bluuebunny/crossref_metadata_2025 huggingface dataset:
Orbital solitary fibrous tumor – Case series and new perspectives
Authors: IRION L , BONSHEK R , KUMAR A , QURESHI F , COOK A , ATAULLAH S , BARBIER J , LEATHERBARROW B
Published: August 2014

Purpose To present a case series of orbital solitary fibrous tumour (OSFT) from a tertiary referral centre focussing on diagnostic features including assessment of STAT6, a recently described antibody for immunohistochemistry (IHC) in which positivity is said to indicate NAB2‐STAT6 gene fusion.

Methods This is a retrospective case series. Among all orbital tumours resected between 2001‐2014, 12 OSFT cases were identified. Data collected included patient demographics, clinical presentation, morphological and IHC features, management and clinical outcome. IHC for STAT6 was also performed in other soft tissue tumours to assess its specificity.

Results There were 3 males and 9 females. The average age was 46 years (18 – 81). The mean follow‐up was 39.3 months (3‐156 months). Presenting symptoms included proptosis(n=6), periocular mass(n=4), foreign body sensation(n=1), and epiphora(n=3). Cellularity, hyalinisation and myxoid areas were variable. Necrosis was seen in one recurrent case. Giant cells were present in 3 cases. <4/10HPF mitoses were seen in 6 cases. All cases showed diffuse strong nuclear positivity with STAT6. In contrast, STAT6 expression was not demonstrated in other pathologies (e.g. neurofibroma, schwannoma, haemangioma, nodular fasciitis). CD34, CD99 and BCL2 ware positive in most cases but with varied staining pattern. One case was CD31 positive and 2 cases expressed SMA focally. All cases underwent elective surgical resection or debulking with complete histopathological clearance in 6 cases.

Conclusion This case series confirms previously described variation in presentation and management challenges associated with OSFT. STAT6 antibody can be a helpful adjuvant in the diagnosis of OSFT.
The outcomes of Mycophenolate Mofetil therapy combined with systemic corticosteroids in acute uveitis associated with Vogt‐Koyanagi‐Harada Disease
Authors: ABU EL ASRAR A
Published: August 2014

To study the effectiveness of mycophenolate mofetil (MMF) combined with systemic corticosteroids in acute uveitis associated with Vogt‐Koyanagi‐Harada (VKH) disease. The outcomes in this group were compared with those of another group of patients with VKH disease who were treated with corticosteroid monotherapy. Nineteen patients (38 eyes) were studied prospectively. Mean follow‐up period was 27.011.1 months. Corticosteroid‐sparing effect was achieved in all patients. Mean interval between starting treatment and tapering prednisone to 10 mg or less daily was 5.11.2 months. Ten (53%) patients discontinued treatment without relapse of inflammation. Mean time observed off of treatment was 17.311.9 months. Visual acuity of 20/20 was achieved by 38% of the eyes in the corticosteroid group and by 74% in the corticosteroid + MMF group (p<0.001). Recurrent inflammation of 3 times was reduced significantly (p=0.0383) in the corticosteroid + MMF group (3%) as compared to corticosteroid group ( 18%). Development of all complications was significantly higher in the corticosteroid group (43%) compared to the corticosteroid + MMF group (8%) (p<0.001). None of the eyes in the corticosteroid + MMF group developed “sunset glow fundus”.
One year results of the follow‐up of patients with asymptomatic idiopathic epiretinal membrane
Authors: FERRERO A , BONNABEL A , GASCARD L , BRON AM , CREUZOT‐GARCHER C
Published: August 2014

Purpose To determine anatomical and functional retinal modifications in patients with idiopathic epiretinal membrane (ERM) without objective symptoms.

Methods This prospective monocentric study included 28 eyes of 28 patients with ERM having a best corrected visual acuity greater than 20/25. All patients underwent a complete ophthalmic examination, including the measurement of the visual acuity on the ETDRS scale, a macular SD‐OCT and a microperimetry at 0, 6 and 12 months. We assessed macular abnormalities on SD‐OCT namely: retinal folds, retrofoveolar deposits, cystoid cavities and external retinal layers alterations.

Results At baseline the mean visual acuity was 85±4 letters, the mean macular sensitivity was 14.3±1.3 decibels, the mean macular thickness was 357±32 micrometers and the score of the SD‐OCT retinal abnormalities per patient was 2.5±0.8. At one year, the score of the SD‐OCT retinal abnormalities per patient was significantly higher: 3.3±1.3 (p=0.007). At one year, the mean visual acuity, the mean macular sensitivity and the mean macular thickness were stable at 84±5 letters (p=0.8), 14.4±1.7 decibels (p=0.8) and 356±43 micrometers (p=0.3), respectively.

Conclusion This study showed an increased number of retinal lesions observed on SD‐OCT with a stable visual acuity and a stable retinal sensitivity measured with the microperimetry after one year of follow‐up.
Automatic identification of eyes at risk of developing idiopathic macular hole
Authors: SILVA AS C. , FIGUEIRA J , LOBO C , SIMÃO S , MEIRELES A , GOMES N , BERNARDES R
Published: August 2014

Purpose To automatically identify eyes with increased risk of developing idiopathic macular hole (IMH). This is proposed based on the fact that fellow eyes from patients with unilateral IMH have a risk increased by up to 29% of developing IMH. Our hypothesis is that there are changes in the topography of the macula that can allow the identification of these eyes prior to the development of IMH.

Methods High‐resolution OCT scans from eyes at risk and control patients are acquired using the Cirrus HD‐OCT (Carl Zeiss Meditec, Dubin, CA, USA), Topcon 3D OCT (Topcon Medical Systems, Inc., Oakland, NJ, USA), and Spectralis HRA+OCT (Heidelberg Engineering GmbH, Heidelberg, Germany). From the volumetric scans, topographic maps are built from the segmentation of the inner limiting membrane and the retinal pigment epithelium. Parameters are extracted by fitting the maps to a set of bidimensional functions and from radial profiles of the region of interest. These are used to train a support vector machine (SVM), an automatic classification system. Optimizations to the system are ran in order to achieve the highest accuracy possible.

Results Forty‐nine eyes with increased risk of IMH development (age: 67.4+‐5.5 yrs) and 44 control eyes (age: 58.5 +‐ 10.2) were imaged. The accuracy of the optimized SVM was 82.8%, sensitivity 85.7%, specificity 79.5%, assessed by 10‐fold cross‐validation.

Conclusion The achieved results support our working hypothesis ‐ that structural changes are present well before being visible at a regular consultation.
Predicting visual outcome after macular hole surgery using fundus ‐ controlled microperimetry
Authors: SURGUCH V , ASATRYAN S
Published: August 2014

Purpose to explore the value of fundus‐controlled (micro)perimetry in determining the functional state of macular retina in order to predict the functional results of vitrectomy surgery in patients with idiopathic macular hole (MH).

Methods Design: prospective study of 16 eyes with idiopathic MH (recruited regardless of the size of the holes and visual acuity). Pre‐ and postoperative examination additionally included microperimetry and fixation assessment performed with Maia microperimeter (CenterVue). Average retinal sensitivity was measured in the area of 1 (foveal) and 3 (parafoveal) degrees from the foveal center.

Results Before surgery foveal retinal sensitivity fluctuated overall on group from 7.6 to 26.76dB (average 19.04 dB), a parafoveal sensitivity – from 16.33 dB to 29.79dB (average 24.83dB). After surgery average foveal sensitivity imroved by 4dB (up to 23.09dB), while parafoveal remained nearly unchanged (average ‐ 25.43dB). Based on microperimetric results patients were divided into two groups: patient with rather high initial foveal sensitivity (more than 21dB, Group A ‐ 9 eyes) and patient with reduced sensitivity (up to 21dB, Group B ‐ 7 eyes). Although both groups were comparable by initial VA (0,18 and 0,11), BCVA in the group A improved after surgery in average up to 0.61 (0,4‐1,0), whereas in the group B improvement of BCVA was less significant ‐ in average up to 0.31 (0,2‐0,5). Preoperative fixation stability was significantly higher in the first group (78% compared to 55%, P<0,05). Baseline MH size was slightly larger in group B (min 416mu vs 342mu; max 984vu vs 650mu in Group A).

Conclusion Preoperative foveal sensitivity correlates with visual outcome in MH surgery and could be used as a predictive factor.
Incidences of visual disorders on academic difficulties
Authors: KOVARSKI C , PORTALIER S , FAUCHER C , CARLU C , MIOTTI H , ORSSAUD O
Published: August 2014

Purpose Many students underestimate their visual discomfort, although it may have an educational impact. We studied the prevalence of visual disorders among students and compared these results to their academic level.

Methods Between September 2012 and April 2013, four hundred students between fifteen and twenty two years of age responded to a questionnaire followed by a visual screening (refraction and binocular vision) in order to detect any visual anomalies they might be unaware of. Then academic performance from participants was appraised and subjects were reviewed to determine whether wearing appropriate optical correction or taking orthoptic care improved their grades.

Results Methods from multidimensional approaches (principal component analysis) and explanatory approaches (econometrics) were used for data analysis. Results indicate that the questionnaire score is very significant to predict probability of having academic difficulties (79%) or vision problems (89.42%). Refraction error (+16.78%) and accommodation anomalies (+16.21%) have effects on academic difficulties and binocular vision disorders are even more disadvantageous (+21.95%). Moreover, not spontaneously expressing visual discomfort doesn’t mean that there are no visual defects.

Conclusion Once controlled by variables known as impacting learning process, a significant proportion of participants academic difficulties are related to vision anomalies. Therefore, screening of vision anomalies among adolescents appears to be necessary, especially if there are academic difficulties. In addition, the questionnaire used in case history seems to be an effective tool in the detection of vision anomalies and should be validated on a larger sample.
Brain structural and functional reorganization due to long term retinal peripheral degeneration in retinitis pigmentosa
Authors: FERREIRA S , PEREIRA AC , QUENDERA B , MATEUS C , SILVA E , CASTELO‐BRANCO M
Published: August 2014

Purpose Retinitis Pigmentosa (RP) is a rare retinal disease with progressive degeneration of photoreceptors leading to early peripheral and later central visual loss. It provides a model to analyze visual cortex plasticity since onset age ranges from infancy to adulthood. Prior studies have mostly covered structural or functional alterations in the same cohort; hence we aimed to determine the impact of RP on brain function and structure using magnetic resonance imaging.

Methods Brain images of 5 RP subjects (age 37‐66 years, RP duration 6‐42 years) and 10 matched healthy controls were acquired. Retinotopy was used to delineate visual cortical areas. Participants also performed a 1‐back visual task.

Results Retinal thickness, visual field, and visual acuity were decreased in RP (p<0.01). Central visual cortex responses were shifted anteriorly into regions usually representing more peripheral locations (p<0.03). Also, V1 and V3 dorsal had higher activation during the task execution (p<0.02). Moreover, cortical thickness was increased in Brodmann areas 7 and 8, and decreased in pericalcarine (p<0.04). Surface area was enlarged in isthmus cingulated, pars orbitalis, and transverse temporal (p<0.02). Caudate volume was also augmented (p=0.01).

Conclusion Results suggest brain functional and structural reorganization in RP which is supported by the absence of a silent cortical visual zone, due to unmasking of peripheral responses to central stimuli. Data also suggest top down modulation of attentional higher level regions, and enhanced recruitment of visuospatial orientation mechanisms due to peripheral vision loss. Results are relevant to the development of rehabilitation methods for RP.
Microcystic macular edema in optic nerve atrophy: case series
Authors: VOIDE N , BORRUAT F
Published: August 2014

Purpose Microcystic macular edema (MME) is a new entity defined as lacunar areas of hyporeflectivity in the retinal inner nuclear layer after severe optic neuropathy (ON). Initially, MME was fortuitously discovered in optic neuritis.

Methods From July 2013, we imaged all patients with ON by SD OCT. Retinal nerve fiber layer thickness (RNFLT), macular cube thickness (MCT) and retinal ganglion cell layer thickness (RGCLT) were assessed. Studied parameters included also the delay between onset of ON and detection of MME and correlation of the visual field defect to the MME topography.

Results Sixteeen patients (19 eyes) exhibited MME. Etiologies of ON were compressive (7), degenerative (4), inflammatory (3), ischemic (1), and hereditary (1). There were 9 women and 7 men, mean age at diagnosis being 34.1 years. Visual acuity ranged from NLP to 12/10 (median 4/10). Mean RNFLT was 61.6µm [97+/‐10µm], mean MCT 271.37µm [261+/‐18µm] and mean RGCLT 57.22µm [82+/‐7µm]. The time from diagnosis until MME detection ranged from 4 months to 23 years. A good correlation was found between the zone of retinal atrophy on infrared photography and MME distribution. However, only 4/16 visual field defects correlated to the MME topography.

Conclusion MME can occur as early as 4 months after ON (ocular trauma in our series) and can persist as late as 23 years after the onset of ON. MME is not only related to inflammatory ON, as postulated initially, but is a nonspecific manifestation from ON of any etiology. The precise mechanism leading to MME is unknown but trans‐synaptic retrograde degeneration is likely. Why only 10% of patients with ON exhibit MME is unknown, but MME might be a transient phenomenon. Further clinical and experimental studies are needed to answer these questions.
Assessment of retinal blood oxygen saturation in patients with primary open angle glaucoma
Authors: SHAHIDI AM , HUDSON C , PATEL SR , TAYYARI F , FLANAGAN JG
Published: August 2014

Purpose: To investigate retinal SO2 in POAG using a retinal hyperspectral camera (HRC). Method: 9 controls and 15 POAG patients were imaged using a prototype HRC, at wavelengths between 500‐610nm. POAG was classified as mild (mean deviation [MD]<‐6) or moderate to severe (MD≥‐6). Arteriolar, venular and arterio‐venous (AV) SO2 difference values were compared between the groups and the correlation with MD was assessed. Result: Mean SO2 values were 93±1.55 and 55.37±2.57 for arterioles and venules respectively in controls and 94.74±2.75 and 58.10±8.85 in the POAG group. No significant differences were found between the two groups (p=0.13 arterioles, p=0.42 venules). AV difference was also not significantly different (p=0.78). In patients with MD≥‐6, significantly higher venular SO2 (p=0.005) and significantly lower AV differences (p=0.01) were found compared to MD<‐6 and controls. No differences were found for arteriolar SO2 (p=0.31). Significant correlations were found between venular SO2 and AV differences with MD (p=0.02 and p=0.03). Conclusion: Patients with moderate to severe POAG have higher venular SO2 and lower AV differences indicating a potential association with decreased oxygen extraction from the retinal capillaries.
Physiology of retinal oxygen extraction
Authors: SCHMIDL D
Published: August 2014

It has been hypothesized that several ocular diseases such as glaucoma or diabetic retinopathy are associated with impaired ocular blood flow and altered oxygen supply of the retinal tissue. The recent development of new and sophisticated instruments for the non‐invasive measurement of retinal oxygen saturation allow now for the investigation of retinal oxygenation in both healthy and disease. In addition, combination of these technologies with non‐invasive measurements of retinal blood flow can provide data on oxygen extraction, which in turn allows for the estimation of oxygen consumption of the tissue. This talk aims to summarize our current understanding of the physiological mechanisms regulating the oxygen supply of the ocular tissues. In addition, recently introduced methods for the estimation of oxygen extraction of the retinal tissue with be presented. Finally, the possible clinical applications for these emerging techniques will be discussed.
Retinal oximetry in glaucoma
Authors: MCNAUGHT A
Published: August 2014

Retinal oximetry is an emerging technology which holds promise across in range of eye disease. Intra‐vascular retinal oximetry measurements have been obtained using both dual wavelength, and hyper‐spectral techniques. Retinal oximetric abnormalities have been demonstrated in central retinal vein occlusion, branch retinal vein occlusion and diabetic retinopathy. Abnormalities have also been described in glaucoma patients: 1) Elevated retinal venous saturation, especially in eyes with reduced visual function, when compared to normal control eyes, possibly secondary to reduced inner retinal oxygen consumption. 2) Reduced arterial saturation at the optic nerve head (ONH) in animal models with acutely elevated intra‐ocular pressure, possibly related to reduced ONH perfusion. The elevated venous oxygen saturation found in retinal vessels in eyes with glaucoma damage may represent an objective measure of inner retinal function, and may hold promise as an index of ganglion cell health/remaining functional cell mass, and may therefore allow insights into the impact of therapeutic intervention eg IOP reduction, or neuro‐protective agents. The available evidence for a role for retinal oximetry in glaucoma will be presented.
Retinal oxgen metabolism under visual stimulation of neuronal activity in health and disease
Authors: HAMMER M , RAMM L , PETERS S , JENTSCH S , SAUER L , AUGSTEN R
Published: August 2014

Goal: To measure retinal vessel oxygen saturation in rest and under stimulation of neuronal activity by flicker light as well as vascular dilation upon flicker. Methods: 18 patients with non‐proliferative diabetic retinopathy (mean age: 62.2±8.3 years), 41 patients with primary open angle glaucoma (64.0+12.8 years) and 40 control subjects (63.6+14 years) were investigated. Vessel diameters (central retinal arterial and venous equivalents – CRAE and CRVE) and oxygen saturation (SO2, dual – wavelength optical oximetry) were determined before and during luminance flicker stimulation (12.5 Hz, modulation depth: 1:20) for 90 s. Results: Flicker light increased CRAE, CRVE, and venous SO2 by 1.42%±3.72%, 2.80%*±2.70%, and 2.03%*±2.43% in diabetic patients as well as 4.98%*±6.23%, 8.94%*±5.26%, and 4.20%*±3.71% in the controls (*: p<0.05). This increase was significantly higher in the controls vs. patients for all parameters (t‐test, p<0.05. In glaucoma, the increase of CRVE (3.7+3.3%, p=0.039) and venous SO2 (2.482+2.453%, p=0.029) was significantly lower than in controls. Conclusions: Combining SO2 and vessel diameter measurements with visual stimulation reveals pathologic alterations in retinal oxygen supply or consumption.

Commercial interest
Vitamins and glaucoma
Authors: CORDEIRO M
Published: August 2014

Oxidative stress is strongly implicated in glaucoma in different tissues including trabecular meshwork, human Tenon’s fibroblasts, and retinal ganglion cells and their axons. An established, naturally occurring anti‐oxidant is Vitamin E. Vitamin E is found in phospholipid cell membranes where it prevents lipid peroxidation and membrane damage by acting as a peroxyl radical scavenger. It is able to move through bilipid membranes and can help in enzyme activity modulation. Likewise, it is involved in vesicle transport and cellular trafficking. Alpha tocopherol is perhaps the best known form of Vitamin E, although d‐ tocopheryl polyethylene glycol 1000 succinate (TPGS), a water soluble form of vitamin E, is also well‐described being used as a drug delivery vehicle. Vitamin E has recently been shown to have other roles including regulating signal transduction, gene expression, and acting as redox sensor and is being investigated in neurodegeneration. This talk will discuss the various applications of Vitamin E in glaucoma.
Fatty acids and glaucoma
Authors: ACAR N , BRON AM , CREUZOT‐GARCHER C , BRETILLON L
Published: August 2014

Retinal cell membranes are known to be rich in ether‐linked phospholipids also termed as “plasmalogens”. Although their functions remain enigmatic, plasmalogens are considered as reservoirs of polyunsaturated fatty acids (PUFAs). These PUFAs were shown to be released from plasmalogens by specific enzymes under specific conditions in order to play several key functions within cells. Data from our laboratory suggest that the metabolism of plasmalogens and PUFAs may be implicated in the pathophysiology of glaucoma, the leading cause of blindness worldwide. Through several experiments on human patients and rodent models of ocular hypertony, we have shown that the metabolism of plasmalogens and PUFAs is affected in patients with primary open‐angle glaucoma (POAG) in a stage‐dependent manner, that the modifications in plasmalogen metabolism may start years prior the first clinical symptoms of POAG, and that several combinations of dietary PUFAs could be efficient in preventing retinal glaucomatous damage in rodents.
Possible pros‐ and cons‐ of the effects of visual light on the progression of glaucoma
Authors: OSBORNE NN
Published: August 2014

The visual spectrum of light reaching the retina ranges from 400‐800nm. Certain photosensitizers associated with photoreceptors and the retinal pigment epithelium are able to absorb short wave blue light (400‐450nm) to cause oxidative stress and irreversible damage. Photosensitizers of specific types also exist in mitochondria that are abundant in intraocular ganglion cell axons. Recent studies show that blue light is detrimental to mitochondria while long wave red light (700‐800nm) has positive effects. Moreover, in vitro studies show blue light to kill cells while red light has beneficial effects on cell survival. We therefore hypothesis that when ganglion cells are stressed, as in glaucoma subjects, then reducing the blue light (with filters) and enhancing the red light components impinging on ganglion cell axons will attenuate the rate of progression. Experimental studies on rats supporting such a notion will be reported.
Can we predict corneal graft rejection based on proangiogenic cytokines level at the time of transplantation?
Authors: DEKARIS I
Published: August 2014

PURPUSE: To evaluate the quantity of vascular endothelial growth factor (VEGF) and its receptors (VEGFR) in the recipient cornea at the time of penetrating keratoplasty (PK). METHODS: Study included 20 eyes scheduled for PK. Quantity of angiogenic growth factors and their receptors: VEGF, sVEGFR1 and sVEGFR3 were analysed using an enzyme‐linked immunosorbent assay. Postoperatively patients were followed‐up for 3 years. Frequency of corneal graft reaction and degree of corneal neovascularisation were recorded. Donor corneas obtained from cadaver eyes were controls (n=20). RESULTS: Overall quantity of VEGF‐A was 287.74 pg/ml (SD=129.181) in the inflammatory group, 115.37 pg/ml (SD=105.93) in non‐inflammatory group and 142.28 pg/ml (SD=93.081) in controls. sVEGFR1 and sVEGFR3 were significantly higher in non‐inflammatory as compared to inflammatory group. Eyes with graft reaction had significantly higher VEGF‐A (307.4 pg/ml, SD= 100.058) as compared to those without graft reaction (182.8 pg/ml, SD=124.987). Statistical analysis was done by t‐test. CONCLUSION: Graft reaction occurs more often in corneas with increased VEGF‐A. Elevated sVEGFR may act as a sink for VEGF and thus as suppressors of angiogenesis and graft reaction.
Surgical treatment of glaucoma following irradiation of uveal melanoma
Authors: SHARKAWI E
Published: August 2014

Uveal melanoma treated by proton beam radiotherapy (PBRT) is associated with uncontrolled glaucoma arising from different aetiological mechanisms and often leads to enucleation. This presentation will demonstrate novel surgical approaches aimed at increasing ocular and visual preservation. Glaucoma subtypes include neovascular glaucoma in addition to concurrent pigmentary and uveitic disease. The role of aqueous shunt insertion, glaucoma filtration surgery, anti‐VEGF and the limited role of cyclodestructive procedures are outlined. Prevention and treatment of surgical complications are discussed. Results from a large cohort of eyes with glaucoma and melanoma, from a tertiary referral center, are analyzed and the importance of a multi‐disciplinary approach is examined.
Gene therapy for RPE65‐related Leber congenital amaurosis
Authors: LEROY BP
Published: August 2014

Purpose The talk will focus on an overview of gene therapy trials for RPE65‐related Leber congenital amaurosis (LCA), which are currently ongoing or have been finalised. Methods Systematic review of trials. Results Currently there are 6 trials around the World focusing on gene therapy for RPE65‐related Leber congenital amaurosis, with good safety outcomes and considerable success in restoring some visual function. So far, no safety issues have been encountered in these trials, whereas some improvement and/or stabilization of retinal function is seen. However, progression of disease is not halted entirely. Conclusions Gene therapy trials for RPE65‐related Leber congenital amaurosis are safe and somewhat successful in restoring and/or stabilizing retinal function, despite early indications of further progression of disease.
Gene therapy for Stargardt disease
Authors: AUDO I , MOHAND‐SAID S , ZEITZ C , BARALE PO , J‐A SAHEL
Published: August 2014

Stargardt disease is the most common cause of macular degeneration and central visual loss in young people. Currently, there is no known effective treatment that can prevent or reverse the vision loss in this disease. The disease is caused by mutations in the photoreceptor‐specific ABCA4 gene cording for a protein involved in the active transport of retinoids from the photoreceptors to the underlying retinal pigment epithelium to initiate the visual cycle. Pre‐clinical studies on animal model of Stargardt disease have shown effects on subretinal administration of viral vectors containing the human ABCA4 gene upon liposfuscin accumulation, the hallmark of the disease, thus providing a proof‐of‐concept for gene therapy. Indeed, the first‐ever gene‐based therapy Phase I/II clinical trial for treatment of Stargardt disease, StarGen™, is currently underway (NCT01367444) at the Casey Eye Institute, Oregon Health & Science University, US and the Centre Hospitalier Nationale d'Ophthalmologie des Quinze‐Vingts, Paris, France. We will discuss the principle and issues raised by the current trial as well as potential alternative therapies.
Hermenegildo Arruga (1886‐1972): an example that the improvement in retinal surgery goes on
Authors: ASCASO FJ
Published: August 2014

Hermenegildo Arruga (1886‐1972) was a versatile Spanish ophthalmologist who specialized in retinal surgery. He designed numerous surgical instruments and introduced significant improvements in ophthalmic surgical techniques. Thus, he was among the first ophthalmologists to advocate the intracapsular cataract extraction. Furthermore, he refined several surgical procedures such as dacryocystorhinostomy, corneal transplantation, evisceroenucleation and pterygium excision. But, above all, Arruga was fascinated with the retinal detachment surgery. He perfected Gonin´s operation and contributed significantly for retinal detachment surgery to be put in place. Later, he adopted the injection of air at the end of retinal surgery. In the 1950s, Arruga simplified the technique of equatorial cerclage using a suture to encircle the equator of the eye. Even though ocular surgery has also developed significantly after Arruga’s time, his achievements played a significant role when they were presented and they formed a good foundation for subsequent developments.
Photocoagulation: early pioneers, pitfalls and progress
Authors: GRZYBOWSKI A
Published: August 2014

Laser photocoagulation is currently a crucial therapy for numerous retinal diseases. Although the effect of solar light on the retina has been known for centuries, the earliest thermal burns in the animals’ retinas by using a concave mirror and a convex lens to focus sunlight through dilated pupils of rabbits, were described by Czerny (1867) and Deutschmann (1882). The first experimental photocoagulation of the human retina was performed in 1927 by Maggiore. It has been nearly completely forgotten that in 1945, the Spanish ophthalmologist José Morón had the idea to close retinal tears using a light source through pupil to produce a retinal burn similar to that of diathermy. Finally, the German ophthalmologist Gerd Meyer‐Schwickerath conceived the idea of using photocoagulation to make burns in the retina to seal holes and prevent retinal detachment and developed in 1947 a sunlight photocoagulator, an instrument of mirrors and lenses that used sunlight.
Natural history and epidemiology of myopic macular disease
Authors: KOURENTIS CHR
Published: August 2014

Pathological myopia (PM) is characterized by a refractive error of ‐6 D and above and/or an axial length of 26.5 mm and above with concomitant degenerative changes in the posterior segment of the eye. The prevalence of PM differs between ethnicities. Myopic retinopathy includes a choroidal pallor pattern in the macular area, a posterior pole ectasia, lacquer cracks in Bruch’s membrane and posterior staphyloma, focal areas of chorioretinal thinning or atrophy and geographic areas of atrophy and choroidal neovascularisation (CNV). PM is the second commonest cause of choroidal neovascularization (CNV) after age related macular degeneration (AMD) and the most common cause of severe visual impairment in myopic patients younger than 50 years old. CNV occurs in 4% to 11% of patients with high myopia, and is the most common vision threatening complication of high myopia. The natural history of untreated myopic CNV is poor with a visual acuity of 20/200 or less. Apart from the macular degeneration there are other causes of visual dysfunction in PM, such as macular hole, retinal detachment associated with macular hole, posterior staphyloma and retinoschisis.
Diagnostic evaluation for myopic macular disease
Authors: KABANAROU S , XIROU T
Published: August 2014

Myopic macular disease (MMD) characterises a spectrum of structural changes of the macula such as epiretinal membranes, posterior tractional detachment, foveoschisis, macular holes, myopic choroidal neovascularisation (mCNV) and chorioretinal atrophy. Review of current literature regarding diagnosis of MMD and an appraisal of older (fluorescein angiographgy and indocyanine green angiography) and modern imaging tools (optical coherence tomography) are being presented. Fundus fluorescein angiography is the gold standard for diagnosis of patients with mCNV and remains an important imaging technique for their follow up. However in the era of spectral domain OCT macular pathology, such as epiretinal membranes, macular holes, foveoschisis, or pathology of the vitreoretinal interface, is better documented and evaluated. The additional use of enhanced depth imaging OCT (EDI‐OCT) and recently developed swept‐source OCT (SS‐OCT) are also employed to evaluate macular pathology further. The diagnostic evaluation of MMD has evolved as the diagnostic tools have become increasingly more sophisticated allowing better visualization and documentation of macular pathology and any alterations occurring after medical and surgical intervention.
Surgical management and treatment outcomes of myopic macular hole retinal detachment
Authors: ZAMBARAKJI H
Published: August 2014

Pathological myopia (PM) complicated by macular hole retinal detachment (MHRD) may lend itself to surgical correction, however severe axial elongation of the globe, the presence of a posterior staphyloma and atrophy of the RPE and choroid make these cases challenging. Whilst vitrectomy has been the mainstay of treatment, macular buckling (MB) was also developed in order to treat the posterior staphyloma. Macular hole closure rates using OCT monitoring have been reportedly low at 10‐72% and retinal reattachment rates have varied from 40‐93%. The reports of surgical outcomes of MB for MHRD are limited, but reported retinal reattachment rates are as high as 93% after primary surgery and 100% after secondary surgery. Surgical and visual outcomes appear better than those seen with PPV surgery but visual acuity improvements were modest in a long term series with a mean log MAR improvement of 1.80 to 1.00. We carried out a survey of the British and Eire Association of Vitreoretinal Surgeons (BEAVRS) to research the UK practice patterns for the management of MHRD secondary to PM. Anatomical and visual outcomes showed variable success rates. A review of the current literature and results of the BEAVRS will be presented.
What is good pressure control
Authors: STEVENS A
Published: August 2014

The diagnosis of glaucoma is based on morphological and functional parameters and not on IOP level, whereas treatment is centered on adequate IOP control. Good IOP control implies that IOP is brought down to values at which no further damage occurs or to values that slow the rate of progression in order to maintain acceptable visual function during the patient’s lifetime. Target pressure for an individual patients will depend on the age of onset of the disease, the amount of damage at diagnosis, the level of untreated IOP, and the rate of progression. The longer the life expectancy, the more severe the functional damage, the lower the untreated IOP and the faster the rate of progression, the lower the target pressure should be and vice versa. An additional number of systemic (blood pressure, family history) and ocular risk factors (disc hemorrhages, PEX, myopia, corneal thickness) should be taken into account. Further follow up will indicate whether the initially chosen target pressure needs adjustment. The determination of target pressure is a dynamic process and from the available evidence it seems that there is a wide gap between preferred practice patterns and real life.
IOP fluctuation and its measurements
Authors: POURJAVAN S
Published: August 2014

This SIS is focusing on the different factors which could cause progression of glaucoma despite correct/good IOP control. One of these factors could be the fluctuations in IOP and its measurements.The variations in IOP can be unpredictable and its behavior over the short and long term is still not fully known. These questions are still unanswered: How does IOP fluctuate over 24 hours? Does the fluctuation follow a repeating pattern? how can we assess this variability? And does the fluctuation affect the course of glaucoma progression? During this session we will discuss different theories and expert's opinions in light of our current understanding.
Femtosecond laser‐assisted anterior lamellar keratoplasty for keratoconus
Authors: PASHTAEV A , MALYUGIN B
Published: August 2014

We report the results of several femtosecond (Fs) laser‐assisted anterior lamellar keratoplasty modifications including Fs‐ALK (11 eyes) and Fs‐DALK (34 eyes). The control group consisted of the manual air‐viscobubble DALK (35 eyes). Optimal Fs‐laser parameters for corneas trephination and lamellar cuts were studied in the donor cadaver eyes. The quality of lamellar interface after laser dissection was assessed with atomic microscopy. Clinical data collected included the numbers of intra‐ and postop complications, VA with and without correction, postop astigmatism, corneal hysteresis and corneal resistance factors (ORA), EC loss and graft long‐tern survival rates. Mean follow‐up was 18.6±5.1 months. Fs‐DALK with optimized cutting algorithm resulted in fastest visual recovery, lesser postop astigmatism and better BCVA. The outcome difference in between the Fs‐DALK and manual DALK was borderline. Fs‐ALK provided the lowest visual outcomes (BCVA was 0.2±0.07 @12 months) due to irregularities and light scattering at the donor‐recipient interface.
Multiple malignancies in uveal melanoma patients ‐ the LOOC experience
Authors: HEUSSEN FM , DAMATO B , KALIRAI H , COUPLAND SE , HEIMANN H
Published: August 2014

Purpose To identify the prevalence of multiple primary tumors in a patient cohort with uveal melanoma and describe the cohort's characteristics.

Methods A data query for all cases of uveal melanoma seen at the Liverpool Ocular Oncology Center (LOOC) since 1993 was performed. Based on systemic information only cases with multiple primary tumors were included. Demographic and clinical information data were analyzed.

Results A total of 5140 (2615 males, 50.9%) patients with uveal melanoma were found, of which 228 (4.4%) were noted to have at least one other primary malignancy. 15 cases (0.6%) had at least 3 primary tumors recorded. The gender breakdown is: 125 males (54.8%) and 103 females. Of 125 men, 45 (36%) had been diagnosed with prostate cancer; 30 with unspecified skin tumors; 8 with systemic lymphoma; 7 with bladder carcinoma; 6 with colon carcinoma; and the remaining patients with less common tumors. Of 103 females, 45 (44%) had suffered breast carcinoma; 19 had unspecified skin tumours; 7 renal cell carcinoma; 5 lung carcinoma; and the remaining patients, other less common tumor types. 43 of the 125 (34.4%) males and 39 of the 103 females (37.9%) were deceased by time of data analysis. The incidence of the commonest tumors in males (e.g. prostate cancer: 45/2615, 1.7%) and females (e.g. breast cancer: 45/2525, 1.8%) in this cohort of patients with uveal melanoma did not differ from the incidence of these tumors in the general UK population.

Conclusion Although rare, additional malignancies can occur in association with uveal melanoma; therefore, the patient history taking should include this aspect. Aside from demographic and clinical data, genetic testing in these cases with multiple malignancies may yet reveal unique common patterns.
Can we trust the biopsy for prognostication in patients with choroidal malignant melanomas?
Authors: KIILGAARD J , BAGGER M , TOLSTRUP ANDERSEN M , HEEGAARD S , KLARSKOV ANDERSEN M
Published: August 2014

Purpose The purpose was to validate the minimal invasive TransVitreal‐RetinoChoridal (TVRC) biopsy as prognostic tool for uveal melanoma.

Methods Thirty‐six patients treated for choroidal melanoma at Rigshospitalet, Copenhagen from 1st January 2009 to 31st December 2011 were included. All patients had a minimal invasive TVRC biopsy performed to confirm the diagnosis before the eye was enucleated. Fluorescence in situ hybridization (FISH) for chromosome 1, 3, 6 and 8 as well as multiplex ligation‐dependent probe amplification (MLPA) were performed on all biopsy samples. Paraffin embedded sections of the enucleated eye were then divided into 3 mm hexagons. Each hexagon were then individually analyzed with MLPA in order to elucidate eventual heterogeneity of chromosomal status of the tumor. The MLPA results from the tumor were then compared to the results from the biopsy.

Results This is an ongoing study and so far results from 6 eyes have been obtained. All tumors showed heterogeneity of their chromosomal status. In 5 of 6 tumors more chromosomal abnormalities were found in the vicinity of the optic nerve compared to the periphery. In 4 of 6 tumors there was a complete correspondence between biopsy result and worst chromosomal status of the tumor. The remaining 2 biopsies underestimated the chromosomal changes, but it did not affect the prognostic value.

Conclusion Minimal invasive TVRC biopsy technique for choroidal melanoma seems to be useful for prognostic purposes.
SF3B1 and EIF1AX mutations in uveal melanoma: a protective factor, or not?
Authors: KILIC E , KOOPMANS AE , YAVUZYIGITOGLU S , VAARWATER J , VAN IJCKEN WFJ , PARIDAENS D , DE KLEIN JEMM
Published: August 2014

Purpose The recent identification of mutations in the splicing factor SF3B1 and translation initiation factor EIF1AX prompted us to investigate the occurrence of these mutations in our uveal melanoma (UM) cohort.

Methods Nineteen tumours were subjected to whole exome sequencing. In addition, the SF3B1 (exon 14) and EIF1AX (exon 1 and 2) mutation status was determined in 95 UM by Sanger sequencing.

Results Mutations in SF3B1 were identified in 26% of UM and 19% harboured a mutation in either exon 1 or 2 of the EIF1AX gene. SF3B1 and EIF1AX mutations correlated significantly with good prognostic features such as spindle cell type, absence of closed vascular loops, positive BAP1 immunohistochemistry staining and disomy 3. Univariate analyses of EIF1AX mutated cases compared to those without EIF1AX mutations showed a significantly increase in disease‐free survival (DFS). Overall, the SF3B1 mutated cases did not show a significant difference in DFS compared to SF3B1 wild types. After stratifying for chromosome 3 status, patients with a disomy 3 UM and a SF3B1 mutation had a worse DFS compared to those with a disomy 3 UM and a wild type SF3B1 (P < 0.01).

Conclusion SF3B1 and EIF1AX mutations occur in approximately a quarter of UM. Mutations in these genes associate with favourable prognostic features. In our study, we also reveal that patients with a normal chromosome 3 UM and a SF3B1 mutation have a higher risk of developing late metastasis.
Identification and characterization of melanin in choroidal melanoma by electron paramagnetic resonance spectroscopy (EPR)
Authors: ROMANOWSKA DIXON B , KLONOWSKA A , PLONKA P , SARNA T
Published: August 2014

Purpose The purpose of this study was to determine the quantity and type of melanin in choroidal melanomas in correlation with patient’s clinical characteristics.

Methods Melanoma‐containing samples were obtained after enucleation surgery, performed because advanced choroidal melanoma was diagnosed, not qualified to preserving eye therapy. Frozen samples were examined at liquid nitrogen temperature by EPR spectroscopy.

Results Examination showed that choroidal melanoma cells had a low eumelanin to pheomelanin index. In most of investigated melanoma‐containing samples the presence of pheomelanin was determined. Also strict correlation between patient’s clinical characteristics such as skin phototype, iris and hair color and melanin type in tumor were observed. No correlation however were found between histopathological type and quality and quantity of melanin in choroidal melanoma. Macroscopic analysing cases of choroidal melanoma were characterized by wide pigment variations. The presence of tide correlation between tumor color and type of melanin was observed.

Conclusion Pheomelanin fenotype occurred in tumors with low content of pigment. Tumors intensively pigmented (black, dark brown) belong to eumelanin tumors.
Optico‐reconstructive surgery after blockexcision of iridociliar tumors
Authors: SAAKYAN S , ANDREEVA T , CHENTSOVA E
Published: August 2014

Purpose To estimate the possibilities and indication for optico‐reconstructive surgery after blockexcision of iridociliar tumors.

Methods 68 patients with iridociliary tumors and complicated cataract were treated. 41 patients underwent combined surgery – block excision with cataract extraction (IOL implantation performed in 37 cases). In 14 of these patients iridectomy was performed using a tunnel corneal incision (in cases of small tumors of iris pupillary margin) followed by simultaneous phacoemulsification+IOL. The other patients underwent cataract extracapsular extraction. Simultaneous operations were carried out only in benign tumors. 27 patients underwent delayed cataract extraction after blockexcision (9 patients with malignant tumors, 18 patients ‐ benign). In 5 cases surgery were performed with implantation of artificial iris, in 17 cases ‐ with IOL implantation.

Results In all cases we detected increase the visual acuity, depending on the type of surgery and the tumor’s sizes.

Conclusion Indications for simultaneous optico‐reconstructive surgery are benign tumors, for delayed – even malignant ones. In cases of small benign tumors of iris papillary margin simultaneous surgery could be done using FEC + IOL, for large benign tumors (no more than 1/3 of iris) – with simultaneous cataract extracapsular extraction, if more than 1/3 of iris – delayed surgery with implantation of artificial iris.
Intravitreal aflibercept for macular oedema due to branch retinal vein occlusion
Authors: CLARK WL , BROWN D , STEMPER B
Published: August 2014

Purpose To evaluate the efficacy and safety of intravitreal aflibercept (IVT‐AFL) injection compared with macular grid laser photocoagulation for the treatment of macular oedema secondary to Branch Retinal Vein Occlusion (BRVO).

Methods VIBRANT was a double‐masked, Phase 3 trial with a duration of 52 weeks in which patients with macular oedema secondary to BRVO were randomised 1:1 to receive IVT‐AFL 2 mg every 4 weeks or grid laser from baseline to Week 20. The primary efficacy endpoint was the proportion of eyes that gained ≥15 letters in best‐corrected visual acuity (BCVA) from baseline at Week 24.

Results The proportion of eyes that gained ≥15 letters from baseline to Week 24 was 52.7% and 26.7% (P<0.001) in the IVT‐AFL and laser groups, respectively. The mean improvement in BCVA from baseline to Week 24 was 17.0 and 6.9 letters (P<0.0001), respectively. The most common ocular adverse events (AEs) in the IVT‐AFL and laser group were subconjunctival haemorrhage (19.8%) and eye pain (5.4%), respectively. There were no cases of intraocular inflammation in either treatment group. One death due to pneumonia and one Anti‐Platelet Trialists' Collaboration (APTC)‐defined event of nonfatal stroke occurred during the first 24 weeks of study, both in the laser group. Week 52 data will be presented.

Conclusion In this study, monthly IVT‐AFL provided statistically significant and clinically meaningful visual benefits which were superior to macular grid laser photocoagulation in eyes with macular oedema due to BRVO over 24 weeks. Compared to IVT‐AFL’s known profile no new safety signals were observed.

Commercial interest
Pathophysiology of vitreoretinal interface disorders
Authors: POURNARAS C
Published: August 2014

Pathologic changes at the vitreoretinal interface and vitreomacular tractions lead to phenotypic lesions such as epiretinal membranes (ERMs), idiopathic macular holes, vitreomacular traction syndrome (VMTS) and myopic foveoschisis. In the presence of clinically evident posterior vitreous (PVD), remnants of vitreous collagen fibers and/or cellular proliferations of fibrous astrocytes or glial cells, migrate outward from the retina. Migration occuring on the inner vitreo‐retinal interface through the internal limiting membrane(ILM), in the presence of growth factors such as laminin or fibronectin, may contribute to the fibrocellular proliferation at the retinal surface. Most studies regarding idiopathic or diabetic epiretinal membranes or late stages of macular holes, described the presence of fibrocytes or myofibroblasts. More recent studies confirmed those observations by using antibodies against alpha smooth muscle actine (a‐SMA). Based on the mechanistic association between a‐SMA expression and a tractional force generation, there is little doubt that these cells represented the source of traction during the evolution of those pathologies.