is the most common form of juvenile-onset macular degeneration. Dry AMD and SMD share an underlying pathophysiology, namely dysfunction and ultimately loss of the retinal pigment epithelium (RPE), suggesting that RPE transplantation may offer a potential treatment strategy for both patient populations. Stem cells have emerged as a promising source of replacement RPE. During the past 15 years, extraordinary strides have been made in the identification, characterization, and differentiation of stem cells. Recently, this large body of basic science and preclinical research has been translated to patient care with the publication of results from Phase 1/2 trials demonstrating safety of transplantation of human embryonic stem cell (hESC)-derived RPE into patients with AMD and SMD. While significant challenges remain before dry AMD and SMD become treatable diseases, the goal has become more tangible.

show abstract

Section: Introductionmentioning

confidence: 99%

Stem Cell-Based Therapy for Diseases of the Retinal Pigment Epithelium: From Bench to Bedside

Sachdeva

Eliott

2016

Seminars in Ophthalmology

View full text Add to dashboard Cite

show abstract

“…103 A phase II clinical trial has been performed with lampalizumab, which showed a 20% reduction rate of the atrophic area, and an even higher reduction rate was seen in a subpopulation of patients carrying a CFI variant. 102 Currently, lampalizumab is entering phase III, and it is anticipated that inclusion or analysis will be based on the CFI genotype. In addition, another C5 inhibitor, LFG316, currently is entering a phase II clinical trial.…”

Section: New Treatments For Amd Targeting Molecular Disease Mechanismsmentioning

confidence: 99%

“…Several antibodies targeting the complement pathway are currently in the clinical trial phase (Table 2). 102 A phase II clinical trial has been performed with eculizumab, a C5 inhibitor, but has been shown not to be effective. 103 A phase II clinical trial has been performed with lampalizumab, which showed a 20% reduction rate of the atrophic area, and an even higher reduction rate was seen in a subpopulation of patients carrying a CFI variant.…”

Section: New Treatments For Amd Targeting Molecular Disease Mechanismsmentioning

confidence: 99%

Omics in Ophthalmology: Advances in Genomics and Precision Medicine for Leber Congenital Amaurosis and Age-Related Macular Degeneration

Hollander

2016

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Citation: den Hollander AI. Omics in ophthalmology: advances in genomics and precision medicine for Leber congenital amaurosis and age-related macular degeneration. Invest Ophthalmol Vis Sci. 2016;57:1378-1387.The genomic revolution has had a huge impact on our understanding of the genetic defects and disease mechanisms underlying ophthalmic diseases. Two examples are discussed here. The first is Leber congenital amaurosis (LCA), a severe inherited retinal dystrophy leading to severe vision loss in children, and the second is age-related macular degeneration (AMD), the most common cause of vision loss in the elderly. Twenty years ago, the genetic causes of these diseases were unknown. Currently, more than 20 LCA genes have been identified, and genetic testing can now successfully identify the genetic defects in at least 75% of all LCA cases. Genespecific treatments have entered the clinical trial phase for three LCA genes, and for seven LCA genes gene-specific therapies have been tested in model systems. Age-related macular degeneration is a multifactorial disease caused by a combination of genetic and environmental factors. Currently, more than 40 loci have been identified for AMD, accounting for 15%-65% of the total genetic contribution to AMD. Despite the progress that has been made so far, genetic testing is not yet recommended for AMD, but this may change if we move to clinical trials or treatments that are dependent on an individual's genotype. The identification of serum or plasma biomarkers using other ''-omics'' technologies may further improve predictive tests and our understanding of the disease mechanisms of AMD. Ultimately, it is anticipated that predictive tests will help to stratify patients for the most suitable therapy, which will enable the development of precision medicine, tailored to individual needs.

show abstract

“…This multifactorial disease results from the combined effects of age, environment, and genetic predisposition. Antibody-based treatment of late-stage neovascular AMD with inhibitors of vascular endothelial growth factor (VEGF) has shown great success and has Ophthalmologica 2019;241:32-37 DOI: 10.1159/000489344 markedly reduced the risk of vision loss [1]. The number of ophthalmoscopies combined with SD-OCTs has been shown to be a significant prognostic factor for vision maintenance or vision gain in patients with neovascular AMD [2].…”

Section: Introductionmentioning

confidence: 99%

Spectral Domain Optical Coherence Tomography Allows the Unification of Clinical Decision Making for the Evaluation of Choroidal Neovascularization Activity

et al. 2018

Self Cite

View full text Add to dashboard Cite

Purpose: This prospective observational clinical study investigated the benefits of spectral domain optical coherence tomography for specialists and residents in the management of neovascular age-related macular degeneration (AMD). Procedures: The study involved 49 eyes of 44 patients. Patients were advised to present for reevaluation 4 weeks after the administration of the loading dose of vascular endothelial growth factor (VEGF)-inhibitors (3 intravitreal injections every 4 weeks after diagnosis). They were examined by residents (3–4 years’ experience in ophthalmology) and specialists (> 5 years’ experience). Each examiner evaluated the clinical situation and the spectral domain optical coherence tomography (SD-OCT) scan. After each evaluation, the examiners independently stated if further anti-VEGF treatment was recommended. The “true outcome” was defined as the specialist decision based on clinical evaluation and SD-OCT. Results: Specialists and residents did not significantly differ in their accuracy in deciding on the correct treatment (p = 0.705 and p = 1), with or without the aid of SD-OCT. Both groups benefited from using SD-OCT to support their recommendations (p = 0.001 and p = 0.0002) and achieved a similar level of accuracy (p = 1 for difference). Conclusions: Residents benefited more than specialists by using SD-OCT to substantiate their recommendation on how to manage exudative AMD after the administration of the loading dose.

show abstract

Antibody therapies and their challenges in the treatment of age-related macular degeneration

Cited by 57 publications

References 121 publications

Stem Cell-Based Therapy for Diseases of the Retinal Pigment Epithelium: From Bench to Bedside

Stem Cell-Based Therapy for Diseases of the Retinal Pigment Epithelium: From Bench to Bedside

Omics in Ophthalmology: Advances in Genomics and Precision Medicine for Leber Congenital Amaurosis and Age-Related Macular Degeneration

Spectral Domain Optical Coherence Tomography Allows the Unification of Clinical Decision Making for the Evaluation of Choroidal Neovascularization Activity

Contact Info

Product

Resources

About