bluuebunny/crossref_metadata_2025 huggingface dataset:
Colour contrast sensitivity and electrophysiological abnormalities in patients undergoing long term desferrioxamine treatment
Authors: KABANAROU SA , ROBSON AG , HOGG CR , EGAN C , HOLDER GE
Published: August 2012

Purpose To describe the spectrum of colour contrast sensitivity and electrophysiological abnormalities in patients undergoing long term desferrioxamine (DFO) treatment for systemic iron overload in blood transfusion‐dependent anaemias.

Methods Thirty five patients on long term DFO treatment with abnormal colour contrast sensitivity and/or abnormal retinal electrophysiology examined in the Electrophysiology Department at Moorfields Eye Hospital were included in this study. They underwent visual acuity testing, colour contrast sensitivity and International‐standard electrophysiological evaluation including pattern and full‐field electroretinography (PERG and FFERG). In most patients follow up investigation also included recording of ocular symptoms, fundus morphology and DFO treatment (dose and route of administration).

Results Most patients manifested colour contrast threshold elevation, mainly along the tritan axis and also pattern ERG abnormalities as an indication of macular dysfunction. Full‐field ERG abnormalities, when present, were consistent with generalised photoreceptor dysfunction involving rods only, cones only, or both rods and cones. In some patients these abnormalities were partly reversible following cessation or reduction of DFO treatment.

Conclusion When DFO retinal toxicity occurs, it can present with a wide range of electrophysiological abnormalities, including macular and/or generalised retinal dysfunction. Early colour vision abnormalities usually involve the S‐cone‐driven pathway. Colour contrast sensitivity and electrophysiological evaluation may be used to detect DFO retinal toxicity and monitor recovery, providing an essential aid to the management of the patient.
Should you decide to perform cataract surgery on your patients, based only on straylight?
Authors: VAN DEN BERG TJTP
Published: August 2012

Purpose A widely accepted validation criterion for cataract surgery is the likelihood that the surgery will be beneficial to the patient. Yet important variation exists between individual ophthalmologists in what constitute criteria for cataract surgery, and optometrists vary widely in their referral criteria. As a consequence huge differences in the amount of cataracts being treated exists between different centres. Some degree of standardisation is wanted. Visual acuity is considered, but predictability of surgical outcome is often difficult because visual acuity is confounded by the retinal condition. Straylight on the other hand is independent of retinal condition, and constitutes a complementary measure of quality of vision, complementary to visual acuity, corresponding to complaints such as glare, hazy vision, face recognition problems.

Methods A population of 217 patients for cataract surgery was studied. Before and after cataract extraction best corrected distance visual acuity (CDVA), and straylight using the C‐Quant from Oculus were recorded for all patients. Subjective complaints were documented before and after surgery by the 39‐item National Eye Institute Visual Function Questionnaire (NEI VFQ‐39) and a home made straylight questionnaire. Data are compared to a 5000 eye database from an earlier study.

Results Before and after cataract extraction, questionnaires show straylight to have almost the same influence on subjective quality of vision as CDVA, as show by correlation analysis. Straylight improvement upon surgery is strongly correlated with preop straylight level.

Conclusion When straylight is added to pre‐operative considerations of cataract extraction post‐operative improvement is better predictable.

Commercial interest
Reproducibility and repeatability of retinal nerve fiber layer parameters measured by scanning laser polarimetry with enhanced corneal compensation in glaucomatous eyes
Authors: ARA GABARRE M , SATUE PALACIAN M , BAMBO M , FERRANDEZ ARENAS B , GIL‐ARRIBAS L , FERRERAS AMEZ A
Published: August 2012

Purpose To determine the reproducibility and repeatability of retinal nerve fiber layer parameters measured using scanning laser polarimetry (SLP) with enhanced corneal compensation (GDx‐ECC) in glaucoma patients.

Methods Fifty‐four consecutive glaucomatous subjects were prospectively selected. All participants underwent a comprehensive eye exam and at least a reliable standard automated perimetry (Humphrey, 24‐2 SITA Standard). Only one eye per patient was randomly included in the statistical analysis. Three scans were acquired during the same visit using the GDxPRO (Carl Zeiss Meditec, Dublin, CA). Two additional scans were obtained within a 2‐month period. Intraclass correlation coefficient (ICC), coefficient of variation (COV), and test‐retest variability were calculated for all SLP parameters.

Results Mean age was 58.27 ± 8.9 years (p=0.09) and mean deviation of standard automated perimetry was ‐7.04 ± 7.0 dB. ICCs were higher than 0.91 for all SLP parameters. The nerve fiber indicator (NFI) showed the highest ICC in the intra‐test sequence (0.982; 95% confidence interval: 0.972‐0.989; p<0.001). The TSNIT average showed the lowest COVs (4.40% and 4.71% in the intra‐ and inter‐test, respectively). Test‐retest variability for the NFI ranged from 10.6 to 12.8.

Conclusion The GDx‐ECC had an excellent intravisit and intervisit reproducibility in glaucoma patients. SLP is an imaging technology that may be useful in monitoring glaucoma progression.

Commercial interest
Defects in macular‐retinal layer analysis of glaucoma patients compared to normative database
Authors: HOLZER S , PEREIRA I , KISS B , VASS C
Published: August 2012

Purpose High‐resolution optical coherence tomography (HR‐OCT) enables a quantitative analysis of the configuration of retinal layers. The aim of this study was to analyze the topographic distribution of pathologic thinning of specific macular retinal layers of glaucoma patients.

Methods Macular 3D‐scans were recorded with HR‐OCT (Cirrus®, Carl Zeiss Meditec). Retinal layers, especially the retinal nerve fiber layer (RNFL) and the retinal ganglion cell plus inner plexiform layer (RGIPL), were automatically segmented with a custom made software (Matlab R2009b®, The Mathworks Inc.). A normative database for the thickness of the RNFL, the RGIPL and the retina was created using healthy subjects (n=84) taking into account for the effects of age. 18 glaucoma patients were compared to the 95% confidence interval of the normative database using the thickness values of RNFL, RGIPL and retina within 65 segments.

Results On average the glaucoma patients showed for RNFL, RGIPL and retina 29.8, 49.4 and 53.9 pathologic segments within the macula. The minimum number of pathologic segments per patient was 5, 24 and 29. The average thickness values for healthy subjects were 32.95 µm (RNFL), 79.02 µm (GCIPL) and 321.46 µm (retina), for glaucoma patients 24.85 µm, 57.46 µm and 281.30 µm, respectively.

Conclusion In our study quantitative analysis of retinal layer thickness based on macular HR‐OCT showed a decrease of RNFL, RGIPL and retinal thickness in glaucoma patients. Within our sample all patients had several pathologic segments for all of the analyzed retinal layers. In most of the cases those segments were clustered. Further studies including larger numbers of patients to confirm our findings are advisable.
Meibography follow up studies in dry eye patients
Authors: RABENSTEINER DF , HORWATH‐WINTER J , BOLDIN I , WOLTSCHE N , SCHMUT O
Published: August 2012

Purpose Meibomian‐Gland‐Dysfunction (MGD) is one of the main causes for the development of a hyperevaporative dry eye. Non‐contact Meibography can achieve a non‐invasive investigation of the meibomian glands inside the tarsal plates of the eyelids. The purpose of this study was to evaluate non‐contact Meibography as a tool for follow‐up studies in dry eye patients.

Methods We examined 50 patients suffering from dry eye disease of the dry eye unit of the Ophthalmological Department of the Medical University of Graz. Subjective dry eye symptoms and objective signs of dry eye were evaluated. Non‐contact Meibography was performed by a Heidelberg Retina Angiograph 1, featuring two infrared diode lasers. Partial or complete loss of the meibomian glands was scored according to meiboscore of Arita and colleagues. After one year non‐contact Meibography was reassessed. Changes in the meiboscore were evaluated.

Results The mean age of the study population was 57.9 ± 14.1 years and 64.7 % were women. There was no statistically significant change in the mean meiboscore.

Conclusion Non‐contact Meibography is a valuable tool in the diagnosis of MGD. Morphological changes and a possible drop out of Meibomian glands can easily be assessed. The ideal follow‐up interval to detect changes in the meiboscore has yet to be determined.
Clinical results on the efficacy of Thealoz vs autologous serum in moderate to severe dry eye
Authors: LEONARDI A , LAZZARINI D , PILIEGO F , FREGONA I
Published: August 2012

Purpose To study the clinical effect and morphologic aspects of the cornea in using corneal confocal microscopy in patients affected by moderate to severe dry eye and treated with either autologous serum or Thealoz.

Methods Twenty two patients were included and randomized in 3 groups: 7 patients (4 affected by Sjoegren Syndrome ‐SS) were switched from autologous serum eye drop treatment to Thealoz 6‐8 times a day (group 1); 7 patients (4 SS) maintained their treatment by autologous serum 6‐8 times a day (group 2); 8 new patients (3 SS) were treated by Thealoz 6‐8 times a day (group 3). The OSDI questionnaire, tear film evaluation by BUT, fluoresceine and lissamine green staining, Schirmer test and corneal confocal microscopy were performed at the beginning of the study (T0) after 4 (T1) and 8 weeks (T2). ConfoScan CS4 (Nidek, Gamagori, Japan) images of the central cornea were obtained with a 40x non‐contact lens and Z‐ring device. The epithelial cell, endothelial cell and keratocyte densities of the central cornea, the characteristics of the sub‐basal long nerve fibers and of the sub‐basal nerve plexus were studied.

Results In group1, 4 of the 7 patients maintained unmodified their clinical benefit and corneal morphology after switching from autologous serum to Thealoz. Two severe SS patients needed to return to the autologous serum treatment because of worsening of the OSDI at T1 without a significant change in the other parameters. However, in remaining 5 patients, the OSDI questionnaire improved at T2 compared to T1. In group 2, all patients maintained a stable clinical and morphological ocular surface condition over the 8 weeks study period. Group 3, at T2, showed an objective improvement of ocular surface morphology and reported a significant subjective relief of symptoms (OSDI) compared to T0 and T1. All patients showed improvement of confocal microscopy parameters after treatment with Thealoz.

Conclusion Thealoz was effective and well tolerated in patients with moderate to severe dry eye. Severe SS patients may need an additional treatment, however even switching from autologous serum, most of the patients maintain a stable clinical condition.
Natural evolution of idiopathic lamellar macular holes (LMH) and macular pseudoholes (MPH)
Authors: GARCIA FERNÁNDEZ M , CASTRO NAVARRO J
Published: August 2012

Purpose To analyze the natural evolution of idiopathic Lamellar Macular Holes (LMH) and Macular Pseudoholes (MPH), in the long‐term, based on Optical Coherence Tomography (OCT) configuration and in Best Corrected Visual Acuity (BCVA) evolution.

Methods We prospectively analyzed 68 eyes (41 right eyes and 27 left eyes) of 61 patients (40 female and 21 male), which were diagnosed as having a MPH or a LMH on OCT examination. The following variables were assessed: BCVA, lens status, and hole size (Diameter ‐D, Residual foveal Thickness –RT, and Perifoveal Thickness ‐PT)(software Caliper of Cirrus OCT), at baseline and final examination. Eyes with significant cataract underwent phacoemulsification.

Results The mean follow‐up period was 34.33 ± 15.02 (12‐78) months. Mean BCVA (logMAR notation) in the total group at baseline was 0.40 ± 0.25 and at final was 0.36 ± 0.13 (p=0,082). PAM showed slightly better BCVA than LMH (p<0.05). BCVA improved in those eyes who underwent cataract surgery and remained unchanged in the rest of the eyes. No statistically significant differences regarding D, RT and PT were observed during the follow‐up period (p=0,125).

Conclusion Most of idiopathic LMH and MPH do not progress anatomically and do not contribute to a significant diminution of visual acuity during the follow‐up period. We must take into account that the diminishment in visual acuity in most LMH and MPH can be due to the presence of an opacified crystalline and not to the lamellar hole itself.
Subfoveal choriodal thickness: the Beijing Eye Study
Authors: JONAS JB , WEI W , XU L , SHAO L , DU K , WANG S , CHEN C , XU J , WANG Y , ZHOU J , YOU Q
Published: August 2012

Purpose To study subfoveal choroidal thickness (SFCT) in adult Chinese subjects

Methods The population‐based Beijing Eye Study 2011 included 3468 individuals. Spectral‐domain optical coherence tomography (SD‐OCT) with enhanced depth imaging was used for measurement of SFCT.

Results Mean SFCT was 253.8 ± 107.4μm (range: 8μm to 854μm). In multivariate analysis, SFCT increased with younger age (P<0.001), shorter axial length (P<0.001), male gender (P<0.001), deeper anterior chamber depth (P<0.001), thicker lens (P<0.001), flatter cornea (P<0.001) and better best corrected visual acuity (P=0.001). In multivariate analysis, SFCT was not significantly associated with blood pressure, ocular perfusion pressure, intraocular pressure, cigarette smoking, alcohol consumption, serum concentrations of lipids and glucose, diabetes mellitus and arterial hypertension. In the myopic refractive error range of more than ‐1 diopters, SFCT decreased by 15µm (95%confidence interval (CI): 11.9, 18.5) for every increase in myopic refractive error of one diopter, or by 32µm (95%CI: 37.1, 26.0) for every increase in axial length of one millimeter. For each year increase in age, the SFCT decreased by 4.1μm (95%CI: 4.6, 3.7) (multivariate analysis).

Conclusion SFCT with a mean of 254±107μm in elderly subjects with a mean age of 65 years decreased with age (4µm per year of age) and myopia (15 µm per diopter of myopia). It was additionally associated with male gender and the ocular biometric parameters of a deeper anterior chamber and thicker lens. The association between SFCT and best corrected visual acuity strongly points towards a functional aspect of SFCT
In vivo confocal microscopic examination of corneal Langerhans cell density, distribution and evaluation of dry eye in rheumatoid arthritis
Authors: MARSOVSZKY L , RESCH M , NEMETH J , KOVACS L , TOLDI G , MEDGYESI E , BALOG A
Published: August 2012

Purpose To examine the density and the distribution of corneal Langerhans cells (LCs) and to compare the results with dry‐eye related parameters in rheumatoid arthritis (RA).

Methods 52 RA patients (mean age: 58 [49‐66]) with various degree of disease activity and 24 healthy subjects (mean age: 61 [52.5‐67]) were enrolled. Central and peripheral LC number and morphology were assessed with in vivo confocal laser corneal microscopy. In addition, lid parallel conjunctival folds (LIPCOF), tear break up time (TBUT), Schirmer’s‐test (ST), and ocular surface disease index (OSDI) were also evaluated. .

Results The prevalence of central and peripheral LCs and the central LC morphology values (LCM) were higher in RA compared to controls (median [interquartile range]: 42.50 [22.95‐93.50] vs 10.00 [0.00‐42.33] cell/mm2, 98.00 [62.00‐154.5] vs 59.50 [45.25‐94.75] cell/mm2, and 2.00 [1.00‐2.00] vs 1.00 [0.25‐1.00], respectively, p<0.05 for all). Within the RA group, LC prevalence and morphology were not affected by disease activity. However, patients on anti‐TNF or corticosteroid therapy exhibited LCM and central and peripheral LC density comparable to controls. TBUT values were lower and OSDI scores were higher in RA than in controls (9.00 [7.00‐12.00] vs 12.00[9.00‐14.00] seconds and 20.00 [10.93‐38.21] vs 9.75 [4.93‐16.28], respectively, p<0.05 for all). ST results were comparable in RA and controls.

Conclusion Dendritic cell accumulation and maturation in the corneal center suggest the involvement of the cornea in RA, even in patients in inactive stage and without ocular symptoms.
Comparison of viral vectors for gene transfer to corneal endothelial cells
Authors: FUCHSLUGER T
Published: August 2012

Purpose Thanks to its anatomical location at the posterior surface of the cornea and its monolayer structure, the corneal endothelium is an ideal target for gene therapy approaches. Lentiviral vectors have been shown by our group to be suitable vectors for the transfer of genes into corneal endothelial cells (EC). Aiming for an alternative to these HIV‐based vectors, it was the goal of this study to determine the suitability of non‐pathogenic adeno‐associated viral vectors (AAV) for gene transfer to EC.

Methods Comparison of protein expression after EC transduction using a lentiviral vector or AAV 2/2 with GFP in murine EC (Balb/C) and in human EC (cell line and primary cells)by flow cytometry.

Results Following transduction of EC using lentiviral vector, kinetics of the protein expression are considerably different compared to gene transfer using AAV. In contrast to AAV with protein expression showing a plateau after two to three weeks, lentiviral transfer results in a very rapid of reporter protein. Moreover, we detected significant differences in transduction rates between human and murine EC lines as well as betweeen human EC lines and human corneas (plateau at 70% versus 50% GFP‐positive cells with AAV, versus 90‐95% with lentivirus).

Conclusion DNA transfer using AAV vectors seems to be an appropriate alternative to lentiviral vectors for gene transfer to EC. Relating to the cultivation of human donor corneas in eye banks over weeks, translation of AAV from bench to bedside, e.g. to reduce apoptosis in corneas, seems to be a promising approach for future gene transfer into donor corneas.
Etiologic diversity in patients presenting with atypical and severe anterior uveitis
Authors: FEL A , ROZENBERG F , TOUITOU V , LE HOANG P , BODAGHI B
Published: August 2012

Purpose To analyze the etiological distribution of long‐lasting and severe anterior uveitis based on the analysis of the aqueous humor.

Methods Retrospective study of patients presenting with atypical and severe anterior uveitis and managed in a tertiary referral centre, between January 2008 and December 2009. Patients with panuveitis, intermediate and posterior uveitis and typical B27‐associated uveitis or herpes zoster ophthalmicus were excluded. Patients were divided into three groups : atypical viral uveitis (group 1), typical herpetic uveitis (group 2), Fuchs uveitis (group 3). An anterior chamber paracentesis was performed in all cases.

Results The medical files of 153 patients were analysed. The mean age was 49 years (range 8‐83 Years), the M/F sex ratio was 84/69. Uveitis was unilateral in 86.5% of cases. Group 1 included 42 patients with sarcoidosis (13 cases), tuberculosis (7 cases), endophthalmitis (6 cases), spondylarthropathy (10 cases), syphilis (2 cases), neoplasia (2 cases) and multiple sclerosis (2 cases). Group 2 included 83 cases. A viral agent was definitely identified in 33 cases (39.8%). The distribution of herpes viruses was the following : CMV (19 cases), HSV‐1 (8 cases) and VZV (6 cases). The yield of anterior chamber paracentesis is increased by repetition of the procedure (up to 77.4% for CMV). The PCR‐negative patients in Group 2 responded well to a specific antiviral treatment. None of the patients with Fuchs uveitis (Group 3) had a positive PCR for CMV.

Conclusion Most cases of atypical anterior uveitis, especially when unilateral, are viral‐induced. Molecular tools applied to ocular fluids may confirm a viral infection in atypical cases of anterior uveitis, leading to a specific antiviral therapy.
Positive interferon‐gamma release assay (IGRA) test in a case of non‐tuberculous mycobacterium associated uveitis
Authors: BOUCHENAKI N , KUZNETCOVA T , SAUTY A , HERBORT CP
Published: August 2012

Purpose It is not always known that Interferon‐gamma release assay (IGRA) tests can also react with some non‐tuberculous atypical strains of mycobacteria (NTM). The aim of this work was to review the cross‐reactivity of IGRA tests and its consequences in a case of with a positive IGRA test associated with of a non‐tuberculous mycobacterium (M. kansasii).

Methods Report of a 66 year old male uveitis patient with cystoid macular oedema and occult bilateral indocyanine green angiography‐detected choroiditis resistant to inflammation suppressive therapy. A QuantiFERON®‐TB Gold test was positive indicating exposure to the Mycobacterium tuberculosis complex. Before starting antibiotic treatment cultures from bronchial aspirates was performed yielding the agent Mycobacterium kansasii. A review of cross‐reactivity of IGRA tests with non‐tuberculous atypical mycobacteria was performed.

Results Drug‐sensitivity of Mycobacterium kansasii was found to be equal to Mycobacterium tuberculosis although a longer duration of therapy is recommended. The patient was treated with anti‐tuberculous drugs for 18 months. Uveitis responded to treatment within three months. A review showed that there are at least 7 NTM strains that cross‐react with IGRA tests some of which do not respond to classical anti‐tuberculous therapy.

Conclusion A positive IGRA test is a support for diagnosing tuberculous uveitis. However, these tests cross‐react with NTM atypical strains, some of which do not respond to classical anti‐tubercultuberculous therapy with deleterious consequences if an adequate therapy is not given.
Evaluation of a complete‐kill assay for anti‐acanthamoeba solutions
Authors: KOWALSKI R , ABDEL AZIZ S , ROMANOWSKI E , SHANKS RM
Published: August 2012

Purpose Acanthamoeba keratitis is a sight debilitating disease that requires effective topical drug therapy to eradicate the pathogenic agent.

Methods An assay was created to determine whether 0.02% poly(hexamethylene biguanide) hydrochloride (PHMB), 0.02% chlorhexidinedigluconate (CHL), 0.1% c‐desomedine (DESO), and 1.0% c‐voriconazole (VOR) were effective in completely killing 15 different isolates of acanthamoeba at time points 24, 48, and 72 hours in comparison to a saline control. Each 0.5 ml volume of solution was inoculated with 0.1 ml of acanthamoeba cysts at a concentration of 1‐5 x 106 /ml determined with a hemacytometer and allowed to incubate at 30o C. At the time points listed, aliquots from each treatment group were inoculated onto non‐nutrient agar overlaid with Enterobacter aerogenes. The plates were microscopically examined for growth at time points 1 and 2 weeks. At 2 weeks, all plates were sub‐cultured onto fresh medium. At 7 days, growth in sub‐culture at each time point was graded 1 for growth and zero for no growth. The time points were combined for each drug with a possible grade from 0 to 3. The grades were non‐parametrically (Mann Whitney) compared to determine any significance in positive growth between the drugs.

Results Complete–kill was determined more frequently with PHMB and DESO (p=1.0) than CHL (p=0.04). PHMB, DESO, and CHL demonstrated more complete‐kill than VOR (p=0.01) which was more effective than the saline control (p=0.0003).

Conclusion The complete‐kill assay appears to provide separation in the effectiveness of different anti‐amoebic drug solutions, and may provide an alternative evaluation of possible new anti‐infectives in the treatment of acanthamoeba keratitis.
Evaluation of retrobulbar hemodynamics and aqueous humor levels of Endothelin‐1 in exfoliation syndrome, exfoliative glaucoma and primary open‐angle glaucoma
Authors: NASR MB , KOUKOULA SC , TRANOS PG , LABIRIS G , KOZOBOLIS VP
Published: August 2012

Purpose To compare mean Endothelin‐1 (ET‐1) concentration in aqueous humor and retrobulbar hemodynamics in patients with exfoliation syndrome (XFS), exfoliative glaucoma (XFG), primary open‐angle glaucoma (POAG), and normal controls, and to evaluate the role of these index in the management of glaucoma.

Methods Aqueous Humour samples were collected from 20 subjects with POAG, 18 with XFG, 20 with XFS and 19 with senile cataract (CONTROL). Pre‐surgery Color Doppler Imaging (CDI) in Ophthalmic Artery (OA), Posterior Ciliary Arteries (PCA) and Central Retinal Artery (CRA) were performed. Samples were frozen at ‐70oC and were analyzed with ELISA method.

Results ET‐1 level in aqueous samples of XFS, POAG, and XFG groups were statistically higher than that in CONTROL group (p1=0,008, p2=0,005, p3=0,020). However, there was no significant difference between aqueous ET‐1 levels of the three glaucoma groups (p< 0,900). Mean EDV of Ophthalmic Artery in subjects with XFG was significantly lower (p<0.05) than the other groups (XFS, POAG, Control). The mean PSV of the Ophthalmic Artery, yet, it was not statistically different between subjects with XFG, POAG and XFS, it was significantly lower (p<0.05) when comparing XFG and control groups. Resistivity index (RI) of OA in subjects with XFG was significantly higher compared with POAG and XFS patients (p<0.05).

Conclusion This study confirms a lower hemodynamics in patients with XFG, a statistically higher levels of ET‐1 in glaucoma subjects, and no significant difference between levels of ET‐1 in glaucoma groups, which may in the future, indicate a useful parameter as a result of glaucoma damage and not as cause
Expression of Lubricin mRNA and protein in human ocular surface tissues
Authors: KNOP E , KNOP N , SCHMIDT T , MORRISON S , SULLIVAN BD , RAHIMI DARABAD R , SULLIVAN DA
Published: August 2012

Purpose Friction is an inherent potential source of wounding for ocular surface tissues during the blink and bulbus movements and is identified as a major contributor to ocular surface disease of the dry eye type. The expression of lubricin, a boundary lubricant in articulating joints that protects against frictional forces, cell adhesion and protein deposition, was investigated at the ocular surface.

Methods Human corneal, conjunctival and control cartilage tissues were fixed with 4% paraformaldehyde, embedded in paraffin, sectioned serially, exposed to antigen retrieval buffers, and stained for lubricin by immunohistochemistry (IHC) with a rabbit polyclonal anti‐human lubricin antibody. Several negative and positive controls were performed. Respective fresh tissues were analysed by reverse transcriptase polymerase chain reaction (RT‐PCR) in order to verify the presence of the mRNA.

Results The mRNA for lubricin was found in human corneal and conjunctival cell lines and in complete ocular surface tissues similar to cartilage. The mRNA is translated and expressed into lubricin protein and protein staining was observed along the complete corneal and conjunctival epithelial surface, most strongly expressed in the corneal epithelium . The specificity of staining was verified in several positive and negative controls including use of irrelevant antibodies and preincubation of the anti‐lubricin antibody with a pure peptide, which had served to generate the antibody.

Conclusion These findings verify that lubricin is synthesized and expressed by epithelial cells of the human cornea and conjunctiva and conceivably serves protective functions against frictional forces at the human ocular surface similar to the joint.
Aquaporin‐1 expression in membranes from proliferative vitreoretinopathy and in epiretinal membranes
Authors: MOTULSKY E , SALIK D , JANSSENS X , PION B , DUFRANE R , CHAPUT F , BOLAKY N , GREGOIRE F , CASPERS L , PERRET J , WILLERMAIN F , DELPORTE C
Published: August 2012

Purpose Aquaporin‐1 (AQP1) is involved in cell migration and proliferation. This study aims to investigate AQP1 expression in membranes from proliferative vitreoretinopathy (PVR) and epiretinal membranes (ERM)

Methods 20 Membranes PVR and ERM were collected following eye surgery from 20 eyes from 20 patients. AQP1 mRNA and protein expression were determined by RT‐qPCR and immunofluorescence in both PVR and ERM

Results AQP1 mRNA and protein were expressed in both PVR and ERM as shown by both RT‐qPCR and immunofluorescence. Moreover, AQP1 protein expression was heterogeneous among and between PVR and ERM, and was highly colocalized with alpha‐smooth muscle actin (SMA or Acta2) and slightly colocalized with glial fibrillary acidic protein (GFAP).

Conclusion AQP1 mRNA and protein were expressed in membranes from PVR and in ERM. Due to the absence of SMA and GFAP colocalization, it is likely that AQP1 is expressed by at least two distinct cells types. AQP1 might play a role in cell migration and proliferation occurring during the formation of PVR and ERM, and could represent a new therapeutic target
Therapeutic targets in glaucoma
Authors: HOFFMANN E
Published: August 2012

Glaucoma leads to irreversible blindness and is characterized by changes in the optic disc and the visual field. The elevated intraocular pressure is considered the most important factor responsible for the glaucomatous optic neuropathy. There are multiple factors involved in the development of retinal ganglion cell death. The goal of glaucoma treatment is to preserve the visual field of patients and prevent the loss of visual function that is associated with the disease (European Guidelines). We should focus at least on three separate targets of glaucoma treatment (Brubaker RF. Survey of Ophthalmology 2003: Three targets for glaucoma management): Intraocular pressure (IOP), outflow facility, and the retinal ganglion cell (RGC). Elevated IOP is still the primary risk factor for the development and progression of glaucoma, and many studies have shown that IOP reduction can limit the progression of glaucoma and slow the loss of visual function. IOP lowering can be beneficial for normal‐tension as well as high‐tension glaucoma patients, and it may also prevent or delay the onset of visual field loss and optic disk damage in individuals with ocular hypertension. The second target of glaucoma treatment is outflow facility. In a healthy eye, aqueous production (flow) equals aqueous outflow through the trabecular and uveoscleral outflow pathways. Any imbalance between flow and outflow results in a change in IOP, yet even a transient elevation of IOP may cause significant glaucomatous damage. The third target of glaucoma treatment is the RGC itself. RGC death in glaucoma might have many causes, including vascular insufficiency, blockage of axonal transport, diffusion of toxic agents into the nerve cell, or initiation of apoptosis. Treatment that aims to directly protect the RGC from every possible insult might be the ultimate treatment for glaucoma because a strategy of neuroprotection could preserve the visual function of patients regardless of the etiology of their glaucoma.
Femtosecond laser and microkeratome preparation of ultrathin (UT) DSAEK grafts
Authors: MURTA J
Published: August 2012

An important limitation of DSAEK is that some eyes do not achieve good visual acuity despite a clear cornea and minimal residual astigmatism. The thickness of the stromal lamella may influence the final visual acuity and better results may be achieved with thinner grafts. We describe a new technique that combines a femtosecond laser with a microkeratome to obtain consistently thin grafts, with no loss of corneas. This clinical study involves ultrathin DSAEK tissue preparation used in 28 patients with endothelial dysfunction. The first cut was performed with an Intralase FS60 laser and the second cut with a Moria CBm 300‐µm microkeratome. The thickness of the first cut was modified for each cornea to obtain a final graft thickness of 120 µm. Post‐op central graft thickness was performed with corneal laser tomography (Spectralis). Associated visual results, disk thickness and endothelial cell loss before and after surgery were evaluated. Final graft thickness was 88.3+27.6 µm, 77.2+26.6 µm and 74.3+27.5 µm at one week, one and three months post‐op, respectively. No loss of corneas due to irregular cuts or perforation during preparation. The mean BSCVA was 0.41, 0.52, and 0.72(0.39, 0.28 and 0.14 LogMAR) after one week, one and three months post‐op, respectively. Precut and post‐op (3 months) ECDs averaged 2553 cells/mm2 and 1882 cells/mm2, respectively, representing 26.3% endothelial cell loss after 3 months of the surgery. Femtosecond laser and microkeratome can be used sequentially to prepare custom ultrathin DSAEK grafts with no loss of corneas. This procedure minimizes the variability inherent to microkeratomes and allows very quick recovery of visual acuity after posterior lamellar keratoplasty.
Inventorisation of European education programs
Authors: TASSIGNON MJ
Published: August 2012

Abstract not provided
RDH12 mutation and early‐onset retinal degeneration
Authors: GARCIA FERNÁNDEZ M , CASTRO NAVARRO J , BAJO FUENTE A
Published: August 2012

Purpose To show the clinical evolution of a child with RDH12 mutation (gene typically associated with Leber Congenital Amaurosis,LCA) and early‐onset retinal degeneration

Methods A 8‐year‐old male who came to our department with a complaint of progressive decline in vision in his both eyes. Full clinical ophthalmological examination, including Best Corrected Visual Acuity (BCVA), anterior and posterior segment examination, Optical Coherence Tomography (OCT), color vision test, visual field, electrorretinogram and genetic study, was performed.

Results At first visit, BCVA was 10/100 in both eyes. Anterior segment examination was unremarkable. Fundus eye examination revealed a bilateral and symmetric pattern of macular hyperpigmentation (of three disk diameters in size)with reticular configuration and patches of hypopigmentation between hyperpigmentated areas. No peripheral atrophy with bone spicule nor optic nerve atrophy were observed. OCT showed an intense macular atrophy with severe disruption of complex pigment retinal epithelium‐photoreceptors. Farnsworth Munsell 28‐hue test revealed preserved color vision. Visual field showed a central scotoma. Electrorretinogram recordings demonstrated a still preserved rod and cone function. Genetic study revealed a compound heterocigotic mutation for RDH12 in exon 6 (p.Ala269fs and p.Arg234His). Two years later VA decreased to <10/100 and we observed progression of the macular damage.

Conclusion RDH12 mutation can be associated, although extremely infrequently, with an early‐onset form of severe retinal dystrophy affecting both rod and cone function (preserved at first stages) and having a phenotype distinct from that resulting from mutations in other known LCA genes.
Perspectives for new treatments at Allergan
Authors: MALTMAN J
Published: August 2012

Allergan, Inc., with headquarters in Irvine, California, is a global specialty pharmaceutical company that develops and commercializes innovative products for the eye care, neuromodulator, skin care and other specialty markets. We design our clinical trials in a scientific manner to investigate the benefits, risks and value of future or current products.
Microkeratome vs femtosecond laser assisted endothelial transplant cut
Authors: TOUBOUL D
Published: August 2012

Abstract not provided
Immune responses to model antigen elicited by immunization via conjunctiva associated lymphoid tissue
Authors: BARISANI‐ASENBAUER T , BELIJ S , STOJANOVIC M , MARINKOVIC E , STOJICEVIC I , MONTANARO J , STEIN E , BINTNER NORA , INIC‐KANADA A
Published: August 2012

Purpose There is an excessive demand to develop vaccines against many of the pathogens that infect mucosal tissues or have a mucosal port of entry. Parenteral vaccination may protect in some instances, but usually a mucosal vaccination route is of vital importance as the strongest immune response is obtained at the site of vaccine application and in anatomically adjacent mucosae. The aim of this study was to assess the efficacy of conjunctiva‐associated lymphoid tissue (CALT) as a mucosal route of immunization.

Methods BALB/c and C57BL/6 mice were immunized via conjunctiva with tetanus toxoid (TTd) as a model antigen. 100 μg/mouse of TTd was applied onto conjunctiva of each eye, together with merthiolate‐inactivated B. pertussis, which served as adjuvant. Control mice were immunized subcutaneously with 100 μg/mouse of TTd.

Results We found TTd‐specific IgG and IgA in tears and sera of both mice strains, in addition to IgG positive TTd‐specific cells. There was strong correlation between the amount of TTd‐specific antibodies in sera and the presence of TTd‐specific B cells in draining lymph nodes. B. pertussis enhanced IgG and IgA immune responses in both mouse strains. T cell activation (increase in CD25 expression and in percentages of CD4+, CD8+, and CD3+ cells) and B cell activation (increase in percentages of CD19+ CD25+ cells) occurred in all mice, but mice immunized with TTd in combination with B. pertussis had the strongest responses.

Conclusion Immunization via conjunctiva induced TTd‐specific local and systemic immune responses. The strongest immune responses developed in mice that received TTd together with B. pertussis.
Secondary choriocapillaritis in infectious choroiretinitis
Authors: KNECHT P , MOKRIM R , HERBORT CP
Published: August 2012

Purpose Primary choriocapillaritis is the mechanism at the origin of diseases such as MEWDS, APMPPE, multifocal choroiditis and serpiginous choroiditis. In case of severe chorioretinal inflammation as in infectious posterior uveitis, indocyanine green angiography (ICGA) shows much more widespread involvement than seen by funduscopy or fluorescein angiography (FA) in form of hypofluorescent areas. The aim of this work was to analyse this occult choroidal involvement.

Methods Charts of patients with toxoplasmic retinochoroiditis (TRC), syphilitic and tuberculous posterior uveitis seen in the Centre for Opththalmic Specialised Care (COS) in Lausanne, Switzerland from 1995 to 2011 were reviewed and patients with occult choroidal ICGA lesions were analysed.

Results Occult ICGA lesions were characterized by a ring of hypofluorescence around the focus as well as small hypofluorescent satellite lesions in TRC and tuberculous posterior uveitis. In syphilitic posterior uveitis the ICGA hypofluorescence was characterized by more extensive areas that could contrast with minimal FA and fundus findings. For all three entities these hypofluorescent areas responded well to treatment, completely regressing in syphilitic posterior uveitis and regressing to a size equivalent to the foci seen on funduscopy and FA.

Conclusion The aspect and the quick response to therapy of occult hypofluorescent areas on ICGA seen in severely inflamed infectious posterior uveitis most probably correspond to inflammatory choriocapillaris hypo or non‐perfusion and its extent needs to be assessed by performing a global appraisal of these cases including ICGA.
Central serous chorioretinopathy misdiagnosed as posterior uveitis: frequency and consequences
Authors: PAPADIA M , HERBPRT CP
Published: August 2012

Purpose Central serous chorioretinopathy (CSC) is one of the differential diagnoses to be kept in mind in case of posterior uveitis. Its diagnosis is of utmost importance as CSC misdiagnosed as posterior uveitis can worsen related to the prescription of corticosteroid therapy. The purpose of this study was to determine the proportion of cases of CSC misdiagnosed as a posterior uveitis.

Methods Charts of patients seen in the section of inflammatory eye diseases at the Centre for Opththalmic Specialised Care (COS) in Lausanne, Switzerland seen from 1995 to 2011 were reviewed and referred cases of CSC misdiagnosed as posterior uveitis were studied.

Results In a collective of 1268 patients seen from 1995 to 2011 at the COS, 12 patients (0.95%) with CSC were misdiagnosed as posterior uveitis. Erroneous diagnoses were Ocular tuberculosis in 3 cases, Vogt‐Koyanagi‐Harada disease in 2 cases, lupus (LED) in one case and undetermined uveitis in 3 cases. In 3 cases CSC developed following corticosteroid therapy for uveitis (2) or systemic inflammatory disease (1) and was misdiagnosed as worsening of the underlying inflammatory disease. Bad functional outcome was proportional to the diagnostic delay of CSC. The most useful means to diagnose CSC retrospectively was either the original angiography, especially indocyanine green angiography (ICGA), or OCT.

Conclusion CSC is not a rare misdiagnosis in posterior uveitis representing a percentage of nearly 1% in a total collective of uveitis cases but reaching a proportion of about 3% when only posterior uveitis cases are considered. Investigative methods such as angiography including ICGA, and OCT are crucial for reaching a diagnosis as quickly as possible to avoid disease worsening corticosteroid therapy.
Retinal vessel analysis in animal models
Authors: SCHMETTERER L
Published: August 2012

Purpose Measurements of retinal blood flow in the rodent is a major challenge because of the small size and the poor optical quality of the eye. We present a technique based on the measurement of retinal vessel diameters using a fundus camera specifically designed for the rodent eye. This is combined with a Doppler OCT technique for measuring retinal blood velocities.

Methods In the rat retinal vessel diameters and retinal blood velocities were measured during several stimuli. These included systemic hyperoxia by breathing 100% oxygen, systemic hypercapnia by breathing increasing concentrations of CO2 and by stimulation with diffuse flicker light.

Results Retinal blood flow was quantified in larger retinal venules in our studies. As expected systemic hyperoxia induced a pronounced decrease in retinal vessel diameter, retinal blood velocity, and retinal blood flow (p < 0.01 each). Breathing increasing concentrations of CO2 on the other hand induced a dose‐dependent increase in retinal vessel diameter, retinal blood velocity and retinal blood flow (p < 0.01 each). Finally, stimulation with flicker‐light also increased retinal vessel diameter, retinal blood velocity and retinal blood flow (p < 0.01 each).

Conclusion Our data indicate that changes in retinal blood flow in the rodent can be adequately measured using combined fundus photography and Doppler OCT. This technique can also be used to study neurovascular coupling. Our results are important, because the mechanisms of retinal blood flow regulation remain largely obscure.
Metastatic uveal melanoma: A liver disease or a systemic disease?
Authors: KEILHOLZ U
Published: August 2012

Abstract not provided
Syndromic ophthalmic genetics
Authors: BLACK GCM
Published: August 2012

Purpose This presentation will provide an overview of recent scieitific progress in understanding multisystemic genetic ophthalmic disorders with specific examples including early‐onset developmental disorders as well as syndromic cataract and retinal disorders.

Methods A review, including case presentations, to illustrate novel insights into pathways underlying common and rare syndromic ophthalmic disorders, the importance of recognising such disorders and the utility (and limitations) in clinical practice of high throughput technologies including next generation sequencing.

Results Syndromic ocular disorders are an important contributor to childhood visual disability. There are many common issues regarding diagnosis and counselling apply to the entire group allowing the development of unified care pathways. An important challenge is to improve diagnosis since management of non‐ocular manifestations is likely key. While current diagnostic genetic testing still focuses on single genes, which will be illustrated through discussion of multisystemic retinal phenotypes such as bardet Biedl and Cohen syndromes, future prospects will employ high throughput technologies (e.g. next generation sequencing, microarray analysis) to enable efficient diagnosis of poorly recognised conditions (eg CTX, ocular auricular syndrome, mitochondial cytopathies)

Conclusion The continued and accelerated identification of genes underlying syndromic disorders associated with microphthalmia; corneal and lens developmental abnormalities or retinal dystrophies sheds light on the underlying pathways. Their identification has a direct bearing on clinical management, allowing the improvement and development of individualised care pathways.
Correlation between spectral‐domain OCT features and fundus auto‐fluorescence patterns in CSCR
Authors: BANDELLO F
Published: August 2012

Purpose Central serous chorioretinopathy (CSCR) is characterized by the development of a macular serous retinal detachment with a focal or multifocal areas of leakage at the level of the retinalpigment epithelium (RPE) that can be identified by fluorescein angiography. Aim of the study is to show the changes on optical coherence tomography (OCT) and on fundus autofluorescence (FAF).

Methods Patients affected by CSCR underwent a complete ophthalmological examination including best corrected visual acuity measurement, OCT and FAF with blue‐light FAF and near‐infrared FAF.

Results Eighty‐nine patients affected by CSCR were recruited for the study. OCT reveals many changes, including swelling of thesensory retina, disruption of the RPE, thickening of the outerretinal surface, and loss of the boundary of the photoreceptor inner/outer segments. Blue‐light FAF can disclose dot‐like deposits located in the sensory retina orsubretinal space. Near‐infrared FAF shows the development of some granular changes according to the fluid changes typical of CSCR.

Conclusion The combination of OCT and FAF imaging provides useful insights to characterize CSRC stages.

Commercial interest
Sparing of the fovea in geographic atrophy
Authors: HOLZ F , SCHMITZ‐VALCKENBERG S , FLECKENSTEIN M
Published: August 2012

Geographic Atrophy (GA) is a common cause for severe visual loss in age‐related macular degeneration (AMD). Typically, atrophic patches initially occur in the parafoveal retina. Over time, several atrophic areas may coalesce, and new atrophic areas may appear. This can temporarily result in a horseshoe conﬁguration of atrophy. In advanced stages, atrophic areas may form a ring encompassing the intact and still functioning fovea. On clinical examination, the fovea may remain untouched by the atrophic process until late in the course of the disease, a phenomenon referred to as ‘foveal sparing’. When the fovea ﬁnally becomes involved, a dramatic deterioration in visual acuity results. Prognostic factors indicating a pending foveal involvement are yet unknown. So far, spread of geographic atrophy has been quantified with regard to the area enlargement of all atrophic patches in an eye. Further clarification of the natural history of the disease needs to include analyses of the directional spread and identification of prognosdtic markers fopr foveal involvement as well as disease modeling. In a prospective, multi‐center, non‐interventional, non‐randomized, unmasked, observational study the natural history will be characterized, prognostic markers identified and to microstructural alterations determined in eyes with a ‘foveal sparing” in GA secondary to AMD by serial simultaneous confocal scanninglaser ophthalmoscopy (cSLO), fundus autofluorescence imaging and spectral domain (SD)‐OCT imaging.