bluuebunny/crossref_metadata_2025 huggingface dataset:
Herpes virus infections
Authors: LABETOULLE M
Published: September 2008

The Herpes simplex virus (HSV) is characterized by its neurotropism and the balance between latent infection and reactivation. Studies on human post‐mortem tissues showed that HSV is widely distributed in the population, with a preferential location within the trigeminal ganglions (innervating the cornea), but also in the superior cervical ganglions (innervating the iris) or in brain/medullar tissues (innervating the retina). It is thus logical to observe in patients some association between neurological and ophthalmologic infection. Whereas retinitis, and in a lesser extent uveitis, may be classically associated to meningitis or meningo‐encephalitis, such association is rarer for herpetic keratitis or conjunctivitis, despite their superior frequency. This discrepancy is probably explained by sites from which virus reactivates, with a higher risk of encephalitis when reactivation occurs in the brain, comparatively to the trigeminal ganglion for example. Ideally, complete work‐up of presumed herpetic retinitis should include neurological examination, brain imaging, and lumbar puncture. In some cases, HSV (or VZV) are found in the cerebrospinal fluid, showing that viral reactivation is not only localized in ocular tissues.

Commercial interest
Corneal biomechanics and IOP measurements: the implications for glaucoma management
Authors: KOTECHA A
Published: September 2008

Whilst the effects of variations in central corneal thickness and corneal curvature on intraocular pressure measurement are well known, it has only been recently possible to measure corneal biomechanical properties in vivo. Reichert has produced an instrument, the Ocular Response Analyzer (ORA; Reichert Corporation; Depew, USA), that measures the corneal response to indentation by a rapid air pulse. The instrument generates a measure of corneal viscoelasticity, corneal hysteresis, which is a direct measure of the cornea’s biomechanical properties. This parameter may more completely describe the contribution of corneal resistance to IOP measurements than CCT alone. This talk will consider the effects of corneal parameters, including biomechanics, on intraocular pressure (IOP) measurement. The potential role of corneal biomechanics as an indicator of globe structural integrity will be discussed.
Is audible alarm useful in increasing adherence?
Authors: KOTHY P , HOLLO G
Published: September 2008

Purpose To investigate if objectively monitored adherence to travoprost administered once daily in the evening, improves if the alarm function of the monitoring device is activated.

Methods Thirty‐nine glaucoma patients were enrolled. Inclusion criteria were topical medication with once daily, evening administered travoprost 0,004% (Travatan, Alcon, Forth Worth, Texas, USA). Adherence to travoprost was monitored with an electronic monitoring device (Travalert Dosing Aid, TDA, Alcon, Forth Worth, Texas, USA). In the initial 3‐month period no alarm function was used, but in the second 3‐month period it was activated. Patients were instructed to instill travoprost at 9 p.m. Adherence was defined with instillation of travoprost at 9 p.m. (+/‐2 hours) as recorded by the device. Non‐adherence for the study period was defined as the ratio (%) of the non‐adherent days and all study days.

Results Thirty‐four participants completed both study periods. Adherence was 81.6 % in the first, and 85.3 % in the second phase. Non‐adherence was 18.4 +/‐ 18.9 % in the first period and 14.7 +/‐ 18.9 % in the second period (Wilcoxon signed rank test, p=0.059).

Conclusion Though the adherence was very good already in the first phase, it improved further when the audible alarm signal became activated. The improvement, however, did not reach the statistically significant level.
Malt lymphoma
Authors: COUPLAND SE
Published: September 2008

Purpose To review the histomorphology, immunophenotype and genotypic features of conjunctival "MALT" lymphomas.

Methods The conjunctival lymphomas represent the malignant end of the spectrum of lymphoproliferative lesions occurring in this site. The new W.H.O. Lymphoma Classification is the most suitable system for subdividing the conjunctival lymphomas, whereby the extranodal marginal zone B‐cell lymphoma of MALT type (or “MALT lymphoma”) represents the most common lymphoma subtype.

Results MALT lymphomas are characterized by mainly small B‐cells in the marginal zone. Their immunophenotype is: CD20+, CD43 (+/‐), BCL‐2, IgM+, and a low Ki‐67 growth fraction. A number of chromosomal changes have been described in conjunctival MALT lymphomas, and include trisomy 3, t(14;18), t(3;14), t(11;18), t(1;14) and loss of 6q23.3‐24. Through differing pathways, these chromosomal alterations result in the dysregulation of NF‐KB, and hence the uncontrolled proliferation of lymphocytes. In some geographical regions, there may be an association between these neoplasms and microorganisms, such as Chlamydia, Helicobacter as well as HCV. Management of patients with MALT lymphomas includes a thorough systemic medical examination to establish the clinical stage of the disease. The majority of patients with conjunctival lymphoma have Stage IE disease (Ann Arbor); however, systemic spread is not uncommon. Reported prognostic criteria for MALT lymphomas are few but include stage of disease at presentation; serum lactate dehydrogenase level; and tumour cell growth rate. A new more refined clinical staging system has been proposed by the TNM/AJCC committee and is to be published in its 7th Edition.

Conclusion Although the most common lymphoid neoplasm of the conjunctiva, there is still much to learn about MALT lymphomas.
Mantle Cell Lymphoma in the Ocular Region
Authors: HEEGAARD S
Published: September 2008

Purpose To characterize the clinicopathological features of mantle cell lymphoma (MCL) in the ocular region.

Methods All lymphoid lesions were retrieved searching the Danish Ocular Lymphoma Database 1980‐2007. Specimens were collected from Danish pathology departments and re‐evaluated with a panel of monoclonal antibodies. For all patients with confirmed MCL the complete clinical files were collected and reviewed.

Results Twenty‐one patients with MCL were identified comprising nine percent (21/230) of all lymphomas in the ocular region. There were 18 male and three female patients with an age range from 60 to 90 years (median 75 years). Ocular region MCL as first presenting symptom included 67% of the patients. Of these, 71% had bilateral involvement and all had lymphoma in more than one site within the ocular region. The orbit (71%) and eyelids (64%) were the most commonly affected sites. At the time of diagnosis 93% of the patients were in Ann Arbor stage III/IV, with bone marrow involvement (79%) and B‐symptoms (50%). Median overall survival (OS) was 30 months and the five‐year OS rate was 21%. Patients receiving anti‐CD20 (Rituximab)‐containing chemotherapy had a significant better 5‐year OS rate (80 %) (p < 0,027) than patients in treatment regimes without Rituximab (5‐year OS rate, 29%).

Conclusion MCL presenting in the ocular region has a male predominance and affects elderly patients. The orbit and eyelids were frequently involved. Patients with ocular region MCL as first presenting symptom had a high proportion of bilateral affection. Patients had advanced stage disease at diagnosis, multiple relapses and a low 5‐year OS rate similar to systemic MCL. Treatment with Rituximab‐containing chemotherapy improved survival significantly.
Current and possible future treatment of ocular adnexal lymphomas
Authors: PETTITT A
Published: September 2008

Purpose To review the current and possible future therapies of ocular adnexal lymphomas.

Methods Ocular adnexal lymphomas represent approx. 8% of all extranodal lymphomas. The majority of these can be classified as extranodal marginal zone (MALT) lymphomas, and are usually staged as Stage IE disease.

Results Recommended therapy in Stage IE tumours is low‐dose radiotherapy, while disseminated disease (>Stage IIE) is treated with chemotherapy. Although often responding to initial therapy, the MALT lymphomas tend to recur in distant extranodal sites. Few biomarkers are available to aid prediction of either recurrence or systemic dissemination, which occurs in up to 25% of patients. The ocular morbidity associated with current therapies is not insignificant, and, therefore, more effective treatment is being sought.

Conclusion The newer treatment options, including rituximab and doxycyclin, will be discussed
A patient preference comparison of two fixed combinations, brinzolamide 10 mg/ml+timolol 5 mg/ml suspension and dorzolamide 20 mg/ml +timolol 5 mg/ml solution in patients with open‐angle glaucoma or ocular hypertension
Authors: NOTIVOL R
Published: September 2008

Purpose To assess patient preference and comfort of Brinzolamide 10 mg/ml+Timolol 5 mg/ml Suspension (Brinz/Tim) compared to Dorzolamide 20 mg/ml+Timolol 5 mg/ml Solution (Dorz/Tim; COSOPT®) after topical ocular administration of a single drop.

Methods This was a double‐masked, randomized, active‐controlled, cross‐over, multi‐center study. Patients were randomly assigned to receive a single drop in both eyes of either Brinz/Tim or Dorz/Tim on day 1 followed by a single drop of the other medication on day 2. Immediately after dosing, the patients completed an ocular discomfort assessment (on a scale of 0‐9; 0 = no discomfort; 9 = substantial discomfort). On day 2 the patients also responded to a preference question.

Results Of the 129 patients enrolled, on day 1, 63 received Brinz/Tim and 66 received Dorz/Tim. Of these patients, 106 (82.2%) expressed a drop preference and met all inclusion/exclusion criteria (PP population). Brinz/Tim was preferred by 84 patients (79.2%) while 22 patients (20.8%) preferred Dorz/Tim (P < 0.0001). The mean discomfort scores (± SE) were 1.5 ± 0.2 for Brinz/Tim and 3.3 ± 0.2 for Dorz/Tim. Brinz/Tim was significantly more comfortable than Dorz/Tim (P < 0.05).

Conclusion Brinz/Tim was preferred by more patients than Dorz/Tim. Patients also responded that Brinz/Tim was the more comfortable medication. This significant advantage in comfort may promote patients compliance with respect to the chronic use of their IOP‐lowering medication.

Commercial interest
Phase III, 24‐month study investigating the efficacy and safety of tafluprost vs latanoprost in patients with open‐angle glaucoma or ocular hypertension
Authors: UUSITALO HMT , PILLUNAT LE , BAUDOUIN C , TRAVERSO C , BERGSTRÖM A , JENSSEN FT , ZAGORSKI Z , NESHER R
Published: September 2008

Purpose This double‐masked, active‐controlled, parallel‐group, multinational, multicentre, phase III, 24‐month study, conducted in 49 centres across 8 countries, investigated the efficacy and safety of tafluprost 0.0015% vs latanoprost 0.005% (once‐daily at 20:00) in 533 patients with open‐angle glaucoma or ocular hypertension.

Methods The primary endpoints were change from baseline IOP after 24 months (1.5 mmHg non‐inferiority limit [tafluprost‐latanoprost]) and safety.

Results Both treatments yielded a substantial IOP reduction, that was sustained for 24 months (tafluprost ‐7.1 mmHg; latanoprost ‐7.7 mmHg; n=402). Non‐inferiority was shown with ANOVA and almost reached with ANCOVA (upper limits of the 95% CI for the treatment difference were 1.38 and 1.52, respectively; RM models). Most ocular adverse events were mild and comparable between groups (48% vs 44%).

Conclusion This 24‐month phase III study demonstrated that both tafluprost and latanoprost yielded a substantial reduction in IOP that was sustained for 24 months, and a similar safety profile.

Commercial interest
Measurement of time‐resolved autofluorescence
Authors: SCHWEITZER D , SCHENKE S , JENTSCH S , QUICK S , GEHLERT S , HAMMER M , BERGMANN N
Published: September 2008

Purpose Functional alterations are first signs of reversible pathologic processes. Whereas microcirculation studies metabolism globally, autofluorescence of endogenous fluorophores has the potential for description of cellular basic processes. Therefore, a discrimination of fluorophores is required in the tissue.

Methods Besides excitation and emission spectra, the fluorescence lifetime after short‐time excitation is a promising substance‐specific mark. Using the opto‐mechanical system of a HRA II (Heidelberg Engineering), a fluorescence lifetime mapper was developed. Picosecond pulse‐lasers (448nm, 468nm, 100ps FWHM, 80MHz) can be used for excitation and the emission will be detected in 2 spectral ranges (490‐560nm, 560‐700nm). The dynamic fluorescence will be detected in time‐correlated single photon counting (SPC 150, Becker/Hickl, Berlin). An on line image registration is realised by simultaneously detected infrared images during measuring time. Approximating the fluorescence decay by 3‐exponential model function, images (lifetime and amplitudes), histograms, and cluster diagrams can be calculated for interpretation.

Results Examples are given for healthy subjects, AMD patients (non‐exudative, exudative, geographic atrophy), diabetic retinopathy, and oedema. Measurements of excitation and emission spectra as well as lifetimes are performed of expected substances and of anatomical ocular structures for comparison.

Conclusion Fluorescence lifetime measurement at the eye is a new method for evaluation of functional metabolic state.
Is there a role for dynamic retinal vessel analysis in internal medicine?
Authors: LANZL IM , SCHMIDT‐TRUCKSÄSS A , KOTLIAR KE
Published: September 2008

Purpose Human retinal vessels and their reaction to stimuli change during life and in disease due to physiological, genetic and pathological influences. Using the Dynamic Vessel Analyzer (DVA, Fa. IMEDOS, Jena) it is possible to assess changes in retinal vessel diameters in response to vasoactive stimuli in real time and non‐invasively.

Methods Retinal arterial vessel reaction in the natural time course and to the average of 3 consecutive monochromatic flicker stimulations (530‐600 nm, 12,5 Hz, 20 s) with a 80 s observation pause between stimulations was investigated in healthy volunteers of different age groups, obese patients, diabetes type 1 patients, systemic hypertensive patients and patients with lysosomal storage disease. Statistical data analysis of vessel reactions independent from the DVA program was performed.

Results There is a statistically significant difference in retinal vascular behaviour in different age groups in a healthy population. The same is true between a healthy population and each of the diseases investigated. Lysosomal storage disease however demonstrated an increase in dilation following flicker stimulation compared to normal persons.

Conclusion Flicker stimulation of the retina light evokes a prompt vessel reaction in all healthy subjects. We could demonstrate an age dependence of the retinal arterial reaction in medically healthy persons and in hypertension, diabetes and obese patients. From the increased reaction in lysosomal storage disease further understanding of different factors leading to the vascular reaction to stimuli may be derived. Application of flicker stimulus to retinal vessels represents a method to assess the endothelial function of vessels which is important to understand in systemic disease.
Mechanisms driving neovascularisation and microangiopathy in DR: VEGF‐triggers cell adhesion via endothelial‐ and leukocyte‐induced pathways
Authors: SHIMA DT , ADAMIS AP
Published: September 2008

Purpose Our research strategy has been to study VEGF‐A and the adaptive response to ischemia, with the aim of better understanding the benefit that VEGF‐A may bring to ischemic tissues, and to characterize the basis for the chaotic and poorly controlled neovascular response that usually accompanies ischemia in retinal diseases such as diabetic retinopathy.

Methods Acute retinal inflammation was induced using VEGF‐A and the mechanisms and consequences of retinal inflammation were examined in STZ‐induced diabetes in mice and rats. Various antagonists of VEGF signaling and of leukocyte adhesion were examined.

Results VEGF‐A induced upregulation of ICAM‐1 on endothelial cells in a VEGFR2‐dependent and Neuropilin‐1 dependent manner. VEGF‐A also triggered leuokocyte invasion via signaling through VEGFR1. These data predict that inhibiting the influx of leukocytes may demonstrate a benefit in DR, which was demonstrated by inhibition of ICAM‐1 function following STZ‐induced retinopathy

Conclusion Targeting of VEGF‐induced inflammation or leukocyte adhesion via ICAM‐1/LFA‐1 may provide a means of normalizing the microvasculature in DR

Commercial interest
Chemokines in proliferative diabetic retinopathy and proliferative vitreoretinopathy
Authors: ABU EL ASRAR AM , STRUYF S , KANGAVE D , GEBOES K , VAN DAMME J
Published: September 2008

Purpose To determine levels of the chemokines I‐309, MCP‐1, MIP‐1α, MIP‐1β, MCP‐3, MCP‐2, ENA‐78, GCP‐2, IP‐10 and I‐TAC in vitreous and serum from patients with proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR) and retinal detachment with no PVR (RD) and expression of MCP‐1, SDF‐1 and the chemokine receptor CXCR3 in epiretinal membranes.

Methods Vitreous and serum samples were obtained from 57 RD, 32 PVR and 88 PDR patients. The levels of chemokines were measured by ELISAs. Epiretinal membranes were studied by immunohistochemistry.

Results MCP‐1 and IP‐10 were the only chemokines detected in vitreous. Levels and incidence of detection in vitreous were significantly higher than that in serum for MCP‐1 (p<0.001 for both comparisons) and IP‐10 (p=0.0035; <0.001, respectively). Levels were significantly higher in vitreous from patients with PVR and PDR compared with RD for MCP‐1 (p=0.0002) and IP‐10 (p=0.0083). Incidence of IP‐10 detection was significantly associated with increased levels of MCP‐1 in vitreous (p<0.001). MCP‐1, SDF and CXCR3 were expressed by myofibroblasts and vascular endothelial cells in membranes.

Conclusion MCP‐1, IP‐10 and SDF‐1 may participate in pathogenesis of PVR. Clinical Relevance: Chemokines and their receptors could be molecular targets for preventing angiogenesis / fibrosis in the eye.
The role of arachidonic acid metabolites in DR
Authors: ABU EL ASRAR AM , MISSOTTEN L , GEBOES K
Published: September 2008

Purpose The inducible enzyme cyclooxygense‐2 (COX‐2) and its metabolic products are important mediators for angiogenesis. We investigated the expression of COX‐2 and its downstream enzymes microsomal prostaglandin‐E synthase (mPGES)‐1, cytosolic PGES (cPGES) and thromboxane synthase (TXS) and correlated it with vascular endothelial growth factor (VEGF) expression and level of vascularization in proliferative diabetic retinopathy (PDR) epiretinal membranes.

Methods Fourteen membranes were studied by immunohistochemistry.

Results Vascular endothelial cells expressed COX‐2, mPGES‐1 and VEGF in 75.6%, 64.3% and 50% of the membranes, respectively. TXS was expressed in stromal cells in 85.7% of the membranes. There was no immunoreactivity for cPGES. There were significant correlations between number of blood vessels expressing CD34 and the numbers of blood vessels expressing COX‐2 (rs = 0.858; p<0.001), mPGES‐1 (rs = 0.743; p = 0.002) and VEGF (rs = 0.845; p = 0.001) and the number of cells expressing TXS (rs = 0.74; p = 0.002). Number of blood vessels expressing VEGF correlated significantly with the numbers of blood vessels expressing COX‐2 (rs = 0.879; p<0.001) and mPGES‐1 (rs = 0.942; p<0.001) and the number of cells expressing TXS (rs = 0.702; p = 0.011).

Conclusion COX‐2 and its metabolic products might contribute to PDR angiogenesis.
Circulating fibrocytes contribute to the myofibroblast population in proliferative vitreoretinopathy epiretinal membranes
Authors: ABU EL ASRAR AM , STRUYF S , VAN DAMME J , GEBOES K
Published: September 2008

Purpose Fibrocytes, circulating cells that co‐express markers of hematopoietic stem cells, leukocytes and fibroblast products, traffic to sites of tissue injury, differentiate into myofibroblasts and contribute to wound healing and fibrosis. We investigated the presence of fibrocytes and the expression of their chemotactic pathways CCL21 / CCR7 and CXCL12 / CXCR4 in proliferative vitreoretinopathy (PVR) epiretinal membranes.

Methods Sixteen membranes were studied by immunohistochemical techniques.

Results Cells expressing alpha‐smooth muscle actin (alpha‐SMA), a marker of differentiation of fibrocytes into myofibroblasts, were present in all membranes. Cells expressing the hematopoietic stem cell antigen CD34, the leukocyte common antigen CD45, CCR7, CXCR4, CCL21 and CXCL12 were noted in 50%, 75%, 68.8%, 100%, 80% and 93.8% of the membranes, respectively. Double immunohistochemistry indicated that all cells expressing CD34, CD45, CCR7, CXCR4, CCL21 and CXCL12 co‐expressed alpha‐SMA. The number of cells expressing CD34 correlated significantly with the numbers of cells expressing CXCL12 (rs = 0.567; p = 0.022) and CCL21 (rs = 0.534; p = 0.04).

Conclusion Circulating fibrocytes may function as precursors of myofibroblasts in PVR membranes.
Sclerocorneal limbus transplantation
Authors: BARRAQUER J
Published: September 2008

Purpose Discussion of the evolution of a technique suggested by José I. Barraquer in 1947, later completed by Strampelli and adopted and modified by other corneal surgeons. The original procedure was based on the clinical observation that regeneration of the corneal epithelial cells is dependant on the state of the limbus. This explained the bad prognosis of chemical burns and severe limbus trauma. At present it is well known that the stem cells located in the corneal limbus are responsible for epithelial regeneration. Penetrating keratoplasty limited to the cornea does not supply stem cells.

Methods The technique consists in obtaining and grafting limbus tissue, in form of an annular or partial conjunctivosclerocorneal limbal graft preferably from the fellow eye or a living donor, or an eye bank eye. A case of chemical burn operated in 1981 is presented to illustrate the original technique of Strampelli. To illustrate the modern approach a case of chemical trauma with superior and inferior symblepharon and total vascularized leucoma operated in 1999 (limbal donor graft)taking advantage of the modern advances available at present (improved instrumentation, pharmacological inhibition of homograft reaction)is shown.

Results The results were encouraging.The patient operated in 1981 died in 1988 with good vision (0.6).In the case operated in 1999, three months after the limbal transplant, re‐epithelization of the cornea was correct and an 8 mm penetrating keratoplasty combined with cataract extraction and IOL implantation was performed. Corrected vision 5 years postoperatively was 0.35.

Conclusion Modern investigation and technology have converted a procedure based on surgical inspiration more than half a century ago into a valuable option in cases of irreversible damage of the corneal limbus.
Impact of culturing on metabolic profile of human corneas
Authors: KRYCZKA T , EHLERS N , MIDELFART A
Published: September 2008

Purpose The aim of this study was to examine possible differences in the metabolic profile between cultured and non‐cultured corneas.

Methods Corneas from 12 donors were obtained post‐mortem and introduced to the tissue culture for 8‐20 days. The control corneal tissues were excised during enucleating of eyes with malignant melanoma in the retina from 4 patients and immediately frozen at ‐80 ºC. The metabolic profiles of the samples were investigated with HR MAS (High Resolution Magic Angle Spinning) 1H NMR (Nuclear Magnetic Resonance) spectroscopy (14.1 T) operating at 600.132 MHz. All data obtained with both methods were analysed using special software for: (i) analysis of complex mixtures, (ii) principal component analysis – PCA, (iii) detailed statistical analysis.

Results Significant deferences in metabolic profiles between cultured and non‐cultured corneas were detected. The levels of several metabolites in cultured tissues were increased in comparison to the control. It was also shown that the levels of some of metabolites in samples cultured for 9‐14 days differed significantly from the samples kept for less than 9 days or 15‐20 days.

Conclusion Corneal culturing results in the changes of the metabolic profile in tissue. The increase of the levels of the metabolites in organ within the second week of culturing may indicate increased enzymatic activity or/and increased response of cells toward stress factors in the tissue.
MMP involment in TGFbeta‐mediated matrix contraction: implications for PCO
Authors: ELDRED JA , HODGKINSON LM , REDDAN JR , EDWARDS DR , WORMSTONE IM
Published: September 2008

Abstract not provided
Intraocular lens features that affect PCO
Authors: SPALTON DJ
Published: September 2008

Purpose To review IOL features that affect PCO

Methods Review of clinical PCO studies using retroillumination imaging and objective quantification of PCO following cataract surgery and laboratory EM studies of IOL profile

Results The optic diameter, haptic design and IOL material all affect PCO performance but the optic edge profile is the most important. Electron microscopy shows IOL edge is of variable profile in so called 'square edge' IOLs and this can be explained by the inevitable interrelationship of the limitations that material imposes on engineering, early closure of the capsular bag around the IOL seems to be important in preventing leakage of LECs into the retro lenticular space soon after surgery that later proliferate and form clinical PCO

Conclusion PCO has a multifactorial pathogenesis. Improved IOL design can limit but does not prevent PCO

Commercial interest
Effect of bimatoprost on patients with primary open‐angle glaucoma or ocular hypertension who are nonresponders to latanoprost or timolol
Authors: BHATT UK , BANERJEE S
Published: September 2008

Purpose To test the efficacy of bimatoprost 0.03% in lowering intraocular pressure (IOP) in patients affected by primary open‐angle glaucoma or ocular hypertension who did not respond to treatment with latanoprost 0.005% or timolol 0.5%.

Methods It was a retrospective case‐note review study with minimum 6 months follow‐up. Between May and October 2007, all patients who were not responsive to latanoprost or timolol (monotherapy) were prescribed bimatoprost. In all, 635 eyes of 330 patients (latanoprost, n=405; timolol, n=230) were included. Eligibility criteria: (1) Patients with original diagnosis of POAG, and (2) Nonresponsives‐ IOP reduction <20% on current treatment.Main outcome measure was IOP reduction.

Results IOP data (mean and standard deviation) were as follows: baseline = 24.85 ± 2.05 mmHg, after latanoprost =21.23 ± 1.6 mmHg, after timolol = 21.5 ± 1.66. When switched over to bimatoprost, mean IOP =18.39 ± 2.32 mmHg. There was statistically significant reduction in the IOP on bimatoprost when compared to baseline, latanoprost, and timolol (P<0.0001). 12.34% of latanoprost and 13.04% of timolol nonresponders did not respond to bimatoprost as well. While 12.72% patients reported significant conjunctival hyperaemia, only 6.96% had to stop the drug because of it.

Conclusion Bimatoprost is better in controlling intraocular pressures in those non‐responsive to latanoprost or timolol. Conjunctival hyperemia remains the most important cause of stopping the use of bimatoprost.
Inhibition of vascular endothelial growth factor reduces scar formation after glaucoma filtration surgery
Authors: VAN BERGEN T , VAN DE VEIRE S , MOONS L , STALMANS I
Published: September 2008

Purpose In 30‐50%, glaucoma filtration surgery fails due to excessive postoperative scarring. This study was designed to elucidate the role of vascular endothelial growth factor (VEGF) in fibrosis after glaucoma surgery. In addition, the effects of the monoclonal humanized VEGF‐antibody bevacizumab (AvastinTM, Genentech) on fibroblast proliferation and outcome after trabeculectomy were studied.

Methods The effect of VEGF and bevacizumab on Tenon fibroblasts in vitro was determined using a Tenon fibroblast mediated proliferation assay. The effect of the antibody was also investigated in vivo in a rabbit model for glaucoma surgery by measuring intra‐ocular pressure (IOP) and bleb area, and by (immuno‐)histological analysis of inflammation and fibrosis. VEGF‐concentration after bevacizumab‐administration was measured in samples of aqueous humor by ELISA.

Results The proliferation of human and rabbit Tenon fibroblasts in vitro was stimulated by VEGF‐delivery and inhibited by bevacizumab‐administration. The antibody also significantly improved glaucoma surgery outcome, more specific the bleb area, in a rabbit model of trabeculectomy. Inflammation and collagen deposition were significantly reduced after bevacizumab treatment as compared to sham injections. VEGF was significantly reduced in aqueous humor after bevacizumab‐administration.

Conclusion VEGF stimulates in vitro fibroblast proliferation suggesting that it plays a role in scarring after filtering surgery. Furthermore, the monoclonal humanized VEGF‐antibody reduces in vitro fibroblast proliferation and improves surgical outcome in vivo in a rabbit model of trabeculectomy.
Epigenetics, chromosome 3 and early detection of metastasis
Authors: VAN DER VELDEN PA , MAAT W , VERSLUIS M , KOUCH‐EL FILALI M , JAGER MJ
Published: September 2008

Purpose Uveal melanoma patients that present a tumor with monosomy 3 have a high propensity to develop metastases. Based on the two‐hit hypothesis, one might expect that the remaining copy of chromosome 3 contains a genetically‐modified gene and that loss of this gene is responsible for malignant progression. Identification of the gene and the genetic or epigenetic mechanisms that influence genes on chromosome 3 will enlighten the pathway(s) that determine uveal melanoma progression. In addition, studying epigenetics may result in useful molecular markers: whereas analysis of monosomy 3 is useful in primary tumors, it is useless in the detection of spreading tumor cells in the blood. We propose that a molecular marker in the form of a (tumor specific) genetic or epigenetic modification will be more helpful in this respect.

Methods We have analyzed genes on chromosome 3 for epigenetic regulation that may suffice in non‐invasive testing for spreading tumor cells.

Results We have identified RASSF1a methylation as a predictor of metastasis in uveal melanoma based on analysis of uveal melanoma tissues. In order to detect disseminating tumor cells in the bloodstream of uveal melanoma patients we have developed a very sensitive assay for methylation of RASSF1a. The detection limit of RASSF1a methylation exceeds 1/10,000 and in combination with isolation cell‐free DNA we are able to detect tumor DNA in the background of a vast excess of normal blood cells. With this assay we will test patient blood and validate the prognostic and diagnostic value of this marker.

Conclusion With this assay we will test patient blood and validate the prognostic and diagnostic value of this marker.
Identification of molecular markers associated with high metastatic risk in uveal melanoma
Authors: SAULE S , LAURENT C , COUTURIER J , DECRAENE C , DESJARDINS L , SASTRE X , BARILLOT E , ALMEIDA A , PIPERNO‐NEUMANN S
Published: September 2008

Purpose Uveal melanoma occurs to the detriment of uveal melanocytes (located in the iris, ciliary body and choroid) and is the most common intraocular malignancy in adults, with 500‐600 new cases every year in France. The survival rate for uveal melanoma has not increased significantly in the last 20 years.

Methods Gene expression profiling from the 63 tumours with a three years follow‐up (33 of which have metastasized) have been already performed, and genes selection using significant analysis of microarays performed between primary tumours that have metastasized (meta1) and those that do not have metastasised (meta0) showed that 1210 probe sets are differentially expressed using a FDR cut off of 5%. Gene expression profiling from 115 liver metastasis have also been performed and compared with the primary tumors.

Results We used real‐time PCR to validate, using a set of selected genes the microarray expression values. The results obtained with 14 uveal melanoma showed a complete concordance with the Affymetrix microarrays. We have already obtained a set of genes involved in cell migration differentially expressed between primary uveal tumors that have, or not, metastazised. These genes included the PTK2 focal‐adhesion kinase, an important mediator of growth‐factor signalling, cell proliferation, cell survival and cell migration. We will also focuss on NEDD9, a gene described by oncogenomic analysis as involved in melanoma metastasis. In our study PTK2 and NEDD9 expression are anticorrelated, (p=0,015), PTK2 is found more expressed in the meta1 group.

Conclusion we hope that deciphering the function of the selected genes will help to identify new pharmacological targets.
Duration of retinal detachment and central retinal artery hemodynamics: repercussion on logmar visual acuity
Authors: ROLDAN‐PALLARES M , MUSA AS , HERNANDEZ‐MONTERO J , BRAVO‐LLATAS C
Published: September 2008

Purpose To analyze if duration of primary rhegmatogenous retinal detachment(RD)influences central retinal artery(CRA) hemodynamics with repercussion on LogMAR visual acuity (VA)

Methods Sixty six healthy patients between 42 and 70 years with unilateral RD candidates for scleral buckling(SB)surgery(PVR<C3)as a first and single surgical procedure were prospectively selected. Central retinal artery(CRA) Doppler sonography parameters:peak systolic(PSV) and end diastolic(EDV) velocities and resistive index(RI); and IOP were measured before SB. Pearson's correlations were evaluated between duration and each CRA parameter and also between both variables and LogMAR VA(preoperative, postoperative and the difference: postoperative minus preoperative)

Results Preoperative LogMAR VA showed significant(p<0.0001) linear correlations with duration of RD(r=0.615) and with CRA parameters: PSV(r=‐0.485), EDV(r=‐0.592), RI(r=0.509). Postoperative LogMAR VA, with (all with p<0.0001) duration (r=0.619), and with CRA parameters: PSV(r=‐0.637), EDV(r=‐0.711), RI(r=0.630). LogMAR VA Difference showed lower correlations with duration(r=0.085, p=0.0498)and with CRA parameters: PSV(r=‐0.266, p=0.031), EDV(r=‐0.236, p=0.057)and RI(r=0.238, p=0.054) than pre‐ and postoperative LogMAR VA.

Conclusion Duration showed a higher correlation with preoperative LogMAR VA and a lower correlation with postoperative LogMAR VA and with LogMAR VA difference than the CRA parameters. (Supported by FIS 04/0446)
Idiopathic epiretinal macular membrane and cataract extraction : combined surgery vs consecutive surgery
Authors: CREUZOT CP , DUGAS B , OULED‐MOUSSA R , LAFONTAINE PO , GUILLAUBEY A , HUBERT I , BRON AM , BERROD JP
Published: September 2008

Purpose To assess the functional and anatomical outcome of cataract and idiopathic epiretinal macular membrane extraction in combined and consecutive surgeries.

Methods A retrospective nonrandomized study of 174 epiretinal macular membranes (ERM) and cataract extractions in 1 or 2 sessions was undertaken in two academic centers. Combined surgery (n=109) and successive surgery (n=65) were performed between 2005 and 2006. All patients underwent ERM and internal limiting membrane removal. We compared the near and far visual acuity and the central macular thickness with OCT (Optical Coherence Tomography) for these procedures.

Results Mean follow‐up was 8 months. The postoperative best‐corrected visual acuities significantly improved in both combined (near and far vision: p<0.0001) and consecutive surgeries (near and far vision: p<0.0001) groups. Similarly, the postoperative macular thickness significantly decreased in both groups (p<0.0001). We noted no statistical differences between the visual acuity improvement in both groups (near vision p=0.54; far vision p=0.38).

Conclusion Combined and consecutive surgeries are effective procedures to treat idiopathic ERM. The functional and anatomical results are equivalent in these two procedures. However, combined surgery is more convenient for the patient.
A new method for fixation and explantation of epiretinal implants
Authors: IVASTINOVIC D , LANGMANN G , HORNIG R , RICHARD G , VELIKAY‐PAREL M
Published: September 2008

Purpose In epiretinal prosthesis surgery the fixation of the implant on the retina is generally performed with retinal tacks in order to achieve a firm and a sufficiently close attachment to the ganglion cells. However, this fixation does not allow the removal of the implant without potentially causing major trauma. We therefore developed a new fixation method for the implant with the goal of enabling a safe and less traumatic explantation procedure.

Methods We implanted an inactive epiretinal device consisting of a polyimide strip and a calotte in 11 Göttinger minipigs. The concept of the new fixation method is to implant the tack first and fixate the implant on the tack with a silicone tube by using a special instrument developed for this purpose. Thus the implant is firmly attached to the retina and removal can be performed by simply splitting the silicone tube and lifting the implant from the tack while the tack remains in place.

Results All animals were implanted successfully without major complications. At the end of the observation periods the retinal tack and the silicone tube fixating the implant on the tack were still in position. The explantation procedure was accomplished easily and without any complications.

Conclusion This new implantation method ensures a firm fixation of the implant whilst also allowing explantation without trauma to the posterior eye segment.
Experimental models of orthotopic limbal transplantation in the mouse. Evaluation of allo‐ and xenograft survival and characterization of cytokine response
Authors: LENCOVA A , POKORNA K , ZAJICOVA A , FILIPEC M , HOLAN V
Published: September 2008

Purpose To establish and characterize experimental model of orthotopic limbal allo‐ and xenotransplantation in the mouse. Evaluation of graft survival and detection of intragraft cytokine response.

Methods Syngeneic (BALB/c donors), allogeneic (B6 donors) and xenogeneic (rat Lewis) orthotopic limbal transplantation was performed in BALB/c mice. Recipients with intact or removed corneal epithelium were used. Limbal graft survival and reepitelization of the cornea were scored clinically (opacity, oedema, neovascularization) or by the presence of graft donor cells as detected by the Real‐time PCR. Expression of genes for IL‐2, IL‐4, IL‐10, IFN‐γ and nitric oxide (NO) in the graft was detected by PCR.

Results Significant differences in opacity, oedema and neovascularization were observed in syngeneic, allogeneic and xenogeneic limbal grafts and in the recipients´ corneal epithelium. The strongest rejection reaction was induced by limbal xenograft. No xenogeneic cells were detected in the graft 2 weeks after transplantation. The rejection reaction was accompanied by an abundant cytokine and NO response in the graft.

Conclusion The experimental limbal transplantation in the mouse can be a useful model to characterize rejection reaction and to test various immunosuppressive treatments after limbal tissue or limbal stem cell transplantation.
The Royal Victorian Eye and Ear Hospital (RVEEH) technique of DSAEK Triple
Authors: BELTZ J , JHANJI V , SHARMA N , VAJPAYEE RB
Published: September 2008

Purpose Descemet stripping endothelial keratoplasty, together with cataract surgery, constitutes the DSAEK triple procedure. This remains an evolving technique, with new modifications continuing to simplify the technique and improve its reproducibility.

Methods At the Royal Victorian Eye and Ear Hospital (RVEEH), we have developed a sutureless technique of DSAEK triple using a glide to insert the donor lenticule. This procedure was performed in 4 eyes of 4 patients with Fuchs’ endothelial dystrophy and cataract.

Results All surgeries could be performed successfully. No intraoperative complications were encountered in any of the cases. At mean follow up of 3 months, all grafts were attached, clear, and well‐centered, with mean BCVA ≥6/18. There were no instances of graft dislocation or failure.

Conclusion The RVEEH technique of Sutureless DSAEK Triple procedure is effective, successful and easy to perform. The use of a glide eliminates the need for folding of the tissue and allows atraumatic transplantation of the donor lenticule.
Full thickness cornea transplantation to lamellar bad managing extensive corneal perforations
Authors: ASOKLIS R , BUTKIENE L , JUODKAITE G , MAKSELIS A , PAJAUJIS M , CIMBALAS A
Published: September 2008

Purpose Present surgical techniques for managing extensive corneal perforations.

Methods In three eyes of the three patients full thickness to lamellar bad cornea transplantations were performed because of the cornea perforations. In all cases previous to corneal grafting amniotic membrane was transplanted in tectonic purposes since donor corneas were not urgently available. Surgical techniques of the amniotic membrane transplantation consisted of intrastromal fluffed–up and intrastromal blanket‐fold multilayered amniotic membrane transplantations. Full thickness corneal grafts were decided because of the extensive descemet defects in the bad of the ulcers. Previously to the surgeries clinical diagnosis of ocular rosacea, herpetic keratitis and keratitis sicca were establisched in every consequent case. Additional sistemic treatment was administered for ocular rosacea and herpetic keratitis patients.

Results In all three cases multilayered amniotic membrane transplantation showed sufficient effect for restoration integrity of the globe for short period. Full thickness corneal transplantation to lamellar bad was effective surgical procedure. In one case double anterior chamber was observed for 1 month.

Conclusion 1.Multilayer amniotic membrane transplantation can be as the bridge to cornea grafting, in cases, when donor corneas are not urgently available. 2. For extensive corneal perforations full thickness cornea transplantation to lamellar bed is reliable method of treatment. 3. If corneal perforations are related to systemic disease it is necessary to administer appropriate regimen of the adjacent systemic medical treatment.
Corneal thickness values in case of patients who underwent lamellar keratoplasty using various evaluation techniques.
Authors: JANISZEWSKA D , WYLEGALA E , DOBROWOLSKI D , MILKA M
Published: September 2008

Purpose To analyze results of pachymetric measurements in patients after deep anterior lamellar keratoplasty (DALK) and endothelial keratoplasty (DSEK) using three techniques of pachymetry estimation.

Methods For the study 35 eyes after various lamellar keratoplasty were qualified. 20 eyes they who underwent DSEK (12 women and 8 men) and 15 after DALK (9 men and 6 women). The subjects age ranged from 23 to 92 years old (mean 45.0.1 years). The follow‐up ranged from 9 to 31 months (mean 16.8 months). Patients underwent routine DSEK and DALK, using “big bubble” technique, surgery. Pachymetric values were achieved using three devices: ultrasonic pachymeter, specular microscope, Anterior Segment OCT. Pachymetric outcomes were analyzed and compared.

Results Total corneal thickness in case of patients who underwent DSEK surgery using ultrasound pachymeter ranged from 581 to 829µm (672.4 ± 89.1), specular microscope registered values from 518 to 719µm (575.4 ± 78.3), OCT Visante ranged from 575 to 911µm (690± 122.1). Total corneal thickness in patients who underwent DALK surgery using ultrasound pachymeter ranged from 382 to 571µm (487 ± 76.8), specular microscope registered values from 380 to 481µm (427 ± 84.2), OCT Visante ranged from 379 to 569µm (439± 143.1). Corneal thickness values received with the use of ultrasound and OCT values significantly differed form obtained using specular microscope.

Conclusion Specular microscope seems to omit graft thickness in corneal pachymetry evaluation, also pachymetric outcomes are underrated, even though is able to calculate endothelial cell density in patients who underwent lamellar keratoplasty.
Factors influencing the outcome of the treatment of allograft corneal graft rejection
Authors: PERERA CM , JHANJI V , BELTZ J , LAMOUREUX E , POLLOCK G , VAJPAYEE RB
Published: September 2008

Purpose To identify clinical characteristics of patients which influence the outcome of treatment of allograft corneal graft rejection.

Methods A retrospective chart review of 197 cases of corneal graft rejections was undertaken at the Royal Victorian Eye and Ear Hospital, Melbourne over a period of ten years from 1997‐2007. Cases were divided into two groups according to the response to the treatment after allograft corneal rejection. Main parameters evaluated were demographic characteristics, primary indication of corneal graft and preoperative donor characteristics.

Results Corneal graft rejection was successfully treated in 163 cases and 34 cases failed to respond to therapy. Both the groups were age (p=0.12) and sex‐matched (p=0.85). Keratoconus was more common as the primary indication for corneal graft in the group that had good response to the treatment (19% vs 5.9%; p= 0.08). Cases that failed to respond to treatment had higher number of recipient grafts > 9mm (9.4% vs 1.3%; p=0.04). Preoperative corneal neovascularization (adjusted odds ratio aOR= 4.8, p=0.03), and corneal edema at presentation of rejection episode (aOR=5.2, p=0.01) were associated with treatment failure.

Conclusion Preoperative corneal neovascularization and corneal edema were found to be associated with failure of treatment in cases with allograft corneal graft rejection.
Acute effects of the sigma‐ receptor agonist on human lens epithelial cells
Authors: KARLSSON JO , JONHEDE S , PETERSEN A , ZETTERBERG M
Published: September 2008

Purpose The aim of the present study was to examine the effect of the sigma‐2 receptor agonist, Siramesine, on morphology, growth, cell death, lysosomal function and effects on extra‐lysosomal proteolytic systems in human lens epithelial cells.

Methods Human lens epithelial cells in culture were exposed to siramesine and examined for morphological changes using Nomarski optics or calcein. Lysosomes were evaluated using acridine orange and MagicRed. Nuclear morphology was studied using Hoechst 33342 and propidium iodide. Enzymatic activities in living cells or cell lysates were studied using different fluorogenic substrates.

Results Siramesine at low concentrations increased the cytoplasmic proteolytic activity of the proteasome and the calpain system. Effects was also observed with respect to lysosomal morphology, acidity and function. Activation of caspase‐3 and the appearance of nuclei with an apoptotic morphology were also found.

Conclusion Siramesine at low concentrations affects lens epithelial cells with perturbation of the major proteolytic systems, lysosomal morphology and results in caspase activation and cell death. Siramesine may be a promising substance for clinical studies concerning the treatment of PCO.