bluuebunny/crossref_metadata_2025 huggingface dataset:
Animal models of glaucoma
Authors: BRON AM
Published: August 2014

Animal models of glaucoma are still useful to better understand the pathogenesis of glaucoma, to decipher biochemical pathways and to evaluate drugs at a preclinical development. Many species have been used but due to practical and economical reasons, rodents have been the most studied. We will detail the methods used to mimic glaucoma with the most common techniques with an elevation of IOP or not. Then we will review the in vivo endpoints mostly used to assess IOP elevation and glaucoma damage. Rebound tonometry has been a great improvement in the IOP recording accuracy in rodents. Electrophysiology is a surrogate of retina and optic nerve function in these animals. The structure is mainly evaluated with optic disc photography, fluorescein angiography SLO and more recently with OCT. We will end this presentation with the pros and cones of different in vitro techniques mainly used to characterise glaucoma damage at the level of the retina and the optic nerve head.
Pigmentary retinopathy
Authors: ASCASO FJ
Published: August 2014

Numerous medications can cause pigmentary retinopathies (PR). Firstly, we discuss the retinal toxicity in patients taking quinolones (chloroquine and hydroxychloroquine), which are traditional antimalarial agents now used to treat autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. Both medications bind to melanin in the retinal pigment epithelium (RPE), altering normal physiologic function and developing a bilateral bull's‐eye maculopathy. PR has also been shown to be related to high dosages of typical antipsychotics, including chlorpromazine and specially thioridazine. The frequency of occurrence of retinal effects seems to be proportional to the total amount of drug used over a long period of time. Furthermore, deferoxamine, an iron‐chelating agent used to treat conditions with excessive serum iron levels, produces a toxicity which is reversible with drug cessation. Other drugs such as etetrinate, quinine, methoxyflurane, didanosine, and clofazimine can be implied in PR. Psychiatrists, ophthalmologists, rheumatologists and patients need to be aware of any medication‐induced PR. Early prevention and intervention can avoid most of the serious and potentially irreversible ocular toxicities.
Retinal vasculopathies
Authors: GRZYBOWSKI A
Published: August 2014

Drug‐induced retinal vasculopathies constitute a group of rare disorders, most often produced by quinine, aminoglycosides, hormone preparations, and interferon. IFN‐ associated retinopathy includes cotton wool spots, retinal hemorrhages and retinal micro aneurysms. Aminoglycosides were often used subconjunctivally after different ocular surgeries as a postoperative prevention of endophthalmitis and intravitreally as a method of endophthalmitis treatment. Both clinical and animal studies have shown vascular changes, including whitening of the retina, retinal hemorrhages, multiple areas of vascular leakage and macular infarction. Although the true pathogenesis remains unknown, the clinical presentation of capillary nonperfusion has suggested a primarily vascular mechanism. The mechanism of quinine‐induced retinal toxicity, although still not well understood, includes probably ischemic/ occlusive type of events occurring in the posterior retinal circulation with relative sparing of choroidal circulation. Hormone‐related retinopathy, mainly due to oral contraceptives, include among others retinal hemorrhage or emboli, macular edema, and papillary edema.
Retinal drug toxicity in the absence of visible fundus changes
Authors: LAWRENSON J
Published: August 2014

A variety of systemic medications cause retinal drug toxicity associated with characteristic ophthalmoscopic changes e.g. pigmentary retinopathies, crystalline retinopathies, retinal vasculopathies, or retinopathies associated with macula edema. However, altered retinal function can occur in the absence of visible fundus changes. For example, the cardiac glycosides, digoxin and digitoxin, are frequently associated with disturbances of colour vision mediated through the inhibition of sodium‐potassium ATPase. Similarly, phosphodiesterase inhibitors such as sildenafil can also act on the photoreceptor transduction cascade to cause reversible changes in colour perception, blurred vision and increased glare sensitivity. Exposure to antiepileptic drugs that modulate GABA, can also lead to altered visual function. The most significant adverse reaction occurs with vigabatrin which can cause irreversible concentric visual field loss in susceptible individuals. It is important for eye care professionals to be aware of the potential for adverse reactions associated with systemic drugs and consider the use of functional vision tests for their detection and monitoring.
Glaucoma pathology: an eye on the brain
Authors: DEKEYSTER E , AERTS J , VALIENTE‐SORIANO FJ , DE GROEF L , SALINAS‐NAVARRO M , VIDAL‐SANZ M , ARCKENS L , MOONS L
Published: August 2014

Purpose Glaucoma is a group of optic neuropathies characterized by loss of retinal ganglion cells (RGC). Since ocular hypertension (OHT) is one of the main risk factors, current therapies are merely based on lowering eye pressure. As a subset of treated patients continue losing vision, more research into the pathological mechanisms underlying glaucoma is needed in order to develop novel therapeutic strategies. Here, we studied the impact of OHT on the main visual areas in the mouse brain: superior colliculus (SC) and primary visual cortex (V1).

Methods Temporary monocular hypertension (5 days) was induced in mice by lasering the episcleral and perilimbal vessels. The impact on the retina and its target areas was examined via immunohistochemistry (Brn3a, VGluT2 and GFAP). Alterations in neuronal activity in V1 were assessed via in situ hybridization for zif268.

Results Transient OHT resulted in diffuse and sectorial RGC death. In the SC contralateral to the OHT eye, we detected a strong decrease in synaptic connections at 1 week after lasering, which was retinotopically linked to RGC degeneration patterns in the retina. Similar retinotopic dropouts were discerned in activity patterns of V1 at 1 week post lasering, while V1 activity resumed 3 weeks later. In the SC, however, no recovery of synapse density was observed and inflammation was not resolved at 4 weeks post lasering. Nevertheless, SC neurons appeared healthy and cell density and cell morphology looked normal.

Conclusion Besides RGC death, OHT also induces loss of synaptic connections and neuronal activity in visual brain centers, accompanied by extensive immune responses. This stresses the importance of including the whole visual system in glaucoma research.
Lateral inhibition in the human visual system in healthy subjects and in patients with glaucoma
Authors: JUNOY MONTOLIO FG , MEENS W , JANSSENS MSA , STAM L , JANSONIUS NM
Published: August 2014

Purpose In glaucoma, the density of retinal ganglion cells (RGCs) is reduced. It is largely unknown whether and how this influences the spatial interactions between the remaining RGCs. A decrease in lateral inhibition might arise and could result in a larger than expected response to some stimuli, which could mask RGC loss on functional glaucoma testing. The aim of this study was to compare lateral inhibition in the visual system between glaucoma patients and healthy subjects.

Methods A case‐control study was performed with 14 glaucoma patients and 50 healthy subjects. Cases were selected to have advanced visual field loss in combination with a normal visual acuity. Controls had to have a negative ophthalmic and family history, normal eye pressure, and a normal acuity. Experiments were performed monocularly. Lateral inhibition was measured psychophysically on a computer screen, with (1) a modified illusory movement experiment and (2) a contrast sensitivity (CS) test. The illusory movement was quantified by nulling it with a real movement; measure of lateral inhibition was the amount of illusory movement. Log CS was measured at 1 and 4 cpd; measure of lateral inhibition was the difference between log CS at 1 and 4 cpd. Both measures of lateral inhibition were compared between cases and controls; analyses were adjusted for age with multiple linear regression

Results There was no difference in lateral inhibition between cases and controls (P=0.76 for illusory movement; P=0.84 for CS testing). Log CS was lower in the cases than in the controls at both 1 (‐0.21; P=0.006) and 4 (‐0.22; P=0.016) cpd.

Conclusion Lateral inhibition is not decreased in glaucoma patients, at least not in patients with a normal visual acuity.
Noninvasive drug delivery to the retina
Authors: STEFANSSON E
Published: August 2014

In general, only a small fraction of drug administered as eye drops enters the eye. This is due to permeability barriers of the eye as well as effective rinsing of the ocular surface. Additionally, lipophilic drug molecules are difficult to dissolve in adequate concentrations in eye drops. We have developed a drug delivery platform, based on cyclodextrins, which can be used to increase drug delivery with eye drops. The cyclodextrins are lipophilic on the inside and hydrophilic on the outside. This allows formation of water‐soluble complexes of cyclodextrins and lipophilic drug molecules, thereby increasing the possible concentration of drug in the eye drop. Cyclodextrins may also increase drug delivery by enhancing mucoadhesion and by facilitating transport of drug molecules through the unstirred water layer at the surface of the eye. We have formulated and tested cyclodextrin‐dexamethasone eye drops. The eye drops have been shown to decrease diabetic macular edema. A recent study also shows higher and extended concentration of dissolved dexamethasone after using cyclodextrin‐dexamethasone, compared to a regular formulation of dexamethasone.

Commercial interest
The Dublin Uveitis Evaluation Tool (DUET) – an algorithm for earlier diagnosis of spondyloarthropathies by ophthalmologists in acute anterior uveitis.
Authors: O'ROURKE M , HAROON M , RAMASAMY P , FITZGERALD O , MURPHY C
Published: August 2014

Purpose The association between anterior uveitis (AU) and spondyloarthritis (SpA) is well established. However, no algorithm exists to advise the ophthalmologist of which patients with AU should be referred to the rheumatolgist as a suspect SpA. Early diagnosis in SpA is key as disease severity and morbidity is related to disease duration. This study firstly establishes the incidence of SpA in an Irish cohort of patients attending eye casualty with previously unknown SpA. It also establishes a highly effective predictive algorithm to advise which patients should be referred to a rheumatologist as potential SpA.

Methods 104 consecutive patients with non‐infectious AU were recruited prospectively and subsequently screened by a rheumatologist for SpA. The most statically significant features were used to generate a predictive algorithm which was subsequently validated in a further cohort of 80 patients.

Results The incidence of SpA is 41.5% with average duration of backache 9.36 years. Multiple regression analysis with detailed step wise post‐hoc analysis identified that patients <45 years, with backache >3 months should have HLA‐B27 checked. If positive, a referral is appropriate. If negative, a history of psoriasis should be ascertained and if present, the patient should be referred. This algorithm has sensitivity of 95% and specificity of 98%. Validation of this algorithm in a second cohort had comparable sensitivity and specificity.

Conclusion The ophthalmologist has a necessary role in identifying SpA. Close collaboration between ophthalmologists and rheumatologists utilizing our algorithm will result in earlier treatment intervention to improve disease outcome.
Changes in vitreous haze over time with intravitreal sirolimus in noninfectious posterior‐segment uveitis (NI‐PSU): results of SAKURA Study 1
Authors: BODAGHI B , ALI Y , YANG Y , CHERNOCK M , THURAU S , PAVESIO C
Published: August 2014

Purpose To evaluate changes in vitreous haze (VH) scores over time in in SAKURA Study 1, a randomized, double‐masked, multicenter, international phase III study of subjects with active NI‐PSU.

Methods 347 subjects with active NI‐PSU (VH score ≥1.5+) were randomized to intravitreal sirolimus (44, 440, or 880 µg), given every 2 months. VH scores were assessed at Week 2 and Months 1–5.

Results At baseline, the mean (SD) VH scores were 1.9 (0.44) for the 440 µg group and 1.9 (0.50) for the 44 µg group. The risk:benefit profile was most favorable with 440 µg: Significantly more patients achieved a VH score of 0 at Month 5 (the primary endpoint) with 440 µg vs 44 µg (22.8% vs 10.3%; p=.025). 440 µg was also significantly more effective than 44 µg in achieving a VH score of 0/0.5+ (51.8% vs 35%; p=.012). Improvement was seen as early as Week 2 with 440 µg (22.8% with VH=0/0.5+) and continued improvement with this dose was seen at every analysis visit (36.0%, 40.4%, 49.1%, 42.1%, and 51.8% with VH=0/0.5+ at Months 1–5, respectively).

Conclusion Intravitreal sirolimus 440 μg significantly improved inflammation in this diverse NI‐PSU population. VH improvement was seen as early as 2 weeks after the first injection and continued through Month 5. Treatment with intravitreal sirolimus 440 µg appears to be effective in treating NI‐PSU, with a balanced safety profile.

Commercial interest
Ghrelin’s effects in diabetic retinopathy: Inhibition of choroid retinal cells migration cultured under a hyperglycemic environment.
Authors: ROCHA DE SOUSA A , SILVA‐GOMES R , PEREIRA‐SILVA P , AZEVEDO‐PINTO S , MOLEIRO A , CONCEIÇÃO G , LEITE‐MOREIRA AF
Published: August 2014

Purpose The purpose of this work is to investigate the effect of ghrelin in a primate choroid retinal cell line cultured under hyperglycemic conditions and its effect on the early changes of diabetic retinopathy in an animal model of type1 diabetes mellitus (DM1).

Methods A RF/6a cell line was used in the in vitro assay. Cell migration was assessed using the wound healing assay under increasing (0‐300mM) glucose concentrations. To test its effect, ghrelin was added (10‐5‐10‐10nM) to the cell cultures for 24h. Positive controls had VEGF added to the medium. For the in vivo studies, diabetic Wistar rats received intravitreal injections of either ghrelin (81nM) or saline every 4 weeks for 3 months. Vascular permeability was assessed using the Evans blue assay.

Results Increasing concentrations of glucose show a reduction in cell migration distance. We defined 10 mM of glucose as the basal and 250 mM as the hyperglycemic condition. At a concentration of 10‐8 nM ghrelin potentiates the reduction of migration induced by the hyperglycemic medium, and reduces the migration induced by VEGF. Regarding the in vivo model, diabetic animals treated with intravitreal ghrelin injections showed no alteration in vascular permeability, when compared with diabetic controls.

Conclusion Ghrelin reduces cell migration in choroid‐retinal cells under hyperglycemic media, but appears to have no effect on the vascular permeability in a DM1 animal model.
Managing the DME patient
Authors: PEARCE I
Published: August 2014

Abstract not provided
Laser Doppler flowmetrie on small animal
Authors: GEISER M , TRUFFER F , MENTEK M , BERNABEI M , APTEL F , CHIQUET C
Published: August 2014

We present a compact fundus camera designed to measure the blood flow in small animals based on laser Doppler flowmetry (LDF). The small animal is immobilized on a modified stereotaxic table and the pupil of the LDF device is superposed by translation to the pupil’s eye of the animal. Then rotation centered at the pupil is used to point the probing beam to the optic nerve head (ONH) or on retinal arteries (RA). LDF parameters Vel, Vol and F were assessed with a rotating teflon wheel simulating Doppler signal. Experiments were conducted on anesthetized adult male Wistar and Brown Normay rats. We demonstrated stable LDF parameters over 1 hours on RA and optic ONH for 6 and 10 rats respectively. Reproducibility is good for Vel on RA and ONH and moderate for Vol and F ONH. Transient ocular blood flow was blocked by increasing intra‐ocular pressure (IOP). Vel decreases significantly by 70% of baseline. Vel on RA was recorded during rat euthanasia. Vel decreases to the same level as for increased IOP. Vel measurement on RA are feasible, however measurement on ONH are more difficult probably due to a scare capillary network.
Current revision of the international classification of corneal dystrophies (IC3D)
Authors: LISCH W
Published: August 2014

The International classification of corneal dystrophies (CD) was published by the International committee for classification of corneal dystrophies (IC3D) in the Journal CORNEA in 2008. In the meantime, we propose some revisions. I`d like to present the main points: 1. New general classification of CD 2. Spliting of ERED (epithelial recurrent erosion dystrophy) into distinct entities 3. The so‐called epithelial‐stromal TGFBI dystrophies 4. Revision of Thiel‐Behnke CD 5. Lattice lines in granular CD, type 2 ? 6. Revision of congenital hereditary endothelial dystrophy (CHED): the so‐called CHED 1 = eponym of posterior polymorphous corneal dystrophy (PPCD).
Preclinical scheduling for metastatic ocular melanoma treatment by using a xenograft model approach
Authors: LEMAITRE S , NEMATI F , THULEAU A , LABIOD D , RODRIGUES M , DE PLATER L , PIPERNO S , SASTRE X , MARIANI P , ROMAN ROMAN S , GENTIEN D , DECAUTIN D , CASSOUX N
Published: August 2014

Purpose The prognosis for patients with disseminated ocular melanoma is poor. Responses to standard chemotherapy are low and serious toxicities are common. Here, we determine the feasibility of treating melanoma xenograft models in mice in order to guide the selection of treatments in metastatic patients.

Methods A patient‐derived xenograft model was established in SCID mice for metastatic choroidal and conjunctival melanoma. Mice bearing growing tumors were randomly assigned to the control or treatment groups. Mice were treated with dacarbazine and everolimus in the choroidal melanoma model. Dacarbazine and dabrafenib were used in the conjunctival melanoma model.

Results Everolimus resulted in tumor stasis in the choroidal melanoma model while dacarbazine had no antitumor effect. In the conjunctival melanoma model the relative tumor volumes in mice treated with dacarbazine and dabrafenib were similar to the control group. Since this is a feasibility study we included only a limited number of cancer drugs. More drugs will have to be screened in future studies. The oncologists in our institution were aware of the results but it had no influence on the choice of treatments for the patients. To our knowledge this is the first report of a conjunctival melanoma xenograft model in SCID mice.

Conclusion Our results suggest that ocular melanoma xenograft models can be used to determine which drugs achieve antitumor activity. These data could help oncologists in the choice of treatments for metastatic patients.
Retinal Oxygen distribution in normal and pathological cases; animal models and humans
Authors: POURNARAS C
Published: August 2014

The distribution of PO2 close to the vitreoretinal interface is heterogeneous, found higher near the arteriolar wall. Preretinal and transretinal PO2 profiles indicate that O2 diffusion from the arterioles affects the PO2 in the juxta‐arteriolar preretinal region. Both the preretinal and inner retinal PO2 recorded far from the vessels remain constant in all retinal areas. The oxygen tension (PO2) in the inner half of the retina remains largely unaffected by moderate changes in perfusion pressure. In addition a constant PO2 is observed during systemic PaO2 changes induced either by hyperoxia or hypoxia. However, an increase of PaCO2 (hypercapnia), as well as an intravenous injection of acetazolamide (carbonic anhydrase inhibitor) can both lead to an increase of preretinal PO2 due to retinal vessels dilatation. In the case of eyes with experimental branch retinal vein occlusion, PO2 values, within the inner retinal layers, are indicative of hypoxic conditions, whereas in adjacent unaffected retinal areas the PO2 remain normal. In diabetic patients undergoing vitrectomy, reports have shown a lowered vitreal POg in the affected retinal areas. Occlusion of the retinal circulation renders most of the inner retina anoxic.
Retinal oximetry in AMD
Authors: HEITMAR R
Published: August 2014

Abstract not provided
Emerging clinical concepts in ocular surface reconstruction
Authors: DUA H
Published: August 2014

Abstract not provided
Physiopathology of neovascular glauoma and preventive Anti VEGF injections
Authors: ZOGRAFOS L
Published: August 2014

Neovascular glaucoma is a major complication after proton therapy of uveal melanomas, and is provoked by vasoproliferative agents produced by the tumor or ischemic retina. Risk factors for the presence of an ischemic retina at presentation are largest tumor diameter (LTD) tumor height and the extent of retinal detachment. In a prospective study the efficacy of preventive anti VEGF treatment was estimated following Proton Beam radiotherapy of uveal Melanomas associated with an ischemic retinal detachment. None of the treated cases and 32% of the controlled group developped an neovascular glaucoma. The anti VEGF treatment was completed with and extensive laser photocoagulation of the ischemic retina. Anti VEGF treatment associated to retina photocoagulation appears as valuable therapeutic modality in selected cases of uveal Melanomas following Protom Beam radiotherapy.
Prevention of neovascular glaucoma by endoresection of the uveal melanoma scar after proton beam therapy
Authors: CASSOUX N
Published: August 2014

The conservative treatment of uveal melanoma by proton beau or plaque irradiation can induce severe side effects such as exudative retinal detachment, hard exudates, neovascular glaucoma. Part of these complications is not due to the irradiation itself but to a tumor necrosis. The scar releases factors not fully discovered (VGEF, TNF…) producing these complications called “toxic tumor syndrome”. The goal of the surgery in this case is to remove the necrotic scar and to prevent long term somplications leading to secondary enucleation. The risk of “tumor toxic syndrome” is correlated to initial tumor volume. This surgical technique could be proposed in tumors of more than 8 mm thick but with a diameter of less than 16 mm, without ciliary body or optic nerve invasion. The surgical technique and the results will be described in this paper.
Prevention of neovascular glaucoma by transcleral resection of the uveal melanoma
Authors: BECHRAKIS N
Published: August 2014

Radiation treatment of large uveal melanomas especially when they are infiltrating the ciliary body is often followed by the development of neovascular glaucoma. The reason for this is associated with the development of large hypoxic retinal areas and also necrosis of the irradiated tumor, that has been defined as “toxic tumor syndrome”. Resection of the tumour after successful irradiation is a very helpful way of treating this potential post irradiation complication. Prevention of the development of secondary glaucoma is even better for log‐term preservation of visual function. Especially when the tumor is located anteriorly where tumor endoresection is hazardous due to ciliary body hemorrhage, transscleral resection is a very helpful alternative. On the long term patients that have undergone this combined treatment regiment have a larger probability of eye and visual function preservation.
Endogenous production of anti‐inflammatory molecules maintaining ocular immune privilege
Authors: WALLACE G
Published: August 2014

Abstract not provided
A journey to Berlin, Utrecht, Paris and London in the footsteps of a cosmopolitan ophthalmologist of the second half of the 19th century
Authors: KESTELYN P
Published: August 2014

Richard Liebreich was born in Prussia in 1830. He studied medicine and graduated at Halle in 1853. He spent several months with Donders in Utrecht to refine his skills in optics and refraction. As a student of Helmholtz he witnessed the invention of the ophthalmoscope and took one of the first instruments to von Graefe’s clinic in Berlin. From Berlin Liebreich moved to Paris, where he achieved great succes. After the fall of Napoleon in 1870, Liebreich moved to London, where he became the head of ophthalmology at St. Thomas hospital and medical school. Following several personal attacks in the medical literature, Liebreich returned to Paris, where he gradually retired from medical practice, yet continued a creative life as an artist. Richard Liebreich improved the ophthalmocope,created the first ophthalmoscope utilized for demonstration purposes, devised a binocular corneal microscope which was a forerunner of the slitlamp, was a pioneer in fundus photography, and wrote the first paper on ophthalmic genetics. However, his lasting claim to fame was the creation of the first atlas of ophthalmoscopy.
Influence of cerebrospinal fluid pressure and its composition around the optic nerve on the development of glaucoma. Overview
Authors: DE GROOT V , WOSTIYN P , VAN DAM D , AUDENAERT K , DE DEYN PP
Published: August 2014

Growing evidence in the literature provides strong support for the concept that cerebrospinal fluid pressure (CSFP) plays a role in the pathogenesis of glaucoma. The CSFP forms the counterbalance to the intraocular pressure (IOP) across the optic disc. The pressure difference across the lamina cribrosa seems to be more important than the IOP on its own. This trans‐lamina cribrosa pressure difference depends on the imbalance between the IOP and the CSFP, and their fluctuations . Several studies have demonstrated that this pressure difference is higher in patients with normal tension glaucoma (NTG), providing an explanation for the mystery of NTG. Secondly, the CSF around the optic nerve may have a deficient clearance. Possible compartmentalization of this subarachnoidal space around the optic nerve has been documented. Also changes in general CSF circulatory physiology result in decreased CSF turnover, decreased CSFP and CSF stasis. Given the central role of CSF turnover in the clearance of potentially toxic metabolites from the brain, one might expect that CSF circulatory dysfunction could ultimately result in reduced neurotoxin clearance in the subarachnoid space surrounding the optic nerve and lead to glaucomatous damage.
Local immunоcorrection with MMSC‐like limbal cells in high‐risk keratoplasty patients
Authors: TONAEVA H , BORZENOK SA , ONISHENKO NA
Published: August 2014

Background. Local immunosuppressive therapy resistance in over that 45% of recipients in high‐risk keratoplasty determines search for the new methods of immune reaction suppression by activation of physiological tolerance mechanisms based on the cell technologies. With this in view mesenchymal stem/progenitor limbal cells with phenotype and properties of bone marrow MMSCs are of great interest as they form an outer cell‐tissue niche of the eyeball, accomplish local immunity regulation, physiological and reparative corneal regeneration. Purpose. To evaluate cadaveric donor graft survival rate in high‐risk recipients by co‐transplantation of pre‐cultured allogenic limbal transplants. Materials and methods. As a first step limbal transplants taken from the cadaver eye were cultured for 25,0±3,0 days in the medium (Borzenok‐Moroz). Functional activity of the cells was monitored by the content of pro‐ and anti‐inflammatory cytokines in the culture medium by ELISA. Phenotype of the cells after culturing was determined by flow cytometry with a panel of antibodies to MMSCs. At the second (clinical) step penetrating keratoplasties were carried out in 69 high‐risk patients. Experimental group (1st) comprised of 36 patients whom cultured limbal cells and cadaver corneas were transplanted simultaneously. In the 2nd (control) group (n=33) standard penetrating keratoplasty was performed. Results. The results of observation during the first 12 months after the surgery showed that in the 1st group transplant survival rate was much higher than in the 2nd group, 31 recipient (86,1%) and 23 recipient (69,7%), respectively. Endothelial cell loss was also much higher in the control group as opposed to the experimental group, 23,8±1,4% and 14,1±0,57%, respectively. Conclusion. Limbal transplants preserve their viability, demonstrate immune‐regulatory activity, and contribute to reprogramming of pro‐inflammatory to anti‐inflammatory local immune response after keratoplasty. Inhibition of local immune reactions by limbal cells co‐transplantation contributes to long‐term survival rate of the corneal grafts and preserved endothelial cells.
Simultaneous penetrating keratoplasty and artificial iris‐lens diaphragm implantation
Authors: POZDEYEVA N , PASHTAYEV NP
Published: August 2014

Materials and methods: Forty four eyes of 44 patients with aniridia after penetrating corneal injuries and traumatic post radial keratotomy wound dehiscences have undergone penetrating keratoplasty (PKP) and simultaneous artificial iris‐lens diaphragm (ILD) implantation. The average age was 36 years (8‐60 years). Time since trauma ranged from 3 months to 17 years. In 27 eyes intraocular pressure (IOP) was normal preoperatively, while 17 eyes were diagnosed with glaucoma. IOP was managed medically in 9 of these eyes, and 8 eyes had been operated for glaucoma before PKP + ILD. PKP was performed with the assistance of femtosecond laser in 10 eyes, and 34 eyes were operated with the use of Barron vacuum trephine. Five eyes had previous successful retinal detachment surgery, and 8 eyes had subtotal vitrectomy for vitreous hemorrhage. Results: Preoperatively mean non‐corrected distance visual acuity (NCDVA) was 0.03 ± 0.04 (m ± SD), corrected distance visual acuity (CDVA) was 0.04 ± 0.07, preoperative corneal astigmatism was 8.3 ± 5.8 diopters (D). Twelve months after the surgery mean NCDVA after traditional PKP was 0.08 ± 0.09, CDVA was 0.2 ± 0.19, corneal astigmatism was 4.7±3.9 D; and after femtolaser‐assisted PKP NCDVA was 0.1 ± 0.12, CDVA 0.3 ± 0.28, corneal astigmatism was 3.9 ± 3.1 D. In the group of 8 eyes previously operated for glaucoma only 1 eye experienced worsening of IOP control, requiring 2 extra filtering procedures including drainage device implantation. In the glaucoma medical management group of 9 eyes 1 eye required filtering surgery 1 month after PKP + ILD, while four more had to be operated for glaucoma as late as 9 to 24 months. Due to transplant failure cornea had to be regrafted in 6 of 9 patients in the glaucoma medical management group, and only in 2 of 8 patients who were previously operated for glaucoma. Conclusion: In patients after simultaneous penetrating keratoplasty and artificial iris‐lens diaphragm implantation surgery corneal transplant failure rate increases with IOP decompensation. Previous glaucoma surgery improves IOP control.
Visual acuity outcomes by baseline perfusion status in the COPERNICUS and GALILEO trials
Authors: PIELEN A , FELTGEN N , STEMPER B
Published: August 2014

Purpose To assess the impact of baseline perfusion status on best‐corrected visual acuity (BCVA) in patients with macular edema due to central retinal vein occlusion treated with intravitreal aflibercept (IVT‐AFL) injection.

Methods Patients received IVT‐AFL 2 mg (IVT‐AFL 2q4) or sham monthly up to Week 24 (W24). From W24‐W52, all IVT‐AFL–treated patients in both studies and sham‐treated patients in COPERNICUS were eligible to receive IVT‐AFL based on visual and anatomical outcomes (IVT‐AFL 2q4+PRN, sham+IVT‐AFL PRN). Sham‐treated patients in GALILEO were eligible to receive IVT‐AFL after W52. Retinal perfusion (<10 disc areas of nonperfusion) was assessed at baseline, W12, and W24 . Macular perfusion was not assessed.

Results COPERNICUS: In the baseline perfused group, mean BCVA change from baseline at W24, W52, and W100 was 17.1, 16.2, and 12.4 letters for IVT‐AFL2q4+PRN and ‐4.8, 2.9, and 0.5 letters for sham+IVT‐AFL PRN. In the baseline nonperfused group, mean BCVA change was 17.8, 16.0, and 14.2 letters for IVT‐AFL2q4+PRN and ‐2.3, 5.9, and 3.7 letters for sham+IVT‐AFL PRN. GALILEO: In the baseline perfused group, mean BCVA change from baseline at W24, W52, and W76 was 17.8, 16.8, and 13.6 letters for IVT‐AFL2q4+PRN and 6.0, 6.8, and 9.1 letters for sham+IVT‐AFL PRN. In the baseline nonperfused group, mean BCVA change was 17.1, 12.7, and 8.6 letters for IVT‐AFL2q4+PRN and ‐11.7, ‐13.0, and ‐9.7 letters for sham+IVT‐AFL PRN. In the overall populations, the most common ocular SAEs in IVT‐AFL2q4+PRN patients were cataract (COPERNICUS) and macular oedema (GALILEO).

Conclusion Both perfused and nonperfused patients treated with IVT‐AFL experienced similar gains in BCVA. Baseline perfusion status may not deter success in treatment with IVT‐AFL.

Commercial interest
Lessons learned from gene therapy for color blindness in primates
Authors: NEITZ J
Published: August 2014

Color blindness is the most common genetic disorder. The possibility of curing color blindness using gene therapy was explored by adding a third type of cone pigment to dichromatic retinas of squirrel monkeys. This opened a new avenue to explore the requirements for establishing the neural circuits for a new dimension of color sensation. The addition of a third opsin in adults was sufficient to produce trichromatic color vision. Thus, trichromacy can arise from a single addition of a third cone class in a primate and it does not require an early developmental process. This has implications for understanding how our brain processes conscious visual information and it illuminates the opportunities and limits of gene therapy for treating human vision disorders.
Case study
Authors: POURNARAS JA
Published: August 2014

Case Study will be proposed and therapeutical options will be discussed with the panel.
Cytological features of inflammatory cells infiltration indicates the etiology of infectious keratitis
Authors: SMEDOWSKI A , TARNAWSKA D , WYLEGALA E
Published: August 2014

Purpose To analyze histological findings of infectious keratitis in corneal epithelium including inflammatory cells infiltrations.

Methods We performed in vivo confocal microscopy (HRT III, Rostock Cornea Module) in 190 patients with diagnosed infectious keratitis of various etiology ‐ 72 viral, 66 bacterial, 34 fungal, 18 amoebal keratitis. For corneal scans we used 400x lens and 63x magnification. Microscopic analysis included inflammatory cells infiltration – number, size and shape of cells; superficial corneal nerve plexus (number and characteristics of nerve fibers) and cytology of epithelial cells. Described features were compared between groups.

Results Inflammatory cells densities showed no differences between groups, however there was clearly different ratio of round/dendritic inflammatory cells, respectively 0.07, 8.0, 1.0, 1.2 for viral, bacterial, fungal and amoebal keratitis (U‐Mann Whitney test, P<0.05). Additionally inflammatory cells presented various stage of polimorphism and polimegatism depended on keratitis type. Differences were observed also in nerve fiber numbers (U‐Mann Whitney test, P<0.05) and epithelial layer architecture.

Conclusion In vivo analysis of corneal epithelial histology shows high specificity and sensitivity in infectious keratitis diagnosis. Correct diagnosis of infectious keratitis is often difficult. In vivo microscopic analysis of both epithelial layer and cytology of inflammatory infiltration might provide fast and highly specific differentiation of keratitis etiology.
Terrien's marginal degeneration: Nordic collaborative study
Authors: KURKINEN M , DROLSUM L , FAGERHOLM P , HJORTDAL J , HOLOPAINEN J
Published: August 2014

Purpose The objective of our study is to describe the clinical and imaging features of Terrien's marginal degeneration (TMD) and subsequently to define the clinical diagnostic criteria for TMD. Lastly we aim to detect the natural course of this disease.

Methods Our study design is cross‐sectional and includes TMD patients diagnosed in Helsinki University Eye Hospital, Aarhus University Hospital, Sahlgrenska University Hospital and Oslo University Hospital by corneal specialists. Analysis include gender distribution, age, symptoms, as well as clinical, topographical and imaging findings. The analysis is based on descriptive variables due the limited sample size.

Results We present here clinical findings of Finnish TMD patients. All patients were asymptomatic and did not suffer from any systemic autoimmune diseases. Topographical analysis showed high astigmatism due to severe corneal thinning as evidenced by optical coherence tomography imaging.

Conclusion TMD is a bilateral corneal disease. Patients are commonly asymptomatic and visit an ophthalmologist because of deteriorated vision due to increasing astigmatism. TMD is thus diagnosed by coincidence. TMD does not seem to be associated with any systemic autoimmune diseases and it is commonly non‐progressing.
Keratoprosthesis. Personal experience
Authors: BARRAQUER J
Published: August 2014

Purpose Comment the Barcelona experience with different types of keratoprostheses

Methods Six cases of different keratoprostheses implanted at the Barraquer Eye Center in Barcelona from 1955 to 2014 are discussed.

Results The first keratoprosthesis implanted in Spain was a Dorzee acrylic keratoprosthesis in a case of bilateral chemical burn in 1955 with good functional and anatomic result for five years, when extrusion ocurred with simultaneous superior retinal detachment. The second case refers implantation of a Dorzee‐Barraquer‐Cardona acrylic keratoprosthesis in 1958 in a patient with terminal glaucoma. There was good anatomical retention until the patient’s death in 1970. In the third case a Cardona keratoprosthesis was implanted in 1960 after severe failure of two corneal transplants. Acute endophthalmitis ocurred after a satisfactory anatomical and functional result for 8 years. The fourth case shows extrusion of a Teflon‐supported keratoprosthesis (Girard). The fifth case discusses implantation of an osteo‐odonto‐keratoprosthesis (Strampelli)after blast injury with good anatomical and functional result for 10 years. The last case refers to the experience with the Boston keratoprosthesis in our Center since 2006.

Conclusion Clinical experience for more than 50 years at the Barraquer Eye Center confirms evolution of the original Dorzee‐Keratoprosthesis to the nowadays widely used Boston keratoprosthesis. In spite of progress in surgical technique, design and postoperative treatment, anatomical and functional results continue being a challenge for KPro surgeons due to the relatively high frequency of unresolvable serious sight‐destructive complications.
UK results for the OOKP
Authors: LIU CSC , AVADHANAM VS , HEROLD J , BUSUTTIL A , THORP TAS
Published: August 2014

The Osteo‐odonto‐keratoprosthesis (OOKP) is a time tested procedure. It is the only KPro with a proven long term track record. There has been a steady improvement in patient selection, surgical techniques, optical cylinder design, and perioperative management protocol, which have resulted in improved outcomes. We aim to present the visual, retention, and complications results from the UK national cohort of OOKP patients.
Indian MOOKP results
Authors: IYER G
Published: August 2014

MOOKP is indicated for bilateral end stage ocular surface disorders. Initiated in 2003, for the first time in India at Sankara Nethralaya, Chennai, the center has so far performed 90 cases of MOOKP. Results of 85 eyes of 82 patients will be described. The two most common indications were chemical injuries and SJS. The anatomical and functional results of MOOKP over a 10 year period will be discussed. Specific focus on lamina resorption and means to combat the same will be the highlight of the talk. The nuances and surgical specifics of combined glaucoma and vitreoretinal procedures in eyes undergoing the MOOKP procedure will be focused upon. Modifications in the technique, issues in eyes with SJS – a more common indication in our series and complications of the procedure will be discussed.
Intraretinal hyperreflective spots in eyes with radiation induced maculopathy
Authors: MIDENA E , PARROZZANI R , MIDENA G , FRIZZIERO L , VUJOSEVIC S , PILOTTO E
Published: August 2014

Purpose To evaluate in vivo the presence of intraretinal hyperreflective spots in eyes with radiation induced maculopathy.

Methods 25 subjects affected by maculopathy secondary to eye irradiation for a primary uveal melanoma were enrolled. All eyes previously underwent I‐125 brachytherapy with a standard apex dose (85 Gy). Full ophthalmic examination, including spectral domain‐OCT (SD‐OCT) and fluorescein angiography, was performed in all eyes. After segmentation of retinal layers, retinal images were analyzed for reflectivity changes (hyperreflectivity spots) at the level of: internal limiting membrane plus retinal nerve fiber layer (ILM+RNFL), inner nuclear layer plus outer plexiform layer (INL+OPL) and outer nuclear layer (ONL). Hyperreflective spots were analyzed in a full retinal section both in the foveal area, and between 500 and 1500 µm from the foveal center. All examinations were performed twice, by two independent masked graders. 

Results The inter‐grader agreement was at least substantial for all measurements. In all studied eyes hyperreflective spots were detected by SD‐OCT. Hyperreflective spots were mainly located in the inner retina (ILM+RNFL and INL+OPL) compared to the outer retina (ONL) (p<0.005), and their expression significantly progressed with the progression of macular (radiation induced) edema (p= 0.002). 

Conclusion The presence of hyperreflective spots may represent an in vivo biomarker of retinal microglia activation in radiation maculopathy, as previously shown in other macular disorders. This aspect may be related to the so‐called senescence process induced by irradiation of solid tumors. This phaenomenon may offer more tailored approaches for the treatment of radiation‐induced maculopathy.
Retrospective study of combined treatments for conjunctival melanoma
Authors: DESJARDINS L , YIN Y , CASSOUX N , LUMBROSO LE ROUIC L , DENDALE R , SASTRE X , ASSELAIN B , PLANCHER C , LEVY C
Published: August 2014

Purpose Since 2OOO, we have been using proton beam therapy after surgery for all invasive conjunctival melanomas. Patients with associated primary acquired melanosis also receive additional treatment with mitmycin 0, 04% drops at least two cycles. We have made a retrospective study to evaluate the results.

Methods Patients were sent to Curie Institute for initial treatment, after the initial surgery or for recurrence. Surgery was performed under general anesthesia; proton beam was applied only on the area of invasive melanoma with a dose of 60 grays in 8 fractions. Results concerning the initial findings, the treatment and the follow up were prospectively registered.

Results 62 patients were treated, 36 for initial treatment and 26 after surgery performed elsewhere. The median follow up is 24 months.(range 7 to 146 months) Median tumor diameter was 8 mm, with a thickness < 2mm for 33, > 2mm for 22 patients. TNM and histology will be described. Surgical excision was considered complete in 21 cases. All patients received proton beam irradiation and 25 received mitomycin drops. 10 patients (16%) presented local recurrence and 4 patients (6%) developed metastatic disease.

Conclusion : Because of direct contact with the sclera, invasive conjunctival melanoma cannot be removed with sufficient margin if the eye is not removed. The use of proton beam therapy immediately after surgery allows good ocular preservation with very low rate of local recurrence .The prognostic of patients with primary acquired melanosis with atypia has been improved by the use of preventive treatment of the conjunctiva by mitomycin before invasive melanoma occurs.
HSP90 inhibitors and conjunctival melanoma
Authors: MADIGAN M , QUAH X , MCALPINE S , CONWAY RM
Published: August 2014

Purpose To investigate the expression of HSP90 in human conjunctival melanoma (CM) cell lines and primary human melanocytes, and to assess the effects of HSP90 inhibitors on cell growth and proliferation.

Methods CM cell lines (CRMM1 and 2; CM2005.1) and primary human melanocytes (n=3, P2 to P4) were immunolabelled for HSP90, and visualised using immunofluorescence and confocal microscopy. HSP90 expression was also examined in cell lysates from CM cell lines (CRMM1 and 2; CM2005.1) and primary melanocytes (n=3). The effect of several HSP90 inhibitors (17DMAG, SM252 and SM122) on cell growth and viability was assessed at 24hrs.

Results CRMM1 and 2, and CM2005.1 cells showed strong cytoplasmic expression of HSP90, with low levels of cytoplasmic expression in primary melanocytes. This was confirmed using western blot. The HSP90 inhibitors induced dose‐dependent cell death in CM cells, 17DMAG (water soluble) being most effective (LD50 at 24 hrs ~30uM compared with ~50um for SM122 and SM122).Primary human melanocytes viability was not significantly reduced by the HSP90 inhibitors.

Conclusion HSP90 is a widely expressed chaperone protein that can regulate cell growth, survival and angiogenesis pathways. CM cell lines expressed high levels of HSP90 protein compared to melanocytes, consistent with a recent study of primary conjunctival melanoma specimens, that found over‐expressed HSP90 in CM, particularly recurrent tumours. HSP90 inhibitors may be useful in inhibiting CM growth alone or in combination therapies. Funding: National Foundation for Medical Research & Innovation (MCM & RMC); Lions NSW Eyebank
Prospective evaluation of intense pulsed light (IPL) therapy for meibomian gland dysfunction (MGD)
Authors: CRAIG JP , TURNBULL PR , CHEN A
Published: August 2014

Purpose To evaluate the effect of intense pulsed light (IPL) applied to the periocular area for meibomian gland dysfunction (MGD) in a prospective, double‐masked, placebo‐controlled, paired‐eye study.

Methods Twenty‐eight participants (aged 45±16 years, 68% female) underwent IPL treatment (E>Eye, E‐Swin, France), with homogeneously sequenced light pulses delivered to one eye (treated eye, randomised, masked), while placebo treatment was performed on the partner eye (control eye) on 3 occasions following baseline (BL) evaluation; on Day 1, Day 15, and Day 45. Lipid layer grade (LLG), non‐invasive tear breakup time (NIBUT), tear evaporation rate (TER), tear meniscus height (TMH) and subjective symptom score (SPEED) were compared to BL and control values at each visit.

Results LLG improved significantly from BL to Day 45 in the treated eye (p=0.0002), but not control eye (p=0.714) with an increase of 1.5 grades exhibited by 75% of treated eyes by Day 45. NIBUT also improved significantly from BL to Day 45 in the treated (p<0.0001), but not control eye (p=0.056). NIBUT in the treated eye was significantly longer than that in the control eye at Day 45 (14.1 ± 9.8s vs 8.6 ± 8.2s, p<0.0001). TER was not significantly lower at Day 45 compared to BL in the control eye (p=0.165), but approached significance in the treated eye (p = 0.080). No change in TMH was noted from BL in either eye at Day 45 (p>0.05). SPEED scores improved at each visit in both the treated (p<0.0001) and control eye (p=0.002), with 86% of participants noting reduced symptoms in the treated eye by Day 45.

Conclusion IPL with multiple sculpted pulses shows therapeutic potential for MGD, statistically and clinically improving tear film quality and reducing symptoms of dry eye.

Commercial interest