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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.

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.

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

Resume Contexte : La greffe de membrane amniotique fait aujourd'hui partie de l'arsenal therapeutique des pathologies oculaires de surface. L'objectif de notre Etude est d'evaluer l'efficacite de cette technique dans le traitement des keratites amibiennes severes. Methodes : Nous avons etudie les donnees cliniques de six patients presentant des formes evoluees de keratites amibiennes, resistantes aux traitements medicaux (antiamibiens, antalgiques, anti-inflammatoires, cicatrisants) et ayant beneficie d'une (ou deux) greffe de membrane amniotique entre fevrier 2001 et janvier 2003. Une analyse histologique de la cornee a 6t6 effectuee chez quatre des six patients ayant par la suite ete operes de keratoplastie transfixiante. Resultats : Huit procedures de greffe de membrane amniotique ont ete realisees sur six yeux. Le suivi moyen apres la greffe etait Oe 14 mois (3 a 21 mois). Tous les patients presentaient des lesions stromales evolutives, sterilisees, induites essentiellement par la reaction inflammatoire postinfectieuse. La greffe de membrane amniotique a ete realisee en moyenne apres 3,6 mois de traitement antiamibien. Elle a permis d'obtenir une reepithelialisation complete et stable dans quatre cas et partielle dans deux cas, ainsi qu'une reduction de l'inflammation dans six cas, une reduction des douleurs dans cinq cas, et la stabilisation de la destruction tissulaire chez tous les patients. Parallelement, nous avons constate dans quatre cas sur cinq, une regression de la neovascularisation limbique. Aucune complication directement liee a la greffe n'a ete observee. L'analyse histologique des cornees a montre que la membrane amniotique etait incluse sous l'epithelium corneen. Interpretation : La greffe de membrane amniotique represente un nouvel apport therapeutique dans la prise en charge des formes evolutives de keratites amibiennes, notamment a la phase d'inflammation postinfectieuse. Cette technique pourrait permettre de retarder une eventuelle greffe de cornee en cas de destruction tissulaire importante.

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 alpha v beta (alpha(v)beta5) heterodimer has been implicated in many biological functions, including angiogenesis. We report the beta5 gene expression pattern in embryonic and foetal mouse tissues as determined by Northern blotting and in situ hybridization. During the earliest stages, beta5 mRNA is widespread in the mesoderm. During later developmental stages, it remains mostly confined to tissues of mesodermal origin, although probable inductive effects trigger shifts of beta5 gene expression from some mesenchymatous to epithelial structures. This was observed in the teeth, skin, kidneys, and gut. Of physiological importance is the beta5 labeling in the developing cardiovascular and respiratory systems and cartilages. Furthermore, early beta5 gene expression was observed within the intra- and extraembryonic sites of hematopoiesis. This suggests a major role for beta5 in the hematopoietic and angiogenic stem cells and thus in the development of the vascular system. Later, the beta5 gene was expressed in endothelial cells of the vessels developing both by angiogenesis and vasculogenesis in the lung, heart, and kidneys. Moreover, the beta5 hybridization signal was detected in developing cartilages but not in ossified or ossifying bones. beta5-Integrin is a key integrin involved in angiogenesis, vasculogenesis, hematopoiesis, and bone formation.

International audience; The RCS rat presents an autosomal recessive retinal pigment epithelium dystrophy characterized by the outer segments of photoreceptors being phagocytosis-deficient. A systematic genetic study allowed us to restrict the interval containing the rdy locus to that between the markers D3Mit13 and D3Rat256. We report the chromosomal localization of the rat c-mer gene in the cytogenetic bands 3q35-36, based on genetic analysis and radiation hybrid mapping. Using a systematic biocomputing analysis, we identified two strong related candidate genes encoding protein tyrosine kinase receptors of the AXL subfamily. The comparison of their expression patterns in human and mice tissues suggested that the c-mer gene was the best gene to screen for mutations. RCS rdy؊ and RCS rdy؉ cDNAs were sequenced. The RCS rdy؊ cDNAs carried a significant deletion in the 5 part of the coding sequence of the c-mer gene resulting in a shortened aberrant transcript encoding a 20 amino acid peptide. The c-mer gene contains characteristic motifs of neural cell adhesion. A ligand of the c-mer receptor, Gas6, exhibits antiapoptotic properties.

La retinite pigmentaire est une degenerescence retinienne hereditaire qui affecte essentiellement le champ visuel peripherique. Un œdeme maculaire peut entrainer une baisse d’acuite visuelle centrale supplementaire.

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal degenerations characterized by progressive degeneration of rod and cone cells that affects predominantly peripheral visual fields. Macular edema may cause additional central visual acuity decrease. Cystoid macular edema (CME) is one of the few treatable causes of visual loss in RP. The prevalence of CME in RP has been found to be between 10 and 20% on fluorescein angiography-based studies, and as high as 49% on reports based on optical coherence tomography. Macular edema can manifest at any stage of the disease and may be unilateral or bilateral. It can be found in any genetic form, but is more often associated with RP caused by CRB1 mutations. The origin of macular edema in RP patients still remains poorly understood. Some mechanisms have been suggested, including antiretinal antibodies (retinal, carbonic anhydrase, and enolase antibodies), vitreous traction, retinal pigment epithelium dysfunction, and Müller cell edema. There is no gold standard therapeutic strategy. Drug therapy is the primary treatment. Systemic carbonic anhydrase inhibitors, such as oral acetazolamide or topical dorzolamide, are still the mainstays of initial therapy. If CME is refractory to acetazolamide, intravitreal corticosteroid injections may be a therapeutic option. However, antivascular endothelium growth factor injections have limited effect and should be avoided. Vitrectomy has also been evaluated, but its exact role remains to be determined. The benefits of these therapies are variable among patients. The establishment of therapeutic approaches is limited by our poor understanding of the pathophysiology of CME in patients with RP. Autoimmune retinopathies (AIRs) are a group of rare diseases characterized by acute or subacute progressive vision loss and are thought to be mediated by autoantibodies specific to retinal antigens. The AIRs encompass paraneoplastic syndromes, such as cancer-associated retinopathy and melanoma-associated retinopathy, and a larger group of AIRs that have similar clinical and immunological findings but without underlying malignancy. These diseases may also be complicated by macular edema. RP is one of the most common forms of inherited retinal degeneration. It displays extensive clinical and genetic variations and leads to progressive blindness with variable onset.

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Background Gene therapy, and particularly gene restoration, is currently a great hope for non-curable hereditary retinal degeneration. Clinical applications require a gene transfer vector capable of accurately targeting particular cell types in the retina. To develop such a vector, we compared the expression of a reporter gene after subretinal injections of lentiviral constructs of various pseudotypes and with the transgene expression driven by various promoters. Methods Lentiviral vectors expressing the green fluorescent protein (GFP) under the transcriptional control of cytomegalovirus (CMV), mouse phosphoglycerate kinase (PGK), human elongation factor 1-α (EF1α), or human rhodopsin (RHO) promoters were pseudotyped by vesicular stomatitis virus (VSV) or Mokola virus envelope proteins. These constructs were injected into the subretinal space of adult rdy rats. GFP expression was analyzed in vivo 1 and 4 weeks after injection by fundus examination. The precise location of transgene expression was then determined by immunohistochemistry and in situ hybridization. Results Constructs of both vesicular stomatitis virus and Mokola pseudotypes with ubiquitous promoters led to a strong expression of GFP in vivo. Histological studies confirmed the production of GFP in the retinal pigment epithelium (RPE) in most cases. However, only the combination of the VSV pseudotype with the RHO promoter led to GFP production in photoreceptors, and did so in a sporadic manner. Conclusions Mokola-pseudotyped lentiviral vectors are effective for specific gene transfer to the RPE. Neither VSV- nor Mokola-pseudotyped lentiviral vectors are adequate for efficient gene transfer to photoreceptors of adult rats. Copyright © 2005 John Wiley & Sons, Ltd.

It is now possible to treat ocular surface disorders by means of amniotic membrane transplantation. We performed a study to determine the efficacy of this technique in the treatment of severe Acanthamoeba keratitis.We studied six patients with severe, painful, nonhealing Acanthamoeba keratitis who underwent one or two amniotic membrane transplantation procedures between February 2001 and January 2003. Histopathological analysis of the corneal buttons was performed in four cases.Eight amniotic membrane transplantation procedures were performed. The mean length of follow-up was 14 (range 3-21) months. The mean interval between institution of medical treatment and the procedure was 3.6 months. All patients had progressive stromal lesions caused by an inflammatory reaction. Complete reepithelialization occurred in four cases, and partial healing in two cases. Ocular inflammation and tissue destruction were decreased in all cases, pain was lessened in five cases, and corneal neovascularization was decreased in four cases. No postoperative complications were observed. Amniotic membrane was observed under dysplastic corneal epithelium on histologic examination.Amniotic membrane transplantation may be a safe and effective treatment of severe Acanthamoeba keratitis, particularly during the inflammation phase. It may permit penetrating keratoplasty to be delayed.

To identify proteins secreted by the retinal pigment epithelium (RPE) and to analyze their cellular distribution in normal and pathologic rat retinas at various stages of eye development.A cDNA library was constructed with RNA isolated from porcine RPE sheets and screened by using the yeast signal sequence trap system. In situ hybridization, immunohistochemistry, and semiquantitative RT-PCR analysis were performed on rat retinas.The cDNA encoding prosaposin was isolated. This is the first time this gene has been shown to be expressed in the retina. Prosaposin mRNA was detected in the rat RPE cell monolayer and in ganglion cells 14, 21, and 45 days after birth. The amount of prosaposin mRNA increased between days 14 and 45 after birth in normal retinas (rdy+), but not in the pathologic retinas (rdy-) of RCS rats.Several techniques were used to determine the localization of prosaposin in rat retinas. The increase in the amount of prosaposin mRNA in normal retinas coincided with the maturation of photoreceptor cells and the beginning of the phagocytosis process. In addition, the RCS rdy- RPE cells, characterized by the abrogation of the ingestion phase of the photoreceptor outer segments, are deficient in prosaposin expression.

Based on the K8/JTS-1-mediated transfection technique, we developed an in vivo protocol for an efficient transfer of plasmid DNA to ocular cells. As determined with condensed plasmids containing reporter genes for either beta-galactosidase (pcDNA-lacZ) or enhanced green fluorescent protein (pREP-EGFP), the immortalized human retinal epithelial cells RPE D407 and human embryonic kidney 293 cells can be transfected with typical efficiencies of 11 and 19%, respectively. Unlike 293 cells, RPE D407 cells had a reduced viability on transfection with both plasmids. In vivo, subretinal injections of DNA-K8/JTS-1 complexes revealed reporter gene expression in choroidal and RPE cells of normal pink-eyed Royal College of Surgeons (RCS) rats. The validity of this transfection technique in terms of retinal cell survival in RCS rats was then examined by using pREP-hFGF2 plasmid, which encodes the human basic fibroblast growth factor isoforms (hFGF2). Subretinal injection of pREP-hFGF2-K8/JTS-1 complexes into 3-week-old dystrophic RCS rat eyes reveals a delayed photoreceptor cell degeneration 60 days postinjection. In this case, the average analyzed field points with delayed cell dystrophy represent 14 to 17% of the retinal surface as compared with 2.6 and 4% in pREP5beta and vehicle-injected eyes, respectively. Peptide-mediated in oculo transfection thus appears to be a promising technique for the treatment of retinal cell and photoreceptor degenerations.

Background: Experimental therapeutic approaches to retinal degenerations often require the subretinal injection of a therapeutic agent. The injected volume and the age of the animal can influence the proportion of the retinal surface affected by the subretinal injection. We have investigated the quantitative effect of a single injection in the subretinal space. Methods: Normal and Royal College of Surgeons rats aged 1 week, 3 weeks or 2 months received subretinal transscleral injections of 1, 3, 5 or 10 µl China ink. After 24 h, animals were killed, injected eyes were enucleated and fixated, and the retinas flattened. An image analyzing program was used to measure the total retinal surface and the retinal surface affected by the dye. Results: The mean retinal surface affected by the injection ranged from 5.24±2.76 mm2 to 14.8±2.3 mm2, depending on ani- mal age and injected volume. The injection affected 8.79±0.89 to 36.9±8.13% of total retinal surface. There was no statistically significant difference between normal and Royal College of Surgeons rats. Intravitreal leakage of the dye was more frequent with increasing injection volumes. Conclusion: The retinal surface affected by a single subretinal injection increases with the injected volume, but this increase is not proportional. Higher volumes lead to a loss of injected solution, either in the vitreous body or through the sclero-tomy. In 2-month-old rats, a 3-µl subretinal injection appears to have the best reproducibility, with 20–30% of retinal surface covered by the injected dye.

Mutations in human BIGH3 (TGFB1), a gene identified after treatment of an adenocarcinoma cell line with TGF-β, have been observed in patients with granular Groenouw type I, Reis–Bucklers, Thiel–Behnke, Avellino, and Lattice type I and IIIa, six autosomal dominant corneal dystrophies linked to chromosome 5q. In order to gain insight into the physiological role of this gene, we characterized the genomic structure of the mouse Bigh3 and its expression in murine embryos. The gene spans 30 kb on mouse chromosome 13 and has 17 exons. Embryonic expression of Bigh3 is observed in the mesenchyme of the first and second branchial archs as early as dpc 11.5 and is particularly strong in the mesenchyme of numerous tissues throughout all the development stages. In fetal eye, the expression is first seen at 11.5 dpc in the mesenchyme surrounding the optic stalk, extends toward the sclera and choroid by 14.3 dpc and reaches the cornea by 17.5 dpc. Because the physiological role of BIGH3/Bigh3 is still largely unknown, embryonic expression in organs like heart, vessels, and intestine may help to identify new functions which could be searched for in patients and in knock-out animal models. The characterization of the murine structure is a prerequisite for the making of such models.

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.

Lentiviral vectors are widely used in experimental gene transfer and are a promising tool for clinical applications, particularly for the treatment of neurodegenerative diseases. However, one of the most important limits to the application of this technology to humans is the risk of insertional mutagenesis through the integration of the viral genome into the host cell chromatin. This risk remains poorly evaluated and uncontrolled. In order to eliminate this risk, we have developed a lentiviral vector derived from the human immunodeficiency virus type 1 lacking integration property. After cell transduction, the vector genome persists in an extrachromosomic circular form in the nucleus and allows an effective and stable transgene expression in vitro and in vivo.