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Purpose: To evaluate the effect of a black-and-white (BW) filter on the optimization of visualization at each stage of cataract surgery. Methods: Prospective, single-center, single-surgeon, consecutive case series of 40 patients undergoing cataract surgery with BW filter. Surgical images and videos were recorded with and without the BW filter at each stage of cataract surgery. Contrast measurements of surgical images and subjective analysis of video sequences were performed. Results: The surgeons assessed the BW filter to optimize the tissue visibility of capsulorhexis contours, hydrodissection fluid wave perception, the contrast of instruments through a nucleus during phaco-chop, and subincisional cortex contrast through the corneal edema. Despite the higher contrasts’ value obtained with BW filter images during nucleus removal, posterior capsular polishing and viscous removal, the surgeons subjectively reported no significant advantage of using a BW filter. Standard color images were found to be better for localizing the limbal area during incision and for nucleus sculpture to assess groove depth. Conclusions: In conclusion, we describe here the potential indications for BW filter use at particular stages in cataract surgery. A BW filter could be used, with caution, in cases of poor visualization.

Purpose: The aim of this study was to evaluate the efficacy of digital visualization for enhancing the visualization of iridocorneal structures during surgical gonioscopy. Methods: This was a prospective, single-center study on a series of 26 cases of trabecular stent implantation performed by the same surgeon. Images were recorded during surgical gonioscopy, and before stent implantation, with standard colors and with the optimization of various settings, principally color saturation and temperature and the use of the cyan color filter. Subjective analyses were performed by two glaucoma surgeons, and objective contrast measurements were made on iridocorneal structure images. Results: The surgeons evaluating the images considered the optimized digital settings to produce enhanced tissue visibility for both trabecular meshwork pigmentation and Schlemm’s canal in more than 65% of cases. The mean difference in the standard deviation of the pixel intensity values was 37.87 (±4.61) for the optimized filter images and 32.37 (±3.51) for the standard-color images (p < 0.001). The use of a cyan filter provided a good level of contrast for the visualization of trabecular meshwork pigmentation. Increasing the color temperature highlighted the red appearance of Schlemm’s canal. Conclusions: We report here the utility of optimized digital settings including the cyan filter and a warmer color for enhancing the visualization of iridocorneal structures during surgical gonioscopy. These settings could be used in surgical practice to enhance the visualization of the trabecular meshwork and Schlemm’s canal during minimally invasive glaucoma surgery.

Choroidal and retinal neovascularization plays an essential role in various ocular diseases. In this study, we examined the role of nestin in this process. Nestin is an intermediate filament protein known to play several roles, including as a marker of neural progenitor and proliferating endothelial cells.We used Brown Norway rats, in which choroidal and retinal neovascularization was induced using intraocular laser impacts. The role of nestin was examined using angiography, western blot from the second to the 14th day after laser impacts, and intraocular injection of nestin siRNA. The localization of the protein was specified by co-immunoreactivity with glial fibrillary protein (GFAP), glutamine synthetase (GS), and von Willebrand factor (vWF).In the control retina, nestin was found principally in glial structures in the ganglion cell layer, as confirmed by nestin/GFAP immunolabeling. Two days after the laser impacts, the nestin expression extended to numerous radial processes at the site of the impacts. With Bruch's membrane ruptured, these processes penetrated into the choroid. Nestin immunolabeling remained high from the third to the seventh day but appeared reduced on the 14th day. The nature of these processes was not clearly defined, but co-immunolabeling with GFAP suggested that they were principally in activated Müller cells from the third day after the laser impacts. However, the co-immunoreactivity of nestin and GS, a marker of mature functional Müller cells, could be observable only from the seventh day. Nestin was also observed in some vascular cells, as demonstrated by the co-immunoreactivity of the protein with vWF in the choroid and retina. As observed on angiography, the numbers of choroidal and retinal blood vessels were significantly increased (principally on the seventh day) after the laser impacts. An intraocular injection of nestin siRNAs led to a significant decrease in the number of blood vessels.Our results confirmed the presence of nestin in glial (e.g., astrocytes), reactive Müller, and endothelial cells. They demonstrated their critical involvement in a rat model of retinal and choroidal neovascularization experimentally induced using ocular laser impacts.

International audience; PurposeTo describe the early topography of corneal swelling occurring after cataract surgery and to evaluate the impact of the three-dimensional (3D) digital visualization system in minimizing corneal oedema.MethodsProspective observational, single-centre, consecutive case series of 134 patients undergoing cataract surgery performed by the same surgeon, with either 3D or conventional visualization systems. Eyes were assigned to two groups based on their anterior chamber depth (group ACD ≤3 mm and group ACD >3 mm). Optical coherence tomography was performed to evaluate postoperative corneal swelling.ResultsThree corneal swelling profiles were identified on the first postoperative day type 1, limited corneal oedema near peripheral corneal incisions; type 2, dome-shaped corneal swelling spreading from the principal corneal incision and reaching the paracentral cornea; type 3, continuous oedema spreading from the principal incision to central cornea, with a generalized oedema predominating in the upper part of the cornea.On the first day after surgery, in group ACD ≤3 mm, visual acuity was significantly better in patients undergoing surgery with 3D visualization (0.023 vs 0.072 logMar, p = 0.014) with reduced central corneal thickening 17.3 µm (±3.2) in comparison with conventional visualization 44.0 µm (±9.3) (p = 0.0082). In group ACD >3 mm, no significant association was found between the use of the 3D system and pachymetry changes and early visual rehabilitation. On day 21 after surgery, no significant differences in corneal pachymetry values were observed between the two surgical approaches in both groups.ConclusionsWe describe early postoperative corneal map profiles providing insight into the pathogenesis of postoperative corneal swelling and possible prevention strategies. By improving visualization of the narrow surgical space in patients with shallow anterior chambers, the 3D system could help to minimize postoperative corneal oedema.

Purpose: To assess the utility of the 3D viewing system in tilted microscope positions for the performance of cataract surgery in challenging positions, for patients with difficulty remaining supine. Methods: Prospective, single-center, single-surgeon, consecutive case series of patients undergoing surgery in an inclined position. Results: 21 eyes of 15 patients who had undergone surgery at inclined positions at angles of 20° to 80°, with a mean angle of 47.62°. Surgeon comfort was considered to be globally good. The surgeon rated red reflex perception and the impression of depth as good and stable in all cases. The operating time was slightly longer for patients inclined at angles of more than 50°. On the first day after surgery, BSCVA was 20/25 or better in all cases. No ocular complications occurred in any of the interventions. Conclusions: Due to the ocular-free design of the 3D system, the surgical procedure and the positioning of the surgeon remained almost identical to that for patients undergoing surgery in a supine position, maintaining the safety of the standard surgical approach.

BACKGROUND AND OBJECTIVE: To compare capillary density (CD) changes assessed by optical coherence tomography angiography (OCTA) during diabetic retinopathy (DR) progression using three previously published methods: binarization, skeletonization, and automated flow density (AFD). PATIENTS AND METHODS: Retrospective study of 98 eyes of 74 patients with diabetes and 18 control eyes imaged using OCTA. The macular CD at each stage of DR was assessed using the three methods and were compared to control eyes. RESULTS: AFD was the only method that detected differences between controls and severe nonproliferative DR eyes. The three methods showed a significant difference in CD between controls and eyes with proliferative DR, except for the “fovea” area. CONCLUSION: Only one of the three methods allowed for the detection of changes from the normal capillary density as early as at the “severe nonproliferative DR” stage due to several refinements from the basic technique. [ Ophthalmic Surg Lasers Imaging Retina. 2017;48:378–384.]

To compare characteristics of functioning blebs (FBs) and nonfunctioning blebs (NFBs) with en-face spectral-domain optical coherence tomography (OCT).We evaluated 41 blebs of 38 patients after a first-time trabeculectomy. Eyes were classified into 2 groups: FBs (22 eyes) and NFBs (19 eyes). En-face OCT images were analyzed semiquantitatively for the density of intraepithelial microcysts (0 to 3), internal fluid-filled cavity (0 to 3), and bleb vascularization (0 to 2). Presence of conjunctival fibrosis and visualization of the scleral flap were also analyzed.FBs showed significantly more intraepithelial microcysts than did NFBs: the mean grading of microcyst density was 1.86 for FBs and 0.11 for NFBs (P0.0001). None of the FBs were rated 0 and none of the NFBs were rated 2 or 3 for the density of intraepithelial microcysts. NFBs presented more conjunctival fibrosis than FBs (63% vs. 32%, P0.05). There was no significant difference between FBs and NFBs for bleb vascularization, visualization of the scleral flap, and presence of subepithelial fluid-filled cavities. There was a direct correlation between postoperative intraocular pressure and intraepithelial microcyst density (r=-0.7655, P0.0001). The long-term administration of preserved eyedrops before surgery was associated with fewer intraepithelial microcysts (r=-0.5436; P=0.0006).FBs were associated with a higher number of intraepithelial microcysts evaluated with en-face OCT. A higher density of microcysts was associated with a lower intraocular pressure and a shorter duration of preserved topical treatment before surgery. En-face OCT provides a simple, noninvasive, and reproducible method to analyze blebs after filtering surgery.

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 study the symmetry in response to bilateral diabetic macular oedema (DME) treated with bilateral intravitreal injections of ranibizumab (IVR). Methods The charts of 36 eyes of 18 patients treated with a loading dose of three monthly IVR in both eyes were retrospectively reviewed. Favourable anatomical response was defined as a decrease by more than 10% in baseline central macular thickness (CMT), and favourable functional response was defined as an increase in visual acuity (VA) ≥5 letters. A symmetric response was defined as a similar anatomical and/or functional response in the first (FE) and second (SE) treated eyes. Results The VA improved significantly after ranibizumab treatment in both eyes (p

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.

Background To evaluate the incidence, evolution, clinical characteristics, possible risk factors or preventive factors, and visual outcomes of epiretinal membrane (ERM) recurrence. Methods Retrospective study of 440 consecutive patients (440 eyes) who underwent pars plana vitrectomy for ERM. The internal limiting membrane (ILM) was peeled in 266 cases, with the help of indocyanine green in 27 cases and brilliant blue in 45 cases. Cases of symptomatic ERM recurrence were reoperated. Results The incidence of ERM recurrence was 5% (22/440), and 2% of the patients were reoperated (9/440). Epiretinal membrane recurrence was symptomatic in 9 cases (41%) and asymptomatic in 13 cases (59%). ILM peeling was the only factor preventing ERM recurrence (adjusted odds ratio = 0.33, P = 0.026). The use of staining dyes did not prevent recurrence (adjusted odds ratio = 0.35, P = 0.338). In the case of ERM reproliferation, the absence of ILM peeling, the existence of ERM on the fellow eye, and poor visual acuity before surgery seemed to be associated with a high risk of symptomatic recurrence and reoperation. The mean duration for follow-up was 3.5 ± 1.7 years. Conclusion ILM peeling not only reduces the likelihood of reproliferation of ERM but also seems to improve the visual prognosis of recurrent ERMs. The use of dyes did not reduce the rate of recurrence compared with when ILM was peeled without dyes.

Background Amyloid precursor protein knockout mice (APP-KO) have impaired differentiation of amacrine and horizontal cells. APP is part of a gene family and its paralogue amyloid precursor-like protein 2 (APLP2) has both shared as well as distinct expression patterns to APP, including in the retina. Given the impact of APP in the retina we investigated how APLP2 expression affected the retina using APLP2 knockout mice (APLP2-KO). Results Using histology, morphometric analysis with noninvasive imaging technique and electron microscopy, we showed that APLP2-KO retina displayed abnormal formation of the outer synaptic layer, accompanied with greatly impaired photoreceptor ribbon synapses in adults. Moreover, APLP2-KO displayed a significant decease in ON-bipolar, rod bipolar and type 2 OFF-cone bipolar cells (36, 21 and 63 %, respectively). Reduction of the number of bipolar cells was accompanied with disrupted dendrites, reduced expression of metabotropic glutamate receptor 6 at the dendritic tips and alteration of axon terminals in the OFF laminae of the inner plexiform layer. In contrast, the APP-KO photoreceptor ribbon synapses and bipolar cells were intact. The APLP2-KO retina displayed numerous phenotypic similarities with the congenital stationary night blindness, a non-progressive retinal degeneration disease characterized by the loss of night vision. The pathological phenotypes in the APLP2-KO mouse correlated to altered transcription of genes involved in pre- and postsynatic structure/function, including CACNA1F, GRM6, TRMP1 and Gα0, and a normal scotopic a-wave electroretinogram amplitude, markedly reduced scotopic electroretinogram b-wave and modestly reduced photopic cone response. This confirmed the impaired function of the photoreceptor ribbon synapses and retinal bipolar cells, as is also observed in congenital stationary night blindness. Since congenital stationary night blindness present at birth, we extended our analysis to retinal differentiation and showed impaired differentiation of different bipolar cell subtypes and an altered temporal sequence of development from OFF to ON laminae in the inner plexiform layer. This was associated with the altered expression patterns of bipolar cell generation and differentiation factors, including MATH3, CHX10, VSX1 and OTX2. Conclusions These findings demonstrate that APLP2 couples retina development and synaptic genes and present the first evidence that APLP2 expression may be linked to synaptic disease. Electronic supplementary material The online version of this article (doi:10.1186/s13041-016-0245-z) contains supplementary material, which is available to authorized users.

Purpose: To compare the 23-gauge (23-G) sutureless vitrectomy incision architecture in macular and non-macular surgery, using anterior segment spectral-domain optical coherence tomography (SD-OCT), and to evaluated its influence on clinical outcomes. Methods: A prospective, observational case series of 43 patients who underwent primary transconjunctival 23-G pars plana vitrectomy (PPV) for macular and non-macular diseases. All sclerotomy wounds were imaged 1 day after surgery using the anterior segment module of SD-OCT (OCT Spectralis; Heidelberg Engineering, Heidelberg, Germany). Sclerotomy architecture, including good wound apposition, presence of gaping and misalignment of the roof and floor of the incisions were evaluated. Preoperative, intraoperative and postoperative medical record data were also prospectively collected. Results: Incision gaping and misalignment of the roof and floor occurred more frequently in the superotemporal and superonasal quadrants than in the inferotemporal quadrant (p

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.

To describe the incidence, clinical features, and evolution of paracentral retinal holes occurring after macular surgery.A retrospective non-randomized study of 909 patients operated on for either a macular hole (MH, n = 400 patients) or an epiretinal membrane (ERM, n = 509 patients) between 2004 and 2009. Six patients (0.6%) developed a paracentral macular hole after surgery. Their clinical, auto-fluorescence, and optical coherence tomography (OCT) characteristics as well as their visual outcomes were studied.The mean age of patients was 70 years. Paracentral holes occurred approximately 5 weeks after surgery (with a range of 2-12 weeks). All patients were asymptomatic. Five patients underwent ILM peeling during initial surgery. Paracentral retinal holes were located superiorly to the fovea in three cases and temporally in the other three cases. Mean pre-operative BCVA was 20/200 and mean post-operative BCVA was 20/40. The eye where the eccentric MHs were closest to the fovea (inferior to 1 optic disc area) had the poorest final visual acuity. Autofluorescence imaging showed a bright fluorescence in paramacular holes. On OCT images, they were shown to be flat full-thickness holes. No treatment was attempted. No rhegmatogenous complications or choroidal neovascularization occurred in any of the patients. Mean follow-up was 2 years.In summary, paracentral MHs are uncommon complications which can occur at the site where ILM peeling has been initiated or completed. Except for the closest holes to fovea, they have good visual prognosis and do not require any treatment underlining the importance of initiating the ILM peeling as far as possible from the fovea.

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.

To compare the safety and functional outcomes of 25-gauge and 23-gauge (G) micro-incision vitrectomy surgery (MIVS) instrumentation with the standard 20-G vitrectomy system in the treatment of epiretinal membranes (ERM). A retrospective comparative study of 553 consecutive cases with epiretinal membrane who underwent pars plana vitrectomy. Twenty-gauge, 25-gauge and 23-gauge vitrectomy was performed respectively in 347, 91, and 115 eyes. Surgery duration, visual acuity improvement, intraocular pressure variation, intraoperative and postoperative complications were analyzed. The mean surgical time in the 23-G group and in the 25-G group was shorter than in the 20-G group (P

To define the optical coherence tomography (OCT) corneal changes predisposing to acute corneal hydrops among patients with advanced keratoconus.Retrospective cohort study.A total of 191 advanced keratoconic eyes from 191 patients with advanced keratoconus cases were studied.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.Evaluation of anatomic corneal changes at risk of developing a corneal hydrops on the basis of OCT findings.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.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.

Purpose To assess the efficacy of a single dexamethasone intravitreal implant (Dex-I) injection for the treatment of diabetic macular edema (DME). Methods This was a retrospective chart review of 39 eyes (34 consecutive patients). Best-corrected visual acuity (BCVA), central macular thickness (CMT), and increase in intraocular pressure (IOP) (>24 mm Hg) were analyzed before treatment and 2 and 4 months after injection. Results Preoperative mean CMT was 559 ± 111 μm and decreased to 338 ± 84 and 477 ± 140 μm 2 and 4 months after injection, respectively. Although all eyes showed a significant decrease in CMT 2 months after injection (pConclusions Thirty percent of DME eyes had gained more than 2 logMAR lines 2 months after Dex-I injection and safety was good. Visual acuity gain was maintained 4 months after injection despite a recurrence of edema in most cases.

We have identified and characterized a spontaneous Brown Norway from Janvier rat strain (BN-J) presenting a progressive retinal degeneration associated with early retinal telangiectasia, neuronal alterations, and loss of retinal Müller glial cells resembling human macular telangiectasia type 2 (MacTel 2), which is a retinal disease of unknown cause. Genetic analyses showed that the BN-J phenotype results from an autosomal recessive indel novel mutation in theCrb1gene, causing dislocalization of the protein from the retinal Müller glia (RMG)/photoreceptor cell junction. The transcriptomic analyses of primary RMG cultures allowed identification of the dysregulated pathways in BN-J rats compared with wild-type BN rats. Among those pathways, TGF-β and Kit Receptor Signaling, MAPK Cascade, Growth Factors and Inflammatory Pathways, G-Protein Signaling Pathways, Regulation of Actin Cytoskeleton, and Cardiovascular Signaling were found. Potential molecular targets linking RMG/photoreceptor interaction with the development of retinal telangiectasia are identified. This model can help us to better understand the physiopathologic mechanisms of MacTel 2 and other retinal diseases associated with telangiectasia.

Immunoglobulin G (IgG) subclass deficiency is a rare primary immunodeficiency syndrome characterized by recurrent infections and autoimmune disorders. However, there have been no reports of ocular involvement, either inflammatory or infectious, in association with IgG subclass deficiency. The authors report the first case of retinal vasculitis that led to the diagnosis of IgG subclass deficiency, in a patient with a history of inflammatory bowel disease and recurrent infections of previously unknown origin.

Purpose To evaluate a possible clinical application of spectral-domain optical coherence tomography (SD-OCT) using en-face module for the imaging of the corneoscleral limbus in normal subjects and dry eye patients. Patients and methods Seventy-six subjects were included in this study. Seventy eyes of 35 consecutive patients with dry eye disease and 82 eyes of 41 healthy control subjects were investigated. All subjects were examined with the Avanti RTVue® anterior segment OCT. En-face OCT images of the corneoscleral limbus were acquired in four quadrants (inferior, superior, nasal and temporal) and then were analyzed semi-quantitatively according to whether or not palisades of Vogt (POV) were visible. En-face OCT images were then compared to in vivo confocal microscopy (IVCM) in eleven eyes of 7 healthy and dry eye patients. Results En-face SD-OCT showed POV as a radially oriented network, located in superficial corneoscleral limbus, with a good correlation with IVCM features. It provided an easy and reproducible identification of POV without any special preparation or any direct contact, with a grading scale from 0 (no visualization) to 3 (high visualization). The POV were found predominantly in superior (P

To compare the long-term outcomes of vitreomacular surgery in eyes with nontractional diabetic macular edema (DME) with those from eyes with tractional DME.Retrospective comparative study from 55 consecutive patients (73 eyes). Twenty eyes were operated on for tractional DME and 53 eyes for nontractional DME unresponsive to laser photocoagulation or triamcinolone intravitreal injections. The best-corrected visual acuity, the central macular thickness, and the surgical complications were analyzed.The mean follow-up duration was 5.3 ± 2.4 years for the group with traction and 4.4 ± 1.7 years for the group without traction (P = 0.13). At 3 years, the mean logarithm of the minimum angle of resolution best-corrected visual acuity had improved significantly from 0.78 to 0.58 for the group without traction and from 0.75 to 0.45 for the group with traction (P0.001). At the final visit, there was no significant difference between the 2 groups in regard to visual or central macular thickness improvement (P = 0.447 and P = 0.742, respectively). The incidence of surgical complications was not significant between the two groups. The preoperative best-corrected visual acuity was the only predictive factor for the final best-corrected visual acuity.The results of vitrectomy were not different in terms of anatomical and visual outcomes and surgical complications between eyes without tractional DME and eyes with tractional DME.

The aim of this study was to describe a novel technique combining deep intrastromal arcuate keratotomy and superficial lamellar keratotomy followed by excimer photoablation for the management of high naturally occurring or postkeratoplasty astigmatism.In this retrospective case series, the first step was deep intrastromal arcuate keratotomy and superficial lamellar keratotomy performed at 100-μm depth by femtosecond laser. Manual incisions were made for flap elevation. The second step, after 1 month, consisted of reopening the flap and using an excimer laser to correct residual ametropia.Nine eyes series were studied. The mean preoperative refractive cylinder correction was 6.11 ± 2.54 diopters (D). The mean postoperative refractive cylinder correction was 2.85 ± 1.31 D. The mean correction index was 1.07 ± 0.28 D. The mean best-corrected visual acuity improved from 20/40 to 20/22 after the 2 steps. The median follow-up was 11 (range, 9-17) months. No complications were observed and postoperative outcome was satisfactory.Permitting correction of a broader range of high astigmatism with good accuracy, this combined approach minimizes excision of corneal stromal tissue and postoperative complications.

Purpose To explore the potential of spectral-domain optical coherence tomography (SD-OCT) using the en-face technology for the imaging of ocular surface diseases and to correlate the findings with in vivo confocal microscopy (IVCM) images. Patients and methods 113 eyes of 75 subjects with various ocular surface diseases were investigated with the RTVue ® anterior-segment en face OCT. En face OCT images were compared to B-scan OCT and IVCM images. Results Patients with corneal dystrophies, corneal deposits, keratitis, pterygium, conjunctivochalasis, or ocular surface squamous neoplasia and patients who underwent lamellar corneal surgeries were included. En-face OCT images showed ocular surface tissue changes that were not discernible using conventional B-scan OCT. Nevertheless, there was a good correlation with IVCM analysis. Compared with IVCM, the major advantages of en-face OCT included easy operation and rapid image acquisition, with minimal operator experience required. In addition, the non-contact method avoided patient discomfort and external pressure on the globe, which was especially useful in patients with corneal dystrophies, ulcers, or corneal abscesses. Although the resolution of en-face OCT was lower than that of IVCM, it allowed useful overall visualization of corneal lesions due to the larger areas analyzed. Conclusion En-face SD-OCT is a novel, valuable tool to assess a wide variety of ocular surface diseases. It can provide additional information and new insight into different ocular surface conditions with no corneal contact.

To determine whether optical coherence tomography (OCT) epithelial mapping can improve the detection of form fruste keratoconus.French National Eye Hospital, Paris 6 PierreMarie Curie University, Paris, France.Retrospective comparative study.Eyes with normal corneas, form fruste keratoconus, moderate keratoconus, or severe keratoconus were assessed using Fourier-domain OCT (RTVue 5.5), scanning-slit corneal topography (Orbscan IIz), and rotating Scheimpflug camera (Pentacam Comprehensive Eye Scanner). Several parameters provided by the software or derived from elevation maps, OCT pachymetric maps, and OCT epithelium parameters were evaluated and compared between the 4 groups.The study involved 145 eyes. There were no significant differences in the keratometry (K) value, inferior-superior value, keratoconus index, central K index, and topographic keratoconus classification indices between the form fruste keratoconus group and the control group (P .05). Form fruste keratoconic corneas had less epithelial thickness in the thinnest corneal zone than normal corneas, and greater epithelial thickness in the thinnest corneal zone than keratoconic corneas (P .005). The epithelial thickness in the thinnest corneal zone in form fruste corneas was located inferiorly (P .005) and corresponded with the zone of minimum epithelial thickness and maximum posterior elevation (P .005). The receiver operating characteristic curve analysis showed good overall predictive accuracy of the epithelial thickness in the thinnest corneal zone, with a 52 μm threshold value for discriminating form fruste keratoconic corneas from normal corneas.The epithelial thickness in the thinnest corneal zone and its location provided by the OCT epithelial mapping might be useful for the early diagnosis of form fruste keratoconus.No author has a financial or proprietary interest in any material or method mentioned.

To study corneal morphologic changes in a large keratoconic population and to establish a structural optical coherence tomography (OCT) classification.Cross-sectional, observational study.A total of 218 keratoconic eyes from 218 patients and 34 eyes from 34 normal subjects.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.Evaluation of the structural corneal changes occurring in keratoconus cases with various stages of severity based on OCT findings.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.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.

To compare the 23-gauge (23-G) sutureless vitrectomy incision architecture in macular and non-macular surgery, using anterior segment spectral-domain optical coherence tomography (SD-OCT), and to evaluated its influence on clinical outcomes.A prospective, observational case series of 43 patients who underwent primary transconjunctival 23-G pars plana vitrectomy (PPV) for macular and non-macular diseases. All sclerotomy wounds were imaged 1 day after surgery using the anterior segment module of SD-OCT (OCT Spectralis; Heidelberg Engineering, Heidelberg, Germany). Sclerotomy architecture, including good wound apposition, presence of gaping and misalignment of the roof and floor of the incisions were evaluated. Preoperative, intraoperative and postoperative medical record data were also prospectively collected. Incision gaping and misalignment of the roof and floor occurred more frequently in the superotemporal and superonasal quadrants than in the inferotemporal quadrant (p0.05) and was more frequent in the non-macular group than in the macular group (p0.05). The incidence of incision gaping increased significantly as the incision angle increased. In the macular group, the mean postoperative intraocular pressure (IOP) did not change from the preoperative value, whereas in the non-macular group, the mean IOP decreased significantly from 15.09 ± 2.58 mmHg preoperatively to 12.18 ± 3.25 mmHg on the first postoperative day (p0.005). The mean IOP did not differ significantly between the two groups of surgery at 1 week, and at 1 month postoperatively. In 23-G PPV, non-macular surgery is associated with a significant postoperative IOP decrease in comparison with macular surgery, which could be explained by the most remodelled wound architecture.

Refers To: Tom Burns, Jorun Rugkåsa, Andrew Molodynski, John Dawson, Ksenija Yeeles, Maria Vazquez-Montes, Merryn Voysey, Julia Sinclair, Stefan Priebe, Community treatment orders for patients with psychosis (OCTET): a randomised controlled trial, The Lancet, Volume 381, Issue 9878, 11–17 May 2013, Pages 1627-1633; International audience

Cyclosporine A is a poorly water-soluble, immunosuppressive drug used to treat a variety of ocular diseases. Its limited solubility makes challenging the development of a cyclosporine A-based eye drop for ocular topical application. Based on the prodrug strategy, the practically insoluble cyclosporine A was converted into a freely soluble prodrug. Such a water-soluble prodrug made it possible to develop water-based concentrated eye drops. The prodrug formulations were tested for their ex vivo permeation and in vivo distribution at three concentrations (equivalent to 0.05%, 0.50% and 2.00% w/v cyclosporine A). The ex vivo permeation experiments were performed on corneal and conjunctival epithelia. The in vivo distribution evaluated the total cyclosporine A present in the ocular structures as well as in serum, spleen and cervical lymphatic ganglions. Each prodrug formulation was compared to conventionally used cyclosporine A eye drops at an equivalent concentration. The experimental results showed that the tested eye drops behaved differently. The prodrug formulation was characterized by the following: i) preferential conjunctival penetration, ii) an interesting capacity to create large tissue deposits and iii) a lower risk of systemic complications and immunosuppression. The prodrug aqueous eye drop was demonstrated to be a patient-friendly option for the treatment of ocular diseases requiring high ocular levels of cyclosporine A, pushing the boundaries of the current therapeutic arsenal.

To evaluate the factors affecting the postoperative intraocular pressure (IOP) decrease in 23-gauge (23-G) sutureless vitrectomy, including incision architecture evaluated by anterior segment spectral-domain optical coherence tomography (SD-OCT). A prospective cohort study of 43 patients who underwent primary transconjunctival 23-G pars plana vitrectomy. All sclerotomy wounds were imaged 1 day after surgery using the anterior segment module of SD-OCT (OCT Spectralis, Heidelberg Engineering, Heidelberg, Germany). 23-G sclerotomy architecture, preoperative and postoperative medical data were also prospectively collected. Multivariate logistic regression analysis, with backward elimination, found that surgery duration (adjusted OR = 9.17, p = 0.020) and loss of wound apposition (adjusted OR = 15.12, p = 0.022) were risk factors for significant postoperative IOP decrease (≥3 mmHg) 1 day after surgery; while age, gender, myopia, and gas tamponade were not risk or protective factors for postoperative IOP decrease. In 23-G pars plana vitrectomy, the early postoperative decrease in IOP is mainly influenced by surgery duration and the self-sealing nature of the sclerotomy. The IOP decrease was not influenced by the presence or the absence of gas tamponade.

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.

Repeated inhalation of poppers may be associated with prolonged bilateral vision loss due to the disruption of foveal cone outer segments. Retinal damage may progressively improve following drug discontinuation.

BackgroundThe systemic antibody responses to SARS-CoV-2 in COVID-19 patients has been extensively studied. However, much less is known about the mucosal responses in the upper airways at the site of initial SARS-CoV-2 replication. Local antibody responses in the nasopharyngeal epithelium, that are likely to determine the course of infection, have not been analysed so far nor their correlation with antibody responses in serum.MethodsThe IgG and IgA antibody responses were analysed in the plasma as well as in nasopharyngeal swabs (NPS) from the first four COVID-19 patients confirmed by RT-qPCR in France. Two were pauci-symptomatic while two developed severe disease. Taking advantage of a comprehensive series of plasma and nasopharyngeal samples, we characterized their antibody profiles from the second week post symptoms onset, by using an in-house ELISA to detect anti-SARS-CoV-2 Nucleoprotein (N) IgG and IgA.ResultsAnti-N IgG and IgA antibodies were detected in the NPS of severe patients. Overall, the levels of IgA and IgG antibodies in plasma and NPS appeared specific to each patient.ConclusionsAnti-N IgG and IgA antibodies are detected in NPS, and their levels are related to antibody levels in plasma. The two patients with severe disease exhibited different antibody profiles that may reflect different disease outcome. For the pauci-symptomatic patients, one showed a low anti-N IgG and IgA response in the plasma only, while the other one did not exhibit overt serological response.