Long-term efficacy of ciliary muscle gene transfer of three sFlt-1 variants in a rat model of laser-induced choroidal neovascularization.

Inhibition of vascular endothelial growth factor (VEGF) has become the standard of care for patients presenting with wet age-related macular degeneration. However, monthly intravitreal injections are required for optimal efficacy. We have previously shown that electroporation enabled ciliary muscle gene transfer results in sustained protein secretion into the vitreous for up to 9 months. Here, we evaluated the long-term efficacy of ciliary muscle gene transfer of three soluble VEGF receptor-1 (sFlt-1) variants in a rat model of laser-induced choroidal neovascularization (CNV). All three sFlt-1 variants significantly diminished vascular leakage and neovascularization as measured by fluorescein angiography (FA) and flatmount choroid at 3 weeks. FA and infracyanine angiography demonstrated that inhibition of CNV was maintained for up to 6 months after gene transfer of the two shortest sFlt-1 variants. Throughout, clinical efficacy was correlated with sustained VEGF neutralization in the ocular media. Interestingly, treatment with sFlt-1 induced a 50% downregulation of VEGF messenger RNA levels in the retinal pigment epithelium and the choroid. We demonstrate for the first time that non-viral gene transfer can achieve a long-term reduction of VEGF levels and efficacy in the treatment of CNV.

[Contribution of respiratory relaxation techniques during intravitreal injections: A pilot study]. / Apport des techniques de relaxation respiratoire au cours des injections intravitréennes : étude pilote.

PURPOSE: To study the effects of breathing techniques for anxiety, perceived pain, and patient satisfaction while receiving intravitreal injections. METHOD: This prospective, randomized clinical study included patients admitted for intravitreal anti-VEGF injections. They were randomized into two groups: a relaxation group who listened to a prerecorded relaxation breathing session before and during the injection, and a control group who received the injection without a relaxation session. Statistical analysis was then performed to assess the factors influencing satisfaction, anxiety, and perceived pain. RESULTS: We included one-hundred four patients in total: 52 in the relaxation group versus 52 in the control group. The relaxation group had a greater decrease in anxiety than the control group (P=0.03) but similar levels of pain (P=0.86). In total, 80.76% of patients in the relaxation group expressed the wish to have a relaxation session during their next injection. Multivariate analysis showed that the patient's usual level of stress as well as the relaxation session affected the level of anxiety experienced before the injection. CONCLUSION: Relaxation techniques before and during intravitreal injections decrease anxiety in patients without decreasing pain during IVT. Prerecorded relaxation breathing sessions are non-invasive, inexpensive, easy to set up, and reduce anxiety during intravitreal injections on an outpatient basis.

[Functional results and prognostic factors in open-globe ocular trauma with presenting visual acuity of no-light perception]. / Résultats fonctionnels et facteurs pronostiques des traumatismes oculaires à globe ouvert avec acuité visuelle initiale à perception lumineuse négative.

PURPOSE: To analyse the clinical ocular characteristics and determine prognostic factors for functional recovery in eyes presenting with no light perception (NLP) after open globe ocular trauma. MATERIALS AND METHODS: In this retrospective study were included all the patients with no light perception after open globe trauma who presented to Amiens University Hospital between October 2014 and June 2018. RESULTS: Fifteen eyes of 15 patients were included in this study. The main mechanism of the trauma was globe rupture (80 %, n=12). The most common location was zone III (66 %, n=10). The wound size was greater than 10mm in 9 patients (60 %). The ocular lesions included expulsion of the crystalline lens or posterior chamber intraocular lens, hyphema, retinal detachment, vitreous hemorrhage and ciliochoroidal lesions. Damage to the ciliary body was a negative prognostic factor for functional recovery (P=0.04). Nine patients remained with no light perception, whereas 6 patients experienced an improvement in visual acuity (2.3 logMAR in 3 patients, 0.7 logMAR in 1 patient, 0.4 logMAR in 1 patient and 0.2 logMAR in 1 patient). These 6 patients had undergone posterior vitrectomy due to vitreoretinal involvement (P<0.001). CONCLUSION: In the case of open globe trauma with no light perception on presentation, a functional recovery is possible if there is no irreversible anatomical damage.

Measurement of full-thickness macular hole size using en face optical coherence tomography.

PurposeTo assess the feasibility and interest of measuring macular hole (MH) size using en face optical coherence tomography (OCT) compared with manual diameter measurements on B-scans.MethodsAmong our previously published series of 100 patients operated for primary MH, patients whose images were acquired with Cirrus 5000 HD-OCT (Carl Zeiss Meditec) with a quality signal strength >5/10 were included. Three segmentations (internal limiting membrane, horizontal, and retinal pigment epithelium (RPE)) were compared for obtaining the most appropriate en face image. MH surface areas were measured using ImageJ software. Mean diameters calculated from surface areas (diameter=2 × âˆš(surface area/π)) were compared with those measured on B-scans.ResultsNineteen patients were included with a mean age of 72±8 years (56-86) and a female predominance (3/16). The mean absolute difference between horizontal and vertical diameters measured on B-scans was of 54±47 µm (0-180) without reaching significance (P=0.874). RPE segmentation provided the best en face image and was feasible without and with adjustment, respectively, in 79% and 100% (cases with vitreomacular traction) of cases. No significant difference in mean diameters was observed between those calculated from en face images (435±143 µm (195-693)) and those measured on horizontal B-scans (426±139 µm (214-705), P=0.482).ConclusionMeasuring MH size on en face OCT images is feasible, reliable, and eliminates the potential bias related to manual measurements on B-scans. Its integration into OCT devices would offer an automated and easy-to-use option for clinical practice.

[Understanding logistic regression]. / Comprendre la régression logistique.

Logistic regression is one of the most common multivariate analysis models utilized in epidemiology. It allows the measurement of the association between the occurrence of an event (qualitative dependent variable) and factors susceptible to influence it (explicative variables). The choice of explicative variables that should be included in the logistic regression model is based on prior knowledge of the disease physiopathology and the statistical association between the variable and the event, as measured by the odds ratio. The main steps for the procedure, the conditions of application, and the essential tools for its interpretation are discussed concisely. We also discuss the importance of the choice of variables that must be included and retained in the regression model in order to avoid the omission of important confounding factors. Finally, by way of illustration, we provide an example from the literature, which should help the reader test his or her knowledge.

[Sclerotomies analysis using Spectral Domain OCT in sutureless vitrectomies complicated by endophthalmitis]. / Analyse des sclérotomies par OCT Spectral-Domain au cours des vitrectomies sans suture compliquées d'endophtalmie.

INTRODUCTION: Transconjunctival sutureless vitrectomy is a recent advance in vitreoretinal surgery. Some authors have reported an increased risk of postoperative hypotony and endophthalmitis and recommend the creation of oblique incisions, intended to be self-sealing, so as to reduce these risks. However, there is still a debate about the best architecture for transconjunctival sutureless incisions. MATERIALS AND METHODS: We report two cases of acute endophthalmitis occurring after 23 and 25 gauge transconjunctival sutureless vitrectomy. We analyzed the scleral incisions using the anterior segment module of the Spectralis(®) OCT. To our knowledge, this is the first direct description of the appearance of sclerotomies associated with endophthalmitis. RESULTS: The anterior segment module of Spectralis(®) OCT permitted a high-resolution evaluation of the architecture of the scleral incisions. We found straight, gaping incisions with misaligned edges and vitreous incarceration. DISCUSSION: By way of these two case reports and a review of the literature, we discuss the contribution of anterior segment OCT in the analysis of scleral incision architecture in sutureless vitrectomy. Our findings are consistent with those reported in the literature. The presence of a direct incision, wound gap or edge misalignment are associated with an increased risk of early leakage and postoperative hypotony. CONCLUSIONS: The anterior segment module of the Spectralis(®) OCT is a valuable tool for non-invasive, painless and high-resolution documentation of sutureless vitrectomy incisions. It allows for causal analysis and better understanding of the conditions associated with endophthalmitis after sutureless vitrectomy.

[Smartphones in ophthalmology]. / Les smartphones en ophtalmologie.

INTRODUCTION: The increased utilization of medical applications for smartphones provides new opportunities for doctors, including ophthalmologists. In this study, we examined the availability of ophthalmological applications in the two largest smartphone app stores (Apple App store and Android Play Store) and then proposed a classification for smartphone ophthalmological applications according to their functionalities. MATERIALS AND METHODS: In November 2012, we searched the Apple App Store and the Android Play Store for ophthalmological themed applications, using numerous ophthalmological keywords. We excluded applications that were not ophthalmology-related. RESULTS: We identified 342 ophthalmological applications. There were two main categories in ophthalmological applications: those for ophthalmologists, and those for patients. DISCUSSION AND CONCLUSIONS: There are numerous benefits of smartphone use for ophthalmologists as well as their patients. Ophthalmological applications are turning cell phones into medical devices. In addition, smartphones may play a very important role in patient education, self-monitoring, and low-vision aids via magnifying systems.

Protein delivery for retinal diseases: from basic considerations to clinical applications.

Because the eye is protected by ocular barriers but is also easily accessible, direct intravitreous injections of therapeutic proteins allow for specific and targeted treatment of retinal diseases. Low doses of proteins are required in this confined environment and a long time of residency in the vitreous is expected, making the eye the ideal organ for local proteic therapies. Monthly intravitreous injection of Ranibizumab, an anti-VEGF Fab has become the standard of care for patients presenting wet AMD. It has brought the proof of concept that administering proteins into the physiologically low proteic concentration vitreous can be performed safely. Other antibodies, Fab, peptides and growth factors have been shown to exert beneficial effects on animal models when administered within the therapeutic and safe window. To extend the use of such biomolecules in the ophthalmology practice, optimization of treatment regimens and efficacy is required. Basic knowledge remains to be increased on how different proteins/peptides penetrate into the eye and the ocular tissues, distribute in the vitreous, penetrate into the retinal layers and/or cells, are eliminated from the eye or metabolized. This should serve as a basis for designing novel drug delivery systems. The later should be non-or minimally invasive and should allow for a controlled, scalable and sustained release of the therapeutic proteins in the ocular media. This paper reviews the actual knowledge regarding protein delivery for eye diseases and describes novel non-viral gene therapy technologies particularly adapted for this purpose.