bluuebunny/crossref_metadata_2025 huggingface dataset:
Ophthalmic combat injuries in the German Sector of Northern Afghanistan 2003 ‐ 2013
Authors: GÜMBEL H
Published: August 2014

During the last decade the German Armed Forces (Bundeswehr) were needed in various missions. Especially in Afghanistan the German Army found their greatest challenge on military medicine. The medical treatment of injured soldiers of all nations, who were on missions, with the highest possible quality, relies to a great extent on the unbroken chain at emergency and trauma therapy from the theater of deployment up to the following medical care and rehabilitation in the homeland. In this talk we will tell the story how to manage the mass of casualities in ophthalmology or how to deal with difficult cases we have seen during our mission. So mostly we have to deal with simple irritations of the cornea by constructions in the camp, but on the other hand blunt trauma by IED (improvised explosive devices) play a key role in case of emergency We report about our experience in Field Hospitals (Role 3) which provide in‐patient and out‐patient specialist medical care. In severe ophtalmic casualities patients were stabilised for direct evacuation back to Germany by StratAIRMedEvac. So we could give you a follow up of the further treatment of patients and casualities who have been evacuated from the area of deployment.
War ocular trauma and burns in Kaboul NATO Hospital
Authors: RIGAL SASTOURNE JC
Published: August 2014

Abstract not provided
Learning about herpes infections by using animal models
Authors: ATHERTON S
Published: August 2014

Ocular infections caused by members of the herpesvirus family may have serious and sometimes, sight‐threatening, consequences. As has been for so many disease processes, animal models have been used to better understand the pathogenesis of herpetic keratitis and retinitis in human patients. While no animal model has absolute fidelity to its human counterpart, careful interpretation and extrapolation of results from animal studies may provide valuable information/insight about the pathogenesis of human disease. This presentation will provide an overview of animal models of keratitis and retinitis, summarize the strengths and weaknesses of the models, and discuss how what has been learned from these models has advanced our knowledge of the mechanisms of human ocular disease and/or has led to new therapeutic approaches to these diseases.
Animal models in ocular oncology
Authors: CASSOUX N , JAGER M
Published: August 2014

Retinoblastoma is a rare cancer in childhood. The goal of current and future therapeutic strategies is to conserve the eye and visual function without using external beam radiotherapy that increases the risk of second cancer in genetically predisposed patients. Multimodality therapy (usual intravenous but also, intra‐arterial, intra‐vitreal chemotherapy, transpupillary thermotherapy, cryotherapy, brachytherapy) has recently improved eye salvage rate and allowed decreased need for external beam radiotherapy. However treatment of advanced intraocular retinoblastoma remains a real challenge, especially in case of vitreous and sub‐retinal seeding. There is a need of alternative and less toxic therapy and a need of new ways for administration of the drugs. Animal models are an integral part of preclinical research in the field of oncology. This paper described the different xenograft rodent models published in the literature. We have also developed a new orthotopic xenografted retinoblastoma model in immunodeficient mice, suitable for pre‐ clinical assays.
Corneal stromal cells: A potential cell source for ocular surface regeneration
Authors: SIDNEY LE , BRANCH MJ , MCINTOSH OD , DUA H , HOPKINSON A
Published: August 2014

Purpose Keratocytes of the corneal stroma are quiescent, dendritic cells, which maintain the extracellular matrix. It is believed that there is a subpopulation of keratocytes that act as multipotent progenitor cells. These cells repopulate the stroma after damage and may play a role in the regeneration of other layers of the cornea, such as the epithelium. Optimisation of culture of these cells is integral for developing potential cell therapies.

Methods Primary human corneal stromal stem cells (hCSC) were extracted from the limbal region of the cornea. A range of culture media were tested for the effect on stem cell phenotype and differentiation potential. The effect of extended passaging and three‐dimensional culture of the cells as spheroids was assessed by RT‐qPCR and immunocytochemistry.

Results The phenotype of hCSC is strongly affected by extraction, passage and the culture medium. The cells form spheroids and upregulate markers, such as CD34. Under the correct conditions, hCSC show potential as a multipotent stem cell, expressing the indicative markers and differentiating in vitro down osteogenic, chondrogenic and adipogenic lineages. The CD34+ population of hCSC demonstrate a higher stem cell potential and differentiate to corneal epithelial cells, with a rounded morphology and high expression of key markers such as cytokeratin 3, HES1 and desmoglein 3.

Conclusion Corneal stromal stem cells demonstrate a multipotent stem cell potential, independent of the role they are traditionally associated with in the cornea. In vitro, this potential depends on the culture environment and on isolation of certain subpopulations. In future, these cells show potential in the regeneration of the ocular surface in cases of disease or trauma.
Effect of hydration on the ultra‐structural distribution of collagen fibrils and proteoglycans in human corneal stroma
Authors: AKHTAR S , KHAN A , PETROVSKI G , ALBERT R , KIRAT O , ALMUBRAD T
Published: August 2014

Purpose We investigated the ultra‐structural changes in the distribution of collagen fibrils (CF) and proteoglycans (PGs) due to hydration in the human corneal stroma.

Methods Six fresh human scleral corneal rings were hydrated separately in deionized water for 2hrs and 48hrs. Corneas were divided into two parts. The first part of each cornea was fixed in 2.5% glutaraldehyde containing cuprolinic blue in sodium acetate buffer and processed for electron microscopy to assess proteoglycans. A second part of each cornea was fixed in 2.5% glutaraldehyde in 0.1M phosphate buffer and post fixed in 1% osmium tetroxide to assess collagen fibril diameter.

Results In the hydrated corneas the mean diameter of CF in the anterior stroma (23.40±2.61nm), middle stroma (22.48±3.28nm) and posterior stroma (23.58±2.46nm) was less than the CF diameter in the anterior (28.27±4.05nm), middle (28.22±3.09nm) and posterior stroma (29.73±3.72nm) of the normal cornea. Micro‐fibrils within the CF in the hydrated cornea were degenerated. In the hydrated cornea, the mean area of the PGs in the anterior stroma was reduced whereas it increased in the middle stroma compared to those in the normal cornea. The density of the PGs in the hydrated cornea was reduced in the anterior, middle and posterior stroma compared to those in the normal cornea.

Conclusion The effect of hydration on the uniform organisation of CF and PGs was higher in the middle and posterior stroma than in the anterior stroma. This could be due to less penetration of water in the interlacing lamellae of the anterior stroma. The reduction in the collagen fibrils diameter could be due to degeneration of microfibrils within the collagen fibrils.
Predegenerated Schwann cells promote neuroprotection and regeneration of retinal ganglion cells in ex vivo rat retinal explants
Authors: SMEDOWSKI A , PIETRUCHA‐DUTCZAK M , KAARNIRANTA K , LEWIN‐KOWALIK J
Published: August 2014

Purpose To investigate neuroprotective and pro‐regenerative potential of predegenerated Schwann cells towards RGCs in ex vivo retinal explants.

Methods In this study we used two models of rat retinal explants culture ‐ reversed explants from P2 Wistar rats pups and insert explants from 4 weeks old Wistar rats. Both types of explants were cultured in Neurobasal A medium with supplements (B‐27, N2 and GlutaMax). In this way we prepared 32 insert explants (16 were cultured with 2 µl of Schwann cells suspension (104 cells) dropped on the each explants surface, another 16 served as control treated with 2 µl of DPBS) and 30 reversed explants (10 of them were cultured in standard medium, 10 explants were with addition of 5 ng/ml BDNF into medium and 10 were co‐cultured with 104 of Schwann cells). After proper culture time, explants were fixed and processed for immunostainings and stereological analyses.

Results In retinal explants cultured in inserts system, there was significantly higher density of RGCs in group treated with Schwann cells in comparison to PBS treated (independent samples t‐test, p<0.05). In reversed retinal explants, there were significant differences between groups expressed in mean and total length and surface of neurites, as well as in number and arboration rate of neurites (U‐Mann Whitney test, p<0.05). Immunofluorescent staining using GAP43 additionally revealed intense neurites outgrowth (also in explants from adult animals).

Conclusion Predegenerated Schwann cells exert neuroprotective action and support regeneration of RGCs in neonatal and adult retina in ex vivo conditions.
Cytotoxicity of mesoporous silicon microparticles with different surface modifications on ARPE‐19 cells
Authors: KORHONEN E , RIIKONEN J , XU W , LEHTO VP , KAUPPINEN A
Published: August 2014

Purpose Retinal pigment epithelial (RPE) cells play a crucial role in the pathogenesis of age‐related macular degeneration (AMD). However, RPE is a challenging target in a therapeutical sense. In addition to its location, the possible hydrophobicity of drug molecules makes its medication even more challenging. Biodegradable porous silicon (PSi) microparticles could be a promising possibility for delivering hydrophobic drugs to RPE cells. In the present study, we aimed at testing the cytotoxicity of thermally oxidized (ToPSi) and thermally carbonized porous silicon (TCPSi) particles with and without additional surface modification with amino groups on human ARPE‐19 cells. Since the cytotoxicity of PSi particles cannot be tested by the commonly used MTT (3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide) assay due to non‐specific redox reactions, our aim was also to search for alternative assays for working with mesoporous silicon materials.

Methods ARPE‐19 cells were treated with microparticles at several concentrations for 24 h. Thereafter, cell viability was measured using a protease viability marker assay (CellTiter‐FluorTM) and a lactate dehydrogenase (LDH) release assay. Cells were also evaluated ocularly under an inverted microscope.

Results All tested particles were well tolerated by ARPE‐19 cells. CellTiter‐Fluor assay seemed slightly more reliable than the LDH test.

Conclusion Our results show that the tested porous silicon particles did not cause major cytotoxicity on ARPE‐19 cells, and CellTiter‐Fluor assay, especially together with ocular examination, could be suitable for testing cytotoxicity in association with mesoporous silicon particles.
Cellular & molecular origins of the electro‐oculogram
Authors: CONSTABLE P
Published: August 2014

The clinical electro‐oculogram has been used to assess retinal pigment epithelium (RPE) function using the changes in the standing potential of the eye in response to light. However, only a part of this mechanism is fully understood. One important clinical finding is that individuals with Best’s macular dystrophy display a reduced light‐rise and therefore a role for bestrophin in the generation of the light‐rise is necessary. It is now evident that bestrophin acts a regulator of intracellular calcium stores interacting with the L‐type‐Ca2+ channel in the basolateral membrane of the RPE to drive the changes in basolateral chloride conductance. This new role helps to explain the cases of Best’s macular dystrophy in which the light‐rise is normal. However, the initiating events surrounding the rise in intracellular calcium are unknown. One possibility is that light itself is able to elevate intracellular Inositol tri‐phosphate that releases calcium from intracellular stores and initiate the light‐rise. The talk will elaborate on the role of bestrophin in the generation of the light‐rise, and examine light and the onset of phagocytosis as possible triggers for the light‐rise.
Phenotypes of bestrophinopathies
Authors: LEROY BP
Published: August 2014

Purpose: To describe the phenotypes of conditions due to mutations in BEST1, the gene encoding bestrophin‐1. Methods: A case presentation format will be used to illustrate the phenotypes and genotypes of the different bestrophinopathies, with special attention to both the clinical and electrophysiological features that distinguish one phenotype from the other, and those they have in common. In addition, the different BEST1 genotypes will be discussed. Results: The phenotypes of Best vitelliform macular dystrophy (BVMD), autosomal dominant vitreoretinochoroidopathy (ADVIRC), and autosomal recessive bestrophinopathy (ARB) are very different. Nevertheless, they share an abnormal electro‐oculography (EOG) as a common feature. Electroretinography is normal in BVMD, whereas a rod‐cone dystrophy is evident in the later stages of ADVIRC and ARB. BVMD is due to a heterozygous missense mutation in BEST1, ADVIRC is due to interaction of several bestrophin protein isoforms, and ARB is probably the null phenotype. Conclusions: The phenotypes of the bestrophinopathies are diverse, although they share an abnormal EOG as the common feature. The specific genotypes are also different, leading to different molecular pathogenetic mechanisms.
RPE Disease beyond BEST1
Authors: MEUNIER I , HAMEL C
Published: August 2014

This presentation will focus on one RPE disease, the vitelliform dystrophies. Vitelliform macular dystrophies include a juvenile form i.e., Best vitelliform macular dystrophy and, an adult form apart from the previous one by Gass. These dystrophies represent the second most common cause of inherited maculopathy, after Stargardt disease. Based on recent human iPS cell studies, impairment in phagocytosis was confirmed, as RPE from BEST1 mutant human iPS‐RPE have disrupted ﬂuid ﬂux and increased accumulation of autoﬂuorescent material after long‐term outer segment feeding when compared with human iPS‐RPE from unaffected siblings. Secondly, the role of the protein in chloride currents activated by intracellular calcium was linked to the regulation and release of endoplasmic reticulum calcium stores. Beyond the major gene BEST1 and a minor gene PRPH2, we will point out the frequencies, the clinical spectrum and mode of inheritance linked to two new causal genes: IMPG1, IMPG2. These new genes introduce a third actor in the causes of vitelliform macular dystrophies; namely, this actor is the interphotoreceptor matrix that joins together the photoreceptors and the RPE.
IgE, anti‐IgE, and allergic keratoconjunctivitis ‐ part 1
Authors: DOAN S
Published: August 2014

Vernal and atopic keratoconjunctivis (VKC, AKC) are severe types of ocular allergy, characterized by acute and chronic corneoconjunctival inflammation that may lead to visual sequelae. Although topical immunosuppressive drugs such as cyclosporine and tacrolimus are usually effective, some severe may be refractory. Omalizumab is a monoclonal anti IgE antibody, administered systematically and authorized for severe asthma. We will report our clinical experience of omalizumab in AKC and VKC patients, and will also detail a review of the literature.
IgE, anti‐IgE, and allergic keratoconjunctivitis ‐ part 2
Authors: CHIAMBARETTA F
Published: August 2014

Vernal and atopic keratoconjunctivis (VKC, AKC) are severe types of ocular allergy, characterized by acute and chronic corneoconjunctival inflammation that may lead to visual sequelae. Although topical immunosuppressive drugs such as cyclosporine and tacrolimus are usually effective, some severe may be refractory. Omalizumab is a monoclonal anti IgE antibody, administered systematically and authorized for severe asthma. We will report our clinical experience of omalizumab in AKC and VKC patients, and will also detail a review of the literature.
Food allergy and ocular surface
Authors: FAUQUERT JL
Published: August 2014

Allergic diseases of the ocular surface are in most cases associated with allergic triggers. Food allergens are more and more frequently involved in children. We analyzed the incidence of ocular symptoms associated with food allergy. The airway contact with some particular food is known to result in ocular symptoms (fish, peeling of various fruits). Ocular symptoms are frequently associated with food oral syndrome. Moreover, according to allergic patients’ questioning, the intake of food results in ocular symptoms in an important amount of cases, reaching almost 20% of the cases of food allergy (rhino conjunctivitis or conjunctivitis). In patients suspected for food allergy, Oral Food Challenge (OFC) to various allergens revealed ocular involvement in 14% of the patients. Furthermore some authors compared the safety and efficiency of the OFC and the Conjunctival Provocation Test to assess food allergy in children. They justify this practice on the frequency of instillation of cow’s milk on the ocular surface and its absence of side effect on one hand and on the difficulties to practice oral food challenges in young children on the other hand. Thus the eye should be considered as an interesting target for food allergy investigation
Molecular allergens and tear investigation
Authors: CHABANE H
Published: August 2014

Tears immunological investigations are limited in routine practice because of the small volume of fluid collected. Only few tests can be performed in tears: Total IgE, screening test or specific IgE to aeroallergen to confirm allergic sensitization. Inflammatory mediators in lachrymal fluid are only measured for a research purpose. During the last decade, an increasing number of specific IgE to molecular allergens became available for routine use. Molecular allergens largely contributed to an improvement of allergy diagnosis by distinguishing between true sensitization and cross‐reactivity and a better indication of allergen immunotherapy in polysensitized patients. However, each of these single tests needs 50‐100 µl of serum. More recently, allergen arrayed biochip technology became routinely available (ImmunoCAP ISAC) enabling the quantification of specific IgE against 112 allergens, using only 30 µl of serum. The allergen biochip technology seems to be a promising tool to assess local synthesis of IgE in tears in case of suspicion of allergy and the negativity of both skin prick tests and serum specific IgE. Large‐scale studies are needed to confirm the usefulness of this tool for tears testing in allergic conjunctivitis.
New therapeutic approaches and challenges for the treatment of dry eye disease
Authors: SULLIVAN DA
Published: August 2014

Innumerable individuals suffer from tear film dysfunctions, which are collectively diagnosed as dry eye disease (DED). In the United States alone DED afflicts tens of millions of people, especially women, and is one of the most frequent causes of patient visits to eye care practitioners. DED is characterized by a vicious cycle of tear film hyperosmolarity and instability and ocular surface stress, leading to increased friction, inflammation and damage to the eye. DED is caused primarily by meibomian gland dysfunction, and is associated with significant pain, decreased vitality and poorer general health. Because of diminished worker productivity, the burden of DED for the United States is estimated to be over $55.4 billion. There is no safe and effective global treatment for DED, and its therapy remains a profound unmet need throughout the world. A virtual kaleidoscope of new therapeutic approaches have been proposed to treat the mucin, aqueous and/or lipid tear film deficiencies, as well as the ocular surface damage, associated with DED. My presentation will highlight these approaches, and also address the significant clinical endpoint challenges that serve as barriers to the successful development of potential treatments for DED.

Commercial interest
Eye and genes: the new ophthalmology
Authors: SCHORDERET D
Published: August 2014

For many years, ophthalmology has based its practice on observing, trying, deducing and remembering. For many pioneers, this approach was not sufficient and tools were designed to improve the diagnostic and intervention capacities for these ocular diseases. Although inheritable eye disorders have been identified many years ago–Dalton described color blindness in 1798 – it is only in the second part of the 20th century that genetics flourished. Franceschetti and Klein from Geneva published numerous reports on dysmorphology, and were part of a great effort to categorize all syndromes so that nature’s experiments were not lost. Although both were ophthalmologists, they founded the first Institute of Medical Genetics in Switzerland and made significant contributions to the field. I was blessed to discover genetics through David Klein and to further do my doctoral thesis with Eric Engel, his successor, in Geneva. Fifteen years later, the identification of the genes responsible for inherited diseases was done either by karyotyping or by linkage analysis followed by physical mapping. The former was based on luck, and often, we didn’t have any. For the latter, we needed large families and new technologies, like autoradiograms or automated
Visual acuity loss in open‐angle glaucoma patients: causes and risk factor
Authors: AYCHOUA N , JANSONIUS NM
Published: August 2014

Purpose To identify causes of visual acuity loss in open angle‐glaucoma (OAG) patients and to determine associated risk factors.

Methods From the visual field database of the University Medical Center Groningen, 400 patients with at least 3 reliable visual fields were randomly selected. Of these, 233 had OAG. OAG patients with a visual acuity of 0.5 or less in at least one eye were considered as cases; controls had to have a visual acuity above 0.5 in both eyes. Causes of visual acuity loss were determined from the medical records. Potential risk factors for visual acuity loss in OAG (age, gender, myopia, baseline IOP, corneal thickness, and visual field mean deviation [MD]) were assessed by comparing cases with acuity loss due to OAG with the controls, using logistic regression.

Results Of the 233 patients with OAG, 134 (57%) were cases and 99 (43%) controls. Concerning the cases, visual acuity loss was caused by OAG in 40%, cataract 17%, AMD 14%, vitreo‐retinal surgery 10%, corneal pathology 4.5%, acquired retinal disorders 10%, and neuro‐ophthalmological disorders 4.5%. Among the assessed risk factors, cases had a lower MD (OR=0.90; P<0.001) and a higher age (OR=1.05; P=0.015).

Conclusion Visual acuity loss in OAG is common but mostly due to other eye co‐morbidities. A lower MD and an older age were highly significant risk factors.
Intraocular pressure modulation by neuropeptides ‐ the effect of vasopressin
Authors: BOGNER B , RUNGE C , STROHMAIER C , TROST A , KASER‐EICHBERGER A , KREFFT K , GRABNER G , KIEL JW , SCHROEDL F , REITSAMER HA
Published: August 2014

Elevated intraocular pressure (IOP) is a major risk factor for glaucoma. Currently, the primary strategy to slow down glaucoma progression is IOP reduction. Numerous studies investigated the IOP lowering effects of neuropeptides, but the complex physiological mechanisms involved are difficult to interpret. Therefore, we investigated the effect of arginine‐vasopressin (AVP) on IOP in a multiparameter approach. In a rabbit model the effect of i.v.‐applied AVP on IOP, ciliary blood flow (CilBF) and aqueous flow (AqF) was measured simultaneously by manometry, laser‐Doppler flowmetry and fluorophotometry. AVP caused a dose‐dependent decrease of IOP, CilBF and AqF. Based on the Goldmann equation the decrease of AqF at 0.08 ng/kg/min AVP (low dose) accounted for 77.1% of the IOP reduction (9.56±2.35%), while AqF at 1.33 ng/kg/min AVP (high dose) accounted for 28.4% of the IOP decline (41.02±3.19%). The results indicate that AqF reduction by low dose AVP is mainly caused by inhibition of ciliary epithelium secretion. At high dose AVP AqF reduction is caused by decreased CilBF or more likely by a combination of CilBF decline and secretory inhibition. This conclusion is only possible with the multiparameter measurement approach presented.
Reconstitution of a corneal endothelium by intracameral injection of cultured endothelial cells
Authors: BRUNETTE I , BOSTAN C , THERIAULT M , FORGET K , PROULX S
Published: August 2014

The only currently available treatment for irreversible corneal endothelial failure is allo‐transplantation, which is overshadowed by optical distortion of the posterior surface, postoperative donor corneal endothelial cells attrition and risk of rejection. Assessment of the in vivo functionality of a corneal endothelium reconstituted by the injection of corneal endothelial cells in the anterior chamber of an endothelial deficiency model allows to consider cell‐injection as a possible therapy for corneal endotheliopathies.
Function follows morphology? New aspects of macula OCT analysis
Authors: GUTHOFF R
Published: August 2014

Factors that are predictive for the outcome of medical or surgical therapy to anatomic success are desirable. Clinical tools such as optical coherence tomography and autofluorescence provide to demonstrate early morphological alterations. The value in identifying subclinical pathologies that affects the macula may help to understand better the natural course. The examination results of these tools may be useful for the correlation with post‐treatment visual acuity to better predict the eventual visual function.
Diabetic macular edema ‐ back to laser therapy?
Authors: JOUSSEN A
Published: August 2014

Treatment of diabetic macular edema has changed considerably since approval of several intravitreal drugs. Several studies demonstrated superiority of intravitreal injections over laser therapy. Nevertheless laser approaches are currently reconsidered with adapted protocols. This overview critically discusses the effectiveness of the treatment approaches on the background of the pathophysiology of diabetic macular edema.
Healthcare resource use and costs in persistent non‐anterior non‐infectious uveitis
Authors: THORNE J , TUNDIA N , SKUP M , MACAULAY D , REVOL C , CHAO J , BAO Y , DICK A
Published: August 2014

Purpose To assess direct and indirect economic burden for privately insured US employees with persistent non‐anterior non‐infectious uveitis (NIU) compared with matched controls without uveitis.

Methods Persistent cases were 18–64 years old with ≥2 ICD‐9 diagnoses for intermediate‐, posterior‐ or pan‐NIU (OptumHealth, 01/1998–03/2012) with ≥90 days of corticosteroid, immunosuppressant, and/or biologic use. Cases were matched 1:1 by sex, age, region and index date to controls. Direct (medical services and prescription drugs) and indirect (disability and medically‐related absenteeism) healthcare resource use (HRU) and costs (2012 USD) were compared using Wilcoxon/McNemar tests and multivariate regression (adjusting for baseline characteristics).

Results Annual unadjusted mean direct HRU and costs, including inpatient (0.3 vs. 0.1 stays; $3,628 vs $586), outpatient (26.3 vs 9.6 visits; $12,038 vs $3,065), ophthalmology/optometry (6.6 vs 0.5 visits; $3,486 vs $83), emergency (0.6 vs 0.1 visits; $267 vs $31), and prescription drugs (13.3 vs 4.5; $10,345 vs $1,499) were significantly higher for cases vs controls (all P<.05). Indirect HRU and costs (35.5 vs 11.5 days; $6,624 vs $1,816), specifically absenteeism (14.3 vs 4.0 days; $3,818 vs $862), also were higher for cases vs controls (all P<.05). Adjusted total direct costs ($35,739 vs $7,670) and indirect costs ($6,902 vs $1,612) were significantly higher for cases vs controls (all P<.05).

Conclusion Persistent non‐anterior NIU is associated with substantial direct and indirect costs.

Commercial interest
The effect of intravitreal adalimumab on the treatment of active noninfectious ocular inflammation: A pilot study
Authors: HAMAM R , MANSOUR A
Published: August 2014

Purpose To evaluate the short term efficacy of intravitreal adalimumab (IVA) for the treatment of eyes with active noninfectious uveitis.

Methods In a prospective noncomparative interventional case series, consecutive eyes with active noninfectious uveitis were injected with IVA at 0, 2 then every 4 weeks for total of 6 months. Change in VA, grade of inflammation (cells, haze, leakage on FA adopted from the angiography scoring for uveitis working group), and central retinal thickness (CRT) were recorded. No systemic or ocular therapies were added to the IVA treatment during the study period.

Results Six out of seven patients (12 of 13 eyes) completed 26 weeks of treatment. One patient (1 eye) failed treatment. Median logMar VA at baseline was 0.243 and improved to 0.049 at 26 weeks. Seven out of twelve eyes had improvement of ≥2 ETDRS lines. All three eyes with anterior chamber cells grade ≥1 at baseline had zero cells at 26 weeks. Also, all nine eyes with vitreous haze grade ≥1 at baseline had zero haze on last follow up. Median CRT at baseline was 317 microns and decreased to 277 microns. Five out of eight eyes with macular edema had complete resolution. Median FA score at baseline was 14 and improved to 4. Using Wilcoxon Signed Rank test, the decrease in logMar, CRT and FA score at 26 weeks compared to baseline was significant (n=12 eyes; p=0.003, 0.021, 0.002 respectively). No local or systemic side effects were detected. Stratifying the data to include one eye per patient revealed similar results.

Conclusion IVA was safe in this pilot study; was effective in improving the VA in 7/12 eyes, resolving macular edema in 5/8 eyes & decreasing AC cells, vit haze and FA score in 12 eyes while 1 patient (1 eye) failed treatment.
Characterization of uveitis in association with multiple sclerosis
Authors: MACKENSEN F , MESSENGER W , HILDEBRANDT L , SUHLER E , ROSENBAUM JT
Published: August 2014

Purpose Characterize uveitis in association withmultiple sclerosis (MS) including anatomic presentations, age, gender, and outcome.

Methods Retrospective chart review of patients with uveitis and MS at two uveitis centers (Portland, Oregon, USA and Heidelberg, Germany). Baseline characteristics and ophthalmic data were collected at the patient’s first and last visits. Additionally, neurologic records were obtained when possible. In a sub‐analysis, controls with idiopathic intermediate uveitis were compared to cases with intermediate uveitis and MS.

Results We identified 113 patients (196 eyes), 83 (73%) female and a mean age of presentation of 41 years (range 13‐64). Vision was fair with mean visual acuity of 20/39. After classifying anatomically, intermediate, anterior, posterior and pan‐uveitis comprised 80%, 15%, 3%, and 2%, respectively. Fifty‐four patients (56%) were diagnosed with uveitis before MS, 15 patients (15%) simultaneously, and 28 patients (29%)after having MS. Optic neuritis was present in 33% of our patients. During an average follow‐up of 4.2 years (range 0.04 – 21), visual acuity improved ‐0.09 logMar/year. Compared to our location‐matched controls with idiopathic intermediate uveitis(n=16), patients with MS and intermediate uveitis were significantly older when diagnosed with uveitis (p=0.027) and more likely to be female (p=0.01). There was no statistical difference in visual acuity or rate of vision change between our cases and controls.

Conclusion Uveitis with MS generally presents as intermediate uveitis with a minority presenting with anterior uveitis. Patients are significantly older and more likely to be female than patients with idiopathic intermediate uveitis. The visual prognosis is generally favorable.

Commercial interest
Pars plana vitrectomy and IOL implantation in uveitic children with cataract
Authors: NYSTRÖM A , PÅLSSON S , SJÖDELL L , JAKOBSSON G , BYHR E , ANDERSSON GRöNLUND M , ZETTERBERG M
Published: August 2014

We have performed a study with the purpose to evaluate the outcome of combined cataract surgery with primary intraocular lens (IOL) implantation and pars plana vitrectomy (PPV) in children with uveitis. This paper is accepted for publication in Journal of ocular immunology and inflammation.
Neurological considerations
Authors: KAWASAKI A
Published: August 2014

Seeing light flashes, scintillations, movement, simple or complex forms which are not based on actual sensory visual input from the external world represents a group of positive visual phenomena , often referred to as « hallucinations ». Such visual experiences arise from abnormal endogenously‐ activated neural discharges and can originate from any part of the visual system. In certain cases of disordered spatial perception, the lesion may even arise from the brainstem vestibular pathway. This lecture will examine the possible central mechanisms by which hallucinations are generated and give clinical examples of different types of positive visual phenomena.
Prognostic factors in myopic choroidal neovascularisation
Authors: SILVA R , WONG TY , ASMUS F
Published: August 2014

Purpose To assess effects of age and baseline axial length on best‐corrected visual acuity (BCVA) in patients (pts) with myopic CNV receiving intravitreal aflibercept (IVT‐AFL).

Methods MYRROR was a 48 week, double‐masked, sham‐controlled, Phase 3 multicentre study (NCT01249664). Pts were randomised 3:1 to IVT AFL or sham/IVT‐AFL (sham to Week 20 [W20]; IVT‐AFL from W24 to W48). Post hoc analyses assessed effects of baseline pt age and axial length on mean BCVA change at W24 and W48. Subgroups were based on median cut‐offs (age: ≤62 y vs >62 y; axial length: ≤28.6 mm vs >28.6 mm).

Results 121 pts were analysed (IVT‐AFL, n=90 / sham/IVT‐AFL, n=31). With age ≤62 y, mean BCVA changes were 13.0/14.7 letters (W24/W48) for IVT‐AFL vs ‐0.8/ 8.1 for sham/IVT‐AFL. With age >62 y, changes were 11.1/12.2 letters for IVT‐AFL vs ‐3.6/‐1.2 for sham/IVT‐AFL. With axial length ≤28.6 mm, mean BCVA changes were 12.6/13.8 letters (W24/W48) for IVT‐AFL vs ‐2.1/1.7 for sham/IVT‐AFL. With axial length >28.6 mm, changes were 11.6/13.2 letters for IVT‐AFL vs ‐2.0/7.0 for sham/IVT‐AFL. Correlation coefficients based on age were ‐0.234 and ‐0.215 (W24/W48) (both P<0.05); coefficients based on axial length were non significant. Ocular AEs were mainly mild and occurred at a similar rate with IVT‐AFL and sham/IVT‐AFL (37.4% vs 38.7%; most common, respectively: conjunctival haemorrhage [11.0%] and punctate keratitis [12.9%]). 7 (5.7%) pts had a serious AE (all IVT‐AFL; only one SAE in study eye [macular hole]). No deaths were reported.

Conclusion IVT‐AFL was well tolerated and associated with clinically meaningful BCVA improvements in pts stratified by age or baseline axial length. Treatment benefits may be greater among younger myopic CNV pts. Baseline axial length did not appear to affect outcomes.

Commercial interest
Correlation between peripapillary choroidal thickness and retinal vessel oxygen saturation in young healthy individuals
Authors: VAN KEER K , ABEGãO PINTO L , WILLEKENS K , STALMANS I , VANDEWALLE E
Published: August 2014

Purpose To investigate the correlation between the peripapillary choroidal thickness (CT) and the retinal vessel oxygen saturation (SO2) in young healthy individuals.

Methods Young healthy volunteers were recruited in this observational, cross‐sectional study. Peripapillary CT was obtained using enhanced depth imaging optical coherence tomography (EDI‐OCT). Arterial (SaO2) and venous retinal oxygen saturation (SvO2) were measured by a noninvasive spectrophotometric retinal oximeter in all four quadrants. Spearman’s rank correlation and multiple regression analysis were used to determine relationships between choroidal thickness and oxymetric parameters.

Results 54 eyes of 54 individuals aged 21.6±1.1 years were analyzed. Average SaO2 (92.3±3.0%) and SvO2 (55.4±4.6%) were positively correlated with the average peripapillary CT at 500µm from the optic disc margin (Spearmans’s R = 0.477 , p < 0.001 and 0.414 , p < 0.002 respectively). These results were confirmed to be independent of intraocular pressure and hemodynamic parameters on multivariate linear regression analysis (p < 0.01).

Conclusion In young healthy individuals, retinal vessel oxygen saturation appears to be positively correlated with the peripapillary choroidal thickness.
Findings in low luminance kinetic and static perimetry
Authors: KRASTEL H , GAGYI‐PALFFY Z , BEUTELSPACHER S , SCHLICHTENBREDE F , JONAS J
Published: August 2014

Purpose To transfer the neutral density filter test to perimetry; i.e. to show that the diagnostic battery can be supplemented by low luminance visual fields, if the standard procedures yield unsatisfactory information.

Methods The Goldmann perimeter uses one single incandescent light source for both stimulus and background illumination (BI). By dimming the luminance was reduced by 0.6 log units. The accompanying change in colour temperature was ignored. The i) Twinfield and ii) Tübingen automatic perimeters were modified to low luminance conditions using neutral grey filters i) in front of the eye, or ii) in the stimulus and the BI light paths. Special attention was paid to perform glaucoma fields at normal IOP level as proven by GAT and/or by Corvis tonometry (the latter to avoid affection of the tear film by anesthetics).

Results Low luminance perimetry produces more pronounced scotomas in kinetic, and more distinct loss of sensitivity in static perimetry than otherwise identical perimetric procedures in standard luminance. Cases concern inflammatory, ischemic and compressive optic nerve diseases, glaucoma, and ischemic and diabetic retinopathies. Results in hereditary, dystrophic and toxic retinal conditions vary depending on whether the rods and the scotopic system are mainly affected, or the cones and the photopic system. Cone diseases lack visual field deterioration in low luminance and instead may show improvement.

Conclusion Low luminance perimetry is a supplementary diagnostic tool which may add helpful diagnostic information, particularly if standard results are insignificant.

Commercial interest
Choroidal blood flow and choroidal thickness
Authors: POURNARAS C , DONATI G , FROUNTZOU E , GEISER M , RIVA CE
Published: August 2014

A progressive decrease of the choroidal blood flow related to macular degeneration was observed with glaucoma and aging. Abnormal regulation of the choroidal blood flow in patients suffering from neovascular AMD or Diabétic microangiopathy was also reported. Recent clinical studies have shown a decrease of the choroidal thicknessof in high myopia, AMD or in retinal dystrophies and increased choroidal thickness in central serous chorioretinopathy. Continuous real time Laser Doppler Flowmetry (LDF) has been used in humans for the evaluation of the subfoveal choroidal circulation and the investigation of the regulatory processes of the choroidal blood flow in response to various physiological stimuli, such as increase and decrease of the ocular perfusion pressure. The correlation of the subfoveal choroidal blood flow with the anatomical changes of the choroidal circulation, as observed by enhanced depth imaging optical coherence tomography(EDI‐OCT), was investigated in healthy volonteeres. No significant correlation was found between the subfoveal choroidal thickness and the choroidal blood flow. However, decreased subfoveal choroidal thickness was associated with decreased refractive error and axial length.
How to get your research published?
Authors: STEFANSSON E
Published: August 2014

The quality of an article depends first and foremost on its scientific content. However, the way in which the scientific material is presented may determine whether it will receive proper attention. The aim of this presentation is to point out general characteristics of good papers. The title can decide whether a potential reader will give your article a proper look. A good title is descriptive and may also give a statement if the journal style allows. The abstract is the most important part of your article. People will proceed to read the article only if they find the abstract interesting. Describe the material or patients and the methods in brief. It is advisable to specify the study design. Present the most important results in a brief manner. Give quantitative data with confidence limits whenever applicable. The reader wants to know what your results were, not just whether they were “statistically significant”. In the discussion, put your data into context with the clinical practice, literature or both. What have we learned? A common mistake is to include general conclusions which are not specifically supported by the data presented. Please check that the conclusions are in line with the stated aim of the study.
How to get your research published?
Authors: DUA H
Published: August 2014

Abstract not provided
Excimer vs Femtosecond laser for nonmechanical keratoplasty – Where are the true benefits?
Authors: SEITZ B , EL‐HUSSEINY M , JANUNTS E , LANGENBUCHER A , SZENTMARY N
Published: August 2014

Purpose: To compare the intraoperative feasibility and postoperative outcome of the excimer (EXL) and femtosecond laser (FSL) for penetrating keratoplasty (PKP). Methods: Since 1989 more than 3500 non‐contact nonmechanical PKPs using the Zeiss‐Meditec MEL70® 193 nm EXL along metal masks with eight "orientation teeth/notches" (PKP) were performed. Since 2006 various groups applied the FSL for PKP with various 3D‐configurations. Results: The technique of EXL PKP may improve donor and recipient centration, reduce "vertical tilt" and "horizontal torsion" of the graft in the recipient bed, thus resulting in significantly less "all‐sutures‐out" astigmatism, higher regularity of the topography and better visual acuity. Clinical results of FSL PKP ‐ requiring variable amounts of applanation thus causing distortion of corneal tissue ‐ are still very limited and not yet finally convincing. Conclusions: Because of undisputed clinical advantages, especially in eyes with keratoconus, EXL trephination is still favoured in Homburg/Saar in daily practise. To determine potential benefits of FSL over EXL PKP, a prospective randomized study for keratoconus and Fuchs dystrophy is ongoing in Homburg/Saar.
Diagnostic contribution of ocular imaging techniques in a multimodal diagnostic approach of small pigmented choroidal tumors
Authors: ZOGRAFOS L , PETROVIC A , SCHALENBOURG A
Published: August 2014

Purpose The differential diagnosis of small pigmented choroidal tumors is based on the evaluation of the tumor diameter, thickness, retinal detachment, pigment epithelium changes, and possible associated symptoms.

Methods The diagnostic contribution of color fundus photography, fluorescein angiography (FA), indocyanine green angiography (ICGA), fundus autofluorescence (FAF) and optical coherence tomography (OCT), was analyzed in 85 eyes with a small pigmented choroidal tumors, measuring 2‐10 mm in diameter and 0.8‐2.5 mm in thickness. The presumed diagnosis was a large choroidal nevus in 60 cases (71%), and a small choroidal melanoma in 25 cases (29%). The identification of the tumor border, the presence of any retinal detachment on the tumor surface or outside the tumor borders, the presence of orange pigment, drusen, pigment epithelium changes and/or pin points were analyzed on each imaging technique.

Results The highest identification score for the tumor margins was reached by color fundus photography. An associated retinal detachment was best identified on OCT. Orange pigment was best detected on fundus color photography and then by FAF. Drusen identification reached the same score on fundus color photography and FA. The appearance of pin points was exclusively seen on FA. Pigment epithelium changes showed the best score on FAF.

Conclusion The majority of the investigated ocular imaging techniques played an important role in the identification of diagnostic elements that contribute to the distinction between a small choroidal melanoma and a large nevus. Multimodal imaging techniques have to be used in order to obtain a higher efficacy in differentiating small pigmented choroidal tumors.
Aquaporin‐4 and potassium channel kir4.1 in amd and serous retinal detachment secondary to choroidal melanoma
Authors: MADIGAN M , DIEP M , JUNGHANS B , VALTER K
Published: August 2014

Purpose Aquaporin‐4 (AQP4) and potassium channel Kir4.1 are normally expressed in retinal Müller glia, and play a major role in controlling retinal fluid and maintaining retinal integrity and function. We examined AQP4 and Kir4.1 distribution and expression in human eyes with late age‐related macular degeneration (AMD) or long‐term serous retinal detachment secondary to choroidal melanoma.

Methods Paraffin sections of central and peripheral choroid/retina from young (<40 years, n=5), aged (>70 years, n=4) and AMD (>70 years, n=5) human post‐mortem eyes, and whole human eyes with choroidal melanoma (n=5), were co‐immunolabelled with antibodies to AQP4, Kir4.1 and GFAP, and visualised using immunofluoresence and confocal microscopy.

Results We found differential expression of AQP4 and Kir4.1 in detached retina of melanoma eyes, with upregulation of AQP4 and downregulation of Kir4.1 compared to unaffected eyes. This was most obvious in the retina overlying melanomas and in detached retina separated from underlying choroid. GFAP immunoreactitvity was upregulated in areas of serous retinal detachment, and retinal thinning; Müller cell processes extended along the anterior surface of melanomas. No apparent difference in distribution or expression of AQP4 or Kir4.1 was observed for retinas with late stage AMD compared to controls.

Conclusion Decreased Kir4.1 expression in long term serous retinal detachment may be associated with Müller cell proliferative gliosis, as suggested in earlier animal studies. Increased AQP4 expression suggests efforts to restore retinal fluid balance in areas with photoreceptor degeneration and compromised outer blood‐retinal barrier. Support: NFMRI (MCM), Lions NSW Eye Eyebank
MAP kinase and pi3k/mTOR pathways involvement in tumor progression of conjunctival melanocytic proliferations
Authors: MOULIN A , BUCHER M , SCHALENBOURG A , NICOLAS M
Published: August 2014

Purpose As activating mutations of BRAF and NRAS have been identified in 47% of conjunctival melanoma, we evaluated the activation status of the MAP kinase and PI3K/mTOR pathways in benign and malignant conjunctival melanocytic proliferations. As loss of PTEN locus has been reported in conjunctival melanoma, we also assessed the expression of PTEN in conjunctival nevi and melanoma.

Methods The phosphorylation status of MEK, ERK, AKT, S6 ribosomal protein and the expression of PTEN was evaluated by immunohistochemistry in 35 conjunctival naevi and 31 conjunctival melanoma. Statistical analysis was performed with JUMP 8,0 software. Immunohistochemistry was assessed independently by three observers.

Results There were 13 subepithelial nevi and 22 compound nevi. There were 14 females and 21 males with a mean age was 36.9 yo. P‐MEK, p‐ERK, p‐S6, p‐AKT and PTEN were respectively found in 59%, 49 %, 49%, 83.9% and 100% of the nevi. The melanoma group was composed of 17 females and 14 males with a mean age of 67.1 yo. P‐MEK, p‐ERK, p‐AKT, p‐S6 and PTEN were respectively found in 87%, 87%, 94.3%, 94% and 96.7% of the melanoma. The phosphorylation of MEK and ERK, AKT and S6 was significantly elevated in the melanoma compared to the nevi (p=0,0050; p=0,0004; p=0,0031;p> 0,0001 respectively). There was also a significant correlation between the activation of MEK and ERK (p=0,0045).

Conclusion Our results demonstrate ex vivo a significant increase in the activation of the MAP kinase pathway in malignant conjunctival melanocytic proliferations as well as a significant increase in the phosphorylation of pAKT and S6 ribosomal protein, suggesting a contribution of the PI3K/mTOR pathway to conjunctival melanoma development.