bluuebunny/crossref_metadata_2025 huggingface dataset:
Melanopsin retinal ganglion cells and circadian dysfunction in Alzheimer´s disease
Authors: LA MORGIA C , GALLASSI R , SAMBATI L , PROVINI F , ROSS‐CISNEROS FN , PAN B , BARBONI P , AVANZINI P , CANTALUPO G , HANNIBAL J , SADUN A , CARELLI V
Published: November 2013

Purpose To evaluate optic nerve and in particular melanopsin retinal ganglion cells (mRGCs) in relation to rest‐activity rhythm in Alzheimer disease (AD).

Methods Retinal nerve fiber layer (RNFL) thickness measurements by optical coherence tomography were performed in 21 AD and 74 age‐matched controls. Actigraphic monitoring was performed in 16 AD patients and 10 age‐matched controls. Non‐parametric methods were applied to assess interdaily stability (IS), intradaily variability (IV) and relative amplitude (RA) of rest‐activity rhythm. We also performed immunohistochemical analysis of mRGCs and axonal count on optic nerve cross‐sections in 14 neuropathologically confirmed AD and 13 control post‐mortem retinas.

Results OCT evaluation showed reduced average (p=0.03) and superior (p=0.005) RNFL thickness in AD patients. Actigraphic monitoring demonstrated an increased IV (p=0.04) and reduced RA (p=0.04) in AD. Furthermore, AD patients were significantly less active during the day (p=0.03). Considering the patients with at least one circadian parameter outside the 2SD from the mean of controls, we found a significant correlation between IV, average (p=0.035), superior (p=0.045) and inferior (p=0.017) RNFL thickness. Melanopsin RGCs density was significantly reduced, independently from age, in AD retinas (p=0.003) and AD optic nerves showed variable degree of age‐related axonal loss.

Conclusion We demonstrated a subclinical optic nerve involvement in AD patients, both by OCT and histopathology. We also documented rest‐activity circadian dysfunction in AD patients. Post‐mortem investigation revealed loss of mRGCs and RGCs with a different pattern in AD. The reduction of mRGCs may contribute to circadian rhythm dysfunction in AD.
Vitrectomy for R.D. in eyes with different/unusual IOLs
Authors: GEORGALAS I
Published: November 2013

Retinal detachment is one of the most serious complications of cataract surgery. Vitreous changes such as ‘anterior movement’ or ‘protuberance of the posterior surface of the vitreous’ have been postulated to occur, and cause posterior vitreous detachment which subsequently may lead to an increased incidence of retinal detachment in pseudophakic eyes. Additionally , several intraocular lenses(IOLs) such as multifocal, iris fixated or scleral fixated IOLs are more and more used by cataract surgeons. Retinal detachment in these eyes pose a new therapeutic challenge to vitreoretinal surgeons.
Problems in vitrectomy and gas for the treatment of Ps RDs
Authors: THEOCHARIS IP
Published: November 2013

The use of gas as a tamponade in vitreoretinal surgery is a major tool in the treatment of rhegmatogenous retina detachment (RRD),but it does not lack problems intraoperatively and postoperatively.The intraoperative problems include the risk of hypotony, poor visualization, dislocation of IOLs, rupture of zonules, the risk of compromising the choroidal and retinal circulation, the presence of a gas bubble in the anterior chamber.Postoperative problems are the lack of clear vision due to the gas bubbles'light reflections, the necessity of avoiding high amplitudes (ie flights),and may include high intraocular pressure, hypotony, inadequate filling of the vitreous cavity, dislocation of IOL, iris capture, contact of the gas with the cornea endothelium, dehydration of the retina, toxicity.Now adays our experience in treating RRDs with gas, make the problems arising from its use rare and reversible and its use the most popular among the vitreoretinal surgeons and patients.
Scleral buckle vs primary vitrectomy in PRDs
Authors: PARIKAKIS EA
Published: November 2013

Pseudophakic retinal detachments seem to have a lower rate of surgical repair due to missed retinal breaks and increased risk of proliferative vitreoretinopathy. Scleral buckling is a practically unchanged low‐budget procedure and was the gold standard in the past, but it involves ocular motility disturbances and refractive changes and needs certain surgical skills and experience. Primary small gauge vitrectomy in pseudophakia rapidly gains ground, as it is an easy, controlled surgical technique with less pain and the surgeon feels confident to have a complete intraoperative retinal attachment. In order to find the current role of conventional surgery in pseudophakic retinal detachments, scleral buckling has to be compared with vitrectomy alone as well as the combined procedure of vitrectomy plus encircling band, in terms of reattachment rate, functional outcome, reoperations and proliferative vitreoretinopathy incidence. Young patients, having clear lens extraction for myopia correction and post ‐traumatic cases with ora dialysis seem to be a reasonable group for conventional management.
360 degrees prophylactic laser retinopexy during the surgery for the treatment of pseudophakic retinal detachment
Authors: KOURENTIS C , XIROU T
Published: November 2013

This is to identify whether 360 degrees prophylactic laser retinopexy during the surgery for the treatment of pseudophakic retinal detachment is predictive for the anatomical and functional outcome. May prophylactic laser treatment be protective for the occurrence of a retinal redetachment?
Does generic latanorpost measure up to the branded, well‐known Xalatan?
Authors: MARINESCU C , POURJAVAN S
Published: November 2013

Purpose To compare the therapeutic efficacy of 0,005% Latanoprost versus Xalatan in the treatment of patients with OHT,POAG or secondary open‐angle glaucoma.

Methods A prospective, single‐center, crossover, two period comparative study including 21 eyes of 13 patients. The patients from our glaucoma outpatient clinic, treated with Xalatan monotherapy were proposed to switch their treatment to 0,005% Latanoprost for 6 weeks. After 6 weeks, they were treated again in monotherapy with Xalatan. The IOP was measured during baseline (Xalatan1), after 6 weeks with the generic (Lat), and again after reintroducing the original medication, Xalatan for 6 weeks, (Xalatan 2). Two consecutive intraocular pressure (IOP) measures were taken during each control at 8 and 10 o’clock am. The primary end‐point was the IOP variations between the brand name and the generic after the 12w. The Anova test was used to assess the difference

Results The mean age was of 67±13 years. 7 men and 6 women were included in this study. The mean IOP at baseline was 15,2± 2.7 mmHg with Xalatan. The mean IOP measurements after switching to Latanoprost and crossover to Xalatan were respectively 17.6 ± 3.5 mmHg and 15.3 ± 2.6 mmHg. There was, on average, an increase of IOP of 2.89 ± 1.2 mmHg with Latanoprost. This difference was statistically significant (p<0.05).

Conclusion Our first results showed an increased of IOP in patients switching from Xalatan to Latanoprost. This is of major importance in treatment of the patients with glaucoma. The patients who are not accurately treated with one drop tend to have multiple drops which affects negatively the quality of life of the patient, the compliance, the persistence and causes neg
24h IOP control by subchronic AMA0076 administration in Dutch Belted rabbits
Authors: VAN DE VELDE S , VAN BERGEN T , HOLLANDERS K , SIJNAVE D , VANDEWALLE E , MOONS L , STALMANS I
Published: November 2013

Purpose To investigate IOP lowering efficacy of rho kinase (ROCK) inhibitors, AMA0076 and Y‐39983, after subchronic treatment.

Methods Dutch Belted rabbits (5 rabbits/concentration) were treated daily with a single topical dose of AMA0076 (0.05, 0.1 and 0.4%) or Y‐39983 (0.025, 0.05 and 0.1%) in a masked fashion for 14 days. Saline was used as control in the contralateral eye. IOP was measured before, 3 and 7 hours after administration of the treatment. AMA0076 is a locally acting ROCK inhibitor, to reduce side effects such as hyperemia otherwise seen after administration of a ROCK inhibitor.

Results Mean baseline IOP before the start of the experiment was 21.02 ± 0.42 and 20.69 ± 0.39 mmHg for AMA0076 and Y‐39983, respectively. Significant IOP reduction was observed in all AMA0076 and Y‐39983 treatment groups. A maximal IOP reduction of 39 and 35% was reached with AMA0076 0.1% and Y‐39983 0.05%, respectively. Initially, IOP returned to baseline values 24h after administration of AMA0076. After 3 days of treatment with AMA0076 a sustained IOP lowering effect was present, IOP did not return to baseline values, but remained significantly lower for all concentrations of AMA0076 (p<0.05). Treatment with Y‐39983 did not show this sustained IOP decrease. As a result of this sustained IOP lowering effect smaller IOP fluctuations were observed in animals treated with AMA0076 compared to Y‐39983. Hyperemia was observed with all concentrations of Y‐39983 whereas only mild hyperemia was induced after administration of AMA0076 0.4%.

Conclusion Once daily treatment of rabbits with ROCK inhibitor AMA0076 resulted in IOP reduction that was more sustained and associated with smaller peak‐through fluctuations than Y‐39983.
SYL040012, a siRNA for the treatment of glaucoma
Authors: PAñEDA C
Published: November 2013

Purpose SYL040012 is a siRNA under developed for the treatment of glaucoma and increased intraocular pressure (IOP). siRNAs are small double stranded RNAs that regulate protein expression at transcription level using the endogenous RNA interference machinery. Therapeutically siRNAs are attractive due to their specificity, potency and ability to silence targets that are not addressable by small molecules. SYL040012 targets ADRB2, a well‐known target for glaucoma.

Methods Silencing activity of SYL040012 was validated in cell lines and IOP lowering efficacy was studied in rabbit. Silencing activity was assessed by extracting total RNA from cells or animal tissues and analyzed by real time‐PCR. IOP was measured using applanation tonometry. Tissue and plasma exposure was evaluated following a single instillation to rabbits using a non‐denaturing Anion Exchange HPLC combined with fluorescence detection. 28‐day regulatory toxicology studies were performed in cynomolgus monkeys following a daily ocular instillation of one of three doses of SYL040012 or vehicle. Phase I clinical trials were performed in healthy volunteers or individuals with increased IOP that received either a single dose or seven repeated administrations of SYL040012.

Results SYL040012 reaches structures of the eye relevant to the treatment of glaucoma when administered in eye drops; but is only detected in systemic circulation and non‐ocular tissues at trace levels. Presence of this compound in the ciliary body it results in specific down‐regulation of the target gene and reduction in IOP in animal models. Preclinical and clinical studies show that SYL040012 is well tolerated both systemically and locally.

Conclusion In summary, SYL040012 is a promising candidate for the treatment of increased intraocular pressure associated to glaucoma.

Commercial interest
Validation of Testvision, an internet‐based test for the detection of visual field loss
Authors: OLSEN AS , LA COUR M , SERUP L , ALBERTI M , DAMATO B , KOLKO M
Published: November 2013

Purpose The aim of the present study was to determine if the program Damato Testvision (DT), www.testvision.org, adequately detects visual field loss from glaucoma.

Methods DT is available in three versions and was tested on 97 patients (188 eyes). The procedure was performed with a laptop connected to a computer monitor and a mouse placed on a height adjustable table. To determine sensitivity and specificity DT was compared to two gold standards: 1; Hodapp, Parrish and Anderson classification (Hodapp) of Humphrey 30:2 and 2; doctors' diagnoses.

Results A total of 361 DT Standard tests were performed on 115 eyes. DT comparisons with Hodapp achieved sensitivity and specificity of 55% and 93% respectively when comparing no disease to early glaucomatous loss (AUC; 0,871). If early loss was merged with the no disease group, the sensitivity and specificity were 78% and 90% respectively (AUC; 0.931) Compared to the doctors' diagnosis DT achieved sensitivity and specificity of 52%; 96% respectively when borderline patients were classified in the glaucoma group (AUC; 0,867). If borderline patients were classified as controls: DT achieved sensitivity and specificity of 63%; 92% (AUC; 0,897).

Conclusion Our study indicates that DT may be a promising tool to detect visual field defects in a pre‐selected population. The test is successful without prior training of the test person but minimal computer knowledge is advisable. The authors believe that internet based visual field examination may play a role as an easy accessible and affordable test. With further development, DT could be a tool for glaucoma screening in the home setting. Future studies need to evaluate DTs performance in the general population without prior selection.
The treatment of retinoblastoma with intravenous chemotherapy + local treatment
Authors: DESJARDINS L , LUMBROSOLEROUIC L , LEVY C , CASSOUX N , AERTS I , SAVIGNONI A , DENDALE R , SASTRE X
Published: November 2013

Patients and method: Treatments protocols applied since 1995 included intraveinous chemotherapy at various dosages with local ophthalmological treatment by transpupillary thermotherapy, cryotherapy and iodine 125 plaque brachytherapy. The data concerning initial findings, treatments used, and results are registered in our database in a prospective way. We performed a retrospective study of children treated between January 1995 and December 2009. Results: There were 317 patients with bilateral retinoblastoma and 411 patients with unilateral retinoblastoma. The median follow up is 72 months. Median age at diagnosis was 7 month for bilateral and 20 months for unilateral. In bilateral patients, 104 had conservative management of both eyes, 204 had a conservative management of one eye and enucleation of the fellow eye and 9 had bilateral enucleation. Among the 312 eyes treated conservatively, 83 eyes were irradiated and 13 had secondary enucleation. (Success rate 70%) Among 411 unilateral retinoblastoma, 87(21%) were treated conservatively. 71 eyes were preserved (67 without external beam and 4 with external beam) (success rate 77%) Conclusion: Chemotherapy associated to local ophthalmological treatments is efficient in the
Pentacam measurements and IOL scattering
Authors: BAUMEISTER M
Published: November 2013

Rigid and foldable intraocular lenses of various materials have shown light scattering phenomena such as surface light scattering and glistenings. The impact of these phenomena on visual function is under controversial discussion. The scattering of light in an IOL can be measured in various ways. In many studies, subjective grading at the slit‐lamp has been used to quantify the intensity of scattering. More recently, evaluation of high‐resolution digital Scheimpflug images has been able to provide an objective assessment of scatter and material inhomogeneities. Better quantification of these phenomena may achieve more meaningful correlations to results of functional measurements.
Who really introduced pneumatic retinopexy for retinal detachment outpatient management?
Authors: ASCASO F
Published: November 2013

The history of Ophthalmology recognizes Dr. George F. Hilton as the first author to report a series of retinal detachments treated by pneumatic retinopexy (Ophthalmology 1986 May;93(5):626‐41). Nevetheless, one and a half years before, Dr. Alfredo Domínguez published in Spanish two papers about gas surgery used in the office to treat "conventional" cases of retinal detachment (Arch Soc Esp Oftalmol 1985;48:47‐54 and Studium Ophthalmologicum 1985, 2ºépoca;IV:11‐18). Our purpose is to give him his due and return his scientific priority.
What's new in atopic keratoconjunctivitis
Authors: BREMOND‐GIGNAC D
Published: November 2013

Specific clinical features of atopic keratoconjunctivitis are well known in adults and lead to a severe ocular surface impairment. However in children’s keratoconjunctivitis, even if common vernal keratoconjunctivitis form predominates, some pediatric presentation differs and must be individualised. A complete clinical evaluation has to be precised for a better knowledge of the prognosis of the disease. Different new explorations physiopathological mechanisms are detailed in the pathology. This evaluation allows a better adjustment of the treatment.
Molecular sensors for the decoding of homeostasis disruptions in the retinal pigment epithelium: towards the understanding of retinal degenerative diseases
Authors: BAZAN N
Published: November 2013

The significance of the selective enrichment in omega‐3 essential fatty acids DHA, docosahexaenoic acid) in photoreceptor cells has remained, until recently, incompletely understood. We contributed to the discovery of a docosanoid synthesized from DHA by 15‐lipoxygenase‐1, which we dubbed neuroprotectin D1 (NPD1: 10R,17S‐dihydroxy‐docosa‐4Z,7Z,11E,13E,15E,19Z hexaenoic acid). NPD1 is promptly made on demand when homeostasis is at stake, as in oxidative stress ,proteostasis dysfunctions and in early stages of neural injury, ischemia‐reperfusion or neurodegenerations. Thus NPD1 is a protective sentinel, one of the very first defenses activated when cell homeostasis is threatened . The availability of anti‐apoptotic BCL‐2 proteins is positively modulated by NPD1, whereas pro‐apoptotic BCL‐2 proteins are negatively regulated, as is activated microglia. Neurodegenerative diseases, in addition to enhancing oxidative stress, disrupt the proteostasis network and leads to a cellular inability to scavenge structurally damaged abnormal proteins. The RPE cell response cascade potentiates disruptors of homeostasis through multiple checkpoints and signaling networks. NPD1 , a key component of this response and of the lipidomic signature, targets neuroinflammatory signaling and proteostasis and in turn promotes homeostatic regulation of the transcription of key genes that in turn act as molecular decoders of input, and thus results in cell survival. (Supported by NIH: NINDS R01 NS046741, NEI R01 EY005121)
Designing clinical trials ‐ How best to optimize ideas, resources and patients
Authors: LEHMACHER W
Published: November 2013

Abstract not provided
Running clinical trials ‐ The challenges of international research
Authors: ANGLADE E
Published: November 2013

Abstract not provided
Bevacizumab together with MMC may have complementary effects in the improvement of surgical outcome after glaucoma filtration surgery
Authors: VAN BERGEN T , HOLLANDERS K , SIJNAVE D , VAN DE VELDE S , VANDEWALLE E , MOONS L , STALMANS I
Published: November 2013

Purpose We first compared the effect of mitomycin‐C (MMC) versus bevacizumab on the surgical outcome of glaucoma filtration surgery (GFS). Secondly, the complementary effects of MMC and anti‐VEGF therapy were investigated.

Methods The effect of bevacizumab and MMC on surgical outcome was investigated in a mouse model of GFS. The 1st group received a subconjunctival (SC) injection of bevacizumab (1 µl; 25 µg); the 2nd group was treated during surgery with MMC (sponge soaked with MMC 0.02% for 2 minutes). Group 3 received a combination of MMC and a SC bevacizumab injection. Treatment outcome was studied by clinical investigation of bleb area and survival every other day. (Immuno)stainings were performed to study angiogenesis (CD31) and fibrosis (Sirius Red) on postoperative day 14 and 30. VEGF‐levels after MMC treatment were measured in rabbit aqueous humor (AH) samples by ELISA.

Results Bevacizumab and MMC were equally effective in improving surgical outcome. In both groups, bleb area was significantly improved with 53%, compared to control (NaCl). Blood vessel density and fibrosis were equally reduced, with 37% and 22%, respectively. Remarkably, one day after surgery, VEGF levels were significantly increased with 90% in the AH of MMC‐treated eyes compared to control treated eyes. As compared to MMC monotherapy, combination of MMC and bevacizumab was able to increase bleb area with 18% by an additional reduction of angiogenesis and fibrosis, with 17% and 10%, respectively.

Conclusion Our data suggest that bevacizumab together with MMC may have complementary effects, due to upregulation of VEGF after MMC treatment.
Risk factors for the development of glaucoma after vitreoretinal surgery
Authors: DE VRIES MM , MüSKENS RPHM , RENARDEL DE LAVALETTE VW , HOOYMANS JMM , JANSONIUS NM
Published: November 2013

Purpose To determine risk factors for the development of glaucoma after vitreoretinal surgery.

Methods Case‐control study. Cases (n=96) were all patients who received a Baerveldt glaucoma implant after vitreoretinal surgery performed between 1991‐2011. Controls (n=288) were a random subset of patients who underwent vitreoretinal surgery without subsequent glaucoma surgery. Cases and controls were matched with regard to the year in which the first vitreoretinal intervention was performed. The role of age, sex, number of interventions, type of intervention (plombe or vitrectomy), indication of first intervention, use of silicone oil, preoperative lens status, IOP and IOP lowering medication one week after the first intervention, history of glaucoma or OHT, and a positive family history of glaucoma were analyzed with logistic regression.

Results Cases were more often men (p=0.03), younger at the moment of the first surgical procedure (p=0.005), underwent more vitreoretinal procedures (p<0.001), had on average a higher mean intraocular pressure (p=0.005) and medication use (p=0.001) 1 week after the first procedure and had more often a history of glaucoma or ocular hypertension (p<0.001). The use of silicone oil became a significant risk factor after removing the number of interventions from the model (p=0.002).

Conclusion Patients who develop glaucoma after vitreoretinal surgery have a different risk‐profile compared to patients who do not develop glaucoma. This gives the opportunity to monitor certain subgroups.
Rigid gas‐permeable contact lens correction of infant aphakia following congenital cataract surgery
Authors: GRUENERT A , KLUEPPEL M , HAUSSER J , REINHARD T , SUNDMACHER R , GUTHOFF T , FUCHSLUGER T , GEERLING G
Published: November 2013

This talk gives an overview of the actual data about the correction of infant aphakia with rigid gas‐permeable contact lenses. The advantages and disadvantages of the use of rigid gas‐permeable contact lenses after congenital cataract surgery will be discussed. Also, we will present our own data regarding the visual outcome of aphakic children treated with rigid gas‐permeable contact lenses.
Stem cells in the central cornea: To be or not to be?
Authors: MAJO F
Published: November 2013

Background: Since 1986, we believe that the cornea is epithelial stem cells free and all the epithelial stem cells are localized in the limbus. As a consequence, if the limbus and the corneal epithelial stem cell niche are destroyed the cornea loses its normal differentiation and transdifferentiate in conjunctiva. We call these diseases: limbal stem cell deficiency. According to the model of corneal epithelial stem cells we also classified diseases of the ocular surface as diseases related to a lake of epithelial stem cells. Discussion: Recent data have shown that there are epithelial stem cells in the central cornea of 5 different mammals. In human, central corneal epithelial cells can divide 50 times in vitro, and central corneal epithelial cells can survive for a long period after total destruction of the limbus. Furthermore, epithelial cells after epithelial ingrowths after LASIK or FEMTOLASIK exhibit corneal epithelial stem cells characteristics. In conclusion, all these data challenge the model we use to explain the renewing of the corneal epithelium and in consequence how we call and classify the diseases of the ocular surface.
Modulators of corneal nerve regeneration
Authors: BAZAN H
Published: November 2013

Damage to corneal nerves results in decreased sensitivity, dry eye, and neurotrophic keratitis. Rabbit corneas treated with pigment epithelial derived factor (PEDF) and the ω‐3 fatty acid docosahexaenoic acid (DHA) after lamellar keratectomy increase nerve regeneration and stimulates the synthesis of neuroprotectin D1 (NPD1). NPD1 also increases nerve density. The regenerated nerves contain similar proportion of calcitonin‐gene related peptide (CGRP) to non‐injured corneas. We compared the action of two smaller PEDF derivatives that maintain part of the bioactivity and can have better penetration. Animals after surgery were treated with a 44 mer‐PEDF, with neuroprotective activity, and with a 34 mer‐PEDF, with antiangiogenic properties, in association with DHA. The 44‐mer PEDF plus DHA‐treated group showed a two‐fold increase in subepithelial corneal nerve area compared to the 34‐mer PEDF+DHA‐ and vehicle‐treated groups. These results demonstrate that the use of NPD1 and 44‐mer PEDF plus DHA could represent novel therapeutic approaches for managing eye conditions that perturb corneal nerve integrity. (Supported by NIH‐NEI grant EY019465)
C‐Kit SCF receptor (CD117) expression and KIT gene mutation in conjunctival pigmented lesions
Authors: PARROZZANI R , BLANDAMURA S , ALESSANDRINI L , PERRINI P , FRIZZIERO L , MIDENA E
Published: November 2013

Purpose to investigate the presence of KIT gene mutations and immunoreactivity in 85 conjunctival melanocytic tumors and clarify the role of KIT as a potential therapeutic target in this group of patients.

Methods 85 conjunctival pigmented tumors (27 melanomas, 12 PAMs and 46 nevi) were immunostained for KIT. Intensity and pattern of expression were evaluated. Molecular analysis to identify KIT mutations was performed in 15 selected cases (tumor‐rich areas >50%). KIT immunostaining score and pattern were statistically related to patients’ age, sex, diagnostic category, presence of relapse, disease‐free survival, presence of metastases, metastasis‐free survival, limbal versus non‐limbal tumor location and thickness of melanomas.

Results KIT stains was documented in 48% of melanomas, 50% of PAMs and 24% of nevi. The mean score of KIT staining in the melanomas/PAMs group was significantly different from nevi (p=0.0076). No statistically significant differences were detected between either c‐kit immunostaining score or pattern and each of the other clinico‐pathologic parameters considered. No KIT gene mutations were detected in melanomas and nevi. A silent mutation/polymorphism in KIT exon 13 was found in one PAM.

Conclusion Despite the high level of KIT immunostains in conjunctival PAM and melanoma, this parameter seems not to be a good predictor for the presence of molecular mutations. KIT‐activating mutations should be considered an uncommon event in these tumors.
Circulating tumor DNA (ctDNA) in metastatic uveal melanoma (MUM): Correlation with outcome in 87 patients (pts) from Institut Curie
Authors: PIPERNO‐NEUMANN S , MADIC J , MARIANI P , RAMPANOU A , SERVOIS V , BIDARD FC , MILDER M , CASSOUX N , DESJARDINS L , STERN MH , LANTZ O
Published: November 2013

Purpose CtDNA can be detected in the plasma of MUM pts using a real‐time PCR based on the pyrophosphorolysis‐activated polymerization (bi‐PAP) targeting the most frequent GNAQ and GNA11 mutations present in 85% of UM (Madic et al, 2012).

Methods May 2011‐March 2013:87 MUM pts were included in 3 prospective studies to assess the bi‐PAP assay and analyse clinical and outcome correlations.

Results Median (med) age 57, primary tumor med diameter 15 mm; enucleation 32, proton beam 52, iodine disk 3. Enucleated eyes showed mostly mixed histotype and genomic high risk by array‐CGH: 8q gain and/or 3p loss. With a med disease free interval of 39 months (mo), 83 pts developed liver metastases first, with radiological miliary disease in 55; 4 had extra hepatic lesions without liver involvement. 35 pts were enrolled at the time of metastasis diagnostic. With a med follow‐up of 8 mo, 28 patients had disease progression and 34 died of metastasis. The med survival was 13 mo. Tumor samples were available in 82 pts, genotyping is ongoing for 8. GNAQ 626A>T or A>C, GNA11 626A>T and rare mutations were found in 9, 19, 26 is and 6 cases respectively; 14 were wild‐type tumors. CtDNA was detected in 51/54 samples (med 30 copies/ml, range 1‐11421) and correlated with the metastatic tumor burden as assessed by liver MRI (med 64 cm3, range 0.2‐7384). Correlation with progression‐free and overall survival will be presented.

Conclusion ctDNA is a promising tool to assess the tumor burden and the micrometastatic dissemination of uveal melanoma, and a potential biomarker to evaluate the efficacy of targeted therapies in pts carrying GNA Q/11 mutated tumors.
Uveal melanoma among Finnish octogenarians
Authors: ALJAMAL RANAA , KIVELä TERO
Published: November 2013

Purpose To report clinical characteristics of uveal melanoma (UM) among Finnish octogenarians.

Methods Population‐based study of 86 patients 80 years of age or older, treated in 1997‐2011 at the Helsinki University Central Hospital for UM. Patients had a minimum of 2 years follow‐up if still alive.

Results Of the 86 patients, 36 (42%) were female and 50 (58%) were male. Median age was 82.9 years (range, 80‐93), 5 had a previous nevus, median tumor height was 4.8mm (range, 1.1‐ 17.9), median largest basal diameter was 12.7 (range, 4.3‐22). Following the 7th edition of TNM tumor classification, 33% were T1, 19% T2, 22% T3, and 26% T4, and 28% were stage I, 32% stage II, 33% stage III, and 6% were stage IV (i.e. metastases at diagnosis). 70 patients were treated with brachytherapy (iodine in 38 and ruthenium is 32), 12 underwent primary enucleation, 1 eye was exenterated and 2 small tumours were observed. Median visual acuity was 0.2 (interquartile range, 0.6 to counting fingers) and in the fellow eye 0.7. At last follow‐up, 20 patients had died of metastasis, 21 of other causes, 3 of a second cancer (prostate, renal, urinary bladder), death certificate was not yet reviewed in 16, and 26 were alive a median of 5.1 years after treatment (range, 1.4‐11.1). The 5‐year Kaplan‐Meier survival was 75% overall, and 93% for stage I, 79% for stage II, and 62% stage III; all patients of stage IV died within 1.3 years. The corresponding all‐cause mortalities were 66%, 55%, and 29%.

Conclusion Taking competing causes of death into account, less than 25% of octogenarians die of uveal melanoma within 5 years.
Uveal metastases from carcinoid tumors: Clinical and therapeutic assessment
Authors: MIDENA E , PILOTTO E , FRIZIERO L , PARROZZANI R
Published: November 2013

Purpose To define the specific clinical characteristics of uveal metastases from carcinoids and the minimal invasive therapeutic approach.

Methods Four consecutive cases of symptomatic uveal metastases from carcinoid tumors were included in this prospective analysis. Each patient underwent full ophthalmological examination, including A‐B scan ultrasonography (US), fluorescein (FA) and indocyanine green angiography (IGA), and optical coherence tomography (OCT) at baseline and during follow‐up. Follow‐up examination was performed at 1 month and every 3 months thereafter.

Results Mean follow‐up was 17±6 months. Tree patients were affected by choroidal metastases (75%) whereas one patients by iris metastasis (25%). Choroidal metastases were ipo‐pigmented, mainly located at the posterior pole and characterized by medium internal reflectivity at US, prominent vascular net at ICG and perilesional serous retinal detachment at OCT. Each patient was treated by photodynamic therapy (PDT) with verteporfine as sole focal treatment. Mean PDT sessions were 1.6 (1‐3 sessions). Two patients (50%) showed clinical regression of the treated lesions, whereas in the others two patients (50%) tumor size remained stable during follow‐up. Subretinal fluid resolved in all choroidal lesions. BCVA increased in three patients (75%) and remained unchanged in one patient (25%).

Conclusion Uveal metastases from carcinoids are characteristically ipo‐pigmented and highly vascularized. Photodynamic therapy appears to be an effective, safe and well‐tolerated treatment option for the management these metastases.
Use of dexamethasone 0.7mg intravitreal implant in radiation macular edema
Authors: BAILLIF S , MASCHI C , GASTAUD P , CAUJOLLE JP
Published: November 2013

Purpose To evaluate the efficacy and safety over one year of follow‐up of dexamethasone 0.7mg intravitreal implant in patients with radiation macular edema (ME) after proton beam therapy for choroidal melanoma

Methods Five patients’ charts were retrospectively reviewed.

Results All patients received a radiation dose of 60 cobalt Gray equivalent. Radiation ME occurred within a mean time of 26 months after irradiation. Mean preinjection VA was 41 ETDRS letters. Two months after injection, mean VA was 47 ETDRS letters. It improved for 3 patients (+4; +9 and +15 letters) and remained unchanged for 2. Mean CRT was 331 µm. Over one year of follow‐up, two patients underwent 2 injections of dexamethasone performed 5 months after the first injection. The gain of VA was +8 and +23 letters with a decrease in CRT of 158 and 262 µm respectively. Intraocular pressure increased for 1 patient. One patient was enucleated due to a local recurrence of his choroidal melanoma. Another patient presented with a radiation neuropathy with a great loss of visual acuity.

Conclusion Intravitreal dexamethasone implant can improve VA in radiation ME. Its beneficial effect lasted up to 5 months. Other causes of vision loss may jeopardize this beneficial effect.
Comparison of the biometric measurements obtained using IOL Master and ALADDIN systems
Authors: MILKA M , WYLEGALA E , NOWINSKA A , JANISZEWSKA D , WEGLARZ B
Published: November 2013

Purpose To compare anterior segment measurements of two optical systems of patients with clear lens and cataract

Methods 34 cataractous eyes and 32 eyes with clear lens were examined using the Zeiss IOL‐Master and Topcon Aladdin system. In all eyes we measured Axial Length (AL), Keratometry (K1, K2) and Anterior chamber depth (ACD). The results were compared and analysed using Bland‐Altman plots

Results Comparison of the eye lengths, as well as of the keratometric and ACD measurements showed good correlation and agreement between the measurements obtained by both methods. Standard Deviation (SD) for Axial Length difference is about 0,034 for clear lens eyes and 0,028 for cataractous eyes. SD for K1 and K2 difference is for clear lens eyes 0,23/0,29 and 0,17/0,18 for cataractous eyes. ACD differences are respectively 0,11 and 0,15

Conclusion The comparisons between IOL Master and the ALADDIN show a very good alignment for Axial Length for both groups of patients. There was also acceptable alignment for K1, K2 and ACD measurement. Both the analyzed instruments show a good correlation and precision
Intravitreal corticosteroids as first‐line adjunctive treatment in acute post cataract surgery endophthalmitis
Authors: KOEHRER P , BRON AM , GARCHER C
Published: November 2013

Purpose To assess the effect of intravitreal corticosteroids as first‐line adjunctive treatment in acute post cataract surgery endophthalmitis.

Methods We conducted a multicenter prospective, randomized, single‐masked study including patients with acute post cataract surgery endophthalmitis. All patients received the initial intravitreal antibiotics (vancomycine 1mg, ceftazidime 2mg) with intravitreal betamethasone (400 μg) in the group 1 but not in the group 2. At day 2, all patients had the same invitreal antibiotics with betamethasone (400 μg). A prompt or deferred vitrectomy could be associated with this treatment if baseline visual acuity was limited to light perception. The primary endpoint was the BCVA (logMAR) and the secondary endpoint was the impact on intraocular pressure

Results We report the preliminary results on the first 54 patients;. 24 patients were included in the group 1 and 30 in the group 2. The BCVA was better in the group 1 at 8 days (1.44 ± 0.90 vs 1.90 ± 1.0 logMAR), at one month (0.50 ± 0.69 vs 1.24 ± 1.11 logMAR) and at 3 months (0.52 ± 0.87 vs 0.99 ± 1.13 logMAR). The confidence intervals were overlapping, except at one month, suggesting a statistical significance at this point. There was no difference in both groups considering the intraocular pressure at day 8: 14.13 mmHg (IC 95%: 10.29‐17.97) in the group 1 and 12.52 mmHg (IC 95%: 10.49‐14.55) in the group 2.

Conclusion Intravitreal corticosteroids as a first line adjunctive treatment in acute post cataract surgery endophthalmitis seem to accelerate the recovery of visual acuity but do not seem to have an impact on the final functional outcome. These results need to be confirmed by the statistical analysis of the cohort of 100 cases.
Mydriasert pupillary dilation for cataract surgery: A clinical and economic study
Authors: SHAH A , JOHAL S , LEE N
Published: November 2013

Purpose Mydriasert® is an ophthalmic insert containing phenylephrine and tropicamide. A prospective clinical evaluation of Mydriasert for pupillary dilatation prior to cataract surgery was conducted. The impact on nurse time of using Mydriasert compared to eye drops was also evaluated.

Methods The following data were collected prospectively: amount of time spent inserting Mydriasert, patient satisfaction score (on a scale of 1‐10), pupil size (on a pre‐defined categorical scale of 1 (small pupil) to 4 (very large pupil) and any adverse events related to the insert. An economic model of mydriasis was also developed.

Results Mean nursing time spent inserting Mydriasert was 1.52 minutes(SD=0.6,n=85), mean patient satisfaction score was 8.97(SD=2.32,n=97) and mean pupil size was 3.32(SD=0.66,n=114) corresponding to a large to very large pupil size. The insert had extruded unnoticed in 3 cases. For a national population (England), the estimated nurse time saved was 1,159 hours per week when using the single application Mydriasert compared to repeated instillation of eye drops to achieve mydriasis.

Conclusion Mydriasert is a safe and efficacious alternative to topical drops for pupillary dilatation. The rate of insert extrusion was low compared to that published in a smaller study reporting on a much smaller sample. This may reflect a learning curve for Mydriasert insertion. The economic analysis demonstrated that using Mydriasert could potentially free up nursing time to spend on other responsibilities.

Commercial interest
The use of laser flare photometry to assess therapeutical approaches for uveitis
Authors: TAPPEINER C , HEINZ C , HEILIGENHAUS A
Published: November 2013

Laser flare (LF) photometry is a standardized and reproducible method for grading the breakdown of the blood‐aqueous‐barrier by in‐vivo measurements of the protein content in the anterior chamber. Whereas anterior chamber cell‐grade directly correlates with the activity of anterior uveitis, high LF values may not only be observed during active inflammation but also as a remnant of chronic uveitis with irreversible damage of the blood‐aqueous barrier. The talk provides an overview of published and own data, analyzing the impact of LF photometry as a decision‐making tool for timing ocular surgery and selection of surgery techniques (e.g., lensectomy vs. phacoemulsification with primary IOL implantation; filtrating vs. non‐filtrating vs. drainage‐implants vs. cyclodestructive surgery). Furthermore, the role of LF in the context of secondary complications (CME, aphakia, glaucoma etc.) and in the management of drug therapy (topical treatment, classical immunosuppressives and biologicals) is elucidated. In this context, interesting LF topics (Do we treat cells, LF or both? Do high LF values necessarily demand for intensification of uveitis treatment? Does LF help us to decide when to stop our treatment?) are discussed.
Welcome and introduction
Authors: LANZETTA P
Published: November 2013

Abstract not provided
Aflibercept: innovation for wet AMD
Authors: TADAYONI R
Published: November 2013

Abstract not provided
Optimising anti‐VEGF therapy for wet AMD
Authors: LANZETTA P
Published: November 2013

Abstract not provided
Retinal oxygen: the good, the bad and the unknown?
Authors: STEFANSSON E
Published: November 2013

Ischemia is suspected in the pathophysiology of several eye diseases including glaucoma. The most direct way to study ischemia is through blood flow and circulatory studies and these have shown abnormalities in glaucoma and other eye diseases. However, blood flow changes per se do not necessarily indicate an unhealthy situation; blood flow indeed varies substantially in healthy tissues. The main metabolic consequence of ischemia is hypoxia and any harmful consequence of ischemia must include hypoxia at some point in time. Therefore, oxygen measurements are a direct way to study pathogenesis in ischemic diseases. Tissue damage would involve hypoxia and lack of hypoxia is not fully consistent with ischemic pathophysiology. The fact that hypoxia has to date not been found in glaucoma patients, suggests that ischemia may not be involved in the pathophysiology of glaucoma. The abnormalities in blood flow and oxygenation seen in glaucoma may be secondary to tissue atrophy, rather than the cause of the disease. Further studies, especially in patients with progressive glaucoma and high intraocular pressure will clarify the issue.
Intravitreal drugs: What is happening to the ganglion cells?
Authors: PINTO L
Published: November 2013

The number of patients undergoing intravitreal injections is growing exponentially. Long term treatments with anti‐VEGF agents and/or steroids are now common in a number of retinal diseases. However, the significance of such treatment strategies on the pathogenesis of glaucoma or even how they may affect glaucoma management is not entirely clear. The possible impact of angiogenic and inflammation modulators in neuron cell survival and activity will be made. From a clinical point of view, it will be discussed if, how and which of these agents are more likely to affect intraocular pressure management.
Results, complications, and future developments of the Boston type 1 KPro
Authors: DE LA CRUZ J , CORTINA S
Published: November 2013

The use of the Boston type 1 Kpro has increased significantly during the past decade not only in the US but around the World. Important device modifications together with changes in postoperative managment have made this success possible. This presentation will review the current most relevant complications encountered in patients implanted with this device including endophthalmitis, retroprosthetic membranes, glaucoma and stromal melt,. Strategies for their prevention and management will be discussed.
Alternating intra‐arterial and intravitreal chemotherapy for advanced intraocular retinoblastoma: First successful results without systemic chemotherapy
Authors: HADJISTILIANOU T , DEFRANCESCO S , DE LUCA MC , BRACCO S , MENICACCI F , GALLUZZI P
Published: November 2013

Purpose Background: To describe the efficacy of intra‐arterial chemotherapy combined with intravitreal chemotherapy for the treatment of advanced stage retinoblastoma

Methods The Authors report the medical records of four patients who presented with unilateral retinoblastoma, (Reese‐Ellsworth stage Vb/ group D of ABC Classification in the affected eye). They underwent clinical and ophthalmoscopic evaluation and MRI to exclude local and CNS dissemination. All 4 patients received 2 cycles (six infusions) of intrarterial chemotherapy (4‐5 mg of melphalan/0.3‐0.4 mg of topotecan), and from 7 up to 9 melphalan injections into the vitreous (10‐30μg in 0.05 mL).

Results Successful control of tumor masses and vitreous seeds was achieved in all cases at long‐term (> 6 months) follow‐up. Tumor control was 100% in all cases. Complications included: posterior lens opacities, acute ischemic papillitis, transient hypotonia, vitreous hemorrhage. There were no cases of orbital tumor recurrence or metastasis (follow‐up range, 6 – 12 months).

Conclusion Sequential intra‐arterial chemotherapy and intravitreal melphalan for advanced retinoblastoma allowed to provide retinal and vitreous seed control
Molecular profiling of ocular surface squamous neoplasia identifies multiple DNA copy number alterations including recurring 8p11.22 amplicons
Authors: ALKATAN H , EBERHART C
Published: November 2013

Purpose Conjunctival squamous cell carcinoma (cSCC) represent some of the most frequently encountered ocular surface neoplasms worldwide, and are particularly prevalent in Saudi Arabia. Our aim in this study is to uncover novel diagnostic biomarkers, as well as molecular pathways which can be targeted using new therapies.

Methods We analyzed DNA extracted from 14 snap frozen cSCC tumor specimens resected at KKESH using Agilent 180K high density oligonucleotide arrays, with 12 samples giving high quality hybridizations. We are now confirming increased gene dosage using the Nanostring platform and investigating mRNA expression at the8p11.22 loci with quantitative PCR.

Results Of these 12, the number of clear regions of DNA loss ranged from 1 to 24 per tumor, while gains (including potential amplifications) ranged from 2 to 14 per tumor. Recurring aberrations were observed in chromosome 6, where the region 6p22.1‐p21.32 was lost in 4 out of 12 specimens (33%), in chromosome 14, where the locus 14q13.2 was lost in 5 of the 12 samples (42%), and in chromosome 22, where 5 samples showed DNA loss and one DNA gain at 22q11.22. However the most frequent alteration was observed in chromosome 8, where the locus 8p11.22 was amplified in 9 tumors (75%) and lost in the other 3 samples (25%).

Conclusion We observed the most profound DNA alterations in the region of 8p11.22 which contains part or all of the ADAM1B, ADAM3A, and ADAM5p genes. It is also very near to the ADAM9 locus, which was recently found to be commonly amplified in oral squamous cell carcinoma (Plos One 2013,8:e54705).
Do we have any effective measure to minimize PCO?
Authors: TASSIGNON MJ , NI DHUBHGHAILL S
Published: November 2013

In the past, posterior capsular opacification (PCO) was considered an inevitable, albeit relatively minor complication of cataract surgery. As technology has improved, the qualities of lens implants have changed. Multifocal intraocular lenses confer visual benefits but the optics are dependent upon a clear optical medium and accurate placement. The development of PCO can distort the centration and function of these advanced optical qualities, such as diffractive rings, rendering lenses suboptimal and in some cases intolerable. Therefore long‐term quality outcomes are dependent on predictability and stability. The Bag‐in‐the‐lens (BIL) implant is currently the most effective measure to prevent PCO. The technique depends on the construction of two comparable anterior and posterior capsulorhexes. The lens is suspended centrally, supported by the integrity of the capsule and seals away lens epithelial cells preventing postoperative opacification. This placement has also been proven to be highly resistant to decentration and rotation. As the uptake of multifocal lenses and patient expectations increase, we propose that the BIL approach is currently the most stable and dependable means of ensuring quality long‐term multifocal outcomes.