bluuebunny/crossref_metadata_2025 huggingface dataset:
Early diagnosis and treatment changes disease phenotype in birdshot retinochoroiditis
Authors: HERBORT C
Published: August 2014

Background and Aim: The diagnosis of birdshot retinochoroiditis (BRC) relies mainly on the presence of oval‐shaped "birdshot lesions" (BL) part of the currently used inappropriate diagnostic criteria that do not use diagnostic tools for choroidal disease such as ICG angiography (ICGA) and do not allow to make an early diagnosis. It is now well‐known that when BL become apparent, the disease has already been evolving since months or years. Patients and methods: Using appropriate diagnostic criteria, including vitritis and retinal vasculitis in at least one eye, presence of ICGA detected choroiditis in both eyes and the presence of the HLA‐A29 antigen, we compared a group of patients treated early (< 10 months of symptoms) with a group of patients treated after more than 10 months of symptoms. Mean follow‐up was 10 years in bothe groups. Results: Patients treated early almost never developed the characteristic BL, whereas patients treated late all presented BL at start of therapy that almost never disappeared after treatment. Conclusion: Early diagnosis and treatment modifies the phenotype of BRC by preventing the apparition of BL clearly indicating that the presently used diagnostic criteria are completely inappropriate.
When disease mechanism is more important than disease phenotype: the example of multifocal choroiditis of the choriocapillaritis type
Authors: NERI P , ARAPI I , PIRANI V , GRESTI G
Published: August 2014

Inflammatory choriocapillaropathies (ICCP) is the name given to a group of diseases affecting the choroicapillaris. Primary inflammation of the choriocapillaris was suspected long before indocyanine green angiography (ICGA) became routinely available. In fact, fluorescein angiography (FA) is not tool capable to detect choroidal ischemia and does not give imaging access to the rest of the choroid. One of the main characteristics described in such group of diseases is represented by their eclectic attitude. The reason why the disease behaviours are so different from one condition to the other is still unknown. Among this group it is recognized a sub‐group of diseases known as multifocal choroiditis. When seen by the clinician most of the cases already show chorioretinal scars, as if preceding silent episodes occur before the disease becomes symptomatic at the time of a recurrence. Multifocal choroiditis occurs in the same age groups as other ICCPs, namely in young to middle aged adults with women being predominantly affected. Lesions tend to leave scars and are not spontaneously reversible but seem to respond corticosteroid therapy. Subretinal neovascular membranes occur in one third of patients.
Disease phenotypes in emerging infectious ocular conditions: how strongly disease defining are they?
Authors: KHAIRALLAH M , KAHLOUN R , ZAOUALI S
Published: August 2014

Emergent and resurgent infectious diseases are major causes of systemic morbidity and death that are expanding worldwide mainly because of climate changes and globalization.An array of ocular manifestations, involving mainly the posterior segment, have been recently described in association with specific arthropod vector‐borne diseases including rickettsioses, West Nile virus, Rift Valley fever, Dengue fever, and Chikungunya. They include anterior uveitis, retinitis, chorioretinitis, retinal vasculitis and optic nerve involvement. Proper clinical diagnosis of any of these infectious diseases is based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular involvement. Several fairly typical fundus findings may help establish the diagnosis in specific emergent infectious diseases while serologic testing is pending.
Inner retinal defects exist preoperatively in patients with epiretinal membrane
Authors: THEOCHARIS IP
Published: August 2014

Purpose To investigate the etiology of the inner retinal defects (IRD) that have been detected postoperatively in patients after membrane (ERM) and ILM peeling

Methods A retrospective comparative study based on enface and b scan OCT findings. Twenty healthy individuals with normal maculas served as control group. Twenty patients with unilateral or bilateral ERM that were not operated comprise one group and served as a tool to study the progress of the defects and the bilaterality of the findings. Twenty patients with preoperative and postoperative OCTs to study the changes of the inner retinal layers postoperatively.

Results No defects were found in the posterior pole of the healthy eyes. 16 out 20 patients with unilateral clinically significant ERM present with IRD at the diseased eye in contrast with the absence of IRD at the normal eye or at eyes with early stage of ERM. In operated eyes, preoperatively the IRDs were detected in 19 out of 20 eyes. Postoperatively the defects seem to faint and disappear when significant diffuse retinal edema is present and reappear when the edema is resorbed. IRD may expand postoperatively by time or new areas of defects may appear. A healing process of the inner layers may not be excluded.

Conclusion The IRDs do not result exclusively by the surgical manipulations but the tractional forces during the development of the membrane seem to cause loss of inner retinal layers tissue. Postoperative edema of the posterior pole in early postoperative period may obscure the presence of IRDs
Retinal detachment in congenital glaucoma
Authors: ZHAO L , WEI B
Published: August 2014

Purpose To investigate the clinical characteristics of retinal detachment in congenital glaucoma and related surgical treatments.

Methods 28 patients(30eyes)with congenital glaucoma suffering from retinal detachment were reviewed retrospectively.

Results 26 of 28 eyes which undergone retinal detachment surgical treatments were anatomic recovered. The postoperative rise of intraocular pressure took place in all eyes. Follow‐up was made on 20 patients(21 eyes), retinal detachment was recurrent in 5 eyes. The final visual acuity was increased in 9 eyes, and the intraocular pressure of 14 eyes were normal.

Conclusion The area of retinal detachment and degree of proliferative vitreoretinopathy (PVR) are identified as the two most significant factors affecting functional prognoses. To stabilize the intraocular pressure, a regular examination is mandatory.
Progressive visual loss in Retinitis Pigmentosa leads to cortical and subcortical reorganization of the human brain
Authors: PEREIRA AC , FERREIRA S , QUENDERA B , MATEUS C , SILVA E , CASTELO‐BRANCO M
Published: August 2014

Purpose Retinitis Pigmentosa (RP) is a retinal disease characterized by photoreceptor degeneration. Usually, symptoms are early onset night blindness followed by progressive peripheral vision loss, with central vision being later affected. Some patients become blind after several years of disease. We studied the consequences of this progressive loss of visual input in the human brain using Magnetic Resonance Imaging.

Methods 13 RP patients (8M, 5F; mean age 47±13yrs; range:23‐66yrs) and 24 age‐matched controls (10M, 14F; mean age 44±13yrs; range 22‐69yrs) were scanned in a 3T Siemens scanner. Cortical thickness (CT), surface area (SA) and subcortical volumes were obtained with Freesurfer.

Results Patients’ visual field ranged from 22deg to almost blindness. Self‐reported symptoms’ onset ranged from birth to 45 years of age (mean symptoms’ duration: 30yrs; range 6‐51). Patients showed decreased CT in pericalcarine(p=0.002); cuneus(p<0.001); lingual(p=0.02) and lateral occipital(p=0.007) regions and increased CT in supramarginal(p=0.02), superior frontal(p=0.02) and the parahippocampal(p=<0.02) gyri. Also, cortical SA was decreased only in superior parietal cortex(p<0.009,) and increased in inferior temporal gyrus(p=0.03), isthmus cingulate(p=0.02), banks of superior temporal sulcus(p=0.007), pars orbitalis(p=0.02) and transverse temporal sulcus(p=0.002). Also, the caudate nucleus was increased in RP(p=0.003).

Conclusion We conclude that visual input deprivation in RP leads to a large scale subcortical and cortical reorganization of brain resources, with loss in visual processing areas and changes in multimodal integration areas that may compensate for this sensory input loss.
Usefulness of ophthalmology psychophysical test for diagnosis and monitoring support in mild Alzheimer’s disease
Authors: GARCIA MARTIN ES , DE HOZ R , ROJAS B , RAMIREZ AI , SALAZAR JJ , GIL P , YUBERO R , TRIVINO A , RAMIREZ JM
Published: August 2014

Purpose Alzheimer’s disease (AD) is a neurodegenerative disorder of the central nervous system characterized by cortical atrophy most pronounced in the medial temporal and posterior temporoparietal regions. The goal of the present study was to examine the visual pathway in patients with mild AD (GDS 4) by means of a different psychophysical test, specifically —visual acuity (VA), contrast sensitivity (CS), colour perception and perception digital test (PDT)— and to compare them with an age‐matched control.

Methods Twenty‐three patients with mild AD and 27 controls were examined at Hospital Clínico San Carlos in Madrid (Spain). Subjects underwent a complete ophthalmological examination (VA, refraction, colour test, biomicroscopy, IOP, dilated fundoscopy, and OCT).

Results In comparison with the control group, patients with mild AD presented a significant decrease in the VA, in the CS (for all the spatial frequencies), in the colour perception (unspecific errors blue axis) and PDT (p <0.05 in all instances).

Conclusion In mild AD, there are alterations in the M, P, and K visual pathways. The psychophysical ophthalmological tests used in this study could serve as a tool for AD diagnosis and follow‐up. (Support: OFTARED (Grant RD12/0034/0002, ISCIII, Spanish Ministry of Science and Innovation)
Visual intelligence in action: A question of balance? Neuroplasticity: recent findings on the visual system for the practitioner
Authors: VANDERMEULEN J
Published: August 2014

Purpose In this presentation I will focus on new insights in the balance of neuroplasticity for brain injury and the effects on vision from a neuropsychological point of view. I will also emphasize on the organisation of the visual pathways ( e.g. ventral and dorsal processing stream and the subcortical processing).

Methods From a literature and integrative research point of view of the last ten years we have found that the vision has changed. I will explain that visual processing is not only taken place by the old reponsibility pathways of eyes and the occipital lobes as key regions. Insight on brain injury in recent has changed this meaning. A case will be presented to support this view

Results There is a new insight in processing information of the brain and od pathways will be abandoned. It may very well that it takes place by other sensoric areas such as the thalamo‐cortical route. The brain is highly sensitive to adverse environments, such as the visual impairment after brain injury, but it shows also resilience to neurological deficits. The visual tracts are no longer seen as the only pathways for sensory information (this is an essential element for ophthamologists and practitionars), because they contains pathways from other areas.

Conclusion It is important for ophthalmologists and practitionars that the old paradigma of the visual system should be abandoned. We have to realize that clinical management on the visual disorders is more complex and that the impact from the newly acquired knowledge affects the diagnosis and intervention: an unbeatable approach for visual processing and daily work. Werner, J.S. & Chalupa . L. M. ( 2014). The new visual neurosciences. London: MIT Press.
Cholesterol and glaucoma
Authors: BRETILLON L
Published: August 2014

The association between cholesterol and glaucoma is still under debate. No real consensus can be drawn based on the effects of statins in the progression of glaucoma. Nevertheless cholesterol must not be restricted to its circulating levels. Indeed, cholesterol is a prominent component of the the retina. One would thus think on how cholesterol is regulated in the retina. Special emphasis would be given on retinal ganglion cells and glial cells, accounting their key roles in the metabolism of cholesterol in the retina and in the course of glaucoma.
Topical antiangiogenic therapy with Aganirsen eye drops reduces need for transplantation in herpetic keratitis
Authors: CURSIEFEN C
Published: August 2014

This first Phase III study on a topical inhibitor of corneal angiogenesis showed aganirsen eye drops to significantly inhibit corneal neovascularization in patients with keratitis. The need for transplantation was significantly reduced in patients with viral keratitis and central neovascularization. Topical application of aganirsen was safe and well‐tolerated.
Stem cells in ocular diseases ‐ implications to physiological and pathological angiogenesis
Authors: PETROVSKI G
Published: August 2014

Abstract not provided
Genetics of keratoconus
Authors: WILLOUGHBY C
Published: August 2014

Keratoconus (MIM 148300), a common bilateral, progressive corneal thinning disorder, is the leading indication for corneal transplantation in the developed world. Despite the visual and social impact of keratoconus, the underlying biochemical processes and pathobiology remain poorly understood. There is strong evidence for a heritable component in the development of keratoconus, but few if any genes had been identified. Recently, the identification of two new keratoconus genes has given insight into the biological processes disrupted in the development of keratoconus. Our group identified mutations in a microRNA (miR184) responsible for keratoconus. MicroRNAs (miRNAs) are small, non‐coding RNAs which are important regulators of eukaryotic gene expression. Subsequently, we have identified a significant enrichment of potentially pathologic heterozygous alleles in ZNF469 associated with the development of keratoconus in 12.5% of keratoconus patients, and highlights ZNF469 as the most significant genetic factor responsible for keratoconus identified to date.
Viral vectors
Authors: BARNARD A
Published: August 2014

There are a number of ongoing clinical trials that utilise viral vectors to deliver potentially therapeutic genetic material to retinal cells. This talk will look at the major consideration of turning a wildtype virus into a clinical trial vector. These include the packaging capacity, tropism (preference for targeting specific cells/tissue) and immunogenicity of the viral vector. The talk will also discuss strategies for increasing transduction efficiency (e.g. by optimisation of the transgene expression construct) to potentially reduce the amount of viral particles that need to be used. The talk will look at ongoing laboratory research that may lead to improvements in the viral vectors that are available for gene therapy trials and potential ways in which the limitation imposed by the starting virus may be overcome. For example, a dual vector, split transgene strategy may be used to effectively double the packaging capacity of adeno‐associated viral (AAV) vectors. As the majority of retinal gene therapy trials so far have used AAV vectors, there will be a bias toward the discussion of this type of virus.
Gene therapy for choroideremia
Authors: BARNARD A
Published: August 2014

Purpose This talk will cover the development and instigation of a clinical gene therapy trial for choroideremia. It will also outline some early results of the trial, which is currently still ongoing. Methods Development of the gene therapy vector involved a range of in vitro and in vivo studies, from cell‐based protein assays to ERGs in laboratory mice. The trial is an open label dose escalation study, involving two groups treated with different doses of adeno‐associated viral vector (AAV2) encoding Rab‐escort Protein 1 (REP1). A range of clinical tests are used to assess the safety and efficacy of treatment. Results Preclinical results show AAV can successfully produce functional REP1 protein in patient fibroblasts. The vector shows targeting of retinal cells and has good safety and efficacy in animal models. So far in the clinical trial, 6 patients have been treated with the low dose AAV.REP1 vector. Early results show good safety and some encouraging functional effects. Conclusions A gene therapy trial for choroideremia is ongoing, with some promising early results. This is the first time gene therapy has been tested in people with normal visual acuity and may have implications for other inherited retinal diseases.
Nicolas Claude Fabri de Peiresc (1580‐1637) and the lost humanism
Authors: GODARD G
Published: August 2014

Peiresc [1580‐1637], councillor in the parliament of Aix‐en‐Provence (France), exchanged voluminous correspondence with many scholars in Europe, including Galileo and the Lincei. He carried out, with his friend Gassendi, researches on astronomy, geology and anatomy. Peiresc’s writings on eye and vision are preserved in an unpublished manuscript of 980 pages, kept in the library of Carpentras (France). They include letters to Luilier, Bourdelot, Gassendi and Schikard, and contain several minutes of dissection of eyes from various animals (eagle, whale, cat, owl, seal and chameleons) carried out in 1634, as well as Peiresc’s observations on his own view. Peiresc also undertook experiments that consisted in removing the eye lens or replacing it with glass lenses, so as to establish the course of light rays in the eye under observation. As the images formed on the retina are upside down compared to the original object, Peiresc imagined that the retina was not the sensitive organ of vision but acted as a mirror, the image being captured on the back side of the lens. These studies precede Descartes’ Dioptrique (1637) and postdate Plempius’ Ophthalmographia (1632); they were not published, so they remain until today almost ignored.
Surgical management and treatment outcomes of myopic foveoschisis
Authors: POURNARAS JA
Published: August 2014

Myopic foveoschisis is relatively uncommon complication of pathological myopia and has been nicely described using OCT examination. Pathophysiology of myopic foveoschisis still remains controversial.It is thought that tractions due to posterior vitreous cortex and epiretinal membrane may lead to foveoschisis formation.In some cases, macular hole or retinal detachment may occur. Surgical indications and timing are still controversial and will be discussed.Pars plana vitrectomy is reported to give good anatomical and functional outcomes.
How protein aggregations and lens fiber disorder result in nuclear and cortical cataracts
Authors: MICHAEL R , BARRAQUER R
Published: August 2014

Commonly, lens opacities and cataract are considered protein aggregation disorders. Increased light scattering is attributed to larger high‐molecular‐weight fractions of proteins. The impact on transparency of fiber membranes and their age‐ and disease‐related changes is addressed to a lesser extent in the literature. In the lens cortex of transparent human lenses, the lens fiber membranes have high refractive indexes compared with the cytoplasm, whereas there is almost no difference in the refractive indexes of membranes and cytoplasm in the lens nucleus. Therefore, in the lens cortex, transparency is obtained by a high spatial order of the lens fiber lattice to compensate for light scattering caused by differences of the refractive indexes. Any disturbance of the ordered lens fiber architecture in the cortex results in light scattering. In typical nuclear cataract, there is no major fiber disruption or extracellular debris to explain the opacity. The strong implication is that local fluctuations in crystallin density, due to the formation of insoluble aggregates, are the major cause of nuclear opacification. These fluctuations in density and refractive index, are considered to produce significant light scattering.
Vision‐related function in the COPERNICUS and GALILEO trials
Authors: PEARCE I , LORENZ K , WITTRUP‐JENSEN K
Published: August 2014

Purpose To examine the impact of intravitreal aflibercept (IVT‐AFL) injection on the 25‐item National Eye Institute Visual Function Questionnaire (NEI VFQ) in the COPERNICUS and GALILEO trials.

Methods Patients (pts) with macular oedema secondary to central retinal vein occlusion received IVT‐AFL 2 mg (IVT‐AFL 2q4) or sham monthly for 24 weeks. After Week 24 (W24) in COPERNICUS all pts were eligible to receive IVT‐AFL based on visual and anatomical outcomes (IVT‐AFL 2q4+PRN, sham+IVT‐AFL PRN). In GALILEO, sham‐treated pts received sham tx until W52. The NEI VFQ was administered at baseline (BL), W24 and W52. Total and subscale scores were compared between groups. W24 data were integrated and W52 data were analysed by study.

Results Mean change from BL to W24 in total score was greater in the IVT‐AFL 2q4+PRN than the sham group (7.3 vs 2.2, p<0.0001). Mean changes from BL to W24 were greater in the IVT‐AFL 2q4+PRN group vs sham for near activities, distance activities, and dependency. In both studies, the mean change from BL to W52 in total score was greater in the IVT‐AFL 2q4+PRN than in the sham+IVT‐AFL PRN or sham groups (COPERNICUS: 7.9 vs 4.5, p=0.0049, GALILEO: 7.5 vs 5.1, p=0.2164). In both studies, mean changes from BL to W52 were greater in the IVT‐AFL 2q4+PRN than the sham and sham+IVT‐AFL PRN groups for near activities, distance activities, and dependency. The most common ocular SAEs in IVT‐AFL2q4+PRN pts were cataract (COPERNICUS) and macular oedema (GALILEO).

Conclusion Pts in the IVT‐AFL 2q4+PRN group experienced clinically meaningful improvements (typically defined as an increase of ≥4 points) from BL to W24 and BL to W52 in total and subscale NEI VFQ scores. Changes with IVT‐AFL 2q4+PRN were greater than those in the sham and sham+IVT‐AFL PRN groups.

Commercial interest
A post‐market surveillance study on the processing and follow‐up of patients with BRVO and CRVO prescribed Ozurdex
Authors: LARSEN L , MERKOUDIS N , LEABACK R
Published: August 2014

Purpose Examine the use in clinical practice of a dexamethasone intravitreal implant (Ozurdex®, Allergan, Inc., CA) in treating macular oedema (ME).

Methods Prospective observational study (20 centres in Sweden, Denmark, Norway and Finland). Patients were enrolled if prescribed Ozurdex® 700 μg for ME after branch or central retinal vein occlusion (BRVO/CRVO). Baseline examinations included visual acuity (VA), central retinal thickness (CRT) and intraocular pressure (IOP). Efficacy measures were time to retreatment, VA (ETDRS) and CRT (OCT) at weeks 6, 12, 24, 36 and 48. Adverse events (AEs) and discontinuations were recorded.

Results 99 patients (51% CRVO, 49% BRVO) were enrolled, mean age 72.9 years. Median follow‐up was 403 days (36–609 days), with 45.5%, 24.2% and 24.2% of participants receiving 1, 2, and 3 injections, respectively (<10% received ≥4). Among retreated patients, 25.3% received the first retreatment at week 24. Mean time to first retreatment was 185 days. Median VA and CRT were similar between BRVO and CRVO groups throughout the study. At baseline, median VA was 54.9 letters, median CRT 499 μm and median IOP 15 mmHg. At week 12, VA increased to 67.5 letters and CRT decreased to 297 μm. At week 36, these were 60.2 letters for VA and 318 μm for CRT. Increased IOP (26.3%) and cataracts (4.1%) were the only AEs recorded in >1% of patients; endophthalmitis, eye complication, eye pain and vitreous haemorrhage were each reported once.

Conclusion In this non‐interventional, open‐label study of routine clinical practice, the major short‐term outcomes of improved mean VA and reduced mean CRT were comparable to those in clinical trials. Implementation of Ozurdex® was not associated with new or unexpected events.

Commercial interest
Topical treatment with a new matrix therapy agent (RGTA, CACICOL‐20) improves epithelial wound healing after penetrating keratoplasty
Authors: JULIENNE R , HAOUAS M , TRONE MC , HE Z , CROUZET E , THURET G , GAIN P
Published: August 2014

Purpose Complete epithelial wound healing is a milestone in the early post‐operative care after penetrating keratoplasty (PKP). It reduces the infectious risk, allows safe instillation of steroids, and conditions discharge from hospitalization. We assessed a new matrix therapy agent, mimicking heparan sulfates, for the management of post PKP epithelial defects

Methods Prospective, open‐label, uncontrolled, single‐centre study on 33 consecutive patients (33 eyes) who benefited from a 8.25 mm PKP for all‐comers indications. Patients were treated with RGTA eye drops (THEA): one drop in the operating theater immediately after graft, then on alternate days. Follow‐up was performed by slit‐lamp examination and photography with fluorescein‐dye testing repeated every day at a fixed time. Dye area was measured using the freeware ImageJ. Main outcome: time of corneal surface healing

Results All corneas displayed complete healing after a mean 2.7±1.1 days (median 3, range; 1 to 6). Complete wound healing was obtained at D1 for 15%, D2 for 33%, D3 for 88%, D4 for 94%, and D6 for 100%. Area of epithelial defect decreased by a mean 75±22% between D1 and D2 (n=28) corresponding to a wound healing speed of 11.5±6.5 mm2/D. There were no systemic or local side effects. For comparison, in the series of all‐comers indications of 1003 PKP without RGTA of Borderie, mean wound healing was 4.6+/‐13.2 days (median 2.5, range 1‐210).

Conclusion RGTA seems a potentially useful, noninvasive therapeutic approach in PKP management. A controlled double blind clinical trial vs placebo will be soon conducted to answer this question conclusively.
The use of amniotic membrane homogenate is improved by a retinoid pre‐treatment in healing corneal alkali burns, in a mouse model
Authors: DANIEL E , BONNIN N , BELVILLE C , COMPTOUR A , BLANCHON L , SAPIN V , CHIAMBARETTA F
Published: August 2014

Purpose The purpose of this study is to establish the effect of a human amniotic membrane (HAM) homogenate previously cultivated with all‐trans retinoic acid (ATRA) on corneal alkali burns,in a mouse model.

Methods 50 CD1 mice with alkali burn were divided in 5 groups: no treatment, saline, amniotic membrane homogenate, DMSO cultivated HAM homogenate or ATRA cultivated HAM homogenate (10‐6mol/L for 24 hours). Before instillation of homogenate, the HAM retinoid induction was assessed by PCR quantification of a well‐known retinoid induced gene: RARβ. Wound healing was first evaluated through slit lamp photographs at days 1,2 and 7 (for corneal re‐epithelialization), then histological analysis of ulcer depth was conducted. Finally, immuno‐histochemical analysis of MMP9 and VEGF expression were done.

Results We demonstrated that there was no difference at day 2 for our main criterion (corneal re‐epithelialization). At day 7, we found an overall difference (ulcer surface) in the corneal healing between the groups (p<0,001). Significant differences were also found by histological analysis between the untreated group and the HAM+ATRA group, between saline group and the HAM+ATRA group and between the HAM group and HAM+ATRA group. Finally, expressions of MMP9 and VEGF were visually weaker for the groups treated with HAM homogenate.

Conclusion Our results support the hypothesis that the effect of HAM seems to be more biological than mechanical. The use of HAM homogenate potentiated by ATRA already appears as a promising therapeutic alternative without the constraints of the more classical HAM graft.
Novel method for the isolation and measurement of microRNA and microRNA related targeted genes in conjunctival epithelial cells in primary Sjogren’s syndrome patients
Authors: PILSON Q , Ní GABHANN J , MURPHY C
Published: August 2014

Purpose Sjogren’s syndrome (SS) is a systemic autoimmune disorder characterized by inflammation that affects exocrine glands notably the salivary and lacrimal glands leading to sicca complex. Dry eye disease in primary SS (pSS) is a combination of reduced lacrimal flow from gland destruction and tear hyperosmolarity leading to inflammatory damage on the ocular surface. Several studies have shown differential expression of certain miRs in PBMCs and salivary glands from SS patients compared to healthy controls, however no functional role has been shown. This study aims to isolate miRs and mRNA from conjunctival epithelial cells by impression cytology to determine if dysregulated miR expression contributes disease pathogenesis in pSS.

Methods Impression cytology (IC) was optimized using different membranes. miRs and mRNAs were isolated from conjunctival epithelial cells (CEC) obtained from pSS patients and healthy controls by IC and sent for screening to Ocean Ridge Biosciences. qPCR was performed to evaluate expression of miRs from CEC.

Results Milicell biopore was the best membrane with significant yield of miRs (47.5ng ± 0.6) and mRNA (158.0 ng ± 21.6) as well as patient comfort. Appreciable levels of miRs and targeted genes were detected from the CEC from healthy controls, confirming that it is possible to isolate miRs and miRs targeted genes from CEC. Screening studies in CECs demonstrated differential expression of miRs and mRNA between pSS patients and healthy controls.

Conclusion Future work will identify and confirm specific roles of these miRs for future diagnostics, prognostics and therapeutics of pSS patients as well as other ocular surface conditions.
Changes of inflammatory cytokines and tear osmolarity in systemic sclerosis after treatment with liposomes sprayed
Authors: GAGLIANO C , AMATO R , FALLICO M , TORO M , AVITABILE T , FOTI R
Published: August 2014

Purpose To investigate the effect of treatment with a liposomal spray solution in patients with systemic sclerosis (SSc) and severe dry eye by measuring the levels of inflammatory cytokines and tear osmolarity.

Methods Twenty‐two subjects (12M, 10F) aged 45.1+/‐7.1 years participated in this prospective, randomised, double‐masked investigation. DES was identified in patients with SSc according to the classification of Dry Eye Disease of International Dry Eye Workshop (2007) and tear osmolarity values (TearLab system) according to recommendations of the manufacturer with a cutoff value of 308 mOsm/L (3). Liposomal spray (nebulized, two sprays each, on the eyelids, 3 times per day for 3 weeks) with vitamin A and E was applied to one eye, and an equal volume of saline spray (control) applied to the contralateral eye. Non‐invasive tear film stability (NIBUT), osmolarity and inflammatory cytokines (IL‐1β, IL6, TNF‐α,IFN‐γ) were evaluated at baseline, and at 5, 10, 15 days after spray solution application.

Results A highly significant reduction (p<0.01‐0.001) was detected in the inflammatory cytokine levels and osmolarity in tears of eye treated with the spray liposomes solution in comparison with fellow eye treated with sprayed saline solution. There were significant differences among the 2 eyes concerning tear osmolarity (p < 0.001) and TBUT (p < 0.05) scores.

Conclusion This study showed the ability of liposomal spray application to modify the pro‐inflammatory cytokine profile and to increase stability characteristics of the pre‐ocular tear film in severe dry eye of SSc patients.This effect could be due to the anti‐inflammatory mechanism of the vitamins and also to the barrier effect of liposomes.
Eye movement examination
Authors: BORRUAT F
Published: August 2014

The eyes move in order either to keep track of an object of interest or to change visual attention from an object to another. An adequate comprehension of the anatomy and physiology of the different types of eye movements is necessary when examining a patient with oculomotility disorder, be it peripheral, central or supranuclear. This presentation will summarize the infranuclear, nuclear and supranuclear pathways of oculomotility with an emphasis on fixation, saccades, pursuit, convergence and basic examination of the vestibulo‐ocular reflex. Guidelines for an examination of eye movements in clinical practice will be provided with video presentations of both normal and abnormal situations. At the end of the session, participants should be able to examine eye movements adequately and recognize abnormal fixation, defective pursuit, and inappropriate saccades.
Third, fourth and sixth cranial nerves palsy
Authors: KAESER PF
Published: August 2014

Acquired binocular diplopia commonly results from dysfunction of the third, fourth or sixth cranial nerve. Some cases need an urgent work‐up and it is mandatory to identify them early. This presentation will summarize the clinical findings and common causes of III, IV and VI cranial nerve palsy, and highlight the necessary investigations. At the end of the session, participants should be able to recognize, provide a differential diagnosis and propose appropriate investigations for III, IV, and VI cranial nerve palsy.
Interactive case presentations
Authors: KAESER PF , BORRUAT F
Published: August 2014

Various cases illustrating the supranuclear and infranuclear oculomotility disorders will be presented. Attendees will actively participate to solve these cases with the use of an electronic audience response system.
Incidence of macular edema following single versus 4 session pattern scanning laser panretinal photocoagulation in diabetic retinopathy
Authors: PALLOT C , KOEHRER P , ISAICO R , KODJIKIAN L , MASSIN P , JONVAL L , BERTAUX AC , D'ATHIS P , BRON AM , CREUZOT‐GARCHER C
Published: August 2014

Purpose The purpose of this study was to investigate a change in macular thickness 9 months after single versus 4 sessions of panretinal photocoagulation (PRP) performed with Pattern Scanning Laser (PSL) in diabetic patients and to make a medico‐economic assessment.

Methods This prospective, multicenter, randomized trial enrolled patients in 2 arms: single session PRP (group A) and 4 session PRP (group B) between October 2011 and October 2013. Patients had non proliferative severe diabetic retinopathy or proliferative non complicated diabetic retinopathy. The primary endpoint was the difference in macular central retinal thickness (CRT) using spectral domain optical coherence tomography (SD‐OCT) at 9 months. CRT with SD‐OCT, ETDRS visual acuity (VA), pain with Visual Analogic Scale (VAS), were recorded at baseline, 7 days, 1, 3, 6, and 9 months. A medico‐economic assessment was also performed.

Results 26 eyes of 26 patients were included. On inclusion, the median CRT was 258 [240‐294] µm in group A and 282 [261‐292] µm in group B (p=0.06), the median VA was 84 [76‐88] letters in group A and 83 [75‐90] letters in group B (p=0.94). At M9, the median CRT was 281 [245‐322] µm in group A and 301[278‐313] µm in group B (p=0.34). At M9, the median VA was 84 [70‐91] letters in group A and 85 [74‐85] letters in group B (0.58). The median VAS value was 3.5 [2.0‐5.0] in in group A and 3.5 [1.0‐7.0] for all sessions in group B. The medico‐economic assessment was in favor of the single session protocol.

Conclusion Single session PSL‐PRP seems to be a possible, well tolerated protocol for the treatment of diabetic retinopathy.
Visual deprivation: mechanism and practical applications
Authors: BREMOND‐GIGNAC D
Published: August 2014

Maturation of the visual system is incomplete at birth. Visual deprivation mechanism, amblyopia, or ocular misalignment, leads to abnormalities in visual development, including abnormal eyeball growth and neurological changes. The current knowledge on ocular conditions related to abnormal visual development in infants, includes prevalence, risk factors, causes, and mechanisms involved. The role of eyeball growth with pathologic mechanism of visual deprivation and development of amblyopia in infants appears essential to be analyzed. Particular developmental issues in preterm neonates, methods of visual assessment and screening, diagnosis, treatment, and nutritional issues will be discussed. Visual deprivation mechanism, amblyopia, or ocular misalignment, leads to abnormalities in visual development, including abnormal eyeball growth and neurological changes. Abnormal visual input can lead to abnormalities in visual development, which can become permanent visual impairment if left untreated. Reduce the risk of abnormal visual development and prevent long‐term or permanent visual deficits needs an early screening and a better understanding of the complex impairment mechanisms.
Vascularized vitreous seeding regression following systemic and intravitrealchemotherapy for advanced "late" retinoblastoma
Authors: HADJISTILIANOU T , DE FRANCESCO S , BORRI M , MICHELI L , GALIMBERTI D , CAINI M , GALLUZZI P , MENICACCI F
Published: August 2014

Purpose To report the regression of vascularized vitreous seeding in advanced "late" retinoblastoma

Methods Case report 8 year old girl with bilateral disease. The affected eye was the left eye (group D ‐ABC classification‐ and group VB ‐Reese Classification‐) while the right eye presented two peripheral retinomas.

Results Complete remission of the massive vascularized vitreous seeding was achieved and multiple retinal tumors regressed following six cycles of systemic chemotherapy (three drugs‐carboplatin etoposide and vincristine) and four intravitreal injections with Melphalan (20 micrograms). Retinal tumors presented type I regression (calcified tumors) while massive vitreous seeding was replaced by spidernet fibrotic formations.

Conclusion This case highlights the successful combination of three‐drugs systemic chemotherapy with intravitreal melphalan in advanced "late" retinoblastoma presenting with vascularized vitreous seeding and multiple retinal tumors.
Summary and discussion
Authors: BARRAQUER R , MICHAEL R
Published: August 2014

We will conclude our SIS with an overview of additional technologies to restore accommodation. This should open a short a discussion between our speakers and the audience about the most promising future approach to resolve presbyopia.
FRO 2014: The pathophysiologic role of SNORD115 and SNORD116 in late‐onset Fuchs' endothelial corneal dystrophy
Authors: DE ROO A , FOETS B , VAN DEN OORD J
Published: August 2014

This project aims to investigate the pathophysiologic role of SNORD115 and SNORD116 in late‐onset Fuchs' endothelial corneal dystrophy (FECD). Whole‐genome microarray expression analyses showed downregulation of several small nucleolar RNAs in CEn of FECD patients. Two of these, SNORD115 and SNORD116, regulate pre‐mRNA editing and alternative splicing of serotonin receptor 2C (HTR2C), and play a role in Prader‐Willi syndrome (PWS). Since the serotonin receptor 2C may regulate transport of fluids across the CEn, we will investigate whether the downregulation of these snoRNAs plays a similar role in FECD as it does in PWS. To this end, we will determine the expression of different splice variants of HTR2C in FECD versus normal controls. Furthermore, we will study the effect of SNORD115 and SNORD116 knockdown and 5‐HT‐2C receptor blockage in immortalised human corneal endothelial cells.
FRO 2014: Potential implications of epigenetic changes in human retinal pigmented epithelium during diabetic retinopathy
Authors: SALIK D
Published: August 2014

Diabetic retinopathy (DR) is a major cause of blindness. Prevention of DR is mainly based on control glycaemia however in vivo and in vitro evidences demonstrate that vascular complications can occur despite adequate glycemic control due to a process called “metabolic memory”. One of the very new hypothesis to explain the metabolic memory involves epigenetic modifications that prevent retinal cells from returning to their physiological status even when the exposure to stimuli has ceased. Our goal is to study in vitro the egigenic modifications of human retinal pigment epithelium ( hRPE) in response to glucose in order to identify new therapeutic targets for diabetic retinopathy. Studies of the epigenetic field, represents an original new approach with consistent and applicable methodology to investigate these mechanisms.
PGE2 and PGF2a stimulation of porcine retinal arterioles in vitro is associated with Ca2+ activity in retinal perivascular cells
Authors: KUDRYAVTSEVA O , BEK T
Published: August 2014

Purpose Disturbances in the regulation of retinal blood flow are a hallmark of vision threatening diseases. Retinal blood flow is controlled by autoregulation, which involves Ca2+ activity in a recently identified population of perivascular cells with pericyte characteristics (PVCs). The purpose of the study was to identify the sources of Ca2+ recruitment in these PVCs during stimulation of porcine retinal arterioles in vitro with PGE2 and PGF2a.

Methods Porcine retinal arterioles with preserved perivascular retinal tissue were mounted in a confocal myograph, placed in a confocal microscope and loaded with Oregon Green. After addition of PGE2 (10‐5 M) or PGF2a (10‐5 M) arteriolar tone and fluorescence from PVCs were recorded simultaneously in the absence and in the presence of Ca2+ channel blockers (ryanodine, nifedipine, LOE908, CPA, 2‐APB).

Results PGE2 induced significant relaxation of preconstricted retinal arterioles and Ca2+ activity in PVCs. The percentage of active PVCs, and the number but not the amplitude of Ca2+ oscillations were significantly reduced by CPA and 2‐APB, but not by ryanodine, nifedipine and LOE908. PGF2acaused arteriolar contraction and the percentage of active PVCs, the number and the amplitude of Ca2+ oscillations were significantly reduced by CPA and 2‐APB.

Conclusion Ca2+ activity in PVCs accompanies porcine retinal arterioles responses to PGE2 and PGF2aSarcoplasmic reticulum and inositol triphosphate receptors are important sources of this Ca2+ activity. The amplitude of Ca2+ oscillations seems to play a particular role in contraction of retinal arterioles.
The evidence: the role of antibiotics in intravitreal injections
Authors: LAM W
Published: August 2014

The current management of many retinal conditions, including age related macular degeneration, retinal vascular occlusion, and diabetic macular edema is not curative and requires prolonged monthly intravitreal injections. The most severe complication of this procedure is endophthalmitis and accordingly, more than two thirds of retinal specialists reported the use of topical antibiotics post‐ injection in a recent survey. However, there is a lack of evidence to demonstrate the effectiveness of topical antibiotics in reducing the risk of post‐injection endophthalmitis. We reported a large, multicentre, retrospective consecutive case series, the incidence of endophthalmitis following intravitreal injections in association with different post‐injection antibiotic practices. We found that the omission of routine topical antibiotic post‐injection did not produce a pronounced increase in endophthalmitis rates, suggesting that the use of topical antibiotic post‐injection might be unnecessary. In fact, the use of antibiotic prophylaxis, both immediately after the injection and for five days post‐injection is associated with greater rates of endophthalmitis, than without antibiotics.
Dynamics of Big Bubble (BB) formation in DALK: in vitro studies
Authors: ELALFY M , FARAJ LANA , SAID DG , KATAMISH T , DUA H
Published: August 2014

Purpose Dua’s layer (DL) has considerable relevance to DALK procedure and the hitherto clinically observed but unexplained formation of Types 1, 2 and mixed BB. In this study we explored the dynamics of the formation of different types of BB

Methods 50 human sclerocorneal discs were injected with air under BSS and recorded. Videos were studied for leakage of air and formation of BB. Height and diameter of BB were measured. Specimens were subjected to electron microscopy and immunohistology for collagens & matricellular proteins. Age ranged from 3wk‐80yr

Results Air injected in the cornea preferentially reached the limbus and moved circumferentially in a clockwise & anticlockwise direction as bands of 2‐3mm till they met, irrespective of direction of needle tip. The air then migrated centripetally to fill the stroma. Air leaked from the TM area at one or more points. Small bubbles formed in the centre and coalesced into a Type‐1BB. This rapidly expanded to attain a height of 5mm and a diameter of ≤9mm. The anterior stomal wall of Type‐1BB showed multiple 'holes' through which air leaked to lift DL. DL was impervious to air. Type‐2BB always started at the periphery. Distinct pores were seen in the peripheral stroma of DL. Most of these were located distal to attachment of DM and explained the leakage of air from TM. Some were located centrally to the attachment and explained formation of Type‐2BB. More than 80% of BB were Type‐1 Immunohistology did not offer an explanation for DL being impervious to air

Conclusion DL is a distinct part of the surgical anatomy of the cornea. Identification of pores in DL periphery is novel and explains the formation of a Type‐2BB and the clinical observation of appearance of air in AC during DALK. Leakage is not through the TM
Interaction between leukocytes and erythrocytes in the human retina: Effects of pentoxifylline on hyperoxia‐induced vasoconstriction during increased neutrophil counts
Authors: FUCHSJAGER‐MAYRL G , TOLD R , WOLZT M , SCHMETTERER L , SCHMIDT‐ERFURTH U , GARHOFER G
Published: August 2014

Purpose We have previously shown that under states of vasoconstriction an interaction between circulating erythrocytes and leukocytes may play a role in the control of blood flow. In the present study we hypothesized that pentoxifylline may alter this interaction during oxygen‐induced vasoconstriction.

Methods 24 healthy male subjects participated in this double masked, randomized, placebo‐controlled 2 way cross over trail. In order to increase white blood cell count (WBC) count, 300 μg of G‐CSF was administered intravenously. Vasoconstriction of retinal vessels was induced by oxygen inhalation. 400mg of pentoxifylline or placebo was infused at two different study days. White blood cell flux was assessed with the blue‐field entoptic technique. Vessel calibers were measured with a dynamic vessel analyzer (DVA) and red blood cell velocity (RBCV) was determined with laser Doppler velocimetry (LDV). Retinal blood flow was calculated based on retinal vessel diameters and RBCV.

Results Retinal vessel diameter, RBCV, calculated retinal blood flow and white blood cell flow were not altered by administration of pentoxifylline. Hyperoxia induced a pronounced decrease in retinal blood flow parameters. No difference was observed between groups during oxygen breathing in vessel diameters (p=0.54), RBCV (p=0.34), calculated retinal blood flow (p=0.3) and white blood cell flow (p=0.26).

Conclusion Our data indicate that short time administration of pentoxifylline does not alter the oxygen‐induced effect on ocular blood flow parameters during leukocytosis.