bluuebunny/crossref_metadata_2025 huggingface dataset:
Ocular inflammatory diseases in ebola survivors
Authors: Hereth E. , Resnikoff S. , Fardeau C. , Bah M.O. , Sagno I.C. , March L. , Izard S. , Lama P.L. , Ouendeno N.A. , Delaporte E.
Published: September 2017

Purpose

The last Ebola outbreak severely affected West Africa and led to 2543 deaths and 1268 survivors in Guinea, where it began. The survivors faced various symptoms and disorders including ocular pain and erythema, itching, tearing, photophobia and blurry vision. The purpose of our study was to describe uderluing ocular diseases.

Methods

This is a prospective observational multicenter cohort study initiated in March 2015 which included survivors followed up in the infectious disease ward of Conakry and Nzérekoré. The patients received multidisciplinary medical follow‐up that included an eye examination.

Results

Systematic examination of 341 survivors highlighted 46 cases of uveitis (13.5%), six episcleritis (1.8%), and three interstitial keratitis (0.9%). Uveitis were more unilateral (78.3%) and anterior (47.8%) and occurred within the 2 months following discharge from the Ebola treatment center. Moreover, relapses were found up to 13 months after healing. Eleven eyes with anterior chamber inflammation presented with cataracts and visual acuity ≤ 5/10. Ten eyes with chorioretinal scars presented decreased visual acuity ≤ 5/10. Among 46 survivors with uveitis, 13 (28%) suffered from visual alteration on at least one eye.

Conclusions

Nearly 17% of Ebola survivors presented ocular disorders that may be very delayed in some patients. Moreover our study brought out relapses. We were not authorized to take intra‐ocular samples to identify the virus. The mechanism behind these uveitis is probably is an association between a direct cytopathic impact of the virus and an immune reaction to it. The corticosteroid therapy that is actually recommended by WHO can't be used safely during the acute infection but seems to be efficient in survivors. The current issue is to perform safely cataract surgery in survivors.
Neurotrophic Keratitis: Definition, clinical presentation and diagnosis
Authors: Said D. , Dua H.
Published: September 2017

Neurotropic Keratitis is a non‐healing or repeated break down of corneal epithelium associated with degenerative changes resulting from impaired corneal innervation. Later complications such as infection scarring and perforation can follow. A reduced or absent corneal sensation is the hallmark of the disease.

Patients present with dryness, photophobia and inability to read for prolonged duration hich is worse by computer work or air draft.

Signs are divided into 2 parts: Signs related to the disease process such as corneal epithelial irregularity and clouding, reduced tear break up time and superficial punctate keratitis mostly inferior, Later persistent epithelial defect, corneal ulcers with rolled edges and loose epithelium surrounding the edges which can later develop infection, melting, scarring or perforation. Signs related to the underlying cause such as lagophthalmous and reduced blink reflex, signs of previous herpetic keratitis with scarring, vascularization and or patches of iris atrophy. Stromal dystrophy or beaded corneal nerves, advanced diabetic retinopathy or retinal laser marks.

Diagnosis includes clinical presentation, duration of non‐healing epithelial defect and measuring corneal sensation with Coche‐Bonnet test.
Medical management of neurotrophic keratitis
Authors: RAMA P.
Published: September 2017

Considerations for the medical management of neurotrophic keratopathy (NK) depend upon the stage/ severity and pathology of the underlying disease process. Therapeutic approaches are broadly divided into strategic areas that encompass categories of treating the underlying disease process, treating any concurrent infections, preventing disease progression, promoting epithelialisation, providing tear replacement, reducing inflammation, preventing stromal tissue loss or perforation and avoiding complications.
Measurement of oculomotor parameters and visual processing times without eye‐tracking
Authors: Barbur J.L. , Llapashtica E. , Connolly D. , Sadler J.
Published: September 2017

Purpose

Oculomotor parameters and visual processing times affect visual performance. In addition, mental health disorders and common drugs can also affect task completion times and the efficiency of visual search. Eye‐trackers are useful in such studies, but expensive equipment and careful calibration is needed. A new, simple method that does not require eye‐tracking is proposed. The EMAIL (Eye Movement and Intrinsic Latency) test captures parameters that describe both the time course of eye‐movement generation as well as the time needed to detect and process specific stimulus attributes at the end of each saccade.

Methods

The test relies on measuring the time needed to detect peripheral targets, carry out an appropriate eye‐movement and process some feature of the stimulus (such as colour, coherent motion, rapid flicker, spatial orientation or acuity). In this round of experiments, the stimulus was a Landolt ring flanked by distractors and presented at a randomly selected location on either side of fixation, 8o in the periphery. The measurement variable is the target presentation time, δT, needed to achieve ~71% correct response. The subject's task is to saccade to the peripheral target, to register the stimulus attribute of interest and to press one of four response buttons to indicate the correct orientation of the gap.

Results

The results obtained so far show a significant effect of stimulus contrast, age and fatigue. The measured times vary systematically with age in the range 160 to 300 ms. Longer times are observed in schizophrenia and other mental health disorders.

Conclusions

The new EMAIL test provides a simple method to assess changes in oculomotor parameters and decision response times with potential applications in the study of fatigue and the evaluation of drug efficiency in the treatment of mental health disorders.
How to explain “flat” electroretinograms when patients with Leber's congenital amaurosis aren't blind
Authors: Parsa C. , Taylor A.
Published: September 2017

Purpose

To explain how a ‘flat” or ‘extinguished” electroretinogram (ERG) in a patient with Leber's congenital amaurosis may not necessarily be indicative of a corresponding loss of vision.

Methods

Basic principles of ocular as well as auditory electrophysiology, wave physics, phototransduction metabolic pathways and ophthalmic genetics were reviewed and organized to reveal heretofore overlooked pathways. Correlations of ocular as well as auditory electrophysiology characteristics for Leber's congenital amaurosis and congenital auditory neuropathy/dys‐synchrony were made.

Results

Variably delayed individual photoreceptor cell signaling secondary to metabolic enzymatic deficiencies involved in phototransduction results in ERG a‐waves produced, and subsequent b‐waves, to interfere destructively with each other, rather than allow for averaging in‐phase summation to permit recordable ERG signals. Despite the delayed visual cycle, intraretinal synaptic transmission may proceed uninhibited to activate retinal ganglion cells and axonal pathways to the visual cortex.

Conclusions

A ‘flat” or ‘extinguished” ERG need not indicate absent vision, but overall destructive interference of individual a‐waves and b‐waves averaged for the recorded ERG. Analogous auditory electrophysiologic findings are noted in corresponding so‐called congenital auditory neuropathy/dys‐synchrony. Such findings are of great diagnostic utility and may be considered pathognomonic. Theoretically, the stability or progression of a patient with Leber's congenital amaurosis, and their response to an interventional genetic or pharmacologic therapeutic regimen, could be followed in more sensitive and objective manner at the cellular level via electro‐oculography, prior to visual acuity, visual evoked potentials, or ERG testing revealing any changes in overall retinal function.
Limits for the indication of multifocal lenses based on the contrast sensitivity function
Authors: Grzybowski A.
Published: September 2017

Multifocal IOLs are more often responsible for lower contrast sensitivity (CS) than monofocal IOLs, especially in mesopic light conditions. Thus, multifocal IOLs are contraindicated in many ocular diseases, which are characterized by decreased contrast sensitivity function. They included irregular astigmatism, Fuchs dystrophy, and many retinal diseases affecting macular function like retinitis pigmentosa, Stargardt disease, diabetic retinopathy, age‐related macular degeneration, epiretinal membrane, and many optic nerve disorders. IOL decentration and tilt lead to decreased contrast sensitivity, aberrations, and ultimately decreased visual acuity, thus zonular weakness, esp. when severe, should be regarded as absolute or relative contraindication to choosing a multifocal IOL. Since contrast sensitivity is found to be most affected in eyes with aberrations and implanted multifocal IOLs, increased aberrations are relative contraindications for multifocal IOL implantation. It was proved that patients with the aspheric multifocal IOL had significantly better contrast visual acuity than patients with the spherical multifocal IOL.
Endoocular OCT assisted epimacular surgery with preliminary vitreoretinal adhesions mapping
Authors: Stoliarenko G. , Doroshenko D. , Ledeneva M. , Salakhutdinov V. , Savostianova N.
Published: September 2017

Membranectomy is critical and one difficult stages of macular surgery. The difficulty is caused by heterogeneity of the adhesion of epiretinal tissue to the retina, and if it is large, traumas of the retina appear that are the main cause of loss of visual fields in the central area. Also, that in the overwhelming majority of cases (more than 50%), the onset of membranectomy is accompanied by a trauma of the retina, which occurs when the epiretinal tissue is first captured with forceps. Selective surgery, in which the map of adhesion of epiretinal tissue to the retina is created with the help of OCT at the preoperative stage and membranectomy is carried out only in areas of low adhesion, significantly reduces the probability of traumas of the retina.

In the process of vitrectomy and membranectomy, the redistribution of mechanical stress occurs in the epiretinal tissue. Because of this, the topology of the adhesion map changes. Dislocations of the boundaries of high adhesion zones in the process of membranectomy can reach 1.5 mm and with the probability greater than 0.7 are greater than 0.5 mm.

Uses endoOCT allows to control these changes in process of surgery, allowing it is essential to increase its efficiency.
Changing the fate of retinal ganglion cells following retinal ischemia: is autophagy the way?
Authors: Russo R. , Varano G.P. , Adornetto A. , Nazio F. , Corasaniti M.T. , Nucci C. , Bagetta G.
Published: September 2017

Autophagy is a highly conserved catabolic pathway for cell components to be degraded through the lysosomes and recycled under normal and stressful circumstances. The involvement of autophagy has been proven in several models of neurodenegerative diseases; however, its role in the neurodegenerative process occurring in retinal ganglion cells (RGCs) exposed to glaucoma‐related stimuli is still controversial.

Here we show that retinal ischemia induced by acute elevation of intraocular pressure (IOP) is associated with a dynamic, biphasic, modulation of the autophagic pathway, characterized by an initial upregulation of the process, which is followed by a reduced efficiency. Increased RGC death was reported in mice with partial genetic autophagy impairment (AMBRA1 +/‐) and subjected to retinal ischemia. Conversely, boosting basal autophagy, either by caloric restriction or pharmacological treatment, improved RGC survival suggesting that the catabolic pathway can be targeted to achieve neuroprotection.
Neurotrophins involved in neuroprotective antibody effect
Authors: Bell K. , Wilding C. , Beck S. , Pfeiffer N. , Grus F.H.
Published: September 2017

Lower levels of different antibodies (abs) can be detected in glaucoma. Several have neuroprotective effects on retinal ganglion cells. Indicated by up‐regulation of glutamine synthetase previous studies show that Müller cells (MC) participate in this effect and we aimed to analyse MC participation in more detail. Primary porcine MC incubated with different abs (0.5 μg/ml γ‐synuclein, 1 μg/ml 14‐3‐3 or GFAP abs for 3 h), a control ab (anti‐myoglobin) or without added abs. To win conditioned medium containing secreted proteins MC were incubated with serum‐reduced medium. BDNF, CTNF, IL6, glutathione, neurotrophin 3, ILG1 and bFGF levels were analysed. Organ cultures were incubated with the conditioned media, medium containing 10 ng/ml CNTF or control medium. MC incubated with 14‐3‐3 (p = 0.045) or GFAP (p = 0.031) abs showed increased CNTF secretion. In comparison to control explants (740 rgc/mm2) rgc/mm2 quantification showed a significant increase in explants incubated with GFAP abs (1014 rgc/mm2, p = 0.04) or 14‐3‐3 abs (910 rgc/mm2,p = 0.07) conditioned medium. Control abs had no effect. We conclude that the neuroprotective antibodies also have an indirect effect on rgcs by increasing CNTF secretion and GS in Müller cells.
Juxtapapillary tumors and pseudo‐tumors of the retinal pigmented epithelium
Authors: Kivelä T.
Published: September 2017

The most conspicuous retinal pigment epithelium (RPE)‐associated lesion, most of which typically occur in the peripapillary region, is known as the combined hamartoma of the retina and the RPE although not all of them extend to the level of the RPE. This congenital lesion, which also has a vascular and an epiretinal component, often will slowly evolve during observation, not infrequently leading to reduced vision from distortion of the macula. It appears as a greyish‐brown, slightly elevated fundus lesion. It may be associated with neurofibromatosis type 2, although most seem to be isolated. None of the other RPE lesions occurs predominantly in the peripapillary region, although congenital hypertrophy of the RPE, simple hamartoma of the RPE, adenomas and adenocarcinomas of the RPE, and acquired reactive proliferations leading to RPE hyperplasia can do so. Except for the first one, these are slightly to moderately elevated lesions. Finally, rare congenital pigmentary changes such as pigmented optic disk, thought to be of RPE origin, can sometimes be observed.
Vascular tumors and malformation of the optic disk
Authors: De Laey J.J.
Published: September 2017

Three main types of angiomatous tumors of the optic disc may be considered: 1. Capillary angiomas associated or not with retinal angiomatosis are considered as a peculiar form of von Hippel or von Hippel‐Lindau disease. If they grow they may provoke extensive exudative response resulting ultimately in functional loss of the eye. However treatment is quite challenging. As long as vision is not threatened observation is advised. Direct laser photocoagulation of the tumor will result in severe nerve fiber damage and major loss of visual loss. PDT with or without intravitreal anti‐VEGF injections can be considered. The use of proton beam irradiation has been advocated in selected cases. 2. Cavernous angiomas of the optic disc are very rare. They may also be associated with a cavernous angioma of the retina. As most cases are non‐progressive, treatment is not advised. Neuro‐imaging has to be considered as cavernous angiomas of the retina can be associated with a cerebral angioma. 3. Angioma racemosum or congenital retinal AV malformations. In such cases the optic disc involvement is only part of the fundus lesion.If associated with cerebrovascular and dermatological anomalies the disease is called Wyburn‐Mason syndrome.
Efficacy and safety of the pars plana clip in the Ahmed valve device in patients with refractory glaucoma
Authors:  Ibanez J. ,  Perez Garcia D. ,  Martinez J. ,  Sanchez I. ,  Idoate A. ,  Berniolles J. ,  Bartolome I. ,  Lopez I. ,  Ascaso J.
Published: September 2017

Purpose

To evaluate the efficacy and safety of the pars plana clip (PPC) in the Ahmed valve tube PC7 inserted via the pars plana in patients with secondary refractory glaucoma.

Methods

Prospective and interventional case series that included 8 patients with secondary refractory glaucoma. The pars plana vitrectomy and the implant of the modified tube were performed during the same surgery. Control of intraocular pressure (IOP) and the development of intra‐ and postoperative complications were evaluated during the follow‐up.

Results

Follow‐up time was twelve months in all the patients. Control of IOP was achieved in 85% of patients, and 75% needed no antiglaucoma treatment. The complications that occurred were transient hypotony in two cases, choroidal detachment in two cases, and one case of intraocular hemorrhage and one case of hyphema. No case of tube extrusion was observed.

Conclusions

Our clinical experince suggests that implantation of the Ahmed tube modified with the PPC via the pars plana is safe and effective in patients with secondary refractory glaucomas.
Supracilliary Micro‐Stent (CyPass®) is associated with lack of disease progression and minimum usage of IOP lowering medications in patients with POAG 2‐years post‐implantation
Authors: Uzunov R. , Ianchulev T. , Dickerson J.
Published: September 2017

Purpose

Glaucoma is a progressive disease marked by deterioration in the visual field, optic nerve cupping and nerve fiber layer thinning. Glaucoma treatment is aimed at slowing disease progression through control of intraocular pressure (IOP). Minimally invasive glaucoma surgery (MIGS) has become available as a treatment modality offering effective IOP lowering without the high rate of complications associated with traditional glaucoma surgery or the reliance on strict patient adherence required for pharmacological intervention.

Methods

One such MIGS device, a supracilliary micro‐stent (MS), implanted during cataract surgery, has recently completed a large 2‐year trial in the US (COMPASS trial) ‐ 505 patients were randomized to MS (n = 374) or cataract surgery control (n = 131).

Results

MS showed sustained 24‐month efficacy > than phacoemulsification alone. Importantly, visual fields (VF) did not progress with MS treatment over control (baseline and 2‐year mean deviation [MD] ‐3.4, ‐3.2 MS; ‐3.7, ‐3.2 control) while the percent of patients requiring IOP lowering medications was 15.2% for CyPass group versus 40.9% for control. The percentage of patients with VF progression (≥2.5 dB MD decrease) was 6.7% for MS and 9.9% for control. There was a three‐fold lower incidence of disc hemorrhage for MS vs. control (0.5% vs.1.6%), fewer IOP spikes (≥10 mmHg) over the 30‐day post‐op period (6.4% vs. 20.6%), and fewer subsequent glaucoma surgeries (0.6% vs.3.8%).

Conclusions

While these are post‐hoc descriptive observations, the data suggest that the benefits of reliable, effective, sustained IOP‐lowering through the use of a supracilliary micro‐stent implant may include limiting disease progression in patients with mild‐to moderate primary open‐angle glaucoma. Additional studies aimed at monitoring progression in patients with the micro‐stent are warranted.
Toric lens implantation in cataract surgery: risk factors of post‐operative lens rotation, analysis of 50 cases
Authors: Loria O. , Raucau M. , Agard E. , El Chehab H. , Lereuil T. , Dot C.
Published: September 2017

Purpose

Toric lens implantation in cataract surgery has improved with the help of automatic alignment methods, which can determine the immediate postoperative angle with great precision. However, unpredictable misalignment sometimes occurs in the following days. The goal of our study is to identify risk factors of toric lens rotation within the first month of implantation.

Methods

We conducted a prospective, monocentric, descriptive study of 50 eyes in 26 patients operated for cataract by a surgeon experienced in toricity, and implanted a Zeiss Asphina709 implant, during September and October 2016. The intraoperative lens alignment was determined by conjunctival recognition with the Callisto system (Zeiss), coupled with the IOL Master 700 (Zeiss). Lens alignment at one month was determined by blinded double reading on slit lamp photographs using EyeSuite (Luneau). Axial length (AL), anterior chamber depth (ACD), lens thickness (LT), and white to white (WTW) distance were measured with the IOL Master 700.

Results

All implants were aligned as planned at the end of surgery. The average postoperative lens rotation at one month was 4.4° (+/‐4.85). There was no statistically significant correlation between implant rotation at one month and AL (p = 0.46), ACD (p = 0.18), LT (p = 0.75), WTW (p = 0.67), Age (p = 0.57), or Gender (p = 0.11).

Conclusions

Our study was not able to identify significant risk factors for postoperative toric implant rotation. Our low average rotation and small sample size may explain why statistical significance was not reached. A larger prospective study is underway. Our study underlines the difficulty to predict which patients will show toric implant rotation and highlights the importance of viscoelastic management at the end of surgery. Understanding and controlling those risk factors may help achieve better refractive results in the future.
Visualization of the light field of multifocal intraocular lenses using a dual wavelength approach
Authors: Eppig T. , Rubly K. , Schröder S. , Rawer A. , Langenbucher A.
Published: September 2017

Purpose

To implement a setup which allows simultaneous visualization of the far and near distance light field of multifocal intraocular lenses (MIOL) with two different wavelengths.

Methods

We used two different laser systems (532 nm and 405 nm) in junction with Powell lenses to create vertical laser lines. One laser line was collimated to simulate far distance imaging while the second laser line was diverging simulating near distance imaging at approximately 0.3 m distance. The MIOL was placed in a glass cuvette filled with balanced saline solution which was doped with two different fluorophores. The fluorophores were chosen to have a large Stokes shift and good separation between their excitation and emission bands. Image acquisition was performed with a slit lamp bio microscope and a digital single reflex camera. We investigated three different IOL types: a bifocal MIOL, a trifocal MIOL and an extended depth of focus IOL.

Results

We found that Propidium iodide and Fluorescein were appropriate fluorophores. Propidium iodide was excited at 532 nm and showed a red fluorescence while Fluorescein was excited at 405 nm showing the green fluorescence. Both lasers required a high power of approximately 30 mW in order to create a visible fluorescent reaction in the cuvette. All three MIOL types provided a good separation between far and near distance light. The regions of overlapping light fields were visible as yellow fluorescence.

Conclusions

In contrast to the previously published setups using a single wavelength with collimated excitation light and axially separated far and near distance foci the current setup allows superposition of the far and near distance foci which is more realistic compared to the situation in the eye. The dual wavelength approach enables an easy optical separation of far and near distance light.
Contribution of microglia and complement activation to glaucoma progression
Authors: Vetter M. , Bosco A. , Anderson S. , Breen K. , Romero C. , Steele M. , Chiodo V. , Boye S. , Hauswirth W. , Tomlinson S.
Published: September 2017

Glaucoma results in decline and loss of retinal ganglion cells (RGCs), and is associated with microglia and complement activation, with correlation between early microgliosis in the optic nerve head and later optic nerve pathology. Inhibiting microglia activation can protect RGC axons, implicating microglia in glaucoma pathogenesis. Thus, microglia and innate neuroimmune events are critical components of glaucoma. Since microglia express receptors for multiple complement factors, we have investigated how the complement pathway contributes to glaucoma and microglial responses. We tested the therapeutic effect of limiting complement C3 activation using ocular gene therapy. We utilized CR2‐Crry, which is the soluble rodent‐specific complement inhibitor (sCrry) linked to a complement receptor 2 (CR2) targeting moiety. This was packaged into an AAV2 vector and delivered to the eyes of DBA/2J mice by intravitreal injection. AAV2‐CR2‐Crry‐treatment was highly neuroprotective, with significant preservation of retinal ganglion cells and improved optic nerve integrity. Molecular analysis showed significant shifts in the gene expression profile of FACS‐sorted myeloid cells, including upregulation of several potentially protective cytokines.
Protein kinase inhibitors for targeting tumor‐initiating cells in uveal melanoma
Authors: Cabre Estivill E. , Pereira E. , Vinyals A. , Lorenzo D. , Varela M. , Piulats J.M. , Caminal J.M. , Fabra À.
Published: September 2017

Purpose

Uveal Melanoma (UM) is the most common intraocular tumor in adults. Surgery and brachytherapies have improved survival rates, but up to 40% of patients develop liver metastases.

Mutations in the Gαq family members GNAQ and GNA11 are present in 80% of UM tumors whereas BRAF mutations are much less common. Consequently, Protein Kinase signaling pathways are dysregulated and specific targets can be identified for precise therapeutic approach. On the other hand, it has been proposed that tumors contain a specialized subset of cells defined as tumor‐initiating cells (TICs) that may be responsible for de novo resistance to drugs and metastatic disease. Thus, targeting TICs may be imperative for achieving a cure.

Methods

To this end, we performed an in vitro screening using the Screen‐Well® Kinase Inhibitor Library (BML‐2832‐0100) on TIC‐enriched populations of UM cells harboring either GNAQ /GNA11 or BRAF mutations.

Results

These UM‐TICs have the capacity to self‐renew and generate tumor spheres (melanospheres) in low‐adherent culture conditions. Furthermore, they display stem cell‐like features such as high expression of CD133, CD44, Nestin or ABCB5 specific markers. The metastatic ability of OMM‐2.5‐enriched TIC cells is currently explored in vivo after their orthotopic injection into the uvea of HL‐SCID mice. Our results revealed that metastatic and TIC‐enriched populations were more resistant to antiproliferative effects of kinase inhibitors. Several kinase inhibitors such as Tyrphostin 51 (EGFRi), DES (PKCi), DRB (CK2i) and ML‐9 (MLCKi) differentially affected growth and survival of TIC‐enriched population from parental cell line Mel270.

Conclusions

Taken together, we showed that EGFR, MAPK, PKC and PI3K signaling pathways are activated in TICs and their respective inhibitors may represent attractive therapeutic candidates for metastatic UM.
Retinal involvement in mitochondrial diseases
Authors: Leroy B.P.
Published: September 2017

Purpose

To describe the retinal phenotypes of mitochondrial conditions.

Methods

A case presentation format will be used to illustrate different retinal conditions due to mitochondrial mutations. Both clinical and electrophysiological phenotypes as well as genotypes will be discussed.

Results

Phenotypes and genotypes of mitochondrial diseases leading to retinal involvement are very different. The degree of retinal involvement is very variable, both between families and within the same family.

Conclusions

Retinal involvement of mitochondrial disease is very diverse. Specialised imaging, psychophysics and visual electrophysiology are important tools to estimate severity of involvement.
Patient management – genetic testing and practical considerations
Authors: Liskova P. , Kolarova H. , Kousal B. , Honzik T.
Published: September 2017

Mitochondrial diseases frequently manifest with ocular signs involving the optic nerves, extraocular muscles and retina; therefore, the ophthalmologist is, in many cases, the first specialist consulted. During the last decade, it has been shown that even disorders originally thought to be an isolated ocular entity may display a broad spectrum of overlapping phenotypes affecting multiple organs. This makes genetic counselling challenging. Ophthalmic examination using state of the art imaging, such as optical coherence tomography and autofluorescence, may identify subclinical disease, therefore ophthalmologists can play an important role in guiding further investigation and molecular testing. It is becoming apparent that clinical classification should be associated with the underlying genetic defect to improve our understanding of genotype‐phenotype correlation for these conditions. Supported by AZV 16‐32341A.
Artistic depictions of the eyes and blindness throughout history
Authors: Bullock J.
Published: September 2017

Sight has always been the fundamental means by which we human beings relate to our environment and to each other. We use our eyesight to perceive, to understand, and to ascertain the truth. For thousands of years, artists have depicted the theme of blindness and have portrayed its transforming effects. The eyes of the blind are frequently illustrated no differently from those of other, presumably sighted, figures. In addition, since neither most artists nor observers are ophthalmologicly sophisticated, with rare exceptions, it is highly unusual for the artist to depict authentic ocular pathology. The various methods of artistic representation of blindness are given with numerous examples. While it is clear that the artistic renderings of blindness, depicted across various media of expression, are extremely varied, there have been some amazing constants throughout recorded history, even though medical understanding of, and our ability to restore, vision, has undergone almost incomprehensible change. Oscar Wilde said: “…art imitates life.” It is clear that the fear of blindness and the appreciation of our precious gift of sight, as depicted in art, have changed little over the ages.
Lifetime Study in mice: radiation‐induced cataract
Authors: Dalke C. , Kunze S. , Rößler U. , Neff F. , Greiter M. , Gomolka M. , Hornhardt S. , Garrett L. , Unger K. , Rosemann M. , Azimzadeh O. , Wurst W. , Zitzelsberger H. , Hölter S.M. , Tapio S. , Kulka U. , Atkinson M. , Graw J.
Published: September 2017

We did a lifetime study in irradiated and control mice with a follow up time until 24 months post irradiation with repeated in vivo analysis of the lens density and the retina.

Mice of different genetic constitution (wild‐type, Ercc2+/‐) were acutely whole body irradiated with low doses of ionising radiation (0, 63, 125 and 500 mGy) and a low dose rate (63 mGy/min). Lens opacification was analysed monthly by Scheimpflug imaging and the retinal fundus and thickness was analysed by OCT. At different time points (4 and 24 hours, 12, 18 and 24 months post irradiation) mice were sacrificed and eyes were analysed by histology and immunohistochemistry.

Mice of all groups, even the DNA repair helicase deficient mice (Ercc2+/−), did not develop clinically relevant radiation‐dependent lens opacities. Only an age‐dependent increase of lens density was identified. Consequently, no major morphological changes were visible in the eye histology of all mice. Immunohistochemical staining against DNaseIIb revealed no differences between the groups as well as 8‐OHG staining resulted in similar ROS levels in all irradiation groups. However, non‐irradiated Ercc2+/‐ mice showed an increased level of oxidative stress compared to wild‐type mice.
Surgical management of diabetic macular edema – Against
Authors: Chatziralli I.
Published: September 2017

Diabetic macular edema (DME) is the leading cause of visual impairment in patients with diabetes mellitus. Disruption of the blood‐retinal‐barrier has been implicated to the pathogenesis of DME. In addition, vascular endothelial growth factor (VEGF) and other inflammatory mediators have been found to be major contributors to angiogenesis and to increased vascular permeability, leading to DME.

Although surgical management of DME has been proposed as a treatment option, since it releases vitreous traction at the macula and improves oxygenation of the posterior segment, complications and persistence of macular edema postoperatively put this treatment modality in suspicion. In fact, eyes with refractory edema and no observable traction seem less likely to improve after surgical treatment. Moreover, in the majority of cases, there is no functional improvement, despite the encouraging anatomical results.

Nowadays, anti‐VEGF agents still remain the standard of care in the management of DME, while intravitreal steroids gain interest as well. In cases, in which DME coexists with vitreoretinal interface pathology, pars plana vitrectomy in selected cases may be useful.
Global histone modifications predict the outcome of glaucoma surgery
Authors: Jeon S. , Park H.Y.L. , Kim J.H. , Jung Y. , Park C.K.
Published: September 2017

Purpose

Conjunctival and subconjunctival fibrosis at the surgical site influences the outcome of glaucoma surgery. Since glaucoma surgery initiates a cascade of events that leads to up‐ or downregulation of various genes and the subsequent release of cytokines and growth factors, we analyzed global histone modifications at the site of glaucoma surgery and their relationship with the outcome of glaucoma surgery.

Methods

44 patients who were scheduled to undergo glaucoma surgery were enrolled in this study. A 4 × 4 mm section of Tenon's tissue with overlying conjunctiva was cut from the eye at the margin of the incision. Primary rabbit anti‐histone antibodies were applied in humidified chamber at the following dilutions: H3 K9 K14 K18 K23 K27Ac at 1:200, H4 K5 K8 K12 K16Ac at 1:200, H3 K4diMe at 1:800 (Abcam), and H4 R3diMe at 1:25 (Millipore). The sections were counterstained with Harris's haematoxylin, dehydrated, and mounted.

Results

Using histochemical staining, we determined the number of cells that were positive for histone acetylation and demethylation of histones H3 and H4. The patients were divided into high‐ and low‐acetylated or ‐methylated groups accordingly. The low‐acetylation group for H3 K9 K14 K18 K23 K27 and H4 K5 K8 K12 K16 had poorer surgical outcomes based on Kaplan‐Meier plots. The preoperative intraocular pressure was significantly related to acetylation of both H3 K9 K14 K18 K23 K27 and H4 K5 K8 K12 K16 in univariate and multivariate regression analyses.

Conclusions

Our findings suggest global histone modifications in the conjunctival and subconjunctival tissues predict glaucoma surgery outcomes. A low acetylation status indicated a poor prognosis for glaucoma surgery. Prognostication using histone modifications might have implications for epigenetic therapy to improve glaucoma surgery outcomes.
Early signs of microglial activation in mice retinas contralateral to experimental glaucoma: quantitative analysis of cells number, processes retraction and reorientation
Authors: de Hoz R. , RAMIREZ A.I. , Gonzalez‐Martin R. , Ajoy D. , Salazar J.J. , Salobrar‐Garcia E. , Rojas B. , Triviño A. , Ramirez J.M.
Published: September 2017

Purpose

To quantify retinal microglia signs of activation after 24 h of unilateral laser‐induced ocular hypertension (OHT) in OHT‐eyes and their contralateral eyes.

Methods

Albino Swiss mice were divided into two groups, naïve (n = 6) and lasered (n = 6). Retinal whole‐mounts were immunolabeled with anti Iba‐1 to quantify the: i) number of microglial cells in the photoreceptor layer (PRL), outer plexiform layer (OPL) and inner plexiform layer (IPL); ii) the area of the retina occupied by Iba‐1 +  in the nerve fiber layer‐ganglion cells layer (NFL‐GCL) and; iii) the arbor area of microglial cells in the OPL and IPL. iv) the number of microglial vertical processes connecting the OPL and PRL.

Results

In OHT eyes and contralateral eyes had no significant differences in cell number with respect to naïve. OHT eyes presented a significant decrease in microglial arbor area in the OPL in comparison with control (p < 0.01) and in the IPL in comparison with control and contralateral eyes (p < 0.01 and p < 0.05 respectively). However the retinal area occupied by Iba‐1 +  cells in the NFL‐GCL was significantly increased: i) in both contralateral and OHT eyes with respect to control (p < 0.01 in both instances); and ii) in OHT eyes with respect to contralateral eyes (p < 0.05). In contralateral untreated eyes, the number of microglial vertical processes connecting the OPL and PRL were significantly increased in comparison with control and OHT eyes (p < 0.01 and p < 0.05 respectively).

Conclusions

At 24 h, laser‐induced OHT produces a reactive non‐proliferative microgliotic response both in OHT eyes and in contralateral untreated eyes. Whether this response favors neuroprotection or neurodegeneration needs to be clarify.
Orbital recurrence of uveal melanoma after 45 years from enucleation
Authors: Hadjistilianou T. , Galluzzi P. , Toti P. , Menicacci F. , Menicacci C. , Daini R. , Pica A. , Zografos L.
Published: September 2017

Purpose

A 52‐year‐old woman who had undergone enucleation of the left eye at the age of 7 years for posterior uveal melanoma, had no further problems until 45 years later, when she developed a multifocal malignancy of the ipsilateral orbit.

Methods

Case report.

Results

MRI documented the presence of nodular multiple masses in the anophthalmic socket suggesting possible metastatic disease. Hepatic examination and ultrasound evaluation, CT scan of the thorax and bone scintigraphy excluded other sites of metastatic lesions.

She underwent excissional of the 3 distinct tumors, 2 inferiorly and one superiorly in the anophthalmic socket. After surgery she received proton beem radiotherapy in the anopthalmic socket for a total of 4.600rads.

Histopathology documented malignant melanoma of the orbit characterized by epitheliod cells.

Conclusions

The long interval between recognition of the primary tumor and enucleation and the appearance of clinically manifest metastatic disease in the ipsilateral orbit is the longest reported in the literature to date.

A similar case of metastatic choroidal melanoma to the contralateral orbit 40 years after enucleation has been reported by Coupland (1996).
Novel gene based therapies for inherited retinal dystrophies in pediatric patients
Authors: Stieger K.
Published: September 2017

Gene based therapies for inherited retinal dystrophies have improved dramatically over the past 10 years. Clinical trials in patients based on the adeno‐associated virus (AAV) mediated gene transfer of a correct cDNA copy of the mutant gene were started for several disorders, including early onset severe retinal dystrophy associated with mutations in the RPE65 gene, and juvenile retinoschisis due to mutations in the RS1 gene. Furthermore, optogenetic approaches and cell based therapies are on the verge to the clinical application. The highest expectations though have raised the recent development of genome editing strategies based on CRISPR‐Cas endonucleases, which together with a template DNA enable the correction of the mutant DNA sequence ex vivo or in vivo in photoreceptor cells. In this lecture, an overview will be given on the current state of the art in gene based therapies for pediatric patients, and limitations and potential solutions will be discussed.
The prevalence of asthenopia and its determinants in a population of university students
Authors: Yekta A.A. , Khabazkhoob M. , Hashemi H. , Ali S.B. , Ostadimoghaddam H. , Najafi A. , Heravian J.
Published: September 2017

Purpose

To determine the prevalence of asthenopia and some of its determinants in a population of Iranian university students

Methods

In this cross‐sectional study, multi‐stage cluster sampling was applied in students of Kazerun's universities in south of Iran. After selecting the subjects, ophthalmic examinations and interview was conducted with each student. In line with previous studies, any person with at least one of the symptoms of eye pain, dry eyes, eye swelling, blurred vision, diplopia, foreign body sensation, photophobia, tearing and low visual acuity was considered to have asthenopia.

Results

Of 1462 selected subjects with a mean age of 22.8 ± 3.1 years, 73% of them were females. The prevalence of asthenopia was 71.2%, 40.6%, and 19.7% based on having 1, 2, and 3 symptoms, respectively. The prevalence of asthenopia was 73.3% in females and 65.5% in males (P = 0.004). The highest (81.5%) and lowest (58.4%) prevalence of asthenopia was seen in the age group 28–29 years and 30 years and above, respectively. The prevalence of asthenopia was higher in hyperopic subjects than myopic and emmetropic subjects (P < 0.001). The prevalence of asthenopia was 77.7% in astigmatic and 79.2% in anisometropic participants. The mean amplitude of accommodation was 9.7 ± 2.6 D and 10.28 ± 4.3 D in asthenopic and healthy subjects, respectively (P = 0.008). The mean near point of convergence was 7.2 ± 2.8 cm and 7.7 ± 3.9 cm in asthenopic and healthy subjects, respectively (P0 < 0.001).

Conclusions

The prevalence of asthenopia is markedly high in university students, may causes difficulty in reading and is important to address this condition in this age group.
Genetic causes of deaf‐blindness in sixteen Czech families
Authors: Kousal B. , Dudakova L. , Bujakowska K. , Liskova P.
Published: September 2017

Purpose

Usher syndrome (USH) is the most common cause of hereditary deaf‐blindness in humans with an estimated prevalence of 3‐6 per 100,000 inhabitants. USH is inherited as an autosomal recessive trait and is clinically divided into three types based on audiological profile and vestibular symptoms. The aim of the project was to phenotype the first cohort of Czech patients with USH (16 families, 21 affected individuals) and to perform investigation into the molecular genetic cause of their disease.

Methods

Sanger sequencing of 6 frequently mutated USH2A exons was performed as an initial step in probands suspected to suffer from USH type II. Unsolved cases were then investigated by a range of techniques including whole‐exome sequencing, targeted gene panel next generation sequencing and single‐nucleotide polymorphism (SNP) array for copy number variation analysis. Detected missense mutations were evaluated for pathogenicity by six in silico tools. Mutations were verified and their segregation within the families was performed by Sanger sequencing.

Results

In total 17 different mutations evaluated as pathogenic were identified in 20 individuals (95%) from 15 families, of these c.1256G>A, c.13342_13347del, deletion of exons 33 and 34 in USH2A, c.871G>A in CDH23 and c.937C>T in USH1C were novel. A known c.11864G>A in USH2A was the most prevalent mutation observed, found either in a homozygous or compound heterozygous state in 9 families. SNP haplotype analysis supported the hypothesis of a founder effect. Investigation into the geographic origin suggested regional clustering of the c.11864G>A allele in Southeastern part of the Czech Republic.

Conclusions

The proposed research will help to elucidate factors involved in the etiopathogenesis of USH, which is important for prognosis, patient counseling, management, development and introduction of novel therapies.
Motile activity and cytoskeleton changes in uveal melanoma after proton beam radiation
Authors: Romanowska Dixon B. , Jasinska‐Konior K. , Sarna M. , Urbanska K. , Olko P. , Elas M.
Published: September 2017

Purpose

Proton beam irradiation is known to invoke different biological response than photons.

We compared the effect of proton beam irradiation and X‐rays on the survival and migratory properties of melanoma cells.

Methods

Mel270, human uveal melanoma cell line was treated with physical doses of 1‐5 Gy of proton beam (58 MeV) from Proteus C‐235 cyclotron or X‐rays (300 kV Phillips) at the dose rate of 1 Gy/min were given to suspended cells.

Results

Invasive potential of cells was slightly diminished after both types of radiation at 20 days post‐radiation and then returned to normal at 40 days. Wound healing ability was decreased after X‐rays. The beta‐1‐integrin level was decreased after both types of radiation in Mel270 cells, and vimentin, a marker of EMT was not changed. Less stress fibers were seen in cytoskeleton of Mel270 cells after radiation.

Conclusions

Low doses of both types of radiation influenced the motile activity and cytoskeleton in Mel270 cells.
SS – OCT angiography in retinal dystrophies with macular edema or cysts
Authors: El Matri L. , Falfoul Y. , Hassairi A. , El Matri K. , Nafaa F. , Chebil A.
Published: September 2017

Purpose

To analyze swept source optical coherence tomography angiography (SS – OCT‐A) findings in retinal dystrophies with macular edema or cysts.

Methods

Optical coherence tomography angiography and structural OCT were performed using a Swept‐source DRI OCT Triton (Topcon, Corporation, Japan) for 3 patients with retinitis pigmentosa and macular edema, 3 patients with enhanced S‐cone syndrome and 1 patient with X‐linked retinoschisis.

Results

In all patients, changes were more pronounced in the deep plexus where macular edema was more evident. Also, there was focal dislocation of the vascular network in correspondence with the serous intraretinal cysts. In patients with retinitis pigmentosa, capillary were visible at the top of the cysts. On the other hand, in case of X‐linked retinoschisis, we found wheel‐like cystoids cavities separated by apparently well‐vascularized walls with a good correspondence with structural en face OCT.

Conclusions

OCT‐A may provide information of great interest in inherited retinal dystrophies with macular edema or cysts.

It reveals particular alterations above all located at the level of the deep capillary plexus and the choriocapillaris. Such information may be useful for phenotyping each case and understanding pathogenesis of cysts development in each dystrophy helping their future therapeutic management.
The development and performance of a new patient derived tool to measure Dimensions in Treatment of Age‐related Macular Degeneration (DITAMD)
Authors: Jelin E. , Wisløff T. , Moe M.C. , Heiberg T.
Published: September 2017

Purpose

A growing aging population increases the number of patients treated for neovascular Age related Macular Degeneration (nAMD). Studies reporting the patient's perspective during treatment are limited. Our aim was to develop and test a tool for monitoring treatment burden and satisfaction among nAMD patients.

Methods

Development: Patients (n = 44), mean (SD) age 80.4 (8.2), 62.8% females, diagnosed with nAMD selected dimensions mattering most during treatment. Reported dimensions were analysed according to similar content, then coded. Test: Recently diagnosed patients (n = 178), with logMAR visual acuity in treated eye 0.43 (0.42), completed DITAMD after 3 months treatment on a Likert scale (1–5). A weight based on the identified importance in the development phase, had a sum score, range 0–10.

Results

Development: Dimensions reported most frequently were included in DITAMD; receive treatment, information, waiting time, confidence, accommodating staff, follow up, planning, continuity, pain relief, injection technique, transportation, hygiene, early treatment access, involvement and visual aids. Test: Patients (n = 178) reported DITAMD score of 8.1 (0.9) suggesting satisfaction with treatment. The score was not significantly associated to age or gender. A subgroup of patients (n = 70) considered relevance (0–10) of the questionnaire; mean (SD) 8.3 (1.3), indicating high level of face validity. Satisfaction during treatment and perceived importance of the dimensions were compared with paired T‐test for each item, for some dimensions, satisfaction was significantly higher than importance. However, information about visual aids had significantly lower satisfaction the importance.

Conclusions

DITAMD allows monitoring patient relevant experience during treatment of nAMD. The discrepancy between satisfaction and perceived importance should guide patient care.