Change in Drusen Volume as a Novel Clinical Trial Endpoint for the Study of Complement Inhibition in Age-related Macular Degeneration

Filho, Carlos Alexandre de Amorim Garcia; Yehoshua, Zohar; Gregori, Giovanni; Nunes, Renata Portella; Penha, Fernando M.; Moshfeghi, Andrew A; Zhang, Kang; Feuer, William J.; Rosenfeld, Philip J.

doi:10.3928/23258160-20131217-01

Cited by 78 publications

(36 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“… 53 Other potential anatomic end points might be prevention of worsening of intermediate AMD pre-GA and decrease in volume and area of macular drusen. 54 The US Food and Drug Administration has recently accepted the anatomic end point of GA enlargement rate as a main outcome parameter in clinical trials for new therapies. 55 …”

Section: Clinical Imaging Assessment Of Gamentioning

confidence: 99%

Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects

Danis¹,

Lavine²,

Domalpally³

2015

OPTH

View full text Add to dashboard Cite

Geographic atrophy (GA) of the retinal pigment epithelium (RPE) is a devastating complication of age-related macular degeneration (AMD). GA may be classified as drusen-related (drusen-associated GA) or neovascularization-related (neovascular-associated GA). Drusen-related GA remains a large public health concern due to the burden of blindness it produces, but pathophysiology of the condition is obscure and there are no proven treatment options. Genotyping, cell biology, and clinical imaging point to upregulation of parainflammatory pathways, oxidative stress, and choroidal sclerosis as contributors, among other factors. Onset and monitoring of progression is accomplished through clinical imaging instrumentation such as optical coherence tomography, photography, and autofluorescence, which are the tools most helpful in determining end points for clinical trials at present. A number of treatment approaches with diverse targets are in development at this time, some of which are in human clinical trials. Neovascular-associated GA is a consequence of RPE loss after development of neovascular AMD. The neovascular process leads to a plethora of cellular stresses such as ischemia, inflammation, and dramatic changes in cell environment that further taxes RPE cells already dysfunctional from drusen-associated changes. GA may therefore develop secondary to the neovascular process de novo or preexisting drusen-associated GA may continue to worsen with the development of neovascular AMD. Neovascular-associated GA is a prominent cause of continued vision loss in patients with otherwise successfully treated neovascular AMD. Clearly, treatment with vascular endothelial growth factor (VEGF) inhibitors early in the course of the neovascular disease is of great clinical benefit. However, there is a rationale and some suggestive evidence that anti-VEGF agents themselves could be toxic to RPE and enhance neovascular-associated GA. The increasing prevalence of legal blindness from this condition due to the aging of the general population lends urgency to the search for a therapy to ameliorate GA.

show abstract

Section: Clinical Imaging Assessment Of Gamentioning

confidence: 99%

Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects

Danis¹,

Lavine²,

Domalpally³

2015

OPTH

View full text Add to dashboard Cite

show abstract

“…The COMPLETE study showed no reduction of GA progression by Eculizumab, but the low luminance deficit at baseline was significantly correlated with the progression of GA over 6 months 34, 35 .…”

Section: Management Of Dry Amd: Current Therapeutic Developmentsmentioning

confidence: 87%

Recent advances in the management of dry age-related macular degeneration: A review

et al. 2017

View full text Add to dashboard Cite

Age-related macular degeneration (AMD), the most important cause of vision loss in elderly people, is a degenerative disorder of the central retina with a multifactorial etiopathology. AMD is classified in dry AMD (d-AMD) or neovascular AMD depending on the presence of choroidal neovascularization. Currently, no therapy is approved for geographic atrophy, the late form of d-AMD, because no treatment can restore the damage of retinal pigment epithelium (RPE) or photoreceptors. For this reason, all treatment approaches in d-AMD are only likely to prevent and slow down the progression of existing atrophy. This review focuses on the management of d-AMD and especially on current data about potential targets for therapies evaluated in clinical trials. Numerous examinations are available in clinics to monitor morphological changes in the retina, RPE and choroid of d-AMD patients. Fundus autofluorescence and optical coherence tomography (OCT) are considered the most useful tools in the diagnosis and follow-up of d-AMD alterations, including the monitoring of atrophy area progression. Instead, OCT-angiography is a novel imaging tool that may add further information in patients affected by d-AMD. Several pathways, including oxidative stress, deposits of lipofuscin, chronic inflammation and choroidal blood flow insufficiency, seem to play an important role in the pathogenesis of d-AMD and represent possible targets for new therapies. A great number of treatments for d-AMD are under investigation with promising results in preliminary studies. However, only few of these drugs will enter the market, offering a therapeutic chance to patients affected by the dry form of AMD and help them to preserve a good visual acuity. Further studies with a long-term follow-up would be important to test the real safety and efficacy of drugs under investigation.

show abstract

“…A drusen baseline volume of 0.03 mm 3 has been shown to be suitable to follow drusen growth [32] and the cube-root strategy should be used to evaluate drusen growth/shrinkage over time [33]. …”

Section: Biomarkers In Age Related Macular Degenerationmentioning

confidence: 99%

The potential of spectral domain optical coherence tomography imaging based retinal biomarkers

et al. 2017

View full text Add to dashboard Cite

BackgroundBiomarker”, a merged word of “biological marker”, refers to a broad subcategory of medical signs that objectively indicate the state of health, and well-being of an individual. Biomarkers hold great promise for personalized medicine as information gained from diagnostic or progression markers can be used to tailor treatment to the individual for highly effective intervention in the disease process. Optical coherence tomography (OCT) has proved useful in identifying various biomarkers in ocular and systemic diseases.Main bodySpectral domain optical coherence tomography imaging-based biomarkers provide a valuable tool for detecting the earlier stages of the disease, tracking progression, and monitoring treatment response. The aim of this review article is to analyze various OCT based imaging biomarkers and their potential to be considered as surrogate endpoints for diabetic retinopathy, age related macular degeneration, retinitis pigmentosa and vitreomacular interface disorder. These OCT based surrogate markers have been classified as retinal structural alterations (macular central subfield thickness and cube average thickness); retinal ultrastructural alterations (disruption of external limiting membrane and ellipsoid zone, thinning of retinal nerve fiber layer and ganglion cell layer); intraretinal microangiopathic changes; choroidal surrogate endpoints; and vitreoretinal interface endpoints.ConclusionOCT technology is changing very quickly and throughout this review there are some of the multiple possibilities that OCT based imaging biomarkers will be more useful in the near future for diagnosis, prognosticating disease progression and as endpoint in clinical trials.

show abstract

Change in Drusen Volume as a Novel Clinical Trial Endpoint for the Study of Complement Inhibition in Age-related Macular Degeneration

Cited by 78 publications

References 43 publications

Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects

Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects

Recent advances in the management of dry age-related macular degeneration: A review

The potential of spectral domain optical coherence tomography imaging based retinal biomarkers

Contact Info

Product

Resources

About