The role of retinal microglial cells (MCs) in age-related macular degeneration (AMD) is unclear. Here we demonstrated that all retinal MCs express CX3C chemokine receptor 1 (CX3CR1) and that homozygosity for the CX3CR1 M280 allele, which is associated with impaired cell migration, increases the risk of AMD. In humans with AMD, MCs accumulated in the subretinal space at sites of retinal degeneration and choroidal neovascularization (CNV). In CX3CR1-deficient mice, MCs accumulated subretinally with age and albino background and after laser impact preceding retinal degeneration. Raising the albino mice in the dark prevented both events. The appearance of lipid-bloated subretinal MCs was drusen-like on funduscopy of senescent mice, and CX3CR1-dependent MC accumulation was associated with an exacerbation of experimental CNV. These results show that CX3CR1-dependent accumulation of subretinal MCs evokes cardinal features of AMD. These findings reveal what we believe to be a novel pathogenic process with important implications for the development of new therapies for AMD.

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Aim: To describe the types and location of choroidal neovascularisation (CNV) in exudative age-related macular degeneration (AMD), including vascularised pigment epithelial detatchments (PED), and most recently described subtypes, such as retinal choroidal anasmostosis, also termed ''retinal angiomatous proliferation'' (RAP). Methods: Prospective multicentre consecutive descriptive case series. A total of 207 consecutive cases of newly diagnosed exudative AMD undergoing fluorescein angiography (FA) were recruited by 7 French referral hospital-based or private centres. Indocyanine green angiography (ICG) also was performed, when judged necessary by investigators. Types and location of CNV were classified by two independent experts and adjudicated by a third when discordant. Results: All patients had FA, while ICG was performed in 50% of subjects. A total of 17.6% had classic CNV only, 5.4% and 8.3% had predominantly and minimally classic CNV, respectively. Occult CNV could be classified in occult CNV without PED (32.7%) and occult CNV with PED, ie, vascularised PED (23.9%). RAP was observed in 15.1% of cases, and accounted for 30% of vascularised PED. In 5.8% of the cases there was haemorrhagic AMD and 4.8% had fibrovascular scars. Lesions were mainly subfoveal (80%). Agreement between the centre's ophthalmologist and the final validated expert classification was moderate (k = 0.52 for location and 0.59 for type of lesion). Conclusion: This study confirms that newly diagnosed cases of exudative AMD are mainly occult and subfoveal. RAP appeared as a common lesion in patients with newly diagnosed exudative AMD.A ged-related macular degeneration (AMD) is the leading cause of blindness in industrialised countries, representing 50% of all blindness cases.1 It is currently the third most common cause of blindness worldwide, behind cataract and glaucoma.1 More than 80% of severe visual loss in AMD is due to choroidal neovascularisation (CNV) and its consequences: exudation, bleeding and disciform scarring.2 At the time of completion of the present study, the only approved treatments for exudative AMD in France were laser photocoagulation and verteporfin photodynamic therapy (PDT). The choice of treatment with these laser-based therapies depended on the location, composition and size of the lesion. Fluorescein angiography has been used to define lesion size and composition. It allows distinction between well demarcated classic CNV, and ill-defined occult CNV. This angiographic distinction is of major importance for the choice of treatment; laser photocoagulation being preferred in cases of extrafoveal or juxtafoveal classic CNV, while PDT was preferred in cases of subfoveal predominantly classic and occult only CNV.3-5 The location and exact boundaries of occult CNV often are difficult to determine precisely on fluorescein angiography due to obscuration of the neovascular membrane by overlying turbid exudates, blood and/or pigment, and rapid fluorescein pooling beneath a serous PED. As the vast majority of CNV at diagnos...

Basic fibroblast growth factor (bFGF), a soluble mitogen, has been isolated and purified from various organs, including the retina. In vivo angiogenic activity of bFGF has been demonstrated with several assays. An experimental model of choroidal neovascularization was developed in the mini pig by perfusion of recombinant human bFGF through an osmotic minipump. Endogenous bFGF and bFGF receptors were localized in the normal pig retina by immunohistochemistry and autoradiography after binding. The perfusion of exogenous bFGF induced well-organized new vessels along the last 3 mm of the catheter in the suprachoroidal space. This neovascularization did not penetrate the normal Bruch's membrane. Vascular cells (identified by von Willebrand factor antibody staining) increased in number and in surface from the proximal part to the end of the intraocular catheter in all bFGF perfused eyes. In eyes perfused with phosphate buffered saline (controls), but not in the bFGF perfused eyes, an inflammatory response occurred (identified by a macrophage specific antibody). These results demonstrate that choroidal angiogenesis can be achieved without an inflammatory response by perfusing an excess of bFGF in the suprachoroidal space.

Background: To review treatment outcomes from real-world data of patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) injection. Methods: RAINBOW (ClinicalTrials.gov, NCT02279537) is an ongoing, observational, 4-year study to monitor the effectiveness and safety of IVT-AFL in patients with nAMD in clinical practice in France. Treatment-naïve patients diagnosed with nAMD who had been prescribed IVT-AFL by their treating physician were eligible. The regimens of interest were regular treatment interval cohort (patients who received three initial monthly IVT-AFL injections followed by regular injections every 2 months) and two irregular treatment interval cohorts (with and without three initial monthly injections). Here we describe results at 24 months in patients according to IVT-AFL treatment regimen. Results: The mean change in best-corrected visual acuity (BCVA) with IVT-AFL from baseline to 24 months was + 3.0 letters in the overall population (P < 0.05 vs baseline). The mean change was positive for the regular and irregular treatment interval cohorts with initial doses (+ 4.9 and + 4.0 letters, respectively; P < 0.05 vs baseline) and negative for the irregular treatment interval cohort without initial doses (− 2.5 letters; P = 0.365 vs baseline) at 24 months. The mean overall number of IVT-AFL injections over 12 and 24 months was 6.0 and 8.8, respectively. The most common ocular adverse events were lack of efficacy (6.3%), vitreous floaters (2.7%), and increased lacrimation (1.7%). Conclusions: In the real-world RAINBOW study, visual outcomes observed at 24 months were consistent with results from the primary endpoint at 12 months. In this study, treatment-naïve patients who received three initial IVT-AFL doses and regular IVT-AFL treatment over the first 24 months experienced better visual outcomes than patients who received no initial doses and an irregular treatment regimen. Trial registration: www.ClinicalTrials.gov (NCT02279537). Registered