bluuebunny/crossref_metadata_2025 huggingface dataset:
Retinal ischemia in radiation retinopathies: radiobiological concepts and clinical spectrum
Authors: Matet Alexandre
Published: December 2019

Eyes irradiated for intraocular malignancies often develop irreversible retinopathy due largely to vascular damage leading to retinal ischemia. In most advanced cases, this severe process leads to refractroy neovascular glaucoma. We will provide an overview of current biological understanding of radiation‐induced retinal vascular damage, in connection with the clinical manifestations observed in irradiated eyes.
Phakic intraocular lens implantation in Keratoconus
Authors: Saw Valerie
Published: December 2019

Phakic intraocular lens implantation can be a highly predictable and successful method of refractive correction and functional visual rehabilitation in patients with grade II – III keratoconus who have a stable corneal shape and good spectacle corrected visual acuity. Effective refractive correction has been reported using several types of toric phakic IOLs in keratoconus and also for keratoconus patients with post‐keratoplasty ametropia. A four stage visual rehabilitation pathway for keratoconus has been described: gross shape correction with intracorneal ring segments followed by cross‐linking, toric phakic intraocular lens implantation, and then fine shape correction with topography‐guideded PRK as necessary. The aim of this presentation is to present an update on current indications, methods and outcomes of toric phakic intraocular lens implantation in keratoconus patients.
Cultivated Oral Mucosal Epithelial Transplantation
Authors: Gatzioufas Zisis
Published: December 2019

Bilateral limbal stem cell deficiency (BLSCD) represents a highly demanding challenge for the clinician dealing with ocular surface disease, due to the underlying causes, clinical presentation, as well as lack of a source of autologous limbal stem cells. Cultivated Oral Mucosal Epithelial Transplantation (COMET) has been successfully employed to achieve visual rehabilitation in patients with BLSCD. This talk will focus on indications, technique, clinical results and complications of COMET. Moreover, it will present current disadvantages and limitations of COMET, exploring potential advancements in the future.
A rational explanation of some miracles of Christ healing blindness
Authors: Javier Ascaso Francisco
Published: December 2019

During his 3‐year earthly ministry, Jesus Christ performed miracles that showed his ability to heal. The canonical Gospels report five separate cases in which Jesus healed blind people. Although Science prefers not to give its opinion and most miracles fall outside rational interpretations, it is certainly possible that some of them might be clarified with non‐divine answers. Did Jesus possess medical skills? Undoubtedly, he was a healer whose time was consumed with encounters with sick people. Following the persecution of Jewish newborns by the King Herod, Mary fled with Jesus to Egypt. According to the Jewish perspective (Talmud), Jesus brought his magic powers from Egypt. He returned to the land of Canaan at the age of 30 and started preaching. His mission ended with Jesus being 33 when he died. Although Christ did not always touch the afflicted in healing, at least in four of the five above mentioned miracles involving the blind, he touched them. But, isn't it possible that Jesus also had the ability to perform a “couching” technique with his own fingers? Taking into account that cataracts were undoubtedly very common in ancient Egypt and that ancient Egyptians and Babylonians used the “couching” procedure to dislodge the cataract away from the pupil, we should consider the possibility that Jesus learned this technique in Egypt.
Haematological diseases with monoclonal gammopathy – treatment
Authors: Jurczyszyn Artur
Published: December 2019

Monoclonal gammopathy (MG) is a wide spectrum of the lymphoplasma cell proliferative disorders manifested by the production of abnormal monoclonal protein, ranging in severity from the premalignant monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) to the malignant: symptomatic multiple myeloma (MM), plasma cell leukemia (PCL) and Waldenström’s macroglobulinemia (WM).

Treatment of MG depends on the character of the disease. MGUS and SMM require only observation, however regular follow‐ups are needed because of the risk of progression to symptomatic MM. Multiple myeloma treatment is based on systemic therapy (with novel agents, preferably triplets) and autologous hematopoietic stem cell transplantation in transplant‐eligible patients (operatively defined as being ≤65–70 years). PCL, as the most aggressive variant of the MG, requires immediate systemic therapy with proteasome inhibitors‐based regimens combined with classical chemotherapeutics including alkylating agents or anthracyclines, followed by transplantation (also allogeneic, in selected cases). In asymptomatic WM watchful waiting is an appropriate approach, while in symptomatic disease systemic therapy with rituximab in monotherapy or combined with bendamustine, an alkylating agent, a proteasome inhibitor, or ibrutinib is needed. In case of ophthalmological manifestation of MG standard management accompanied with local treatment (eg. keratoprosthesis) is reported as effective.
Pediatric retina imaging in aniridia
Authors: Daruich Alejandra
Published: December 2019

Aniridia is a congenital complex ocular malformation characterized by complete or partial iris hypoplasia and foveal hypoplasia, resulting in nystagmus and low visual acuity from early infancy. In the majority of cases, aniridia is caused by the loss of function of one functional copy (haploinsufficiency) of the PAX6 protein resulting from mutations in PAX6 gene or chromosomal rearrangement at the 11p13 locus. High‐resolution foveal imaging by spectral‐domain optical coherence tomography (SD‐OCT) has improved over recent years the evaluation of foveal architecture analyze. We have analyzed foveal anomalies on SD‐OCT in a large cohort (89 patients) of aniridia patients. We have shown that the grade of foveal hypoplasia is correlated to visual acuity. We have also shown that foveal hypoplasia is a constant finding in PAX6 aniridia patients, although iris defects could vary from complete aniridia to slight iris defects, even in the same family. Foveal imaging and grading by SD‐OCT could offer a non‐invasive tool to determine the visual potential of aniridia eyes and indicate further investigations or treatments. Additionally, SD‐OCT could contribute in the diagnosis of congenital aniridia by detecting foveal hypoplasia as the first sign of the disease.
CImmune reactions after PKP and DMEK–do they differ only in frequency?
Authors: Hos Deniz
Published: December 2019

The incidence of immune reactions after Descemet membrane endothelial keratoplasty (DMEK) is significantly reduced when compared to penetrating keratoplasty (PKP). Recent reports also suggest that the risk of endothelial decompensation is reduced after an immune reaction episode occurring after DMEK when compared to immune reactions occurring after PKP. This presentation will therefore summarize recent findings regarding incidence, treatment, prognosis and prophylaxis of immune reactions after DMEK in comparison to PKP.
The spectrum of disorders related to pachychoroid: an EDI‐OCT evaluation
Authors: Ambresin Aude
Published: December 2019

Pachychoroid disease is defined as: hyperpermeability on ICG angiography, loss if the inner choroid and dilated outer choroidal vessels (pachyvessels), presence of pachydrusen (drusenoid deposits) and diffuse or focal increased choroidal thickness visualized on OCT. The pachychoroid disease spectrum is divided in non‐neovascular pachychoroid disease and pachychoroid neovasculopathy (type 1 aneuvrysmal CNV, PCV). The non‐neovascular pachychoroid disease is divided in pachychoroid pigment epitheliopathy, central serous chorioretinopathy, peripapillary pachychoroid syndrome and focal choroidal excavation. The enhanced depth imaging module of the Spectral domain OCT (Heidelberg Inc®) allows measurement of the choroidal thickness and precise visualization of the different layers of the choroid thus guiding clinicians through differential diagnosis of pachychoroid disease and its related therapeutic management. At the end of the talk, participants should be able to recognizes key signs on EDI OCT of each subgroup of pachychoroid disease.
Cataract surgery in patients with uveitis
Authors: Grzybowski Andrzej
Published: December 2019

Cataract surgery in patients with uveitis requires special considerations. Active inflammation, particularly anterior or intermediate uveitis, increases the risk for postoperative complications. Other problems include the development of postoperative adhesions between the iris and lens capsule postoperatively, membrane formation, IOL deposits, zonular problems, and cystoid macular edema (CME). Inflammation should be inactive or controlled as much as possible prior to elective surgery, minimum 3 months prior to surgery, as this reduces the risk of posteoperative CME. Collaboration with the physicians treating the patient's uveitis prior to cataract surgery will help to provide for appropriate prophylactic anti‐inflammatory therapy and improve postsurgical outcomes. Surgical planning should include the possible need for other procedures, such as managing pre‐existing posterior synechiae, pupillary membranes, zonular compromise, and fibrotic scarring of the pupillary margin. Current evidence supports a superior effect of hydrophobic acrylic lenses over silicone lenses, specifically for posterior synechiae outcome. Periocular or intraocular corticosteroids at the time of surgery should be considered. Posteoperatively the use of short‐acting topical mydriatic agents and greater frequency and duration of topical anti‐inflammatory treatment is recommended.
Pharmacological treatment of presbyopia
Authors: Grzybowski Andrzej
Published: December 2019

Accommodation is the dioptric change in power of the eye produced by the changes of shape and position of the lens and the modification of the focus depth produced by the changes in the pupillary size. Presbyopia occurs in the 5th decade of life and is a consequence of the normal age‐related recession of the near point making it difficult to read at a normal working distance when the eye is fully corrected for distance vision. There are many strategies to correct presbyopia available nowadays, including eyeglasses, contact lenses, cornea or intraocular surgery, however, none of them is without limitations and fits every patient. Pharmacological treatment of presbyopia is based on using ophthalmic drops, which by impact on ciliary muscle, changing pupil size and elasticity can improve near vision. Many different modifications, including combination of two parasympathomimetics and a NSAID, two parasympathomimetics and one parasympatholytic, carbachol 2.25% with brimonidine 0.2%, and a combination of Pilocarpine 0.247%, Phenylephrine 0.78%, Polyethyleneglycol 0.09%, Nepafenac 0.023%, Pheniramine 0.034%, and Naphazoline 0.003% were studied. A different strategy based on lipoic acid derivative drops aims to soften the crystalline lens.
The advantage of low concentration of PVI in cataract surgery
Authors: Grzybowski Andrzej
Published: December 2019

Rationalizing medicine through verification of different practice patterns as well as the identification and elimination of unnecessary procedures is of increasing importance worldwide. The Choosing Wisely Campaign named in ophthalmology preoperative medical tests for eye surgery unless there are specific medical indications, the use of topical antibiotics in intravitreal injections and employment of topical antibiotics in adenovirus conjunctivitis as non‐beneficial and disadvised. The problem is not trivial as the impact of unnecessary tests and procedures in the U.S. was estimated be as high as 30% of all health care spending. Moreover, rationing and waste avoidance are complementary, and elimination of wasteful, non‐beneficial interventions was proposed to be ethically mandated. Cataract surgery is the most common surgical procedure worldwide, thus verification of different practice patterns related to this procedure is very justified.
Long‐term effects of inherited and acquired retinal degenerations on the retinal ganglion cell population
Authors: Villegas‐Pérez Maria‐Paz
Published: December 2019

Inherited photoreceptor degenerations cause loss of photoreceptors and retinal remodeling which, when severe, is accompanied of retinal vessel displacements that cause retinal ganglion cell (RGC) axonal compression and death. Light‐induced photoreceptor degenerations cause similar pathologic events and ultimately RGC loss. RGC death is secondary to photoreceptor degeneration and is a delayed event that occurs in retinal sectors where there is maximal photoreceptor degeneration. Other types of acquired retinal diseases, such as taurine deficiency‐induced retinal degeneration, which may be similar to vigabatrine‐induced retinopathy, can also cause photoreceptor degeneration and RGC loss. However, in taurine deficiency, RGC loss may not be secondary to photoreceptor degeneration, but occur as an independent event and thus, RGC loss is diffuse. The combination of two treatments: taurine deficiency and light toxicity increases photoreceptor loss but not RGC loss (García‐Ayuso et al., 2018). The population of intrinsically photosensitive RGCs (ipRGCs) may respond differently than the normal population of RGCs to different types of photoreceptor degeneration because they die in similar proportions to the other RGCs in inherited photoreceptor degenerations (García‐Ayuso et al., 2015), but are selectively affected by taurine‐deficiency and may show only a temporary decrease of melanopsin expression after light‐induced damage. The investigation of RGC loss in different retinal degenerations provides us with information on the mechanisms of cell death in order to plan strategies for its prevention.
Pseudoxanthoma elasticum
Authors: Nevalainen Pasi
Published: December 2019

Pseudoxanthoma elasticum (PXE) is an inherited an autosomal recessive disease caused by a homozygous mutation of ABCC6 gene. The prevalence of PXE has been estimated to be 1:25 000–100 000.

PXE is an inborn error of metabolism. The pathophysiologic problem is defective adenosine triphosphate (ATP) transport from the hepatocytes to extracellular space where ATP is cleaved to pyrophosphate and adenosine monophosphate (AMP). The result is systemic deficiency of pyrophosphate. Pyrophosphate is a critical anticalcifying agent. Deficiency of pyrophosphate causes causes calcification of elastic fibers in skin (typical xanthoma‐like nodules in lateral neck and armpits), occlusive vascular calcification (especially in lower extremities), and the Bruch's membrane (BM) in the retina.

There is little longitudinal data to describe the natural course of retinal disease in PXE.

Peau d'orange is probably the first ocular sign of PXE in the fundus. It can be found in 95% of PXE‐patients if the skin is affected. Peau d'orange is characterized by small dark spots within an area of a slightly whitish or opaque fundus reflex. Angioid streaks (AS), which are breaks in BM, are most consistently observed fundoscopic finding in PXE but it may be difficult if there is widespread atrophy present. At diagnosis 60–90% and after 20 years from diagnosis 100% of patients with PXE have AS. Peripheral comet and comet tail lesions have been suggested to be the only pathognomonic characteristic of PXE. Other lesions include choroidal neovascularization, pattern‐like atrophy and optic nerve drusen.

Except treatment with inhibitors of vascular endothelial growth factor there is no accepted treatment for PXE. Clinical trials on pyrophosphate supplementation and pyrophosphate analogs are being planned.
Topical ciclosporine: New clinical insight
Authors: Bremond‐Gignac Dominique
Published: December 2019

Rare severe ocular diseases, as vernal keratoconjunctivitis and atopic keratoconjunctivitis, represent a group of ocular diseases that can lead to severe ocular impairment in children. The ocular manifestations mostly appear before 10 years‐old and usually resolve at adolescence. However, treatment is the critical point to avoid steroid dependence and complications. Topical ciclosporin has been used in preparation since the 80’ however only few studies with variation of formulation were published. Vektis study is a randomized prospective multicenter study using cationic emulsion ciclosporine A 0.1% in VKC. The results of ciclosporine studies in VKC will be exposed in order to evaluate safety and efficacy of topical cyclosporine A.
Glaucoma Surgery; How to manage the failing tube
Authors: Besinis Dimitrios
Published: December 2019

Glaucoma drainage devices (GDDs) have been commonly used for refractory glaucoma as the last resort of managing the progression after a failed trabeculectomy. However there are certain types of glaucoma, where a primary tube is more effective in IOP control, like neovascular glaucoma and anterior segment dysgenesies. The two most commonly used tubes are the Ahmed valve and the Baerveldt shunt. Even though both of them are effective in giving adequate control of IOP, there are cases where the pressure begins to rise and the tube starts to fail. Tube failure can happen in either the early postoperative period or as a late complication. Mangement of the hypertensive phase and tube failure is different between the devices because of the different mechanism of action. In this talk I will present the management of failure of Ahmed and Baerveldt tubes and the next step in the treatment strategy.
Laser it!
Authors: Ameen Sally
Published: December 2019

When drop compliance is an issue, we can use laser treatment modalities to control the eye pressure without the use of drops. In this talk, we will discuss the different types of laser treatments available, which one is suitable for which patient and the safety profile as well as their efficacy. We will be discussing lasers performed in the outpatient setting (SLT and PI) and those that need to be done in the operating theatre (ECP, TSC, MDLT).
Glaucoma surgery: how to manage failing MIGS
Authors: Porteous Alastair
Published: December 2019

Glaucoma surgery is very effective at achieving good and long‐term pressure control with an acceptable safety profile. There are, however, patients for whom a previously successful procedure starts to fail. Minimally invasive glaucoma surgery (MIGS) techniques are becoming widely used for mild to moderate glaucoma. These techniques have an improved safety profile compared to more traditional filtration surgery, but there are still occasions when these techniques fail. This presentation, using surgical videos, personal experience and evidence from the literature, will aim to discuss a range of the most recently used MIGS techniques, including the iStent, Cypass microstent, endocyclophotocoagulation and Xen gel stent. The presentation will cover patient selection, complications, techniques to improve success and device misplacement.
Phaco it
Authors: Porteous Alastair
Published: December 2019

Non‐compliance is a major factor of poor control of glaucoma eye disease. There are many reasons for this, including forgetfulness, difficulty with drop administration and intolerance from side effects. This presentation will focus on how to tackle this chronic problem using cataract surgery to stabilise the disease and lead to a better quality of life for patients. Minimally invasive glaucoma surgery (MIGS) techniques are becoming widely used for mild to moderate glaucoma. These techniques have an improved safety profile compared to more traditional filtration surgery. This presentation will cover how cataract surgery alone and cataract surgery combined with MIGS techniques, using surgical videos, personal experience and evidence from the literature, can be used to reduce drop burden, improve the control of the disease and improve non‐compliance.
Cataract type in mouse exposed to moderate doses of ionizing radiation depends on mouse age at irradiation
Authors: Pawliczek Daniel
Published: December 2019

One noxious agent for cataract formation is ionizing radiation (IR). For doses till or equal 2 Gy it is still unclear, whether opacification occurs and if, how cataract type depends on the animals age at irradiation. Wild‐type and heterozygous Ercc2+/‐ mice were whole‐body irradiated by 0.5 Gy, 1 Gy and 2 Gy of γ‐radiation (dose rate = 0.3 Gy/min), 10 weeks after birth (P70). Another cohort was exposed to 2 Gy, 2 days after birth (P2). All cohorts were investigated by optical coherence tomography (OCT) and eyes were collected for histology after death. OCT revealed frequent lens alteration in the mice irradiated at P2 and P70. These lesions were only subcapsular located in P70 mice and are dose‐dependent in size. Mice irradiated at P2 showed scattering structures within the posterior cortex, 8.5 mth after irradiation. At least 80% of the irradiated animals displayed at least mild posterior cortical cataracts. Histology of irradiated eyes (P70) unravelled the OCT‐detected lesions as cataractous accumulations of enlarged fibre cells, accompanied by subcapsular placed cells with nuclei. Lesions of P2 mice displayed no correlate to the in vivo data. Therefore, we conclude that IR leads to lens opacification in a dose‐dependent manner and its magnitude correlates strongly with age at irradiation. These results help to assess the sensibility of eye lenses to IR in case of exposure. The LDLensRad project received funding from Euratom in the framework of CONCERT, grant No 662287.
Anti‐glaucomatous medication and ocular surface
Authors: Sakellaris Dimitrios
Published: December 2019

The purpose of this talk is to explore the interaction between ocular surface disease (OSD) and anti‐glaucomatous medication, whether a preexisting OSD can affect the success of the anti‐glaucomatous medication in terms of discomfort and non‐compliance and whether the anti‐glaucomatous medication can initiate or worsen OSD.
Objective assessment of progressive macular changes in glaucoma
Authors: Normando Eduardo M.
Published: December 2019

The role of OCT macula scans in glaucoma has been extensively investigated. However, to date, only subjective and qualitative analyses can be performed for macula scans in glaucoma. We propose a novel method to objectively assess glaucoma progression based on the Longitudinal Analysis of the Poster Pole (LaPo). Forty eyes were assessed over 3 years. Conventional Posterior Pole (PPole) and Peripapillary RNFL protocol were acquired using Spectralis OCT. Longitudinal measurements of Total Retina (TR), Retinal Nerve Fiber Layer (RNFL) and Ganglion Cells Layer (GCL) thickness were performed. Thickness gradients and Lineal regression analyses were calculated in each eye over time. All data are expressed as mean ± SD. p < 0.01 was considered as significant. Linear regression analysis of individual super pixel showed that LaPo can detect progression significantly earlier than peripapillary RNFL in 90.4% (TR, p < 0.01), 96% (RNFL, p < 0.01) and 83% (GCL, p < 0.01) of eyes. In this study we have shown a novel method for objectively quantify glaucoma progression using the PPole scanning protocol. We suggest that macular thickness changes are a potential biomarker for glaucoma diagnosis and progression. Our methodology could contribute to the early identification of progressing patients and may also have a role in glaucoma surveillance schemes.
The concept of cataratogenic load to understand ageing and radiation‐induced damage to the lens
Authors: Quinlan Roy , Quinlan Roy
Published: December 2019

Lens cataract is an iconic age‐related disease. The age of onset is subject to lifestyle, genetic and environmental factors and in this presentation I will review the case for considering the term “cataractogenic load” to explain the variability and nature of age‐related cataract. As we age so there is accumulated biomolecular damage to lens proteins, lipids and DNA. The very nature of lens biology ensures that this damage is accumulated throughout our lifetime and therefore the appearance of cataract could be explained by a threshold that when crossed results in light scatter, the loss of optical function and the appearance of cataract. Ionising radiation is just one of many environmental hazards that could be encountered but especially by those in the airline, space, energy and medical healthcare industries. Ionising radiation generates free radicals causing oxidative stress and indiscriminate damage to all lens biomolecules changing also the biochemical landscape. Ionising radiation therefore can add to the ageing effect and increase the cataractogenic load to accelerate lens aging and the loss of optical function. We will discuss how this affects cataract phenotype and how the timing of the exposure to ionizing radiation might influence the timing of cataract appearance.
In vitro expanded corneal endothelial cell sheets: towards a new therapeutic approach
Authors: Oellerich Silke
Published: December 2019

Corneal transplantation is currently the only effective treatment solution to restore corneal clarity in patients with endothelial disorders. Descemet membrane endothelial keratoplasty (DMEK) is the most recent corneal transplantation technique that selectively replaces only Descemet membrane (DM) and endothelium with the same layers of a healthy donor. However, its application is limited by shortage of high‐quality healthy donor tissue. In order to increase the pool of endothelial grafts, new strategies have been developed, which include surgical‐based and tissue‐engineering based approaches.

Tissue‐engineered approaches such as endothelial cell sheet transplantation and cell injection rely on the in‐vitro expansion of cultured corneal endothelial cells (CEC). For endothelial cell sheet transplantation suitable cell carriers are required, which could either be natural carriers (e.g. human anterior lens capsules (HALC)) or bioengineered matrices (e.g. 20 µm thick collagen‐based carriers (LK20)).

Within the ARREST BLINDNESS project, CEC were cultured on different carriers and the suitability of the cell‐carrier sheets as tissue‐engineered grafts for DMEK‐like procedures was evaluated by performing in‐vitro surgeries. Upon in‐vitro DMEK surgery, CEC‐HALC sheets behaved similarly to a standard DMEK‐graft on all scored aspects such as graft implantation, unfolding and adherence to bare stroma, whereas graft adhesion and surgical handling, respectively, are issues that still need to be addressed for CEC‐LK20 and CEC‐‘denuded DM’ sheets. First results of in‐vivo tests in an animal model will be presented as well as measures to approach legislative issues.
Animal models to study radiation retinopathy
Authors: Matet Alexandre
Published: December 2019

Retinal damage following irradiation is a challenge in the current management of eyes treated for intraocular tumors. However, the mechanisms involved in this deleterious process remains non‐elucidated, and therapeutic strategies are limited. To advance in the understanding of this sight‐threatening complication, the development, validation and analysis of reproducible animal models of ocular irradiation is crucial. We will review existing models and discuss their advantages and limitations, in the perspective of reproducing closely radiation‐induced retinal damage as observed in humans.
Molecular and cellular consequences of retinal ischemia
Authors: Behar‐Cohen Francine
Published: December 2019

We will review concepts and develop hypotheses on potential mechanisms resulting from retinal ischemia including vascular consequences and subsequent occlusive events. Examples of diabetic retinopathy, vein occlusion and retinal detachment will be envisaged.
Advanced in early‐ and adult‐onset glaucoma genetics
Authors: Pasutto Francesca
Published: December 2019

Glaucoma is a genetically and clinically heterogeneous disease that can affect individuals at all ages. Rare genetic variants are known to cause early‐onset glaucoma while common variants contribute to adult‐onset open angle glaucoma (POAG). Genome‐wide association studies (GWAS) are an effective approach for discovery genetic risk factors of diseases with complex inheritance such as the adult POAG. The International Glaucoma Genetics Consortium (IGGC) including investigators worldwide has collected over 50,000 POAG samples. The results of recent GWASs of the IGGC leading to the discovery of more than 50 genes will be discussed providing important novel insights into disease pathogenesis. For the early onset‐ and congenital glaucoma currently 9 genes are known and using these genes for genetic testing can inform genetic counseling and risk assessment. However, the diagnostic yield for these genes is less than the half of all early glaucoma implicating the contributions of additional genes. Whole exome sequencing (WES) has been revealed a useful approach for gene discovery particularly in smaller families leading, for example, to the identification of the novel ANGPT1‐TEK signaling pathway in primary congenital glaucoma. Interesting, using WES in our cohort of patients with early onset glaucoma we could identify mutations in different genes involved in others forms of glaucoma and anterior segment anomalies, thus helping not only to identify novel candidate genes but also helping to define the correct diagnosis. Interesting by large patients screening, some genes involved in early onset glaucoma forms, i.e. ANGPT1, contribute also to adult glaucoma.
2000 years under pressure – The history of glaucoma research
Authors: Krogmann Frank
Published: December 2019

Since antiquity, glaucoma is known as a rather vaguely defined disease. The Ancient Greeks were the first who described the disorder we call “glaucoma” today already in 400 BC. “Glaykoseis” was first mentioned in Hippocratic writings as a blinding disease occurring most commonly in the elderly. The present talk will describe the very first beginnings of understanding the ophthalmic disease “glaucoma”. The definition of glaucoma has changed drastically since its introduction around the time of Hippocrates. The very first recognition of a disease which might be associated with a rise in intraocular pressure can be found in the Arabian writings, “Book of Hippocratic treatment”, of At‐Tabari (10th century), it took until 1622 to proof this. In Hippocratic writings the term glaucoma was used to describe blindness developing in advancing years associated with a glazed appearance of the pupil. Galen associated the glaucous hue with a large, anterior, or hard crystalline lens. Medieval Arabic authors translated “glaukos” as “zarqaa”, which also commonly described light irides. Ibn Sina (also known as Avicenna) wrote that the zarqaa hue could occur due to anterior prominence of the lens and could occur in an acquired manner. The disease defined by the glaucous pupil in antiquity is ultimately indeterminate. The specific association of elevated intraocular pressure and the eye disease glaucoma was first described by Richard Banister in 1622.
Modeling spinocerebellar ataxia type 7 in the mouse
Authors: Roux Michel
Published: December 2019

Autosomal dominant spinocerebellar ataxia 7 (SCA7) is associated with cone‐rod dystrophy. The causative gene codes for ATAXIN‐7, a ubiquitous protein part of the transcriptional complex SAGA. The coding region contains a CAG triplet repeat translated into a poly‐glutamine (Q) stretch. While there are 4 to 36 repeats per allele in the healthy population, higher numbers are found in SCA7 patients. Longer expansions are typically associated with early onset and cause visual loss before cerebellar ataxia. The SCA7 retinal degeneration has previously been modeled using an overexpression of 90‐repeats ATAXIN‐7 only in rods using the rhodopsin promoter (Rho‐90Q) or a knock‐in with 266 repeats in the mouse Ataxin‐7 gene (KI‐266Q). Rho‐90Q may not be a good model for a cone‐rod dystrophy due to the promoter used. KI‐266Q showed reduction of both photopic and scotopic ERG, but the early and severe phenotype compromises animal fertility and causes death at 4‐5 months, thus offering limited possibilities to test therapeutic approaches, especially in the pre‐symptomatic phase. We have thus characterized the retinal phenotype of KI‐140Q mice, in which mouse Ataxin‐7 includes a shorter (140) polyQ stretch. While the photopic ERG and cone opsins expression is comparable in the mutant and control mice at 5 weeks, they progressively decrease and are extinct around 20–25 weeks in KI‐140Q. The retinal structure is preserved at 9 weeks, followed by a moderate thinning of the segments and outer nuclear layer. Overall, the KI‐140Q recapitulates the symptoms of the cone‐rod dystrophy found in patients, and offer a reasonable time‐window to assess treatment efficacy in both the pre‐symptomatic and symptomatic phases of the disease.
The role of the retina in colour vision impairments in ophthalmological and neurological disorders
Authors: Branco Miguel Castelo
Published: December 2019

Colour vision impairments have been identified in early stages of neurological disorders such as Parkinson′s disease, and the relative contribution of retinal versus cortical mechanisms remains a matter of intense debate. Similar considerations can be raised concerning other neurological disorders such as Multiple Sclerosis (with or without optic neuritis) and Alzheimer's Disease.

This may be due to the fact the retina may mirror the brain in terms of pathology, or suffer from retrograde degeneration in the case of multiple sclerosis. Moreover cortical changes secondary to retinal disease, such as glaucoma and diabetic retinopathy may also bias colour perception. Here we review current evidence concerning the relative role of the retina in colour vision deficits in a broad range of neurological and ophthalmological disorders. In particular, we discuss the potential role of colour vision measures as disease related biomarkers that can be used for diagnostic, prognostic and treatment effects assessment.
Trace elements in glaucoma – The impact of analytics
Authors: Michalke Bernhard
Published: December 2019

Eye diseases, such as glaucoma are leading causes of irreversible vision loss in industrialized countries. Eye diseases have multifactorial pathogenesis, where heavy metal body burden and/or trace element misbalances are accepted causes aside from genetic factors or intraocular pressure in glaucoma. Heavy metals and misbalances in redox‐active trace elements are prone to affect eye‐related health via increased oxidative stress. In this study trace elements and heavy metals were analyzed in aqueous humour samples by Flow‐Injection (FI)‐Inductively Coupled Plasma Mass Spectrometry. The FI‐mode was used to adopt sample introduction to the very low sample volume available. Samples were analyzed in triplicates using standard mode (best sensitivity for Co, Cd, Hg, Pb), dynamic reaction cell (DRC) mode with ammonia as reaction gas (interference elimination best for Mn, Fe Cu, Zn) and DRC with methane as reaction gas for Se. 5‐point calibration curves in the ranges 0‐1000 ng/l for Cd, Hg, Mn, Pb, Se or 0‐100 µg/l for Cu, Fe, Zn showed R2 = 0.989 for Zn and R2 better than 0.999 for the other elements. Analysis of glaucoma patients revealed an unchanged selenium aqueous humor level of POAG patients compared to controls. However, age‐group and sex dependent trends were seen, i.e. a slight increase for the selenium quantiles in POAG and PEXG patients (age 47–60 years), decrease for the first selenium quantile (61–68 years) and an increase of the third tertiles for 70–85 years.
Posterior segment imaging and anomalies in children with Aniridia
Authors: Wowra Bogumil
Published: December 2019

Congenital aniridia is a rare, occurring on both sides always malformation of the eye. It occurs at about 1/50 000 births. This feature is inherited. One of ocular manifestation of congenital aniridia is macular hypoplasia which have significant impact for visual aquity and development of vision in early childhood. Fovea and macular structure is changed.
Ocular surface diseases following ocular irradiation
Authors: Horwath‐Winter Jutta
Published: December 2019

Radiotherapy is used for many ocular and periocular indications in malignant and benign diseases. In this talk an overview of ocular surface damage secondary to radiotherapy will be provided. Significant side effects on the external eye occur after irradiation including atrophy of the lacrimal and meibomian glands, damage to the conjunctiva and cornea. These may result in the development of ocular surface diseases such as dry eye syndrome, causing severe patient discomfort. The incidence and severity of the side effects varies depending on the type, location and dose of the radiation treatment. The effects can be clinically subtle, but also devastating to the eye. The discussion of characteristic clinical changes and underlying pathophysiologic mechanisms should provide a rational approach to prevention and treatment of irradiation associated side effects. Tear film and ocular surface evaluation should be performed before irradiation and during follow‐up in order to detect acute and chronic complications and to initiate treatment on a timely basis.
The retinal venous pressure ‐ A new measurable parameter in glaucoma risk assessment
Authors: Stodtmeister Richard
Published: December 2019

Low ocular perfusion pressure (OPP) is a risk factor for the progression of glaucoma. OPP is calculated as the difference between mean ophthalmic artery pressure and the venous pressure in the eye which is assumed being equal to the intraocular pressure (IOP). Thus lowering IOP lowers the ocular venous pressure and increases the OPP. This view, however, needs a modification because in the past 25 years it has been shown that the retinal venous pressure (RVP) may be considerably higher in approximately one third of glaucoma patients. In an own series of 50 glaucoma patients 16 patients could be identified just because of a lacking spontaneous pulsation of the central retinal vein. These patients had an IOP of 15(4)mmHg (median (interquartile range) and a RVP of 31(12)mmHg. Also other study groups reported on patients with a high RVP despite an inconspicuous IOP. In a long‐term study of 82 months the RVP was strongly predictive for an increased excavation of the optic disc (odds ratio 1.3/mmHg RVP). We hypothesize that the RVP may be a more potent risk factor than the IOP. Until now, the RVP has been measured by the Dynoptor or by contact lens dynamometry. Due to the hesitant acceptance of these measurement techniques a new method has been developed in which the cornea is no longer touched. By including the RVP in glaucoma diagnostics a new parameter may be available for the risk assessment of this disease.
Antisense oligonucleotide‐induced splice modulation for the treatment of Usher syndrome type 2A
Authors: van Wijk Erwin
Published: December 2019

Mutations in USH2A exon13 are the most frequent cause of both syndromic and non‐syndromic retinitis pigmentosa (RP), for which currently no treatment options exist. It is generally believed that RP due to mutations in this gene is caused by a loss‐of‐function mechanism. In total, over 600 different mutations have been identified in USH2A of which at least three are known to be derived from a common ancestor and are therefore seen more commonly: c.2299delG (p.Glu767fs*21), c.2276G>T (p.Cys759Phe) and c.7595‐2144A>G (p.Lys2532Thrfs*56). The size of the coding sequence (15,606 bp) and the presence of multiple alternatively spliced USH2A transcripts with unknown significance, hamper the development of gene augmentation therapy. Another difficulty in the development of a therapy is the lack of a suitable animal model. The currently available Ush2a mouse model displays only mild retina degeneration with a very late age of onset. Zebrafish ush2a mutant models however, show an early onset retinal dysfunction and are as such provide a unique opportunity to evaluate future therapeutic strategies. Antisense oligonucleotide (AON)‐based splice modulation has been proven to hold great promise as a therapeutic strategy for a number of hereditary conditions, including Usher syndrome. Upon pre‐mRNA binding, AONs will prevent or stimulate binding of the spliceosome thereby modulating splicing events. AONs can be designed and applied for different genes and genetic disorders as the specificity depends on their nucleotide sequence. In this study we explored the therapeutic potential of AON‐induced splice modulation as a therapeutic approach for the future treatment of USH2A‐associated retinal degeneration.
The challenge of optimising topical ocular formulations
Authors: Clive Wilson Clive
Published: December 2019

In theory, introducing a drug directly into the eye should localise drug effects permitting efficient exchange of the drug between the vehicle and the cornea. Moreover since the blood supply to the eye represent such a small proportion of the output of the heart, the bystander effects should be greatly reduced by confining the dose, and other unwanted actions including metabolic clearance should be minimised. In practice, as appreciated by scientists and medical practitioners, topical ocular delivery is inefficient, the efficiency of dosing variable and compliance in the order patient questionable. The major factor contributing to pre‐corneal loss is the rapid drainage of the installed dose through the nasolacrimal duct to the sinuses and veins draining the face. The sensations and the immediate changes in visual acuity associated with ocular dosing, prompt blinking and in children rubbing of the eye. Many drugs such as cyclopentolate cause an uncomfortable stinging or after a period of use, a formulation may precipitate changes in tear structure associated with a measurable decrease in TBUT, conjunctival hyperaemia and reflex tearing. The development of better formulations which would be more acceptable to patients young and old, Is therefore of significance both in commercial and healthcare terms. The basic ingredients in a topical formulation designed for ocular use include a solution of the drug, buffering agents to optimise the pH permitting best absorption, tonicity adjusting agents (simple aqueous solutions with very low osmolality are uncomfortable as even slightly hypertonic formulations), wetting agents and preservatives. The formulation must be sterile on manufacture and remain with a low bioburden during use and where possible, packaging should assist maintenance of the medicine as designed. The drugs are Incorporated into the formulations are usually at a fairly low concentration and therefore there may be issues of stability or oxidation. The in life use is designed to be around one month although patients may hoard opened medicines for a much longer time. In my experience, this appears to particularly apply to ointments as patients assume that ointments do not contain water. This is not a safe assumption as although the water content may be very low in petrolatum‐based ointments, vegetable‐based ointments formulations usually contain more water. From these preliminary remarks, there are several elements to be considered in constructing a best‐in‐class formulation. There is no doubt that convenience and ease of use is an advantage in general medical device ergonomics. All elements of design need to be considered: bottle design, formulation, interval between dosing and preventing contamination whereas efficacy is not generally obvious to the patient except in treatment of acute conditions. The space for innovation is wide provided that the lowest cost option is not the only route available to the healthcare providers.
Fungal involvement (Pityrosporum) in ocular allergy
Authors: Chabane Habib
Published: December 2019

Allergic conjunctivitis to atmospheric molds is well documented, Alternaria being by far the most common. However, the role of microbiota fungi in conjunctivitis is less documented. Several old reports until the seventies have underlined the implication of allergy to Candida albicans in some chronic conjunctivitis. Pityrosporum orbiculare allergy has been well documented in head and neck atopic dermatitis in adults, but there is no report showing the involvement of this fungi in chronic conjunctivitis, even if some authors suspected his involvement in blepharitis. Here we describe some case‐reports of atopic keratoconjunctivitis associated with IgE sensitization to Pityrosporum in adults with seborrheic dermatitis or head and neck dermatitis. Patients was initially treated by ciclosporin since no sensitization to aeroallergens have been highlighted. After local and systemic anti‐fungal treatment, ciclosporin was stopped and sustained improvement was observed under discontinuous treatment. When no sensitization to aeroallergens has been highlighted in atopic keratoconjunctivitis, we suggest to seek for sensitization to microbiota fungi particularly Pityrosporum spp. and Candida a. in patients with head skin lesions.
Simulation centers accreditation guidelines and good practice
Authors: Sachdeva Ajit
Published: December 2019

In 2005, the American College of Surgeons (ACS) launched an innovative program to accredit simulation centers based on rigorous standards and criteria. These standards and criteria were developed through an intense two‐year process that involved internationally‐renowned experts in the field of surgical simulation and individuals who were leading technical skills training centers in the US and Canada. We pilot‐tested the accreditation model, as well as the standards and criteria to ensure that they were robust and reliable. A few years ago we revised the accreditation model to one of continuing certification with longer accreditation cycles and detailed annual reports and targeted reviews as necessary. The accredited simulation centers are called ACS‐accredited Education Institutes given their broad scope of activities focusing on skills training, verification, and validation. The accreditation model includes two levels – comprehensive and basic, and there are different standards and criteria for each level of accreditation. The program has grown significantly and now includes 92 ACS‐accredited Education Institutes of which 82 are in the US and 10 in other regions of the world, including Canada, UK, Europe, Middle East, and Latin America. The program continues to grow and there is an annual meeting in Spring each year called the ACS Surgical Simulation Summit that provides opportunities to present scientific work, best practices, and latest advances in surgical simulation. In addition to the representatives from the ACS‐accredited Education Institutes, several other experts participate as well. The program continues to support the needs of practicing surgeons, surgery residents, medical students, and members of surgical teams. The ACS Division of Education looks forward to increasing international participation in this unique and one‐of‐a‐kind network.