Prevalence and quantification of geographic atrophy associated with newly diagnosed and treatment-naïve exudative age-related macular degeneration

Sikorav, Anne; Semoun, Oudy; Zweifel, Sandrine; Jung, Camille; Srour, Mayer; Querques, Giuseppe; Souied, Eric H.

doi:10.1136/bjophthalmol-2015-308065

Cited by 13 publications

(15 citation statements)

References 43 publications

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“…5 ). Choroidal neovascularization has been observed in a sub-population of patients diagnosed with GA and points to disruption of the outer blood-retinal barrier 6 , 7 . To address the in vivo consequences of complement activation on POS, we recapitulated RPE cell death and loss of outer blood-retina barrier (BRB) function by treating mice with NaIO 3 39 that induces death of RPE within hours 40 , 41 .…”

Section: Resultsmentioning

confidence: 99%

“…Complement risk alleles predispose to both the neovascular and dry forms of AMD 9 , 61 , consistent with complement being implicated in early pathophysiological processes, including the formation of drusen and subretinal drusenoid deposits, that have been reported to precede both neovascular AMD and GA 5 , 24 . The source of complement observed in the retina of a subset of GA cases needs further investigation but may be systemic in origin and the result of transient disruption of the blood-retinal barrier as evidenced by the presence of sub-retinal choroidal neo-vessels observed in a sub-population of patients diagnosed with GA 6 , 7 .…”

Section: Discussionmentioning

confidence: 99%

“…There are two main types of AMD: exudative, or neovascular AMD, which is characterized by disruption of the Bruch’s membrane and retinal pigment epithelium (RPE) with subsequent invasion of the retina by choroidal neovessels; and geographic atrophy (GA), which is associated with characteristic extracellular deposits and loss of RPE and photoreceptors 4 , 5 . While GA is generally seen as an avascular disease, quiescent microvasculature associated with GA has been observed in a subpopulation of patients 6 , 7 . Vision loss associated with neovascular AMD can be treated with VEGF inhibitors with favorable outcomes, but there are currently no approved or effective therapies for the treatment of GA 8 .…”

Section: Introductionmentioning

confidence: 99%

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Classical and alternative complement activation on photoreceptor outer segments drives monocyte-dependent retinal atrophy

Katschke¹,

Xi²,

Cox³

et al. 2018

Sci Rep

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Geographic atrophy (GA), the advanced form of dry age-related macular degeneration (AMD), is characterized by progressive loss of retinal pigment epithelium cells and photoreceptors in the setting of characteristic extracellular deposits and remains a serious unmet medical need. While genetic predisposition to AMD is dominated by polymorphisms in complement genes, it remains unclear how complement activation contributes to retinal atrophy. Here we demonstrate that complement is activated on photoreceptor outer segments (POS) in the retina peripheral to atrophic lesions associated with GA. When exposed to human serum following outer blood-retinal barrier breakdown, POS act as potent activators of the classical and alternative complement pathway. In mouse models of retinal degeneration, classical and alternative pathway complement activation on photoreceptors contributed to the loss of photoreceptor function. This was dependent on C5a-mediated recruitment of peripheral blood monocytes but independent of resident microglia. Genetic or pharmacologic inhibition of both classical and alternative complement C3 and C5 convertases was required to reduce progressive degeneration of photoreceptor rods and cones. Our study implicates systemic classical and alternative complement proteins and peripheral blood monocytes as critical effectors of localized retinal degeneration with potential relevance for the contribution of complement activation to GA.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Classical and alternative complement activation on photoreceptor outer segments drives monocyte-dependent retinal atrophy

Katschke¹,

Xi²,

Cox³

et al. 2018

Sci Rep

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“…[ 8 – 10 ] The appearance of MA is an important indicator of poor visual prognosis in eyes with AMD. [ 11 – 13 ] Although, anti-VEGF therapy was a major breakthrough in treating exudative AMD, a treatment protocol that halts or reverses MA progression has not yet been developed. Protein complex formation, retinal pigment epithelial (RPE) hypertrophy, and cell death, the first events in MA, have been observed after anti-VEGF treatment.…”

Section: Introductionmentioning

confidence: 99%

One-year outcomes of fixed treatment of intravitreal aflibercept for exudative age-related macular degeneration and the factor of visual prognosis

Ono

Shiragami²,

Manabe³

et al. 2018

Medicine

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The aim of this study was to investigate the efficacy of periodic intravitreal aflibercept (IVA) in exudative age-related macular degeneration, and to explore the predictive factors for visual outcome.This is a prospective interventional case series.Fifty-two eyes of 52 treatment-naïve age-related-macula-degeneration patients were enrolled. All participants received IVA bimonthly following 3 monthly loading dose. The primary endpoint was change in best corrected visual acuity (BCVA) and central retinal thickness (CRT), and the secondary outcomes included changes in subfoveal choroidal thickness (SCT), macular atrophy (MA), and retinal average sensitivity (AS) determined by microperimetry at 12 months compared with baseline. The predictive factors for the change of BCVA were examined.Of 52 enrolled patients, 4 patients were drop out. Remaining 48 patients were examined. Mean logMAR BCVA significantly improved from 0.42 ± 0.37 at baseline to 0.29 ± 0.34 at 12 months (P = .008). Mean CRT and SCT significant reduced from 285.6 ± 135.2 μm, 247.9 ± 96.7 μm at baseline to 233.4 ± 98.0 μm, 208.1 ± 94.6 μm at 12 months, respectively (P < .001). At 12 months, 35 eyes of 48 eyes (72.3%) were archived dry macula. MA occurred in 7 eyes of 35 eyes with dry macula at 12 months (20.0%). AS was significant improved (P = .027) between baseline (median: 15.7 dB) and 12 months (median: 19.5 dB). The BCVA of the cases with MA involved fovea was significant worse. Age was significantly predicted for the BCVA at 12 months.IVA administered over 1 year improved BCVA, AS, and morphological findings, and the predictive factors for BCVA were age and MA-involved fovea.

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“…Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. There are two subtypes of this condition: neovascular (wet) AMD and dry AMD [ 1 – 3 ]. The inadequacy of current treatments for AMD has focused attention on preventive approaches [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Attenuation of choroidal neovascularization by dietary intake of ω-3 long-chain polyunsaturated fatty acids and lutein in mice

et al. 2018

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Dietary ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) and lutein each protect against age-related macular degeneration (AMD). We here examined the effects of ω-3 LCPUFAs and lutein supplementation in a mouse model of AMD. Mice were assigned to four groups: (1) a control group fed an ω-3 LCPUFA–free diet, (2) a lutein group fed an ω-3 LCPUFA–free diet with oral administration of lutein, (3) an ω-3 group fed an ω-3 LCPUFA–supplemented diet, and (4) an ω-3 + lutein group fed an ω-3 LCPUFA–supplemented diet with oral administration of lutein. Mice were fed the defined diets beginning 2 weeks before, and received lutein with an oral gavage needle beginning 1 week before, induction of choroidal neovascularization (CNV) by laser photocoagulation. The area of CNV measured in choroidal flat-mount preparations was significantly reduced in mice fed ω-3 LCPUFAs or lutein compared with those in the control group, and it was reduced in an additive manner in those receiving both ω-3 LCPUFAs and lutein. The concentrations of various inflammatory mediators in the retina or choroid were reduced in mice fed ω-3 LCPUFAs or lutein, but no additive effect was apparent. The generation of reactive oxygen species (ROS) in chorioretinal lesions revealed by dihydroethidium staining as well as the expression of NADPH oxidase 4 (Nox4) in the retina revealed by immunohistofluorescence and immunoblot analyses were attenuated by ω-3 LCPUFAs and lutein in a synergistic manner. Our results thus show that dietary intake of ω-3 LCPUFAs and lutein attenuated CNV in an additive manner and in association with suppression of inflammatory mediator production, ROS generation, and Nox4 expression. Dietary supplementation with both ω-3 LCPUFAs and lutein warrants further study as a means to protect against AMD.

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Prevalence and quantification of geographic atrophy associated with newly diagnosed and treatment-naïve exudative age-related macular degeneration

Abstract: GA is associated with nAMD in 1/4 of cases at initial presentation. Combined imaging, including RFA is an effective tool to identify and quantify GA at diagnosis.

Cited by 13 publications

References 43 publications

Classical and alternative complement activation on photoreceptor outer segments drives monocyte-dependent retinal atrophy

Classical and alternative complement activation on photoreceptor outer segments drives monocyte-dependent retinal atrophy

One-year outcomes of fixed treatment of intravitreal aflibercept for exudative age-related macular degeneration and the factor of visual prognosis

Attenuation of choroidal neovascularization by dietary intake of ω-3 long-chain polyunsaturated fatty acids and lutein in mice

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