bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti‐VEGF treatment in ocular oncology
Authors: ZOGRAFOS L
Published: December 2011

Purpose To present the indications of Anti‐VEGF treatment in ocular oncology.

Methods Intraocular anti‐VEGF injections were used for: • The prevention or the treatment of neovascular glaucoma following irradiation treatment of intraocular tumors (uveal melanomas, choroïdal hemangiomas, choroïdal metastasis). • The control of cystoids macula edema related to the conservative management of intraocular tumors. • The treatment of secondary retinal detachment related to vascular tumors and pseudo tumors and mainly the Coat’s disease.

Results A dramatic decrease of the risk of neovascular glaucoma was obtained with intravitreal anti‐vasoproliferative treatment following irradiation treatment of intraocular tumors. The presence of retinal ischemia associated to the secondary exudative retinal detachment is observed with panoramic (150°) fluorescein angiography. The anti‐vasoproliferative treatment is delivered during the period preceding the reatachment of the retina which allows a photocoagulation treatment. Anti‐vasoproliferative treatment in case of established iris neovascularisation allows a functional success (IOP less than 20mm Hg) in 84% of the cases and anatomical success (reduction of the iris neovascularisation and of diffusion of the dye in fluorescein angiography) in 75% of the cases. Impressive reduction of the secondary retinal detachment is obtained following anti‐vasoproliferatives treatment in cases of Coat’s disease allowing the photoablation of the reattached retina.

Conclusion Anti‐vasoproliferative treatment in ocular oncology is a major contribution for the reduction of side effects induced by irradiation treatment and to maintain useful function in treated eyes.
Hyposmotic stress triggers ATP release from porcine lens via connexin and pannexin hemichannels
Authors: DELAMERE NA , BEIMGRABEN C , MANDAL A , SHAHIDULLAH M
Published: December 2011

Purpose Purinergic receptors in the lens suggest function can be altered by agonists present in aqueous humor. Some agonists may originate from the lens itself. Here, we examine the ability of osmotic shock to trigger ATP release from the intact lens.

Methods Porcine lenses were exposed to hyposmotic (200 mOsm) or hyperosmotic (500mOsm) solution and ATP in the bathing medium was measured by luciferase assay. Because hemichannels are permeable to large solutes, the ability of propidium iodide (PI) (MW 668) to enter the epithelium was examined.

Results ATP release into the bathing medium was stimulated when lenses were exposed to hyposmotic solution. Hyperosmotic solution did not detectably increase ATP release. Hyposmotic solution‐induced release of ATP was partially suppressed by the connexin hemichannel inhibitor, 18α glycyrrhetinic acid (AGA) or by probenecid, a pannexin hemichannel blocker, and was abolished by AGA and probenecid added together. Consistent with opening of connexin and/or pannexin hemichannels, lenses exposed to hyposmotic solution displayed a ~4 fold increase in the ability of PI to enter the epithelium. In parallel studies, hyposmotic solution was shown to activate a Src family tyrosine kinase (SFK) and cause an SFK‐dependent increase of Na,K‐ATPase activity in the epithelium.

Conclusion Hemichannels contribute to ATP release when the intact lens is subjected to hyposmotic shock. The amount of ATP release appeared sufficient to activate purinergic receptors that cause tyrosine kinase‐dependent stimulation of active Na‐K transport. The responses could perhaps signify an autoregulatory loop initiated by mechanical stress or osmotic swelling.
Stimulation of adrenergic β‐receptors enhances mydriasis in a porcine eye model
Authors: JANBAZ CC , LUNDBERG B , BEHNDIG A
Published: December 2011

Purpose In order to achieve an improved mydriasis in human eyes during cataract surgery, the effect of intracameral phenylephrine was compared to the combination of isoprenaline plus phenylephrine, to epinephrine alone and to a negative control, in a porcine eye model.

Methods A total of eighty‐nine eyes from newly slaughtered pigs were acquired and randomly split into four groups. In order to gain miosis all eyes received 2.0 mg of acetylcholine intracamerally, and after 60 seconds the eyes were injected with 0.15 ml 0.3% isoprenaline and 0.15 ml 3.0% phenylephrine sequentially with a 90‐second interval (n=21), the same substances in the reverse order (n=22), 0.15 ml of 0.025% epinephrine (n=20), or 0.15 ml of saline solution (n=26). The diameter of the pupils were measured every 15 seconds, and compared using Student’s t‐test.

Results Phenylephrine injected after isoprenaline had a significantly (p<0.01) larger mydriatic effect than epinephrine. The mydriatic effect of phenylephrine, however, was significantly (p<0.05) smaller than that or epinephrine without the isoprenaline pretreatment. Isoprenaline also exhibited a small mydriatic effect of its own.

Conclusion This study shows that the β‐receptor has a role in the dilation of the pupil, here demonstrated with the β‐receptor stimulator isoprenaline which augments the mydriatic effect of intracamerally injected phenylephrine. The superior mydriatic effects of a nonspecific adrenergic stimulator such as epinephrine in compare to the specific α1‐receptor stimulator phenylephrine may be explained by this β‐receptor mediated mydriasis.
Cationic oil‐in‐water emulsions protect and restore function of the injured ocular surface
Authors: DAULL P , LIANG H , BAUDOUIN C , GARRIGUE JS , BUGGAGE R , BRIGNOLE‐BAUDOUIN F
Published: December 2011

Purpose Ocular surface damage is a consequence of tear instability arising from numerous inciting events: preserved eye drops, contact lens wear, systemic medications, environment and age. While unpreserved eye drop reduce iatrogenic toxicity they do not restore the deficient tear film which leads to ocular surface injury. Cationic oil‐in‐water emulsions have been shown to restore and reduce evaporation of the tear film. We studied the effect of cationic emulsions (Cationorm® and Catioprost®) in established animal models of ocular surface injury.

Methods Acute toxicity and local tolerance were evaluated in rabbits. Healing properties were assessed in a rat model of corneal scraping. Abrasions were treated for 5 days, and corneas were evaluated clinically and histologically. Conjunctival function was assessed by goblet cell (GC) count and MUC5 immunostaining. The kinetics of ocular surface healing was assessed in an in vitro scraping assay.

Results Neither Cationorm® nor Catioprost® induced toxicity as evidenced by clinical and confocal microscopy scoring. Catioprost® was well tolerated, with a reduced (‐42%) occurrence of hyperemia when compared to Xalatan®. In rats, Catioprost® improved healing, protected GC and maintained normal MUC5 secretion. In vitro, the cationic emulsions improved cell migration and maintained MUC4 expression.

Conclusion Cationic emulsions were well tolerated. In contrast to preserved and unpreserved ophthalmic drops, cationic emulsions promoted healing, restored function of injured ocular surface, and protected against ocular surface injury. The findings suggest that cationic emulsions by augmenting the tear film may benefit patients with ocular surface disease.

Commercial interest
Structure of solitary sebaceous glands in the Sea Lion eye lid – a Meibomian gland equivalent ?
Authors: KNOP E , KNOP N , KELLEHER DAVIS R
Published: December 2011

Purpose Pinnipeds stay not only in the sea but also on land and may then require a stable tear film. It was of interest to determine whether sea lions have meibomian glands for a superficial lipid layer that prevents tear evaporation.

Methods Eyelids of a normal sea lion were embedded in parafﬁn and sections of 10‐20 µm thickness stained with H&E.

Results A distinct tarsus was not detectable, the lid consisted mainly of muscular tissue with the lid margin forming a tip. Underneath the epidermis was a whitish granular layer that consisted of hair follicles and sebaceous glands. Bundles of holocrine acini were arranged between hair follicles. Towards the lid margin, the number of hair follicles decreased whereas the relative volume of sebaceous glands increased. At the lid margin, the sebaceous glands formed solitary glands without association to hairs or with only rudimentary hair shafts. The acini drained via short ductules into a straight duct with a four‐layered stratiﬁed squamous epithelium. The straight ducts opened via a terminal duct onto the outer lid skin.

Conclusion The results show that pinnipeds have solitary sebaceous glands at the eyelid margin that resemble human meibomian glands in structure but are different in orientation and size. It remains to be determined whether the sea lion eyelid sebaceous glands represent an equivalent to human meibomian glands.
Characteristics of goblet cells in the conjunctival epithelium of the lid wiper explain the hydrodynamic type of ocular surface lubrication during the blink
Authors: KNOP N , KORB DR , BLACKIE CA , KNOP E
Published: December 2011

Purpose The lid wiper at the inner aspect of the posterior eyelid border forms an epithelial lip apposed to the globe for distribution the pre‐ocular tear film. The present assumption of a squamous may not explain sufficient lubrication in order to avoid friction during the blink movement.

Methods Conjunctival whole‐mounts including the lid margins from twelve normal human body donors were investigated by routine histology and semithin plastic sections, using histological stains, histochemistry and immunohistochemistry for MUC5AC.

Results In routine histology the lid wiper showed a conjunctival epithelium with goblet cells, single and in clusters, at the luminal surface and also deep within the epithelium. Semithin sections revealed that the goblet cells at a greater depth were connected to cryptal epithelial infoldings that opened to the surface. Most goblet cells produced mucins of the neutral (PAS) and acidic (Alcian blue) type and also stained positive for the mucin MUC5AC. Surprisingly, MUC5AC negative goblet cells were also observed in the lid wiper.

Conclusion In contrast to conventional assumptions, the lid wiper is a part of the conjunctiva and contains goblet cells & goblet cell crypts that are suitable to provide by a hydrodynamic type of lubrication for sufficient reduction of sheer stress between the lid margin and globe during the blink. This is another strong indication that the lid wiper is the area of the lid margin for the distribution of the thin preocular tear film.
Differential effects of various VEGF isoforms on endothelial cells and Tenon fibroblasts
Authors: VAN BERGEN T , VANDEWALLE E , VAN DE VEIRE S , MOONS L , STALMANS I
Published: December 2011

Purpose We have previously shown that VEGF plays an important role in scar formation after glaucoma surgery. To clarify the differential effects elicited by VEGF isoforms, we compared the biological responses and signaling pathways activated by the various isoforms on endothelial cells and Tenon fibroblasts in vitro.

Methods VEGF‐R2 and neuropilin‐1 (NRP‐1) expression was analyzed on endothelial cells (HUVEC) and Tenon fibroblasts (TF) by RT‐PCR. The effect of different VEGF isoforms (VEGF189, VEGF165 and VEGF121) on HUVEC and TF proliferation was determined by WST‐1 assay. The extracellular signal‐regulated kinase (ERK) pathway was evaluated by TransAM c‐Myc assay.

Results HUVEC showed a higher expression of VEGF‐R2 and NRP‐1 mRNA as compared to TF. VEGF189 only significantly increased the growth of TF, whereas VEGF165 only increased HUVEC proliferation. VEGF165 strongly binds VEGF‐R2 and NRP‐1. As such, the combined reduced expression of VEGF‐R2 and NRP‐1 on TF explained why VEGF165 was more potent in inducing proliferation of HUVEC as compared to TF. VEGF121 exerted significant proliferative effects on both cell types by binding VEGF‐R2. However, similar concentrations of VEGF121 stimulated HUVEC more than TF, due to the lower expression of VEGF‐R2 on TF. All these stimulating effects on proliferation were associated with an activation of the ERK pathway.

Conclusion Our data indicate that VEGF165 and VEGF121 predominantly affect blood vessel growth, whereas VEGF189 may be more important in fibrosis. Selective inhibition of VEGF165 (pegaptanib) may therefore be less effective to reduce ocular scar formation than non‐selective VEGF‐inhibition (bevacizumab), presumably due to retained action of VEGF121 and VEGF189.
Cis‐urocanic acid inhibits SAPK/JNK signaling pathway in UV‐B exposed human corneal epithelial cells in vitro
Authors: PAIMELA T , JAUHONEN HM , KAUPPINEN A , LAIHIA JK , LEINO L , SALMINEN A , KAARNIRANTA K
Published: December 2011

Purpose Urocanic acid (UCA) is a major endogenous UV‐absorbing chromophore in the epidermis and it is also an efficacious immunosuppressant. The effects of cis‐UCA on UV‐B‐induced inflammatory and apoptotic responses in HCE‐2 cells, focusing on the nuclear factor kappa B (NF‐kappaB) and AP‐1 signalling pathways were studied.

Methods After exposing HCE‐2 cells to UV‐B and cis‐UCA, the DNA binding of c‐Fos, c‐Jun and NF‐kappaB were measured with ELISA. In addition, the endogenous levels of phosphorylated stress‐activated protein kinase/c‐Jun N‐terminal kinase (phospho‐SAPK/JNK and phospho‐c‐Jun were determined. The proliferative capacity of HCE‐2 cells was also quantified, and the cytotoxicity of the cis‐UCA and UV‐B treatments was monitored by measuring the release of lactate dehydrogenase enzyme in the culture medium.

Results UV‐B irradiation induced the binding of transcription factors c‐Jun, c‐Fos, and NF‐kappaB to DNA. Cis‐UCA inhibited the binding of c‐Jun and c‐Fos but not that of NF‐κB. Moreover, UV‐B increased the levels of phospho‐c‐Jun and phospho‐JNK, and the expression of both was attenuated by cis‐UCA. Cis‐UCA also alleviated the UV‐B‐induced apoptosis and proliferative decline in human corneal cells.

Conclusion The results from this study suggest that cis‐UCA suppresses JNK signaling pathway, which provides potential for treating UV‐B‐induced inflammatory defects in human corneal cells.
Parkinson´s disease and retinal optical coherence tomography
Authors: JIMENEZ DEL RIO B , ASCASO FJ , LOPEZ DEL VAL J , CABEZON L , CASAS P , CRUZ N , PEIRO C , CRISTOBAL JA
Published: December 2011

Purpose The aim of the study was to assess the retinal measurements and optic nerve head (ONH) morphology in patients with Parkinson's disease (PD) and to determine whether there is any correlation among these parameters and the disease´s duration.

Methods Thirty patients affected by PD (mean age 67,3 ± 8,4; range: 49 ‐ 83) were compared with 28 age‐matched controls. In all subjects, peripapillary retinal nerve fiber layer (RNFL) thickness, ONH measurements, and macular thickness and volume were measured by optical coherence tomography (OCT).

Results PD patients showed a statistically significant reduction of the overall peripapillary RNFL thickness [95±9µm, range: 73‐117] compared with those values observed in control eyes [103±7µm, range:87‐117] (p<0.0001, Mann‐Whitney U test). Furthermore, a statistically significant reduction of RNFL thickness was observed in nasal [74±20µm, range:18‐114](p=0.004), inferior [118±14µm, range:88‐147] (p<0.0001) and superior quadrants [120±13µm, range:88‐145] in PD patients when compared with controls [84±14µm, range:54‐106], [132±14µm, range:101‐165] and [125±13µm, range:101‐151] respectively (p=0.023; Mann‐Whitney U test). The temporal peripapillary quadrant, ONH measurements, macular thickness and volume did not reveal any statistically significant differences between both groups.

Conclusion PD patients show a decreased peripapillary RNFL thickness evaluated by OCT. We also observe that the further evolution of PD, the lower average peripapillary RNFL thickness. Our results suggest that axonal degeneration could be present in the retina of PD patients and that RNFL thickness measured by OCT could be used as a biomarker for early diagnosis and for monitoring PD progression.
Immune modulation in the next decade
Authors: PLEYER U
Published: December 2011

Abstract not provided
Roles of human antimicrobial peptides in innate immune defense at the ocular surface: arming and alarming corneal and conjunctival epithelial cells
Authors: PAULSEN F , GARREIS F
Published: December 2011

Purpose The ocular surface including the lacrimal system and lids have evolved several defence mechanisms to prevent microbial invasion. Included among this armory are several host‐defence (so‐called antimicrobial) peptides. These multifunctional molecules are being studied not only for their endogenous antimicrobial properties but also for their potential therapeutic effects.

Methods The talk summerizes the current knowledge of antimicrobial peptide (AMP) expression at the ocular surface and lacrimal apparatus focusing on beta‐defensins, psoriasin, and a protein of the S100 fused‐type namely hornerin.

Results The role of these molecules in ocular surface disease will be discussed with the primary focus being on infectious keratitis and inflammatory conditions including dry eye.

Conclusion Finally the potential of using AMP and their mimetics/derivatives for the treatment and prevention of ocular surface diseases is addressed.
Anti‐apoptotic Gene Transfer to Corneal Epithelial Grafts modulates Immune Response and leads to increased Graft Survival
Authors: FUCHSLUGER T
Published: December 2011

Purpose To study whether anti‐apoptotic gene transfer to allogeneic corneal epithelial sheets in mice improves graft survival. Transplatation of cultured allogeneic epithelium is a viable therapy for patients bilaterally blind after bilateral limbal stem cell deficiencies, e.g. after chemical burn. Gene therapy to cultured epithelial cell sheets in vitro before engraftment could promote the success in this most demanding ocular surface disease.

Methods Epithelial denuded syngeneic Balb/C corneas were manufactured with syn‐ or allogeneic epithelium, grafted and compared to epithelial grafts treated with the anti‐apoptotic gene p35 (total n=40). Feasibility of gene therapy was determined by examining kinetics of IZsGreen protein expression. Allo‐response was studied by delayed type hypersensitivity (DTH).

Results Transfer of IZsGreen was successful obtaining high rated of expression. Interestingly, gene‐therapeutically treated allogeneic epithelial grafts showed significantly less opacity and a significantly faster restoration of the epithelial barrier compared to allo‐untreated epithelial grafts (p<0.01, respectively). In addition, DTH analysis consistently showed significantly reduced T‐cell response in the treated group (p<0.01).

Conclusion We were able to demonstrate that gene therapy of transplanted cell sheets may be a viable option to improve allogeneneic epithelial graft survival. This might set the stage for future studies of gene therapeutic interventions of epithelial allo‐grafts, and its impact on graft survival and immune response.
[Mu]anometric measurement of the outflow facility in the human eye
Authors: GINIS H , KARYOTAKIS NG , DASTIRIDOU A , TSILIMBARIS MK , PALLIKARIS IG
Published: December 2011

Purpose The intraocular pressure (IOP) is determined by a dynamic equilibrium between the production and the outflow of the aqueous humor. The dependence of outflow facility on IOP may be related to the biomechanical properties of the eye. This study examines the relationship between the outflow facility and IOP for the living human eye using an invasive manometric device.

Methods An intraoperative invasive manometric device was used to measure the IOP of fifty four eyes from fifty four cataract patients. The measurements were performed before cataract surgery. The anterior chamber of the eye was cannulated to a microstepping pump and the pressure was recorded by a pressure transducer through special developed computer software. The IOP was artificially increased to 40 mmHg by infusion of BSS in the anterior chamber of the eye. The IOP decay curve was recorded. A mathematical model was developed to calculate the outflow facility coefficient.

Results The average outflow facility coefficient was 0.328 (SD 0.093) μl/min/mmHg. From the data analysis the outflow facility coefficient was proved to have a non linear correlation with IOP. This non linear behavior of outflow facility was approximated with an exponential mathematical model.

Conclusion The invasive method of measuring in vivo outflow facility coefficient employed in this study, avoiding the errors of tonography may provide accurate data on the dependence of outflow facility coefficient on IOP. These data, in conjunction with ocular rigidity measurements may facilitate our understanding of the relationship between the biomechanical properties of the eye and the anatomical changes in the trabecular area at elevated IOP levels.
Ocular rigidity assessment in the decision making for glaucoma patients
Authors: DETORAKIS ET
Published: December 2011

Purpose So far there have been controversial reports concerning ocular rigidity in glaucomatous eyes, ranging from reduced values (which may rise following treatment with b‐blockers or pilocarpine), to increased values, compared with non‐glaucomatous eyes. Ocular rigidity may play an important role in glaucoma pathogenesis, since it determines ocular wall changes in response to pressure changes and thus affects the anatomical course of optic nerve fibers as well as the local vascular autoregulation. Despite the importance of ocular rigidity in glaucoma pathogenesis, its role in the clinical practice has so far been compromised, mainly due to the difficulties in the accurate calculation of a rigidity coefficient in vivo. The traditional approach to ocular rigidity calculation by differential tonometry and insertion of readings into Friedenwald’s chart has received criticism, mainly because Friedenwald’s nomogram was based on data from cadaveric eyes, which may display significantly altered rigidity values, compared with living eyes.

Methods Related literature review.

Results Recent developments, such as the manometric in vivo calculation of a rigidity coefficient, the determination of ocular elasticity through ultrasound elastography and the differential tonometry between applanation and dynamic contour tonometers may enable a minimally invasive and reliable assessment of ocular rigidity values for living eyes.

Conclusion The possibility to reliably calculate ocular rigidity in vivo using non‐invasive or minimally invasive methods could lead to the incorporation of rigidity in the decision making process for glaucoma patients.
Ocular Rigidity and Age‐Related Macular Degeneration
Authors: TSILIMBARIS MK , KYMIONIS G , GINIS H , KOUNIS G , PALLIKARIS IG
Published: December 2011

Purpose To compare ocular rigidity in patients with age‐related macular degeneration (AMD) and control subjects.

Methods The ocular rigidity coefficient was measured in 32 patients with AMD (16 with neovascular and 16 with nonneovascular AMD) and 44 age‐matched control patients (control group) who underwent cataract surgery. The measurement procedure involved injection of microvolumes of a balanced salt solution (in steps of 4.5 microl) through the limbus in the anterior chamber, with continuous monitoring of intraocular pressure with a transducer, up to the limit of 30 mm Hg.

Results There was no difference in age (p = 0.195), gender (p = 0.513) and axial length (p = 0.725) between the groups. Ocular rigidity coefficient was 0.0142 +/‐ 0.0077 μl‐1 in the AMD group and 0.0125 +/‐ 0.0049 μl‐1 in the control group (p = 0.255). In subgroup analysis, the average ocular rigidity was 0.0186 +/‐ 0.0078 μl‐1 in patients with neovascular AMD and 0.0104 +/‐ 0.0053 μl‐1 in patients with nonneovascular AMD. Ocular rigidity was higher in patients with neovascular AMD, compared to patients with nonneovascular AMD (p = 0.004) and controls (p=0.014).

Conclusion Patients with neovascular AMD have increased ocular rigidity measurements compared with patients with nonneovascular AMD and control patients.
The physiological role of reactive oxygen species (ROS) in lens and corneal epithelial cells
Authors: LOU M , XING KY , PAN Q , HUO YN , QIU WY , YAO YF
Published: December 2011

Purpose ROS have been shown to mediate growth factor mitogenic function in many cell types. This study is to explore if H2O2 (a stable ROS species) at low levels can promote proliferation in lens epithelial cells, and facilitate adhesion, migration, and wound healing in corneal epithelial cells

Methods Human lens epithelial (HLE) B3 cells were treated with H2O2 (0‐50 μM) and analyzed for cell proliferation by thymidine assay. H2O2 (0‐70 μM) treated primary rabbit corneal epithelial (RCE) cells were tested for viability by MTT assay, adhesion by centrifugation assay, focal contacts of vinculin and F‐actin by immunoﬂuorescence. Activations of Src (pY416), EGF receptor (pY845), vinculin (pY1065), FAK (pY397 and pY576) were examined by immunoblotting. The cell migration was tested by a scratch wound method, while the cornea wound healing in vitro (pig), and in vivo (mouse) was examined by scraping off an area of the epithelial cells, and treated by H2O2 with and without N‐acetylcysteine (NAC)

Results Compared with the untreated control, H2O2 at 20 μM stimulated HLEB3 cell proliferation. This level of H2O2 also enhanced RCE cell viability, facilitated adhesion and migration with activations of EGF receptor (Y845), and the downstream Src (pY416), FAK (Y576), and vinculin (Y1065). H2O2‐treated RCE cells also showed focal adhesion rich in vinculin, and stress fibers containing F‐actin. Low level of H2O2 induced a faster wound healing in cornea both in vitro and in vivo, and the healing was weakened if treated by H2O2 + NAC.

Conclusion H2O2 at low levels can benefit both lens and corneal epithelial cells in growth and wound healing. This novel physiological function of H2O2 confirms the importance of redox balance for the general health of cells and tissues.
Oxidative stress in the eye in diabetes
Authors: OBROSOVA IG
Published: December 2011

Purpose The characterize manifestations of oxidative stress in lens and retina in diabetes, and to evaluate the roles for aldose reductase (AR), Na+‐H+‐exchanger‐1 (NHE‐1), and poly(ADP‐ribose) polymerase‐1 (PARP‐1) in oxidative stress in both tissues, cataract formation, and retinal apoptosis.

Methods The experiments were performed in streptozotocin‐diabetic rats and high glucose‐exposed cultured human lens epithelial cells (HLEC) and bovine retinal pericytes and endothelial cells (BRP and BREC). Cataract formation was evaluated by indirect ophthalmoscopy and slit lamp examination, oxidative stress by combination of biochemical and immunohistochemical methods, and retinal apoptosis by TUNEL assay in flat‐mounted retinae.

Results Diabetes‐induced oxidative‐nitrosative stress manifested by accumulation of free lipid peroxidation products, malondialdehyde and 4‐hydroxyalkenals, as well as 4‐hydroxynonenal protein adducts, and nitrated and poly(ADP‐ribosyl)ated proteins, is present in both diabetic lens and retina as well as in high glucose‐exposed HLEC and BRP and BREC. Depletion of GSH and ascorbate and changes in the glutathione and ascorbate redox states are present in thre lens only. Activation of AR, NHE‐1 and PARP‐1 promotes oxidative damage. Inhibition of AR, NHE‐1, and PARP‐1 prevents diabetes‐induced oxidative stress, and prevents or delays cataractogenesis and retinal apoptosis.

Conclusion Ozidative stress is present in lens and retina in diabetes and plays an important role in diabetic ocular comp‐lications.

Commercial interest
The evidence of oxidation in ultraviolet radiation cataract
Authors: SÖDERBERG P
Published: December 2011

Abstract not provided
Mouse models of accelerated lenticular aging by carbonyl and oxidant stress
Authors: MONNIER VM , FAN X
Published: December 2011

Purpose Age‐related human cataracts form as a result combined of carbonyl and oxidant stress and other crystallin modifications that destabilize their chaperone function. However, without appropriate models it has been very difficult to demonstrate cause‐and effect and implicate protein modifications in the disease process. To test the role of vitamin C oxidation products (carbonyl stress) and protein oxidation in the formation of crystallin aggregates, we have generated two types of mice that exhibit rapid protein damage.

Methods The first model of increased carbonyl stress is the hSVCT2 mouse in which we overexpressed the human vitamin C two transporter under control of the mouse alphaB‐crystallin promoter. (Fan et al. PNAS 2006). The second model of increased protein oxidation is the LEGSKO (Lens Glutathione Synthesis Conditional Knockout mouse) in which we conditionally knocked out gamma‐glutamyl cysteine ligase (Gclc) in order to mimic the low GSH levels of the old lens nucleus.

Results Gamma glutamyl cysteine ligase mRNA, activity and glutathione (GSH) levels are severely depressed in the lens of the homozygous mouse, but not in the heterozygous mouse. GSSG/GSH ratio, methionine oxidation and protein disulfide formation are increased at 6 mos of age. Nuclear opacities turn into full nuclear cataracts at 6 mos. Protein disulfide formation reveals a shift from intra‐ to interdisulfide bonds similar to aging human lens. Dramatic upregulation of several candidate transporters is noted.

Conclusion Availability of two mice strains with increased carbonyl and oxidative stress, respectively, will allow us to test the hypothesis that rapid modification of crystallins predisposes to protein aggregation and cataractogenesis when bred together. It will also help us develop drugs that slow down the progression of cataractogenesis and study molecular events that precede cataract formation.
From corneal topography to wavefront aberrometry
Authors: GICQUEL JJ
Published: December 2011

In this presentation we will see the how, after more than a century of constant improvements, mapping of the surface curvature of the cornea, progressively evolved into state of the art technologies objectively measuring the quality of vision. We will also discuss how these new tools can help us in our daily refractive surgery practice.
An update on adaptive optics and the vision simulator
Authors: CHATEAU N
Published: December 2011

Abstract not provided
Optical coherence tomography in the evaluation of patients with mild cognitive impairment of amnestic type
Authors: CASAS P , CRUZ N , ASCASO FJ , PASCUAL LF , LOBO A , JIMENEZ B , CABEZON L , CRISTOBAL JA
Published: December 2011

Purpose Some cases of amnestic mild cognitive impairment (aMCI) represent the earliest clinically detectable phase of the trajectory toward dementia and Alzheimer's disease (AD).To our knowledge, neither macular retinal thickness nor macular volume have been previously documented in vivo in aMCI patients. The aims of this study were to determine the differences in the retinal nerve fiber layer (RNFL) thickness between aMCI patients and control subjects.

Methods We compared by optical coherence tomography (OCT) 40 eyes of twenty aMCI patients (15 males and 5 females, mean age: 70.4±8.9 years; range: 50‐88) to 40 eyes from twenty age‐matched healthy controls (10 males and 10 females, mean age: 69.8±6.3 years; range: 58‐85), measuring peripapillary RNFL thickness, macular thickness and volume.

Results Overall RNFL thickness was within 94.9 and 128.8 µm (mean: 107.1 ± 7.2 µm) in control subjects and within 32.0 and 102.1 µm (mean: 84.5 ± 11.4 µm) in a‐MCI patients. The difference was statistically significant (p=0.0001, Mann‐Whitney U test). Peripapillary RNFL thickness evaluated in all the separate quadrants (superior, inferior, nasal and temporal) of aMCI patients was also significantly reduced when compared with that of control subjects. Nevertheless, macular thickness and volume are increased in aMCI patients compared to control subjects. We found no significant correlation between Mini‐Mental State Examination (MMSE) scores and OCT values.

Conclusion These findings suggest that neuronal degeneration could be present in the retina of aMCI patients as previously observed in patients with AD.
Peculiarities of accommodative esotropia
Authors: BUSHUYEVA NN , SENYAKINA A , MARTYNYUK S
Published: December 2011

Purpose To study the visual functions and the state of accommodation–convergence–papillary system (ACPS) in children with different forms of accommodative esotropia(AE)

Methods Except of the standard ophthalmological examination the pupillography was performed in 88 patients aged 6‐18 years with refractive AE (45), nonrefractive AE (31), combinated AE (12)

Results Results, with optical correction the visual acuity below 0,3 took place of 55,8±7,6% patients with refractive AE, 42,0±18,7% cases with combinated AE, 33,3±9,1% children with nonrefractive AE. Convergence was normal in all cases of refractive and nonrefractive AE, but was weak in 42,8±18,7% patients with combinated AE. Fusion in haploscopic condition was absent in 65,1±7,3% cases of refractive AE, 51,9±9,6% patients with nonrefractive AE and in all cases of combinated AE. Worth´s four dot test showed monocular vision in 88,4±4,9% cases of refractive AE, 85,1±13,2% of combinated AE and 66,7±17,1% of nonrefractive AE. Accommodative insufficiency was inherent to all patients. Pupillography showed narrowing of pupils in all patients in comparison with healthy children. Pupil reaction to light was weakened considerably. The latent periods of the direct, consensual pupillary reaction to light and the latent periods of pupillary reaction after light stimulation and after convergences weakening were increased more than three times as in healthy children.

Conclusion Besides the already known differences in the state of refraction and the value of index AC/A, the These types of AE differ from each other in such functions as visual acuity, fusion power, binocular vision, convergence. Disturbances of pupillary reactions indicate on reduction of lability, increase ACPS’s passivity due to functional changes in brainstem.
The effect of intravitreal injections of anti‐VEGF on the Pigment epithelial detachment (PED) in eyes with the exudative type of age related macular degeneration (AMD)
Authors: KALOUDA P , TSIKA X , ANASTASAKIS A , TSILIMBARIS MK
Published: December 2011

Purpose To evaluate the morphological changes of the PED after treatment with intravitreal injections of anti‐VEGF in eyes with the exudative type of AMD.

Methods Retrospective chart review of patients with PED and exudative type of AMD treated with anti‐VEGF. Alterations of the PED were defined as unchanged if it appeared qualitatively similar to the baseline exam, reduced if it appeared qualitatively smaller, disappeared if no PED could be detected and increased if it appeared qualitatively larger. Changes in BCVA and number of injections were compared to an age similar control group with the exudative type of AMD treated with intravitreal injections of anti‐VEGF without PED on the OCT examination.

Results 30 eyes were included in each group. Mean age of the PED group was 75.7 years (SD: ± 5.8 years), while the control group’s was 77.7 years (SD: ±6.2 years). Mean follow up period was 19.8 months (SD: ±10.7 months). Changes of the PED morphology were found as follows, unchanged: 9 eyes, reduced: 16, disappeared: 2, increased: 3. The mean paired difference in BCVA comparing the two groups was ‐0.08 logMAR (p=0.46) and in the number of injections was 2.1 injections (p=0.04).

Conclusion Our study revealed that a substantial number of the studied patients showed reduction of the extent of the PED. The PED group required a greater number of injections compared to the control group.
AMD and Atherosclerosis coincidence: the role of complement system activation and endothelial dysfunction
Authors: MACHALINSKA A , MACHALINSKI B , KARCZEWICZ D
Published: December 2011

Purpose Age‐related Macular Degeneration (AMD) shares several pathological and epidemiological similarities with systemic atherosclerosis (AS). There is considerable evidence implicating endothelial dysfunction in the pathogenesis of both disorders, and complement system (CS) activation appears to be a common denominator underlying those processes. It is widely recognised that both AMD and AS are not only related to local stimulation of the CS, but also result in its systemic activation.

Methods We recruited 77 subjects with clinical diagnosis of AMD and 46 age/sex–matched controls. The concentration of C3a‐desArg complement compound,the number of circulating endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) was measured in the subjects’ peripheral blood (PB).

Results We demonstrated increased numbers of CECs in the PB of AMD patients, a finding which reflects a severe vascular disturbance and clearly indicates that there is an endothelial alteration accompanying AMD. We also postulated that EPC enumeration could serve as a novel method for the assessment of AMD‐related choroidal neovascularisation and demonstrated significantly elevated EPC counts in the PB of patients with the exudative form of AMD.We found that the levels of C3a‐desArg were significantly elevated in plasma of exudative AMD patients compared to the control group. Additionally, the patients and controls with documented AS displayed significantly higher levels of C3a‐desArg in PB compared to subjects without AS.

Conclusion We propose a linking hypothesis between CS activation, endothelial dysfunction and the pathogenesis of two common and age‐related pathological processes, AS and AMD.(Grant‐N N402 172137)
Looking at the ONH ‐ Pros and cons of vascular involvemnt in glaucoma
Authors: JONAS JB
Published: December 2011

The appearance of the optic nerve head of normal eyes, eyes with vascular optic neuropathies and eyes with glaucoma will be compared and potential hints for the pathogenesis of glaucomatous optic neuropathy will be discussed.
Looking into clinical studies ‐ Pros and cons of vascular involvemnt in glaucoma
Authors: ORGUL S
Published: December 2011

Purpose To assess the strength of the evidence for ocular blood flow involvement in glaucoma.

Methods Because of lack of a large number of randomized trials, the assessment of the question must rely on case series and observational studies, and on the replicability of these studies.

Results Currently, evidence that measurement of blood flow can diagnose glaucoma or detect progression of glaucomatous disease is lacking, but several aspects are considered consensual, including low blood pressure association with preponderance and progression of POAG, altered OBF parameters, increased variability of OBF, and insufficient vascular autoregulatory response in glaucoma. It is unclear how much these features are independent from each other. Potential pathogenic keys are endothelial dysregulation and conditions with intermittent hypoxia such a sleep apnea.

Conclusion Designing a proper study may still be failing because of the difficulties in defining the pathogenesis and exact nature of OBF alteration in glaucoma. Nevertheless, the cumulative information makes it unlikely that blood flow has no role in glaucoma. Although evidence that measurement of blood flow supports a specific treatment recommendation for patients with glaucoma is lacking, it is of interest that some antiglaucoma drugs have a potential to protect blood flow in ocular tissues relating to glaucoma, while the effect of surgery remains unclear.
The Vascular Aspect of Glaucoma ‐ What should we look at?
Authors: SCHMETTERER L
Published: December 2011

Purpose Glaucoma is an optic neuropathy of unknown origin. Increased intraocular pressure is the most important risk factor for the disease. In addition, reduced ocular perfusion pressure has been identified as a risk factor for glaucomatous optic neuropathy.

Methods In a variety of studies we have focused on the complex interaction between intraocular pressure, mean arterial blood pressure, ocular perfusion pressure and ocular blood flow. In these studies various strategies were used to manipulate intraocular pressure, mean arterial blood pressure and ocular perfusion pressure and choroidal and optic nerve head blood flow were measured.

Results In vivo the capacity of choroidal and optic nerve head blood flow to regulate its vascular tone during changes in ocular perfusion pressure strongly depends on the way how perfusion pressure is manipulated. Generally ocular vascular beds regulate better during changes in blood pressure than during changes in intraocular pressure.

Conclusion With the improved understanding of ocular blood flow regulation in humans our understanding of perfusion abnormalities in glaucoma has also increased. Most importantly these studies show that any reduction in intraocular pressure has a strong impact on ocular blood flow regulation.
Corneal Epithelium in Ocular Pharmacology
Authors: URTTI A
Published: December 2011

Purpose Corneal epithelium is the main barrier of ocular drug absorption form the tear fluid to the anterior chamber. The aim was to generate corneal epithelial cell culture model for drug permeability testing.

Methods Human corneal epithelial cell line was used and cultured on filters to build the model. The model was characterised in terms of permeability, electrical resistance, intercellular space, and gene expression of drug transporters and 11,000 other genes. Human corneal epithelium and rabbit cornea were used as positive controls.

Results The results indicate that the corneal epithelial model has similar morphology and permeability characteristics and intercellular space as the normal corneal epithelium. However, significant differences were seen in the gene expression patterns.

Conclusion Even though tight corneal epithelial organotypic culture model can achieve some features of the corneal epithelium, it deviates from the in vivo counterpart substantially. Thus the model has only limited utility.
Ocular manifestations in Duane radial ray syndrome
Authors: GARCIA MARTIN E , ALMARCEGUI C , FERNANDEZ J , PINILLA I , SATUE M , CALVO P , FERRANDEZ ARENAS B , FUERTES I
Published: December 2011

Purpose To present two related cases with Duane Radial Ray syndrome, ophthalmologic affectation with Duane syndrome and retinal nerve fiber layer (RNFL) hypoplasia.

Methods The first patient (15‐years woman) showed Duane syndrome, reduction of visual acuity and pale optic discs. The other patient (12 years woman) presented Duane malformation. Both patients underwent a complete ophthalmologic evaluation with best corrected visual acuity, visual field examination, optical coherence tomography (OCT), scanning laser polarimetry, visual evoked potentials, pattern electroretinogram, and a genetic study.

Results OCT and scanning laser polarimetry showed diffuse decrease of RNFL thickness, mainly left eye, retaining the typical morphology as double hump, in patient 1. Neurophysiology evaluation showed decrease in amplitudes of visual evoked potentials and pattern electroretinogram, and increased latency of P100 component. Neuro‐ophthalmologic exploration in patient 2 showed subclinical reduction of RNFL average thickness provided by OCT and increase of P50 and N95 latency by pattern electroretinogram. RNFL average thickness presents reduced scores in both patients, but without glaucomatous morphology.

Conclusion Duane radial ray syndrome, also named Okihiro syndrome, may affect retinal nerve fiber layer development and visual acuity.
An Introduction to Binocular Vision & Stereopsis. Why 2 Eyes are better than 1!
Authors: BARRETT BT
Published: December 2011

Purpose In visual normals, covering one eye does not markedly alter central vision. However, having two eyes confers at least 2 advantages. 1. Binocular Summation: performance is generally better on tasks when both eyes are open; and 2. Stereopsis: the recovery of information about depth that results from disparity in the retinal images in the right & left eyes. Indeed stereopsis is usually considered to be the ultimate in binocular co‐operation.

Methods The precise value of stereopsis remains somewhat controversial. Good stereopsis is highly valued by those who enjoy it and its loss due to trauma/pathology has a major negative impact. However, a significant minority of the population (>5%, many of whom have strabismus and/or amblyopia) have never had clinically measurable stereopsis and they appear to behave little different from visual normals in everyday tasks. If stereopsis is so valuable, why does its absence seemingly have so few consequences?

Results Here we examine the many facets of this conundrum, highlighting how, for example, many of those apparently without stereopsis when tested with standard clinical tests may in fact be capable of extracting depth‐from‐disparity information in lab‐based testing. It also emerges that those with reduced/absent stereopsis do exhibit differences relative to normals on fine motor tasks. And, when asked, these individuals often report avoidance of, or poor performance in, tasks relying upon good stereopsis.

Conclusion As well as introducing the symposium presentations, this talk will summarise the recent research literature on the importance of binocular vision & stereopsis. This shows that, as in visual normals, 2 eyes are better than 1 in seemingly stereo‐deficient individuals, but the binocular advantage is reduced.
Radiation induced optic neuropathy. Clinical presentation and treatment
Authors: GRAGOUDAS E
Published: December 2011

Abstract not provided
The preservation of ocular surface following complete irradiation of the anterior segment
Authors: SCHALENBOURG A , MAJO F , OTHENIN‐GIRARD P , ZOGRAFOS L
Published: December 2011

Purpose Diffuse iris or ciliary body (‘ring’) melanoma is still considered an indication for enucleation. We perform proton beam irradiation of the whole anterior segment as an alternative, conservative treatment for these eyes with often good vision.

Methods Since 1992 we treated more than 70 patients with total anterior segment irradiation, 60 of whom presented primary diffuse iris and/or ring melanoma. We studied local tumor control, eye retention probability, final visual acuity, radiation induced side effects and their management.

Results Local tumour control was 100%. Three eye were enucleated. Vision was influenced by tumor and radiation induced side effects such as cataract, intraocular hypertension and ocular surface toxicity. Their management consisted of phacoemulsification, trabeculectomy, deep sclerectomy or tube surgery and preventive limbus deposition and reposition (LDR).

Conclusion Proton beam irradiation of the whole anterior segment is a safe alternative to enucleation in diffuse iris or ring melanoma. Management of actinic cataract, glaucoma and ocular surface toxicity through modern techniques is essential for maintaining the eye and a useful vision.