bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptional dynamics, denucleation, and gene regulation in embryonic lens development
Authors: Cvekl A. , Limi S. , Zhao Y. , McGreal R. , Zheng D.
Published: September 2017

Transcription of genes occurs in apparently irregular pulses of activity termed transcriptional bursts. In contrast, cellular differentiation is marked by coordinated gene expression of batteries of genes required for cellular specialization. Ocular lens is comprised of two compartments: the lens epithelium and lens fibers. Position of individual cells within the lens is directly related to their differentiation status, marked by expression of individual crystallin genes. Another hallmark of lens fiber cell differentiation is organized degradation of their organelles. It is currently not known how transcription is terminated in the disintegrating lens fiber cell nuclei and what are the external and internal components of this process critical for lens transparency. Onset of expression of different crystallins follows the temporal pattern Cryaa > Crybb1 > Cryga in differentiating lens fibers. Surprisingly, expression of Cryaa is terminated in “normal” fiber cell nuclei while expression of Cryga persists even in highly condensed nuclei just about to be disintegrated. Differentiation influences both transcriptional burst size and frequency as well as spatial pairing of different chromosomes that carry crystallin genes.
Scanning laser ophthalmoscopy – basic optical principles
Authors: Irsch K.
Published: September 2017

Scanning Laser Ophthalmoscopy (SLO) produces an ocular fundus image by moving a focused laser beam via scanning mirrors over the retina in a grid pattern and registering the reflected light from each scanned point. In confocal SLO, a pinhole is placed in front of the detector to cut off scattered or defocused light coming from outside the point of interest, which otherwise can blur the image. This results in a focused, high‐contrast image of a single tissue layer located at the focal plane. Tomographic information can be extracted by moving the plane of the pinhole. The use of various wavelengths allows for different applications, such as fluorescein angiography, indocyanine green angiography, and autofluorescence imaging. This lecture will present the basic principles of SLO, as well as discuss notable applications and variants of the technology.
Adaptive optics – basic optical principles
Authors: Irsch K.
Published: September 2017

Adaptive Optics (AO) refers to a technique to compensate for distortions caused by optical aberrations in the media between the camera and the object being imaged. It was originally developed for use in astronomical telescopes to compensate for optical distortions induced by the inhomogeneous earth atmosphere. It has since evolved to become a powerful clinical tool in ophthalmology. In the eye, a “wavefront sensor” (aberrometer) measures the distortion of incoming light induced by inhomogeneities within the cornea and crystalline lens, which is then “undistorted” via reflection by a deformable mirror. AO thus enables imaging of the human retina with unprecedented resolution in vivo, such as revealing individual photoreceptors or the walls of blood vessels. One should note that AO by itself does not provide an image; rather an AO subsystem is incorporated into an existing imaging device. AO subsystems have thus far been successfully integrated into three ophthalmic imaging devices: fundus cameras, scanning laser ophthalmoscopes, and the OCT device. This lecture will introduce the basic principles of AO, illustrate its value with state‐of‐the‐art clinical examples, and discuss potential future applications in ophthalmology.
Vision improvement in dry and wet Age‐Related Macular Degeneration (AMD) patients after treatment with new corneal CPV procedure for light redirections onto the retina
Authors: Serdarevic O. , Tasindi E. , Dekaris I. , Berry M.
Published: September 2017

Purpose

To evaluate in two clinics vision improvement in AMD patients treated with a new corneal elastic modulus‐altering procedure (CPV) for light redirections onto multiple retinal areas.

Methods

Ten eyes (6 wet, 4 dry), with best‐corrected near and distance visual acuities (CNVA and CDVA) between 20/80 and 20/400, without pathological retinal morphology completely affecting the central 10° (3 mm) on OCT, were given a single treatment of CPV and were examined for 12 months post‐CPV.

Results

LogMAR Mean CNVA and CDVA in treated eyes improved (p < 0.01) from pre‐CPV 0.957 and 0.942 to 0.512 and 0.638, 0.544 and 0.602, 0.531 and 0.672 at 1, 6 and 12 m, respectively. The number of ETDRS letters gained in mean binocular CNVA/CDVA were 22/15, 25/19, 25/18 at 1, 6, and 12 m, respectively. Administered NEI VFQ‐25 at 3 m improved from pre‐CPV. No CPV complications or adverse events occurred.

Conclusions

CPV effectively, safely, rapidly and comfortably redirects light onto functional retinal areas after a single treatment to provide, without visual training, significantly improved monocular and binocular near and distance vision without causing peripheral field restriction or diplopia in patients with atrophic or neovascular AMD with poor vision, including after anti‐VEGF therapy to which CPV is complementary and for which CPV may improve compliance because of improved vision restoration.
Macular thickness after intraocular pressure reduction following trabeculectomy
Authors: Drukteiniene E. , Strelkauskaitė E. , Kadziauskienė A. , Ašoklis R. , Schmetterer L.
Published: September 2017

Purpose

The aim of the study was to assess changes of macular thickness after trabeculectomy and compare them in respect to the usage of preoperative prostaglandins and status of diabetes mellitus.

Methods

The prospective observational study included 93 glaucomatous eyes (90 patients) that underwent trabeculectomy. 81 (87.1%) patients were on prostaglandins treatment preoperatively. 5 (5.38%) patients had type 2 diabetes. The foveal and sectoral macular thicknesses were measured preoperatively, 1 week, 6 months and 12 months after the surgery using spectral domain optical coherence tomography. Retinal thickness was compared across the follow‐up visits and in respect to the preoperative use of prostaglandins and diabetes.

Results

There was a reduction in mean ± SD intraocular pressure of 18.5 ± 8.6mmHg 1 week, 15.4 ± 7.9 mmHg 6 months and 14.4 ± 8.3 mmHg 12 months after trabeculectomy (p < 0.001). 1 week postoperatively retinal thickening was observed in all macular subfields (p < 0.001); the central macular thickness increased from 267.23 ± 19.20 μm at baseline to 271.12 ± 19.59 μm. 6 months postoperatively macula remained slightly thicker in central, nasal, inner superior and outer temporal sectors (2.10 ± 5.97 μm, p < 0.001 in central subfield). 12 months after trabeculectomy retina showed thinning in the outer nasal and superior subfields (‐3.54 ± 8.57 μm; ‐1.94 ± 7.02; p < 0.01, respectively). There were no differences in the changes of macular thickness when compared in respect to preoperative prostaglandins (p > 0.05). The retinal changes did not differ between diabetic and nondiabetic patients (p > 0.05).

Conclusions

Trabeculectomy induced mild macular thickening, more pronounced in the early postoperative period. Neither diabetes nor the use of prostaglandins before surgery had impact on these changes regardless their potency to increase vascular permeability.
Alternated intra‐arterial and intravitreal chemotherapy: successes and failures of advanced intraocular retinoblastoma treated without systemic chemotherapy
Authors: De Francesco S. , Hadjistilianou T. , Borri M.
Published: September 2017

Purpose

To report the efficacy of combined intravitreal chemotherapy (IViC) and intra‐arterial chemotherapy (IAC) for the treatment of advanced stage retinoblastoma.

Methods

The medical records of twenty patients affected by unilateral advanced retinoblastoma (Reese‐Ellsworth stage Vb/D of ABC classification). After clinical and ophthalmoscopic evaluation, they underwent MRI to exclude local and CNS dissemination. The IAC was given to treat retinal masses and intravitreal injections to treat vitreous seeding. Patients had received two cycles (six infusions) of IAC, and from six up to ten melphalan injections into the vitreous, with an interval of 7–10 days between them.

Results

All patients underwent to bimonthly MRI examination, during treatment and every 3 months for 1 year after last injection, to exclude orbital dissemination. Successful control (57.8%) of tumor masses and vitreous seeds was achieved in all cases at 12 up to 60 months follow‐up. No permanent complications have been reported. Transient omplications disappeared throughout the months. No intraocular or orbital tumor recurrence or retinoblastoma metastases were observed.

Conclusions

Sequential IAC and intravitreal melphalan for advanced retinoblastoma is a good tool to provide retinal and vitreous seed control.
OCT‐A et critères d'activité
Authors: Coscas G. , Lupidi M. , Coscas F.
Published: September 2017

Optical coherence tomography angiography (OCT‐A) might be a useful tool to describe different morphological findings in treatment‐naive exudative AMD (eAMD) before and after VEGF‐trap intravitreal injections. Trough a prospective case series of 60 consecutive treatment naïve eAMD eyes diagnosed with different types of CNV a micro‐structural analysis, based on 5 Activity Criteria (shape, branching pattern, presence of anastomoses, vessel's termini and presence of perilesional halo) was performed. Treatment‐induced changes in choroidal neovascularization, CNV area and greatest linear dimension were assessed along with the variation in subretinal and/or intraretinal fluid. After treatment tiny branching vessels, anastomoses and peripheral arcades reduced from 100% of the cases to 40%, 50% and 30% respectively. Considering still‐active lesions, persistent tiny vessels were observed in 75% of the cases, anastomoses in 60% of the cases and a residual activity of CNV was associated with a peripheral arcade in 100% of the cases. OCT‐A Activity Criteria and quantitative findings, may help in the diagnosis of CNV, guiding decisions for treatment, as well as in monitoring the evolution of CNV and its response to treatment.
OCT‐A and Diabetic maculopathy; automated assessement
Authors: Lupidi M. , Cagini C. , Coscas F. , Coscas G.
Published: September 2017

A fully automated quantitative assessment of OCT‐Angiograms is a useful imaging system for detecting diabetic‐induced focal vascular impairment both in retinal and choroidal layers. Through a retrospective case series of 48 DM eyes and 47 healthy controls evaluated by Spectralis HRA‐OCT2 (Heidelberg Engineering, Heidelberg, Germany) it was shown that capillary density values were significantly lower (p < 0.05) in all retinal vascular layers and choriocapillaris of DM patients compared with healthy subjects. Moreover retinal and choroidal vascular networks, although distinct entities, seem functionally interconnected: varying the degree of perfusion may be a mutual compensatory mechanism in response to an ischemic injury.
Doctor is there anything else that I can do for my glaucoma?: Alternative therapy for glaucoma, what is the evidence?
Authors: Sunaric Megevand G.
Published: September 2017

The usual algorithm for the treatment of glaucoma consists of medical or/and laser therapy, followed by surgical intervention if the IOP does not lower to the target or the disease progresses despite maximal medical therapy. Understandingly, just as for many other chronic diseases, patients are willing to do more for their glaucoma in order to prevent progression and ultimately blindness. The question: “Doctor is there anything else that I can do for my glaucoma?” is therefore often asked. Several studies have suggested that some lifestyle habits or alternative therapies may influence glaucomatous neuropathy and many patients admit using them either in conjunction or as replacement of their prescribed glaucoma medication. This talk will focus on the evidence that is behind these therapies. Education of ophthalmologist and patients is of great importance in order to avoid misleading beliefs and erroneous therapies with the risk to harm patients visual function.
Flat‐mount preparation of cornea
Authors: Thuret G. , He Z.
Published: September 2017

Flat mounting of the whole cornea has two main advantages over conventional cross sections: it provides an overview of the whole tissue while allowing precise subcellular localization. We first described how to improve immunostaining for the analysis of the endothelial cells of flat‐mounted corneas, by using fixation with methanol or 0.5% PFA at room temperature, and not the conventional fixation with 4% PFA. We then applied a similar technique for the multilayered epithelium. Flat mounting is essential to study the distribution of rare cells inside large area of cells.
Flat‐mount preparation of lens epithelium
Authors: Löfgren S.
Published: September 2017

The lens capsule with its attached epithelium is a relatively accessible epithelial model system, suitable for various cell culture assays, histology, and histochemical assays. The optical requirements for imaging of lens capsule‐epithelium can be challenging, especially if the tissue is not flat. The lecture will cover various techniques for preparation of flat‐mount capsule‐epithelium, including differences among species, removal of cortical tissue, and fixation of the capsule‐epithelium to various base materials.
Flat‐mount of retina, including preparation of choroid and iris
Authors: Andre H.
Published: September 2017

Flatmount methods have been applied to multiple animal models to grant a panoramic view of specific tissues. Mouse models of retinopathy of prematurity (oxygen‐induced retinopathy) and age‐related macular degeneration (laser‐induced choroidal neovascularization and iodate‐induced geographic atrophy) have generally been assayed from whole‐tissue flatmount studies. We have recently developed a method for mouse iris flatmounts as a model of rubeosis iridis, a clinical diagnosis associated with proliferative diabetic retinopathy and neovascular glaucoma. The aim for the course is to illustrate technical aspects of mouse retinal, choroidal, and iris flatmounts, as well as methods for analysis and interpretation of results.
The 8‐fold quadrant dissection method for ex vivo human interventional retinal experimentation
Authors: Murali A. , Ramlogan‐Steel C. , Andrzejewski S. , Dhungel B. , Steel J. , Layton C.
Published: September 2017

Purpose

Retinal research relies on animal and in‐vitro models which lack many of the characteristics of human retina. We have instead established a reproducible ex‐vivo model of primary retinal explants derived from human donor eye cups.

Methods

A dissection strategy performed independently by two investigators was designed to maximize retinal tissue whilst maintaining experimentally reproducible fragments of retina suitable for experimental purposes. The retina was divided into 4 quadrants through the fovea and equivalent distribution of photoreceptors between quadrants was confirmed with CD73 staining in 7 pairs of donor eyes with flow cytometry. In the 8 quadrants from each of the 7 donors, the standard error in proportion of photoreceptors was 0.8–2.3%.

Results

Cellular composition of free floating retinal explants were followed for 2 months in 10 retinas with quadrant dissection and 8 with random dissection. Explants could be maintained for 2 months with live populations of photoreceptors, ganglion cells and Müller cells detected by flow cytometry. In contrast, amacrine and horizontal cells, decreased by 90% at 7 days. Only quadrant dissection from the same patient showed reproducible and reliable proportions of cell populations between dissections at any time point. There was no statistically significant relationship between the proportion of any cell population and donor age, time after death, time to storage or time in storage.

Conclusions

The 8 fold quadrant dissection method from a single donor forms an attractive human experimental model for interventional testing in retinal research. We demonstrate the utility of this model in a simple neuroprotection study, showing that insulin protected against CoCl2 induced hypoxia in human photoreceptors.
Electrical direct current stimulation affects retinal vessel diameter and vasodilation in healthy subjects
Authors: Freitag S. , Klee S. , Haueisen J.
Published: September 2017

Purpose

Electrical stimulation (ES) of the human eye is an emerging technique in the treatment of ophthalmic diseases since several studies showed improvements of visual functions in patients. Neuroprotective effects are assumed to cause beneficial impacts of ES. We investigated the acute effects of ES on retinal vasculature in healthy subjects using dynamic vessel analysis (DVA). This method enables continuous measurements of vessel diameters and assessment of flicker‐induced vasodilation.

Methods

DVA was performed in 7 healthy subjects (5 females, 25.7±1.7 years, one eye) to examine retinal vessel behavior. Two primary vessel segments were analyzed in each eye (temporal artery (tA) and vein (tV)) regarding baseline vessel diameter (BLD) and vasodilation provoked by flicker (VD). For non‐invasive ES a ring‐shaped rubber electrode surrounding the eye and a square rubber electrode at the occiput were used. Positive direct current (800μA) was applied for 20min at the eye. Each subject participated in two experimental trials in random order, applying real and sham ES (rES/sES) once. DVA was conducted before and immediately after rES/sES to observe changes in BLD and VD. Results were analyzed using paired t‐test to check for changes in BLD and VD due to rES/sES on a level of p=0.05.

Results

All subjects showed retinal vessel reactions to flicker in DVA. BLD decreased significantly after rES for tA (‐3.4±1.7%; p=0.003) but not for tV (‐0.2±1.6%; p=0.814). In contrast, VD of tA showed an upward trend (+0.7±1.2%; p=0.162), while VD of tV was reduced after rES (‐0.4±1.6%; p=0.547). For sES no significant changes of BLD and VD were observed.

Conclusions

Real ES affects both arterial BLD and VD by narrowing tA in resting state and enhancing vessel reaction to flicker provocation. These results provide evidences for beneficial effects of ES on circulatory processes.
Influence of metabolic control in patients with refractory diabetic macular edema treated with Ozurdex
Authors: Sanchez Ramon A. , Lopez Galvez M.I. , Ortega Alonso E. , Hernandez Rodriguez R. , Portilla Blanco R.R. , Roberts I. , Zarzosa Martin E.
Published: September 2017

Purpose

To analyze the relationship between glycemic, lipid, and blood pressure control following the American Diabetes Association(ADA) goals, and the response of refractory diabetic macular edema (DME)in patients treated with Ozurdex.

Methods

A retrospective, descriptive and observational study was conducted on patients with refractory DME treated with Ozurdex® in the University Hospital of Burgos, Spain, between 2012 and 2015.

Results

21 patients were included. Almost all (95%) patients had type 2 diabetes mellitus (DM), and 81% were treated with insulin. The mean time of evolution of DM in this series was 16 years (± 12). The mean HbA1c was 7.22 ± 1.06. The mean initial best corrected visual acuity (BCVA) was 0.72 (log Mar ±0.33) and improved to 0.58 (log Mar ±0.31) after 6 months of follow up. The initial central macular thickness (CMT) was 506μ ±99, and a reduction to 384μ ±128 was observed after 6 months of follow up. Taking into account the overall metabolic control of the patient, a statistically significant difference was found in the improvement in BCVA after 3 months of follow up in patients with good metabolic control. A greater central macular thickness reduction was observed in patients with a better metabolic control at six months of follow up. This study also suggests that patients with an optimum HbA1c control have a tendency to achieve a better visual acuity after an Ozurdex implantation. No statistical differences were found between blood pressure and lipid parameters, and the anatomic or functional response to Ozurdex.

Conclusions

Ozurdex is an effective and safe treatment in the treatment of DME in patients that did not respond or poorly responded to other therapies. The overall metabolic control of the patient following the criteria of the ADA is related to the success of the treatment with Ozurdex.
The place of OCT‐angiography in uveitis
Authors: Khairallah M. , Khochtali S. , Abroug N.
Published: September 2017

Optical coherence Tomography (OCT) angiography is a newly developed, dye‐less, imaging method that provides high‐resolution, depth‐resolved en face images of the retinal and choroidal microvasculature. OCT angiography has shown to be helpful in evaluating retinal vasculitis. It is better than fluorescein angiography in detecting perifoveal retinal ischemia and other microvascular changes. In such cases, the deep capillary plexus appears to be more severely involved than the superficial capillary plexus. On the other hand, OCT angiography may play a critical role in the differential diagnosis, evaluation, and monitoring of various choroidal inflammatory diseases involving the macula. It may show evidence of choroidal flow reduction. In these conditions, the choriocapillaris seems to be the primary site of a reversible or persistent ischemic process. OCT angiography is also useful for noninvasive detection of inflammatory choroidal neovasculization, and for monitoring of its response to therapy. Further studies are needed to definitely establish the role of OCT angiography in the diagnosis and management of retinal and choroidal inflammatory conditions and in assessing predictive factors for visual outcome.
The potential impact of new OCT technology for the measurement of ocular inflammation
Authors: Pichi F.
Published: September 2017

One of the greatest challenges when caring for patients with sight‐threatening uveitis is the lack of objective markers of disease activity, whether in the context of routine clinical practice (to direct treatment) or for use in clinical trials (to establish efficacy of new therapies and standardization of care). For example, the use of slit‐lamp microscopy to grade anterior chamber cells is quiet subjective, depending on the empirical ability of the grader, thus nowadays spectral domain‐OCT can be used to highlight cells in the anterior chamber, and new automated algorithm are being developed to measure the number of cells in a 3D volume scan.

In the anterior segment the iris tissue bed would also be a desirable site to monitor the progression of acute anterior uveitis, in which it is well known that the iris vessels dilate. OCT angiography is a novel technique that uses motion‐contrast imaging to non‐invasively create depth‐resolved angiographic maps of the vasculature. As such, OCT angiography can be used to analyze the iris vasculature in acute anterior uveitis, and new software are available to isolate the iris vessels, create a 3D rendering and measure the vasculature volume.
New protein drugs for retinal diseases: Attributes, efficacy, and safety
Authors: Behar‐Cohen F.
Published: September 2017

One of the major challenge in the field of retina is to reduce the need for frequent re‐injections of proteins in the vitreous. Sustained release of proteins is the eye remains an unmet need. To prolong the duration of protein efficacy, higher doses are injected, carrying the risk of off target effects and toxicity. Solid non biodegradable implants, dispersed polymeric systems, micro‐pumps have been proposed. Gene therapy has also appears as an appealing strategy to produce secreted proteins. Beside viral vectors, non viral vectors are also developped with this purpose in mind. We will detail the advantages and drwabacks of each technology and present the latest development of ciliary muscle electroporation of plasmid encoding therapeutic proteins, from pre clinical development to first in man. The regulatory developement and safety issues will also be described.
Does ethnicity and foveal morphology play a role in the spatial distribution of macular pigment?
Authors: Ctori I. , Huntjens B.
Published: September 2017

While macular pigment optical density typically follows an exponential decline with eccentricity from the fovea, atypical profiles have also been described, including reports of increased prevalence of ring‐like and central dip profiles among non‐white ethnicities. However, classification of macular pigment (MP) profile phenotypes varies and is often based on subjective visualisation. We present data showing that compared to visual assessment, objective MP profiling (taking into account measurement repeatability) is a more reliable method that should be considered in future observational and interventional studies. We will also describe ethnic variations in MP spatial distribution (among white, black and South Asian individuals) in relation to variations in foveal architecture, including data regarding individual retinal layers, foveal width and pit slope taken from SD‐OCT images. Our data suggests that although ethnicity explains around 10% of the variance in MP profile, gender plays no significant role. In addition, although white subjects demonstrate thicker retinal layers than non‐whites, the significant differences in the amount and distribution of MP between ethnicities is not explained by variations in foveal morphology.
Proteomic tools for studying RPE functions
Authors: Hongisto H. , Jylhä A. , Nättinen J. , Rieck J. , Ilmarinen T. , Veréb Z. , Aapola U. , Beuerman R. , Petrovski G. , Uusitalo H. , Skottman H.
Published: September 2017

Human embryonic stem cell‐derived retinal pigment epithelial cells (hESC‐RPE) provide a promising cell source for studying retinal development, for disease modelling, and retinal cell replacement therapies. Several research groups, including ours, have demonstrated that hESC‐RPE structure, function, and physiology resembles that of native RPE regarding cellular fine structure and expression of many RPE signature genes and proteins. To characterize the hESC‐RPE proteome in larger scale, we have compared hESC‐RPE protein expression to primary human RPE using isobaric tags for relative quantitation (iTRAQ) technology. The hESC‐RPE proteome reflected that of native RPE with a large number of metabolic, mitochondrial, cytoskeletal, and transport proteins expressed. No adverse signs such as increased stress, proliferation, or retinal degeneration‐related changes were seen in hESC‐RPE, while proteins involved in key RPE functions such as visual cycle and phagocytosis were detected. Proteomics provides valuable tools for validation of hESC‐RPE, studying disease mechanisms, and discovery of new biomarkers and therapeutic targets.
Towards a shared care model for stable diabetic retinopathy patients: a feasibility trial in Singapore
Authors: Mathur R. , de Korne D.F. , Wong T.Y. , Chiang P.P. , Wong E.Y. , Goh D. , Chakraborty B. , Nguyen H. , Wai C. , Tan D.H. , Lamoureux E.L.
Published: September 2017

Purpose

While diabetic retinopathy (DR) is a chronic disease, patients in Asian’ health care systems are often managed within hospital settings. Aim of this feasibility study is to assess the quality of care and economic benefits of a shared care model managing patients with stable DR in a primary eye care clinic (PEC) compared with a current tertiary specialist outpatient clinic (SOC) in Singapore.

Methods

A randomized equivalence feasibility trial was performed, to compare a PEC with a SOC. The trial patients included those previously seen at the SOC, and having no DR or stable mild non proliferative (NPDR) with no macular edema, no visual and DR deterioration. Primary outcomes were clinical management. Secondary outcomes were patient satisfaction and cost of consultation. Differences analysis used equivalence testing and generalized odds ratios (GOR).

Results

The trial included 231 patients, 83.1% classified as no DR (PEC: 79.1%; SOC: 87.1%) and 16.9% as stable mild NPDR (PEC: 20.9%; SOC: 12.9%). DR management at PEC was significantly equivalent to that received at the SOC (rate difference 2.56%; CI:(−1.61% to 6. 74%)) and 4.29%;CI: (0.14%–8.45%), respectively. Patient satisfaction at the PEC was high when compared to SOC (GOR: 1.71; CI: (0.50–2.00)). Direct costs per patient visit were 45% lower at PEC compared to SOC.

Conclusions

Our feasibility trial showed that patients with no or stable DR receive similar clinical care and management at a lower‐cost PEC setting, are equally satisfied with the service compared to tertiary eye care. A follow‐up study is necessary to validate these findings. Managing stable DR patients at a PEC may be a safe and effective shared care model to improve accessibility for patients while enhancing professional collaboration between hospital and community settings.
Leber's hereditary optic neuropathy: the ophthalmologist point of view
Authors: Barboni P.
Published: September 2017

Leber hereditary optic neuropathy (LHON) is a maternally inherited genetic disorder, associated to mitochondrial DNA mutations, with incomplete penetrance and variable expresivity, usually leading to large bilateral centrocecal scotomas in otherwise healthy young adults. The smaller‐caliber fibers of the papillomacular bundle are selectively lost at a very early stage of the pathologic process. Clinically, most patients with LHON go through pre‐symptomatic ophthalmoscopic changes before the acute phase, including peripapillary microangiopathy, small vessel tortuosity, swelling of the retinal nerve fiber layer (RNFL). Once the disease becomes symptomatic, the vascular changes increase with swelling of the superior and inferior fiber arcades and rapid loss of the papillomacular bundle. As the pathologic process progresses, temporal pallor may become evident. Then nerve fiber swelling decreases concomitantly with the extension of optic disc pallor toward complete atrophy; vascular changes follow a similar pattern. By 6 months after onset, optic atrophy is usually evident, and visual loss stabilizes. The chronic phase is reached by 1 year after onset.
MSand optic neuritis
Authors: Normando E.M.
Published: September 2017

Neurodegenerative disorders such as Alzheimer Disease, Parkinson Disease and Multiple Sclerosis present ocular manifestations which could precede general signs and symptoms. This correlation between the eye and the brain has been confirmed by recent advances in imaging technologies. Hardware and software improvements have given the possibility of examining structures previously inaccessible. The assessments of these structures could lead to novel diagnostic and therapeutic approaches. The first objective of this SIS is to generate a multidisciplinary discussion between ophthalmologists and non‐eye experts; novel synergic approaches to neurodegenerative conditions will be discussed. The second objective is to explore the current application of retinal imaging in neurodegenerative diseases.
INFLIXIMAB and ADALIMUMAB in uveitic macular edema
Authors: Lejoyeux R. , Diwo E. , Vallet H. , Bodaghi B. , Le Hoang P. , Fardeau C.
Published: September 2017

Purpose

To compare the efficacy of infliximab versus adalimumab for the treatment of uveitis related refractory macular edema (ME).

Methods

We included in this retrospective case series patients diagnosed with uveitis related refractory ME and treated with infliximab (IFX) or adalimumab (ADA) at Pitie Salpetriere hospital between 2006 and 2016. All patients were assessed including best corrected visual acuity (BCVA), clinical inflammatory parameters, multimodality imaging, fluorescein angiography, ICG and SD‐OCT. Central foveal thickness (CFT) and retinochoroidal architecture were analysed with SD‐OCT at baseline, 6 and 24 months after treatment initiation. Findings of patients treated with IFX were compared with those of patients treated with ADA. Success was defined as a decrease of more than 50 microns of CMT.

Results

Twelve patients with a mean age of 40 years and 13 patients with a mean age of 46 years were respectively treated with ADA and IFX. At baseline, the mean BCVA of ADA patients was 0.59 logMar ((0; 1,3); median=0,54; SD=0,41) and the mean BCVA of IFX patients was 1,01 logMar ((0,52; 1,3) mediane=1; SD=0,31). The mean CFT of ADA patients was 417μ ((247; 732); median=350; SD=171) and the mean CFT of IFX patients was 450.4μ ((202; 617); median=521; SD=145). Six of the 12 patients (50%) were sucessfully treated by ADA at 6 months, and 8 of the 13 patients (61%) treated by IFX were successful at 6 months. At 6 months, CFT median decreasing from baseline was 61 microns for ADA groupe [range: 17; 136] showing no significant difference vs 92 microns for IFX [9; 165] showing no significant difference (p=0,32).

Conclusions

Anti TNF alpha therapy seems to be an efficient treatment at 6 month for uveitis related refractory macular edema. No difference in efficacy was observed between IFX and ADA.
Results from the SAKURA program: central retinal thickness changes with intravitreal sirolimus in subjects with non‐infectious uveitis of the posterior segment and macular edema at baseline
Authors: Bodaghi B. , White S.
Published: September 2017

Purpose

To evaluate the effects of intravitreal (IVT) sirolimus on central retinal thickness (CRT) in subjects with non‐infectious uveitis of the posterior segment (NIU‐PS) with macular edema (ME) in the SAKURA program.

Methods

The SAKURA program consisted of two Phase 3 international, randomized, double‐masked studies evaluating the efficacy and safety of every‐other‐month IVT sirolimus in subjects with active NIU‐PS. Inclusion criteria included vitreous haze (VH) ≥1.5 + . Subjects from both studies comprised the integrated intent‐to‐treat population evaluating IVT sirolimus 440 μg (n = 208) vs 44 μg (active control; n = 208). Primary endpoint: VH=0 at Month 5 (M5). Change in CRT at M5 was assessed in subjects with baseline ME (CRT ≥300 μm).

Results

In the integrated analysis, 21.2% vs 13.5% of subjects in the 440‐ vs 44‐μg groups achieved VH=0 at M5 (p = 0.038). 68 (32.7%) subjects in the 440‐μg group and 65 (31.3%) in the 44‐μg group had ME at baseline (mean CRT 501.65 μm and 507.89 μm, respectively). Of these, 19.1% and 12.3% in the 440‐ and 44‐μg groups, respectively, achieved VH=0 at M5 (p = 0.282). M5 CRT data were available for 47 and 51 subjects not rescued before M5 in the 440‐ and 44‐μg groups, respectively, with corresponding median % CRT changes from baseline of ‐20.6% and ‐15.5%. Median % CRT changes at M5 were greatest in subjects in the 440‐μg group without epiretinal membrane: ‐55.6% vs ‐2.3% in the 440‐ vs 44‐μg groups (p = 0.029). Serious ocular adverse events were reported in 14.9% and 14.3% of subjects with baseline ME in the 440‐ and 44‐μg groups, respectively.

Conclusions

An integrated analysis of the SAKURA program demonstrated that the mTOR inhibitor IVT sirolimus 440 μg can result in statistically significant improvements in VH in subjects with active NIU‐PS and can improve CRT in subjects with ME.
OCT angiography in ONH disease
Authors: Schmetterer L.
Published: September 2017

OCT angiography is a technique that has attracted much interest over the recent years. The main application is in retinal disease such as diabetic retinopathy or age‐related macular degeneration. The technique has, however, also been applied to patients with optic nerve head disease such as glaucoma or optic neuropathies. This talk summarizes what has been achieved so far and highlight problems such as quantification of perfusion.
Updates on retinal imaging technology for screening and diagnosis
Authors: Wong T. , Schmetterer L.
Published: September 2017

There has been a revolution in retinal imaging, allowing better screening, diagnosis, risk stratification and management of diabetic retinopathy (DR), age‐related macular degeneration (AMD), and retinal vascular disorders. In terms of DR screening, current imaging techniques employ fundus photography and skilled readers for DR assessment. There has been development of automated retinal image analysis software such as deep learning techniques using artificial intelligence. Current screening programs also do not effectively screen for diabetic macular edema (DME). Optical coherence tomography (OCT) can potentially provide cost‐effective solutions for improving DME detection. New screening techniques to image the peripheral retina such as ultra‐widefield imaging offers further potential.

For diagnosis and risk stratification, spectral domain OCT (SD‐OCT) and swept source OCT (SW‐OCT) are increasing used to diagnosis AMD, DME, and other conditions. Traditionally, FFA is used to evaluate AMD and DR. OCT angiography (OCT‐A) technology is a major advance that offers the opportunity to non‐invasively visualize different retinal capillary layers without injection of dye. OCT‐A is primed to replace FFA for most clinical scenarios.
Targeted NGS: an effective approach for molecular diagnosis of hereditary vitreoretinopathies
Authors: Burin des Roziers C. , Rothschild P.R. , Barjol A. , Clément C.A. , Edelson C. , Derrien S. , Metge F. , Michau S. , Robert M. , Prévot C. , Dollfus H. , Layet V. , Delphin N. , Bernardelli M. , Ghiotti T. , Hanein S. , Fourrage C. , Bonnefont J.P. , Rozet J.M. , Brézin A. , Caputo G. , Brémond‐Gignac D. , Valleix S.
Published: September 2017

Hereditary vitreoretinopathies (VRPs), traditionally divided into the groups of exudative and degenerative VRPs, encompass a number of diseases affecting the vitreous and the retina. These disorders are the commonest cause of inherited retinal detachment with high risk of vision loss during infancy. We designed a next generation sequencing (NGS) assay including ATOH7, COL2A1, COL9A1, COL9A2, COL9A3, COL11A1, COL18A1, FZD4, KCNJ13, KIF11, LOXL3, LRP5, NDP, TSPAN12, VCAN and ZNF408 allowing an exhaustive genetic screening with the most frequently mutated genes reported to be associated with all inherited VRPs. The diagnostic performance of this new design was evaluated on a cohort of 166 probands with a suspected clinical diagnosis of exudative or degenerative VRPs comprising 47% of children under 15 years old. We identified a large spectrum of causative mutations (single nucleotide changes as well as copy number variants) diagnosing molecular defects for 60% of the patients. Our NGS panel is therefore a promising screening method to be used efficiently in routine practice, able to detect a higher number of molecular defects than Sanger sequencing, improving significantly the molecular diagnosis of inherited VRPs.
Scleral lens as lifeline for dissatisfied patients after refractive reshaping corneal surgery
Authors: Mekki M.B. , Yahiaoui S. , Titah O. , Belaoudmou R.
Published: September 2017

We present our experience of scleral lens fitting after refractive failure of corneal reshaping surgery. 100 eyes of 90 patients unsatisfied after corneal reshaping surgery: Lasik (55), PKR (15), Radial keratotomy (10) and intra corneal ring segment implantation (20) are enrolled in this retrospective study. Visual acuity outcomes, quality of life using the contact lens impact quality of life (CLIQ) questionnaire and complications of scleral lens wear are discussed.
Revisiting corneal collagen crossliniking (CXL) safety: Evaluation of the effect of ultraviolet‐A (UVA) radiation on the retina with multifocal electroretinogram (mf‐ERG) and optical coherence tomography (OCT)
Authors: Lazaridis A. , Tsamassiotis S. , Besgen V. , Sekundo W. , Wenner Y. , Droutsas K.
Published: September 2017

Purpose

The evaluation of the effect of UVA radiation on the photoreceptors after CXL.

Methods

Seventeen eyes of 17 patients with keratoconus (n=15), pellucid marginal degeneration (n=1) and post‐LASIK ectasia (n=1), underwent CXL (Dresden protocol). The patients were examined preoperatively, at 2 and 6 weeks postoperatively with mf‐ERG and OCT. The P1 amplitude of the photoreceptor response was documented in 4 concentric rings, with ring 1 (R1) representing the foveal response and rings 2–4 (R2‐R4) corresponding to the successive annuli of stimulation. Uncorrected (UDVA) and corrected distance visual acuity (CDVA), corneal densitometry and central retinal thickness were also recorded.

Results

The preoperative mean values of P1 amplitudes for the 4 rings were R1=109.96±28.96 nV/deg2, R2=49.8±14.46, R3=29.85±8.9 and R4=19.33±6.3. At 2 weeks after CXL these values were R1=77.54±24.47, R2=36.55±12.53, R3=21.53±7.71 and R4=15.3±6.13, showing a statistically significant reduction for all rings (P<.05). At 6 weeks postoperatively P1 amplitudes were R1=99.8±31.23, R2=40.67±16.39, R3=24.98±7.13 and R4=16.35±4.84, showing for each ring no significant differences compared to preoperative values (P>.05). Corneal densitometry increased to statistically significant level at 2 (P<.001) and 6 weeks (P<.001), demonstrating a weak negative correlation with the postoperative P1 amplitudes. UDVA and fovea thickness showed no significant changes at 2 and 6 weeks.

Conclusions

This is to our knowledge the first study assessing the photoreceptor response after CXL with the Dresden protocol. Although a temporary dysfunction of the photoreceptors the first postoperative weeks cannot be excluded, the increase of 6‐weeks‐P1 amplitudes at preoperative (physiologic) values confirms the safety standards of the duration and intensity of UVA radiation as proposed by the Dresden protocol.
Hydrops: Not that bad!
Authors: Mekki M.B. , Said Y. , Okba T. , Taibi A.
Published: September 2017

Purpose

To demonstrate that hydrops is not a disaster and often evolves favorably especially under surgical treatment.

Methods

Prospective study of 30 eyes of 30 patients with corneal hydrops who underwent clinical examination with anterior segment photography, corneal topography, ultrasound corneal pachymetry and corneal OCT. All of them underwent in an outpatient setting and under topical anesthesia, anterior chamber air injection, peripheral iridotomy and deep corneal sutures perpendicular to Descemet membrane tear then kept under observation for 1 hour. Patients were asked to stay laying on their backs for 3 days. All patients were able to wear scleral lens after 1 week post surgery.

Results

Corneal edema decreased dramatically since the first day concomitantly with corneal thickness and average SimK reading. Mean LogMAR with scleral lens was 0.4.

Conclusions

Proper surgical approach of hydrops can provide a spectacular quick healing with visual improvement avoiding corneal graft.
The first consultation
Authors: De Zaeytijd J.
Published: September 2017

Photophobia is a common yet debilitating symptom. Patients experience an abnormal intolerance or even pain in the eye from a light source that should not be painful. The anatomy and pathophysiology of this phenomenon will be discussed. The clinical characteristics and disorders associated with photophobia will be reviewed. And finally, a practical approach will be presented to allow you to differentiate patients with common treatable causes such as dry eye disease from patients who need an in‐depth ophthalmic or neurologic evaluation to find the underlying disease.
Photophobia in retinal disease
Authors: Leroy B.P.
Published: September 2017

Purpose

To describe the phenotypes and genotypes of photophobia due to inherited retinal disease.

Methods

A case presentation format will be used to illustrate different genetically determined conditions leading to photophobia. Both clinical and electrophysiological phenotypes as well as genotypes will be discussed.

Results

Phenotypes and genotypes of genetically determined diseases leading to photophobia are very different. An important distinction to be made is the one between stationary and progressive diseases. Indeed, such distinction is important as the visual outcome may differ considerably between different conditions.

Conclusions

Genetically determined retinal diseases leading to photophobia are very diverse. Visual electrophysiology allows an important distinction between progressive and stationary conditions.
Tumors and pseudo‐tumors of the iris: classification and imaging techniques
Authors: Zografos L.
Published: September 2017

Tumors and pseudo‐tumors of the iris are classified as:

Iris cysts

Pigmented tumors

Vascular tumors

Myogenic tumors

Tu. of the non pigm. cil. epithelium

Neurogenic tumors

Juvenile xanthogranuloma

Metastatic tumors

Pseudotumors

Split lamp examination, split lamp photography, gonioscopy and photography of anterior chamber angle as well as high frequency ultrasound are the main examination techniques.
Update in genetics of corneal dystrophies
Authors: Bourges J.L. , Burin des Roziers C. , Beugnet C. , Nedelec B. , Hoffart L. , Delbosc B. , Muraine M. , Hamel C. , Lacombe D. , Moriniere V. , Fourrage C. , Robert M. , Bremond‐Gignac D. , Valleix S.
Published: September 2017

Hereditary corneal dystrophies are a group of diverse bilateral disorders usually classified anatomically according to the layer of the cornea affected. They include many types, which differ by their clinical manifestations, their histological characteristics, and their pathophysiology. The molecular basis of these corneal inherited disorders have expanded greatly, and mutations in several genes have been identified. We develop a genotype‐based approach by using a targeted Next‐Generation Sequencing panel including 15 known genes, and a cohort of 90 French index patients were recruited after detailed ophthalmic examination. All exons of the 15 genes were amplified using the kit TrueSeq Custom Amplicon (TSCA, Illumina). The subsequent amplified libraries were sequenced using a MiSeq (Illumina, Inc, San Diego, CA, USA) sequencer. All pathogenic variants were confirmed by Sanger sequencing, and familial analyses were performed. A large spectrum of molecular defects were identified with numerous novel variants. This NGS approach is an efficient tool to improve molecular diagnosis, and provides insight into the genotype‐phenotype correlation of all these corneal disorders in a cost‐effective way.
Peters anomaly new insights
Authors: Atilla H.
Published: September 2017

Developmental anomalies are one of the the main pathologies seen in infancy and childhood. Embryological development of the anterior segment structures are closely related to each other and the clinical manifestations can be complex with associated glaucoma and lens opacities. Also in infancy and childhood amblyopia is needed to addressed in order to support visual system development. The spectrum of developmental anomalies known as anterior segment dysgenesis can be mild as posterior embryotoxon or can affect iris, cornea and even crystalline lens in severe cases of Peters anomaly. Peters anomaly can be seen as a genetic syndrome (Axenfeld‐Rieger syndrome) or after congenital rubella. As the clinical manifestation vary, the treatment modalities vary accordingly.