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International audience; Iron is essential for retinal function but contributes to oxidative stress-mediated degeneration. Iron retinal homeostasis is highly regulated and transferrin (Tf), a potent iron chelator, is endogenously secreted by retinal cells. In this study, therapeutic potential of a local Tf delivery was evaluated in animal models of retinal degeneration. After intravitreal injection, Tf spread rapidly within the retina and accumulated in photoreceptors and retinal pigment epithelium, before reaching the blood circulation. Tf injected in the vitreous prior and, to a lesser extent, after light-induced retinal degeneration, efficiently protected the retina histology and function. We found an association between Tf treatment and the modulation of iron homeostasis resulting in a decrease of iron content and oxidative stress marker. The immunomodulation function of Tf could be seen through a reduction in macrophage/microglial activation as well as modulated inflammation responses. In a mouse model of hemochromatosis, Tf had the capacity to clear abnormal iron accumulation from retinas. And in the slow P23H rat model of retinal degeneration, a sustained release of Tf in the vitreous via non-viral gene therapy efficently slowed-down the photoreceptors death and preserved their function. These results clearly demonstrate the synergistic neuroprotective roles of Tf against retinal degeneration and allow identify Tf as an innovative and not toxic therapy for retinal diseases associated with oxidative stress.

Purpose To define the optical coherence tomography (OCT) corneal changes predisposing to acute corneal hydrops among patients with advanced keratoconus. Design Retrospective cohort study. Participants A total of 191 advanced keratoconic eyes from 191 patients with advanced keratoconus cases were studied. Methods Data collected from patients with advanced keratoconus cases were studied during a minimum period of 24 months of follow-up. High-resolution Fourier-domain corneal OCT (5 μm of axial resolution) and corneal topography were performed every 4 months during the follow-up. Several anatomic features at the keratoconus cone were analyzed with OCT, including epithelial and stromal thicknesses, the aspect of Bowman's layer, the presence of Vogt's striae, and stromal opacities. A comparative analysis between anatomic corneal features in eyes that developed corneal hydrops and those that did not develop this complication during the follow-up was performed. Main Outcome Measures Evaluation of anatomic corneal changes at risk of developing a corneal hydrops on the basis of OCT findings. Results Eleven cases of corneal hydrops (5.8%) occurred in our series during a mean follow-up of 30 months (24–36 months). All of these patients were male and younger (23.7±5.9 years) than patients with no acute keratoconus (32.7±11.3 years). Increased epithelial thickening with stromal thinning at the conus and the presence of anterior hyperreflectives at the Bowman's layer level were significantly associated with corneal hydrops, whereas the presence of corneal scarring was a preventive factor. At the healing stage, a pan-stromal scar occurs, with a significant stromal thickening and cornea flattening. Conclusions Increased epithelial thickening, stromal thinning at the keratoconus cone, anterior hyperreflectives at the Bowman's layer level, and the absence of stromal scarring are associated with a high risk of developing corneal hydrops. These aspects should be taken into account by the clinician in the evaluation of keratoconus eyes and in the planning of corneal keratoplasty.

Objective To study corneal morphologic changes in a large keratoconic population and to establish a structural optical coherence tomography (OCT) classification. Design Cross-sectional, observational study. Participants A total of 218 keratoconic eyes from 218 patients and 34 eyes from 34 normal subjects. Methods A Fourier-domain OCT system with 5-μm axial resolution was used. For each patient, 3 high-resolution scans were made across the keratoconus cone. All scans were analyzed by keratoconus specialists who were not given access to patients' clinical and topographic data, and who established an OCT classification. The reproducibility of the classification and its correlation with clinical and paraclinical characteristics of patients with keratoconus were evaluated. The OCT examinations were performed every 4 months to follow up structural corneal changes. Main Outcome Measures Evaluation of the structural corneal changes occurring in keratoconus cases with various stages of severity based on OCT findings. Results Fourier-domain OCT classification containing 5 distinct keratoconus stages is proposed. Stage 1 demonstrates thinning of apparently normal epithelial and stromal layers at the conus. Stage 2 demonstrates hyperreflective anomalies occurring at the Bowman's layer level with epithelial thickening at the conus. Stage 3 demonstrates posterior displacement of the hyperreflective structures occurring at the Bowman's layer level with increased epithelial thickening and stromal thinning. Stage 4 demonstrates pan-stromal scar. Stage 5 demonstrates hydrops; 5a, acute onset: Descemet's membrane rupture and dilaceration of collagen lamellae with large fluid-filled intrastromal cysts; 5b, healing stage: pan-stromal scarring with a remaining aspect of Descemet's membrane rupture. The reproducibility of the classification was very high between the corneal specialist observers. Clinical and paraclinical characteristics of keratoconus, including visual acuity, corneal epithelium and stromal thickness changes, corneal topography, biomechanical corneal characteristics, and microstructural changes observed on confocal microscopy, were concordant with our OCT grading. Conclusions Optical coherence tomography provides an accurate assessment of structural changes occurring in keratoconus eyes. These changes were correlated with clinical and paraclinical characteristics of patients. The established classification not only allows structural follow-up of patients with keratoconus but also provides insight into the pathogenesis of keratoconus and treatment strategies for future research. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Photoreceptors and retinal pigment epithelial cells (RPE) targeting remains challenging in ocular gene therapy. Viral gene transfer, the only method having reached clinical evaluation, still raises safety concerns when administered via subretinal injections. We have developed a novel transfection method in the adult rat, called suprachoroidal electrotransfer (ET), combining the administration of nonviral plasmid DNA into the suprachoroidal space with the application of an electrical field. Optimization of injection, electrical parameters and external electrodes geometry using a reporter plasmid, resulted in a large area of transfected tissues. Not only choroidal cells but also RPE, and potentially photoreceptors, were efficiently transduced for at least a month when using a cytomegalovirus (CMV) promoter. No ocular complications were recorded by angiographic, electroretinographic, and histological analyses, demonstrating that under selected conditions the procedure is devoid of side effects on the retina or the vasculature integrity. Moreover, a significant inhibition of laser induced-choroidal neovascularization (CNV) was achieved 15 days after transfection of a soluble vascular endothelial growth factor receptor-1 (sFlt-1)-encoding plasmid. This is the first nonviral gene transfer technique that is efficient for RPE targeting without inducing retinal detachment. This novel minimally invasive nonviral gene therapy method may open new prospects for human retinal therapies.

This study aimed to assess application of ultrasound (US) combined with microbubbles (MB) to transfect the ciliary muscle of rat eyes. Reporter DNA plasmids encoding for Gaussia luciferase , β-galactosidase or the green fluorescent protein (GFP), alone or mixed with 50% Artison MB, were injected into the ciliary muscle, with or without US exposure (US set at 1 MHz, 2 W/cm 2 , 50% duty cycle for 2 min). Luciferase activity was measured in ocular fluids at 7 and 30 days after sonoporation. At 1 week, the US+MB treatment showed a significant increase in luminescence compared with control eyes, injected with plasmid only, with or without MB (×2.6), and, reporter proteins were localized in the ciliary muscle by histochemical analysis. At 1 month, a significant decrease in luciferase activity was observed in all groups. A rise in lens and ciliary muscle temperature was measured during the procedure but did not result in any observable or microscopic damages at 1 and 8 days. The feasibility to transfer gene into the ciliary muscle by US and MB suggests that sonoporation may allow intraocular production of proteins for the treatment of inflammatory, angiogenic and/or degenerative retinal diseases.

Purpose To investigate the features of corneal epithelial basement membrane dystrophy using spectral-domain optical coherence tomography (SD OCT) and to examine the reliability of SD OCT in distinguishing epithelial basement membrane dystrophy from the normal cornea. Design Diagnostic test study. Methods Forty-five individuals with epithelial basement membrane dystrophy and 45 age- and sex-matched controls with normal corneas were examined, and SD OCT scans of their corneas were performed. In vivo confocal microscopy was performed to confirm or rule out the diagnosis of epithelial basement membrane dystrophy. The structural corneal changes occurring in eyes with epithelial basement membrane dystrophy based on SD OCT findings were described. Results Epithelial abnormalities were observed in 86 of 87 eyes with epithelial basement membrane dystrophy (45 patients) on SD OCT scans. The 2 main features were the presence of an irregular and thickened epithelial basement membrane duplicating or insinuating into the corneal epithelium layer, or both, and the presence of hyperreflective dots. In some cases, we detected hyporeflective spaces between the corneal epithelial layer and the Bowman layer similar to a corneal epithelial detachment. This corneal epithelial detachment sometimes was associated with a cleavage with a stair-step appearance within the corneal epithelial layer. We found a perfect correlation between in vivo confocal microscopy and SD OCT findings in the diagnosis of epithelial basement membrane dystrophy (κ = 0.98). Conclusions SD OCT provides an accurate assessment of the structural changes occurring in eyes with epithelial basement membrane dystrophy. These changes, visible on SD OCT scans, are easily detectable and permit an accurate diagnosis, especially in patients with no biomicroscopically visible corneal changes.

To evaluate the outcomes of epiretinal membrane (ERM) surgery in highly myopic eyes without traction maculopathy, and to compare them with those from non-highly myopic eyes.Retrospective nested case-control study from a cohort of 509 consecutive patients (509 eyes) who underwent pars plana vitrectomy with ERM removal.Thirty-two highly myopic eyes (with a refractive error of more than -6.00 diopters [D]), which underwent surgery for isolated ERM, were included in the study. For each case studied, we selected from the same cohort 2 age-matched controls who had ERM surgery (n = 64 non-highly myopic eyes). The best-corrected visual acuity (BCVA), the central macular thickness (CMT), and the surgical complications were analyzed.The mean follow-up duration was 3.2 ± 1.5 years for the study cases and 3.4 ± 1.6 years for the control group (P = .608). At the final follow-up examination, the mean logMAR BCVA had improved significantly, from 0.56 to 0.26 (P.001) for the case group and from 0.54 to 0.22 (P.001) for the control group. At the final optical coherence tomography (OCT), the mean CMT had improved significantly, from 433 to 314 μm (P.001) for the case group and from 428 to 303 μm (P.001) for the control group. There was no significant difference between the 2 groups as regards visual or CMT improvement (P = .526 and P = .483, respectively). The incidence of surgical complications was not significant between the 2 groups.The results of ERM surgery were not different in terms of anatomic and visual outcomes and surgical complication between highly myopic and non-highly myopic eyes.