bluuebunny/crossref_metadata_2025 huggingface dataset:
Alterations of the lid wiper zone in ocular surface disease
Authors: NEPP J
Published: November 2010

Purpose The marginal part of the tarsal conjunctiva forms a lid wiper structure that wipes the ocular surface and distributes the tear film during the blink. It was attempted to investigate whether this region of the upper and lower lid shows specific changes in several kinds of ocular surface diseases.

Methods 44 eyes of patients from the outdoor department of the university eye clinic Vienna were observed by slit lamp investigation of the ocular surface, vital staining with fluorescein and lissamin green. It was focused on evaluation of the tarsal conjunctiva including the lid margin and the wiper. Vessel dilatation, teleangiectatic changes and vital staining were each designed in three stages. The patients suffered from inflammation or affections of the lid, the conjunctiva and the cornea including chemical burns, graft versus host disease and injuries

Results Compared to normal eyes dilatation of vessels and staining was observed more in patents with inflammations but although in serious affections like chemical burn or injuries. Even in corneal affections changes of vessels were observed.

Conclusion Changes of the wiper can be observed in several diseases of the ocular surface and may be a sign of strain in this region.
A critical look at meibometry as a means to monitor Meibomian gland function
Authors: VERSURA P , PROFAZIO V , CAMPOS EC
Published: November 2010

Purpose To evaluate the diagnostic performance of meibometry in classifying and quantifying Meibomian gland dysfunction(MGD)

Methods Ninety‐six patients with MGD (138 eyes, 62 women, 34 men) and 30 normal control subjects(55 eyes)were enrolled. Eighty six eyes were classified as high delivery (HD)‐MGD (meibomian seborrhea/hypersecretory MGD), 52 as low delivery (LD)‐MGD on the basis of expression quality scores and morphological signs. Direct Meibometry (DM) measurements were made with an MB550 Meibometer (Courage‐Khazaka GmbH). Standard curves were constructed relating arbitrary Meibometer optical density units (AU). Integrated Meibometry (IM) was performed on scanned images of the lipid blots. Symptoms were scored by OSDI,Schirmer test I, Break Up Time (BUT), tear osmolarity (Tearlab, Ocusense), conjunctival scraping cytology were performed. Statistical analysis used SPSS 14.0 and MedCalc 5.0

Results AU values plotted on a log scale correlated highly with the lipid equivalent values (R2= 0.913). Significant differences were found between control subjects vs all MGD patients and between HD vs LD‐MGD patients for all the parameters evaluated. In particular: controls: 300+/‐121 AU (0.04+/‐0.015 microliter), LD‐MGD: 218+/‐122 AU (0.03+/‐0.015) and HD‐MGD: 564+/‐115 AU (0.07+0.015) (median+/‐SD). Significant correlation was found DM vs IM (r=0.691,p<0.0001) and DM was shown to be correlated with BUT, OSDI score, scraping score and tear osmolarity, especially in LD‐MGD patients. The selected DM diagnostic cut off for LD‐MGD was <275 AU (sens 73, spec 60, PPV 63) and for HD‐MGD was >450 AU; (sens 86, spec 87, PPV 91)

Conclusion Meibometry is confirmed to be a reliable method to distinguish normal subjects from MGD subgroups with a good degree of accuracy
Can cytology differentiate Norrie's disease from Retinoblastoma?
Authors: TODOROVA M , BUBENDORF L , PRüNTE CH , FLAMMER J , MEYER P
Published: November 2010

Purpose Objective: To describe the cytology characteristics in a case of Norrie’s disease.

Methods This is a retrospective case report of a 3‐weeks‐old boy. Diagnosis was based on findings at the initial and follow‐up examinations, cytology of the pseudotumor mass and the retina of both eyes and genetic work up.

Results The excised material was rich of cells with dense structures of small, round and blue nuclei. The cells stained positive for synaptophysin and displayed a proliferation rate of less than 5%. DNA sequence analysis revealed a heterozygosity of the mother and a hemizygosity of the child for the Norrie's disease associated NDP gene c.1A>G (p.M1V) sequence variant.

Conclusion The small proportion of proliferating cells as well as the synoptophysin positive phenotype of the retina point towards dysplastic retina and argue against retinoblastoma. Taken the cytological results together with the genetic analysis into account a X‐linked Norrie’s disease could be confirmed. Thus, cytology complemented by immunocytochemistry seems to be a useful tool to promptly differentiate patients with Norrie’s syndrome from those with retinoblastoma.
OCT evaluation of progression in dry forms of age‐related macular degeneration
Authors: CORTES MORA N , PASTOR IDOATE S , LOPEZ MI
Published: November 2010

Purpose To determine if OCT measure of the central mean macular thickness (CMMT) is a usefull parameter in the assesment of progression in dry forms of age related macular degeneration (d‐AMD)

Methods Retrospective, comparative cohort study. Patients with initial diagnosis of Age Related Maculopathy (ARM) and follow up of at least 2 years were included. Exclussion criteria were stablished geographic atrophy and wet forms of AMD. Clinical recordings were reviewed to collect data about age, sex, tabaco and alcohol habit, HTA, DM, ETDRS visual acuity, atrophy area measured by autofluorescence and follow up. CMMT was assesed through SDOCT, that calculates the mean thickness of a central disc of 1,5mm, in order to obtain an objetive messure of the retinal atrophy. CMMT and the signal noise index (SNI) of the OCT were calculated at the begining and at the end of the follow up. Univariate analisys was performed to detect relationship between clinical variables and CMMT.

Results 14 patients and 17 eyes with diagnosis of ARM were included. Mean Follow up was 20 months (SD=6). CMMT decreased from 235um to 210um in the follow up (p=0,043). There was a linear correlation between the CMMT and atrophy area measured by autofluorescence (R=0,621, p=0,031) and between CMMT and visual acuity (R=‐0,62, p=0,008). There wasn’t a diference in the SNI during the follow up. There weren’t relations between the other studied clinical variables and the CMMT.

Conclusion Central mean macular thickness is an objetive, easy and usefull parameter in order to asses the progression of dry AMD.
Patients in the DARC: drops revealing retinal ganglion cells in vivo
Authors: CORDEIRO MF
Published: November 2010

Purpose To provide a review of current & future DARC imaging technologies and their application to neuroprotection

Methods Currently, lowering IOP remains the only clinical therapy available in the treatment of glaucoma, despite the evidence that vision loss can continue in the presence of “significant” IOP reduction. Neuroprotection has been increasingly recognized as an important alternative treatment approach, but its emergence has also highlighted the need for both better defined end‐points in clinical glaucoma research, as well as earlier and better detection and measures of progression. This could have been a factor in the recent memantine trial. A recent FDA/NEI meeting on end‐points in glaucoma emphasized the need for new measurements. As the RGC is the primary injured neuron in this disease, it would seem logical that any modality that could directly measure RGC dysfunction and disease would be ideal. Perhaps the greatest changes that we have encountered recently are in the field of imaging technologies, which have only relatively recently been applied to the eye.

Results Advances in this area have allowed unprecedented in vivo access to the retinal layers, using many different properties of light to differentiate cellular structures. DARC is a technology shortly to enter clinical trials which allows the visualization of “sick” RGCs.

Conclusion Over the next few years, developments in therapy & diagnostic using DARC should offer great potential in glaucoma and other neurodegenerative conditions.

Commercial interest
Optic disc in the picture: novel imaging techniques
Authors: DREXLER W
Published: November 2010

Purpose Advances in light sources and detection technologies enabled a paradigm shift in retinal OCT imaging performance. ‘Snap‐shot OCT’ enabling isotropic sampling over 512x512x1024 voxels with 600 frames/second in less than a second is now possible.

Methods The resolution advantage in conjunction with full volumetric sampling has enabled the development of more informative indices of axonal damage in glaucoma compared with measurements of RNFL thickness and cup to disc ratio provided by other devices. A novel mapping method was developed, the three‐dimensional minimal distance (3D‐MDM) as the optical correlate of true retinal nerve fiber layer thickness around the optic nerve head region. In a preliminary study relation between the cross‐sectional areas of the retinal nerve fiber layer and the optic nerve was found to be a sensitive measure of axon loss.

Results In addition to all the major layers of the retina, the entire choroid down to the lamina cribrosa and sclera can now be visualized. This enables unprecedented information about choroidal vasculature without any contrast agents, choroidal thickness and will enable quantification of choroidal blood flow in the near future. Furthermore this technique allows tissue to be imaged in vitro with an image resolution better than 1‐2 µm, allowing to image single cells and detect pre‐apoptotic signatures using OCT. RGC‐5 cells were imaged using a sampling rate 1024x512x1024 voxel at 800 nm central wavelength and a bandwidth of 230 nm, enabling the detection of optical signatures at different pre‐stages of programmed cell death.

Conclusion Significantly increased OCT imaging speed and tissue penetration might enable novel insights and diagnostic opportunities in the diagnosis and therapy monitoring of glaucoma.

Commercial interest
Distribution of light on the retina over extended periods
Authors: BONE R , GIBERT J
Published: November 2010

Purpose Implicated in the etiology of age‐related macular degeneration (AMD) is photooxidative damage. Our purpose was to measure light distribution on the retina integrated over extended periods. Our hypothesis was that such distributions would peak in the macula where AMD is most evident.

Methods Using an eye‐tracker, the subject's field of view, gaze position and pupil size were continuously recorded. 5 subjects familiar with the study formed a control group; 10 naïve subjects formed a test group. In phase 1, subjects viewed photographic images projected on a screen. In phase 2, they were seated before a monitor and asked to perform typical computer tasks. In phase 3, they moved freely around the lab. The control group was asked to gaze at bright objects in the field of view and, in a second test, at dark objects. The test subjects were allowed to gaze freely. Based on the subject’s gaze position and pupil size over 5 to 15 min periods, the cumulative light distribution on the retina was calculated

Results For the control group, retinal illuminance peaked or dipped in the fovea for the tests in which subjects gazed at bright or dark objects respectively, thereby validating the experimental procedure. The retinal illuminace obtained from the test group in phase 2, but not in phase 1, consistently peaked at the fovea. In phase 3, such peaking occurred in 2 subjects.

Conclusion Our data indicate that there may be specific tasks (e.g. computer usage) that expose the macula to increased illuminance compared with the surrounding retina, and that there may be some individuals for whom this is true under general viewing conditions. In these cases, higher illuminance in the macular region could result in increased photooxidative damage with implications for development of AMD.
Increasing complexity of ocular genetic diseases : the case of BEST disease
Authors: ABITBOL M , LACASSAGNE E , PUECH B
Published: November 2010

Purpose Monogenic diseases until recently appeared simple from a molecular genetics point of view but correlations between genotypes and phenotypes still remain difficult to establish in many diseases and for many genes. For autosomal dominant diseases such as Best Vitelliform Macular Dystrophy, supposed to be a juvenile disease, it appears that mutations of BEST1 gene can cause multiple phenotypes including early onset and late onset phenotypes as well as unexpected phenotypes such as RP. We report several novel mutations and their associated phenotypes and describe phenotypes linked to previously reoported mutations for which the phenotype had not been describe at all previously. The role of SOX9, MITF and OTX2 in the incomplete penetrance and the variable expressivity of BVMDs is duscussed as well the potential roles of SNPs occuring in coding exons

Methods We used genomic PCR with appropriate primers flanking all the exons of the BEST1 gene in order to amplify them. This Genomic PCR was followed by automated sequencing and careful analysis of the sequences obtained.

Results We report the case of an unusual family where the Mother II2 of the proband III1, his maternal aunt II3, his brother III3 and his first cousin IIIIV, the son of his maternal aunt, carry a missense mutatation causing apparently only electrophysiological abnormalities. The Father II1 of the proband III1 turned out to carry a stop codon instead of the fifth normal BEST1 codon. The father did not display any electrophysiological nor any clinical abnormality and has a perfect monocular and binocular vision. In contrast the proband III1 carries both mutations with a severe phenotype.

Conclusion This report exemplifies the necessity to study all family members in the case of BVMDs.
Phenotype/genotype in congenital central hypoventilation syndrome
Authors: BREMOND‐GIGNAC D , TRANG H
Published: November 2010

Purpose To report and to classify the ocular motility disorders in congenital central hypoventilation syndrome. This rare syndrome, 1 of 200,000 livebirths, is characterized by a lack of ventilation due to defects of autonomic control especially of hypercapnia.

Methods We examine in a study 34 children (range 9 days‐old to 15 yo) with congenital central hypoventilation syndrome. They underwent a complete ocular and orthoptic consultation. An informed consent was signed to perform a DNA analysis to precise PHOX‐2B gene mutations.

Results Anisocoria, stabismus, eso and exotropia or phoria, ptosis, craniofacial palsy were found and we evaluated disorders considering intrinsic ocular motility and extrinsic ocular motility. We classified ocular anomalies in minor and major types with a score. The phenotype score was established in correlation with genotype. The score is higher in patients with genotype of equal or more 7 ALA mutations and a precise table correlation was established.

Conclusion The high incidence of ocular motility disorders may result of neurologic defects of the oculomotor nerves and muscles involving neural crest development. A precise phenotype contributes to an evaluation of the severity of the disease and can also lead to a better reeducation of oculomotor anomalies.
Phenotype/genotype in Gardner disease
Authors: MILAZZO S
Published: November 2010

Purpose Gardner syndrome is a variant of familial adenomatous polyposis and results in the manifestation of external and internal symptoms including gastrointestinal polyps, osteomas, tumors, epidermoid cysts and congenital hypertrophy of retinal pigment epithelium.

Methods Three families of Gardner syndrome including 23 patients underwent complete check‐up to characterize ocular and general phenotype. Ophthalmologic manifestations are simple, non invasive reliable and very sensitive. The gene responsible for this disorder was localized on the long arm of the fifth chromosome. APC‐associated polyposis conditions are caused by mutations in the APC gene. A subset of individuals with clinical features of FAP will instead carry a mutation in the MUTYH gene.

Results Of the 23 patients, 13 presented a bilateral congenital hypertrophy of retinal pigment epithelium. In these patients 6 had a positive coloscopic exploration. This inherited autosomal dominant disorder has a marked propensity to malignant transformation, so, it is important to detect affected patients early.

Conclusion Currently, there are no specific screening recommendations for Gardner syndrome, but testing following general screening recommendations for extra‐colonic malignancies, genetic counseling, and endoscopy are encouraged.
Phenotype/genotype evolution in corneal dystrophies
Authors: CHIAMBARETTA F
Published: November 2010

Purpose The corneal dystrophies are a group of genetically determined diseases usually characterized by loss of corneal transparency, which may be caused by a progressive accumulation of abnormal material within the cornea. The genetic characterization of corneal dystrophies revealed both genetic heterogeneity, that is, different genes (KRT3 and KRT12) causing a single dystrophy phenotype (Meesmann dystrophy), and phenotypic heterogeneity with a single gene (TGFBI) causing different allelic dystrophy phenotypes (RBCD, TBCD, granular type 1, granular type 2, and lattice type 1).But less is known about the evolution of the phenotype during life.

Methods We were interesting in following the corneal phénotype progressive evolution during childhood. During several years we analyzed corneal phénotype of families of Lattice type 1 and granular type 1, using Scheimpflug camera.

Results We were able to follow the accumulation of abnormal material, his corneal localisation and evolution during years.

Conclusion The phenotype of both Lattice type 1 and granular type 1 is totally different in childhood, with subepithelial localization.
Blue cone nonochromacy gene mutation in Asia: phenotype variability
Authors: BITOUN P , RIGAUDIERE F , PAPKE M , KOHL S , WISSINGER B
Published: November 2010

Purpose A far East asian family with 4 affected maternal cousin males with congenital nystagmus, low vision and dyschromatopsia was investigated for a genetic cause after informed consent. Blue cone monochromacy is a rare form of X‐linked visual handicap with dyschromatopsia.

Methods Family members had ophthalmologic examination including visual acuity, fundoscopy , slit lamp, biomicroscopy,colour vision testing and ERG and VEP recordings.DNA analysis of the composition of the cone ospin gene cluster was performed by PCR and PCR/RFLP as well as direct sequencing of LWS opsin gene.

Results A novel nonsense Mutation in the single Long wave sensitive opsin gene was identified in all affected males and carrier females. The variability of the phenotype as well as the added role of parental myopia transmission in the phenotype will be discussed.

Conclusion This is the first reported molecular diagnosis of blue cone monochromacy in the Asian population.The compound effect of dominantly inherited myopia offers insight of the effect of the added mutational load in these patients.
Prevalence of age‐related macular degeneration in rural Central India. The Central India Eye and Medical Study
Authors: LIBONDI T , NANGIA V , JONAS JB , KULKARNI M , MATIN A
Published: November 2010

Purpose To evaluate the prevalence of age‐related macular degeneration (AMD) in the adult population of rural Central India.

Methods The participants underwent a detailed ophthalmic and medical examination including standardized questions on the socioeconomic background, lifestyle, and social relations. Prevalence of AMD as defined by the Wisconsin Age‐Related Maculopathy Grading system.

Results Including only subjects with an age of 40+ years revealed a prevalence of early AMD of 3.6±0.2 % (95%CI: 3.1%‐4.0%) per eye and of 6.1±0.4% (95%CI: 5.3%‐6.9%) per person; and of late AMD of 0.1±0.5% (95%CI: 0.1%‐0.2%) per eye and of 0.2±0.8% (95%CI: 0.1%‐0.4%) per person. Neovascular AMD was found in 5 (0.06±0.03%) eyes. Geographic AMD was detected in 4 (0.04±0.02%) eyes. Late AMD was found in 9/8943 (0.1±0.03%; 95%CI: 0.03%‐0.2%) eyes or 8/4542 (0.2±0.03%; 95%CI: 0.1%‐0.3%) subjects. The prevalence of early AMD increased from 1.3±0.3% in the 30‐ to 40‐year age group, to 3.6±0.5% in the 41‐ to 50‐years old group, to 7.9±0.9% in the 51 to 60‐ years old group, to 10.0±1.1% in the 61‐ to 70‐years old group, to 8.3±0.2% in the 71‐ to 80‐years old group, and to 8.0±5.5% in the 81+ year old subjects. AMD was causative for visual impairment (best corrected visual acuity in the better eye: <20/60 and ≥20/400) in 3 out of 342 (0.9%) subjects, and it was causative for blindness (visual acuity <20/400) in none out of 17 subjects.

Conclusion Age‐related macular degeneration was found less frequently in the adult population in rural Central India than in Caucasian populations. Accordingly, visual impairment due to age‐related macular degeneration was relatively uncommon in the adult population in rural Central India.
Diurnal variation in diabetic macular edema measured by optical coherence tomography
Authors: IBANEZ ALPERTE J , PEREZ GARCIA D , MATEO OROBIA A , PEIRO EMBID C , SAINZ A , CRISTOBAL BESCOS JA , FAURE NOGUERAS E
Published: November 2010

Purpose To investigate diurnal variation in diabetic macular edema using the Stratus OCT ( Carl Zeiss Meditec).

Methods Forty eyes of twenty diabetic patients with diabetic macular edema underwent four optical coherence tomography (OCT) measurement of macular thickness with the fast macular thickness mapping protocol of the Stratus OCT at 9 AM, 12 AM, 3 PM, 6 PM. ETDRS visual acuity and refraction data were also collected at each time. Retinal thickness measurements from each of the nine areas of the retinal map, visual acuity and refraction were correlated over time.

Results In our study we find a decrease delk macular thickness by means of OCT of 4%, 5%, 6% at 12 a.m. am 15 am 16 pm. In the group of patients with macular thickness bigger than 300 microns, we find change in the refraction of 2 patients. In the rest of patients (absence of macular edema,. slight macular edema), there were no significant changes of the macular thickness.

Conclusion This study suggests that macular thicknening, as measured by the Stratus OCT, may spontaneously decrease in some patients with more severe macular diabetic edema over the course of the day.
Optic nerve and macular thickness studied by CirrusTM OCT in Type 1 Diabetes Mellitus patients without retinopathy
Authors: IDOIPE M , GARCIA‐MARTIN E , FUERTES I , FERNANDEZ PEREZ S , PINILLA I , GUERRI MONCLUS N , EGEA ESTOPINAN MC , PRIETO CALVO E , CRUZ N , BORQUE RODRIGUEZ‐MAIMON E
Published: November 2010

Purpose To compare optic nerve and macular thickness in patientes with Diabetes Mellitus (DM) type 1 without retinopathy, with healthy subjects.

Methods Comparative cross‐sectional study. One eye per patient was randomly selected from fifty healthy subjects and 50 patients with type I DM without retinopathy with intensive glycemic control. Patients were scanned using Cirrus HD‐OCT (Carl Zeiss Meditec, Inc., Dublin, CA). The scan protocols were optic disc cube 200x200 and 512x128 volumen cube to assess the retinal nerve fiber layer and the macular thickness respectively.

Results Mean age of control group was 30.26 years and 30.08 in DM patients. In optic nerve study, statistically significant differences were found in temporal and nasal quadrants. In macular thickness study we did found differences in all the studied parameters including macular volumen, average thickness, superior, nasal ant temporal of the 3 mm ETDRS ring, and all of the 6 mm ETDRS ring; excluding the central 1 mm ETDRS ring and inferior value of the 3 mm ETDRS ring (all the values were higher in DM patients).

Conclusion Cirrus OCT is no able to detect retinal nerve fiber layer lost in type I diabetes mellitus patients without retinopathy. Cirrus showed an increase of retinal thickness in patients with DM, even when there is no sign of retinopathy or macular edema, and even when these patients are preserving the foveal shape. These data support the importance of increasing our knowledge of optic nerve study in diabetic patients and the follow up of macular thickness.
Non‐invasive retinal imaging of central serous chorioretinopathy
Authors: BEUTELSPACHER SC , JONAS JB
Published: November 2010

Purpose Central serous chorioretinopathy leads to a serous detachment of the retina and a deterioration of visual acuity, contrast sensitivity and color vision. This is due to a leakage of serous fluid into the subretinal space through a defect in the retinal pigment epithelium.

Methods A female patient aged 34 years experienced a drop in best corrected visual acuity to 20/40 with mild hyperopization and dyschromatopsias for two weeks. The diagnosis of a central serous chorioretinopathy was substantiated by optical coherence tomography (Stratus OCT, Zeiss Meditec, Jena, Germany) and infrared autofluorecence imaging (HRA classic; Heidelberg Engineering, Heidelberg, Germany). The patient additionally underwent retinal imaging by the Retinal Function Imager (RFI, Optical Imaging, Rehovot, Israel).

Results The findings suggest that the technique applied by the Retinal Function Imager can be helpful to diagnose central serous chorioretinopathy and to visualize abnormal areas at the level of retinal pigment epithelium in a non‐invasive manner. This finding may suggest that the Retinal Function Imager was able to demonstrate a small motion in the subretinal space, originating at the site of detached retinal pigment epithelium. The finding fits with the observation of “smoke stacks” of fluorescein seen in patients with central serous chorioretinopathy when conventional fluorescein angiography is used.

Conclusion The technique applied by the Retinal Function Imager can be helpful to diagnose central serous chorioretinopathy and to visualize abnormal areas at the level of retinal pigment epithelium in a non‐invasive manner. This finding may suggest that the Retinal Function Imager was able to demonstrate a small motion in the subretina
Evaluation of wound architecture in oblique 20‐gauge sutureless transconjunctival sclerotomies with VisanteTM optical coherence tomography
Authors: MANGIORIS G , MENDRINOS E , PAPADOPOULOU DN , POURNARAS CJ
Published: November 2010

Purpose To investigate the in vivo real‐time wound morphology of 20‐gauge transconjunctival sutureless oblique sclerotomy wounds with anterior segment optical coherence tomography (OCT).

Methods Subjects underwent three‐port pars plana vitrectomy with a 20‐gauge trocar/cannula microincision surgical system (Synergetics™) . All incisions were created in an oblique fashion (10º) and were imaged with the Visante OCT device on postoperative days 0, 1 and 8.

Results Thirty patients were included. Slit‐lamp examination revealed no evidence of leakage from the sclerotomy sites. Visante OCT demonstrated closed wounds in all eyes on postoperative days 0, 1 and 8.

Conclusion This study demonstrates that 20 gauge sutureless transconjunctival oblique incisions provide adequate wound apposition as shown by OCT even at the day of operation.
Dietary supplementation of genistein (geniVida®) ameliorates scopolamin‐induced dry eye syndrome in rats
Authors: SCHALCH W , ROOS F , BARKER FM
Published: November 2010

Purpose Dry Eye Syndrome (DES) is an ocular surface disease with higher prevalence in women than in men. It is characterized by decreased tear gland secretion, altered tear composition and tear film instability. We investigated whether supplementation with the isoflavone genistein (GEN) could alleviate artificially induced DES in rats.

Methods DES was induced in 24 female Sprague Dawley rats by daily trans‐dermal treatment with scopolamine (SCOP). Animals were housed on an AIN feed containing 0, 50 or 250 ppm of GEN provided as geniVida® by DSM Nutritional Products. 8 additional animals served as not‐stressed control. After 2 and 4 weeks, levels of GEN in plasma were measured by LC/MS and the status of DES was assessed using the Zone Quick Test (ZQT). After 4 weeks, animals were sacrificed and cornea and conjunctiva were examined for Goblet Cell Density (GCD) and the extent of lid keratinization (LK). Pairwise comparisons of endpoint values were done by t‐test or Mann‐Whitney test.

Results Genistein feeding resulted in significant increases of plasma genistein concentrations. The achieved levels were commensurate to those reported in a human study supplementing 60 mg/day (Ullmann et al. (2005), Planta Med. 71: 891‐896), equivalent to 100g soy beans per day. In the 0 ppm GEN group, SCOP treatment increased the extent of LK and drastically reduced ZQT and GCD values, while genistein supplementation restored tear volume (p=0.0007), GCD (p=0.0028) and LK (p=0.0009) in a dose‐dependent manner.

Conclusion While these results still need to be confirmed in humans, genistein supplementation may become a treatment option that fundamentally restores natural tear physiology, offering a major improvement over the currently used topical agents.

Commercial interest
Therapeutic potential of human hair follicle‐derived stem cells for ocular surface reconstruction using a rabbit stem cell deficiency model
Authors: MEYER‐BLAZEJEWSKA EA , SCHLöTZER‐SCHREHARDT U , KRUSE FE
Published: November 2010

Purpose To examine the therapeutic potential of human hair follicle (HF)‐derived stem cells (SC) for ocular surface reconstruction.

Methods HF SC were isolated enzymatically and enriched on a 3T3 layer by clonal growth assay. To support differentiation into a corneal cell phenotype, clones were transferred onto a fibrin carrier and cultivated in a conditioned medium (CM) derived from limbal stromal keratocytes. Following generation of a limbal stem cell deficiency a multilayered cell sheet grown on a fibrin carrier was transplanted onto a rabbit eye (n=3). Cell phenotype was examined by means of real time RT‐PCR, immunohistochemistry, and Western‐blotting using antibodies against corneal markers, K12 and Pax6, as well as the epidermal marker K10. To identify secreted factors in the limbal CM a Human Growth Factor Antibody Array was performed.

Results Cultivation of HF cells in limbal keratatocyte–derived CM induced the expression of K12 and Pax6 on the mRNA and protein level, whereas the expression of K10 was strongly downregulated, in comparison to an unconditioned control. Several potential candidates (FGF‐4, IGFBP‐2, 4,6 and IGF‐II) involved in the corneal differentiation process could be identified. Following transplantation onto a limbal SC deficient rabbit eye, HF‐derived SC could regenerate the corneal epithelium and express the corneal differentiation marker K12 while suppressing K10 expression.

Conclusion These findings suggest that human HF‐derived SC are capable of being reprogrammed into corneal cell phenotype when exposed to factors of the limbal niche in vitro and maintain the reprogrammed phenotype in vivo following transplantation onto an animal model.
Central corneal thickness and corneal curvature in patients with rheumatoid arthritis
Authors: OZCURA FATIH , AKSAKALLI ELIF
Published: November 2010

Purpose To determine the central corneal thickness (CCT) and corneal curvature (CC) in patients with rheumatoid arthritis (RA), and to evaluate the correlations between the CCT, CC and RA activity and duration.

Methods Thirty‐three RA patients (64 eyes; 20 with dry eye, 44 without dry ye) and 21 age and gender matched control patients (42 eyes) were enrolled in the study. The CCT, and CC were measured by ultrasonic pachymeter (Sonomed Micropach Model 200P, Lake Success, NY, USA), and autorefractokeratometer (Topcon KR 8800, Tokyo, Japan), respectively. RA activity was assessed using the disease activity score (DAS) 28. The independent samples t test and Pearson correlation analysis was used in the statistical analysis.

Results Mean CCT were found 541.73 ± 39.55 μm, 531.45 ± 38.34 μm, 546.41 ± 39.63 μm, and 543.40 ± 39.55 μm in all RA eyes, RA with dry eyes, RA without dry eyes, and control eyes, respectively. Mean keratometry (K) readings were found 43.87 ± 1.98 D, 43.84 ± 1.23 D, 43.88 ± 2.25 D, and 43.60 ± 1.48 D in all RA eyes, RA with dry eyes, RA without dry eyes, and control eyes, respectively. There were no significantly difference in CCT (p values, 0.834, 0.275, and 0.729 respectively) and K readings (p values, 0.448, 0.524, and 0.493 respectively) between the RA and control eyes. CCT and K readings were not significantly associated with DAS (p values, 0.791, and 0.861 respectively) and RA duration (p values, 0.238, and 0.155 respectively).

Conclusion Our results show that CCT and CC were not significantly different between the RA and control eyes. CCT and CC were also not associated with RA activity and duration.
Complications after IntacsTM: presentation of cases
Authors: PEREZ GARCIA D , IBANEZ ALPERTE J , JIMENEZ DEL RIO B , CRISTOBAL BESCOS JA , MATEO OROBIA A , CRUZ N , CABEZON L
Published: November 2010

Purpose To report the postoperative complications developed after INTACS implantation in our series.

Methods Retrospective, observational study of complications occurred after INTACS implantation for keratoconus in our hospital between May 2006 and January 2010 . We evaluated possible risk factors associated and the therapeutic management.

Results We found after data analysis two extrusions,one corneal abscess and one late corneal neovascularization requiring explant as major complications. The extrusion rate was 0.6% and after explantation there was no decrease in corrected visual acuity in each patient. The incidence of infections in our series was 0.5%, with a single case. The therapeutic management was performed by topical fortified antibiotic,and resolved completely in in 11‐day period. Final visual acuity was close to 0.2. Corneal neovascularization was reported as a single case referred to our center. The patient was treated with topical cyclosporine A and corticosteroids.After 3 months of treatment the patient was asymptomatic with complete remission of the corneal neovascularization. No cases of intractable eye pain or other complication occurred in our series.

Conclusion Implantation of Intacs is safe and effective, however like any surgical procedure is not without complications. Minimize the risk factors associated and an early management of complications are determining to achieve the best functional results is these patients.
Use of Phenol Red Thread Test as a rescue test in diagnostic strategy of severe ocular syndrome
Authors: LABETOULLE M , GENDRON G , POGORZALEK N , KASWIN G , MARIETTE X , DE MONCHY I
Published: November 2010

Purpose To define a combination between Schirmer I and phenol red thread test (PRT) that improves the screening of patients with ocular sicca syndrome.

Methods The PRT test was performed before (PRT1) and after (PRT2) the Schirmer I test, in both eyes of 143 patients complaining of ocular dryness secondary to Sjögren’s syndrome (SGS) or Sicca Asthenia Polyalgia Syndrome (SAPS) (72 and 71 patients respectively), and in 40 patients with no sign of dry eye. Groups were matched by age and gender. After determining the best cut‐off values using the ROC procedure, several combinations of PRT and Schirmer I were assessed to improve the predictive values of the procedure.

Results The best cut‐off value for PRT2, estimated at 15mm, provided a satisfying match between sensitivity and specificity indexes (68% and 90% respectively), similar to those obtained with the Schirmer I test. If PRT1 alone was ineffective to screen SGS from control patients, the comparison between PRT 1 and PRT2 (”delta‐PRT”) was found as a good marker to detect patients with persistent tear reflex. The combination of positive Schirmer I, PRT 2 and/or delta‐PRT tests was found as highly predictive of severe ocular sicca syndrome.

Conclusion The combination of Schirmer I and PRT test improves the screening procedure to detect patients with severe ocular dryness. Since PRT test is non‐invasive and time‐effective, it could be more widely used in daily clinical practice, besides Shirmer I test, to optimize the work‐up of patients presenting with dry‐eye subjective signs.
Identification of breaks in choroidal coloboma eyes with retinal detachment using subretinal trypan blue injection
Authors: NAITHANI P , SANKARAN P , MISHRA S , GARG SP
Published: November 2010

Purpose To describe the use of subretinal trypan blue to localize retinal breaks during vitrectomy for rhegmatogenous retinal detachment in choroidal coloboma eyes.

Methods Trypan blue 0.03% was injected subretinally through a retinotomy superonasal to optic disc in 108 choroidal coloboma eyes in which no breaks could be identified pre‐ or intra‐operatively outside the coloboma margins. Eyes were rotated to evenly spread the dye subretinally and plume of trypan blue into the vitreous cavity was used to locate the breaks. Communication between breaks in the intercalary membrane (ICM) and coloboma margin was also studied.

Results Eighty six eyes had breaks within the coloboma margins only whereas 7 eyes had breaks within as well as outside the coloboma. In 7 eyes breaks were seen in peripheral retina alone and no breaks could be found in 8 eyes even intra‐operatively. In all eyes with break inside the coloboma there was a single communication at its margin between the detached retina outside the coloboma and the break in ICM through which trypan blue entered vitreous cavity. Mostly it was in the infero‐nasal or temporal quadrant outside the inferior vascular arcade.

Conclusion Majority of retinal detachments that involve the coloboma were caused by breaks within the ICM. Moreover there is a small defect at the coloboma margin through which the sub‐ICM fluid seeps under the normal retina from the break. Based on intraoperative findings in this study, prophylactic laser to margins of coloboma sparing the vascular arcades may seal off this potential communication and prevent retinal detachment in such eyes.
Maintenance of anticoagulant and antiplatelet agents for patients undergoing vitreoretinal surgery
Authors: CREUZOT C , PASSEMARD M , KOEHRER P , BRON AM
Published: November 2010

Purpose To establish the prevalence of anticoagulant, aspirin, and clopidogrel use in patients undergoing vitreoretinal surgery, and to compare the outcome of peribulbar anesthesia between users and non‐users.

Methods We conducted a retrospective case series in one academic center between January and June 2009. We analyzed the chart of 239 eyes who underwent posterior segment surgery with peribulbar anesthesia. No changes in the anticoagulant regimen were made prior to surgery. We divided patients into 7 groups: group 1: patients with no anticoagulants and 6 groups defined according to the type of anticoagulant or antiplatelet medication.

Results 239 eyes (206 patients) were included: 168 eyes without any anticoagulant medication (70.3%) and 71 eyes with anticoagulant and/or antiplatelet agents (29.7%). Only 3 cases of long‐term sight‐threatening hemorrhagic complications (4.2%) were noted: 2 from patients with pseudo‐tumoral form of age‐related macular degeneration associated with vitreous hemorrhage, and 1 from patient with tractionnal retinal detachment secondary to complicated diabetic retinopathy. No surgery was post‐poned or cancelled due to an anesthetic complication.The incidence of postoperative hemorrhagic complications was increased in patients taking anticoagulant and/or antiplatelet medications (P=0.001) vs non‐users.

Conclusion Peribulbar anesthesia for vitreoretinal surgery can be safely performed in patients receiving anticoagulant and/or antiplatelet agents.
Algorithms and instrumentation for quantified retinal oximetry in a snapshot
Authors: HARVEY AR , ABBOUD I , GORMAN A , MUYO G , CROWE J , MORGAN S , RODMELL P , MORDANT D , MCNAUGHT AI
Published: November 2010

Purpose To develop an instrument and techniques for useful absolute and relative clinical oximetry of the retina.

Methods A novel snapshot multispectral imaging system has been optimised for retinal oximetry. Eight monochromatic images of the retina are recorded with a field of view of 24 degrees. Algorithms calculate the absorption of light at each point along delineated blood vessels and for each of the eight wavebands. Data inversion using an analytical model for light propagation enables oximetry at along the blood vessels. Spectral inversion has been refined using ray tracing and Monte Carlo modelling of light propagation using a realistic phantom eye.

Results A comparison of Monte Carlo modelling of light propagation in the phantom retina with recorded images for blood of various oxygenations indicates the influence of several unknowns, including scatter from optical surfaces within the ophthalmoscope and eye, the geometry of the blood vessels and eye, the optical constants of the ocular media and the complexity of light propagation in the retinal structure. Relative oximetry within the retina is possible with repeatability of about 1% in the phantom and 5% in a real eye but the influence of various systematic effects can introduce systematic differences between actual and calculated oxygenation that can significantly exceed these values.

Conclusion Although oximetry using only a very small number of spectral bands is possible, this is prone to systematic errors that can effect both absolute and relative oximetry. The ability to record eight spectral images in a single snapshot offers promise to provide an enhanced clinically useful and validated oximetry technique.
Pre‐cut posterior corneal lamellae with a stromal rim used for Descemet’s membrane endothelial keratoplasty with a stromal rim (DMEK‐S)
Authors: KRABCOVA I , STUDENY P , JIRSOVA K
Published: November 2010

Purpose To standardize a technique for the manual preparation of posterior corneal lamellae for DMEK‐S under the conditions of an ocular tissue bank. To assess the qualitative and quantitative parameters of the lamellar endothelium with the aim of establishing the parameters of corneas intended for preparation.

Methods Corneoscleral buttons 17mm in diameter not suitable for grafting were used. Group 1 contained 12 corneas with a live endothelial cell density ≥ 2500 cells/mm2. Group 2 contained 10 corneas with a density lower than 2500 cells/mm2. The lamellae, consisting of a central 6mm zone of endothelium‐Descemet’s membrane surrounded by a supporting peripheral stromal rim, were prepared manually using the big bubble technique. The percentage of dead cells and the live endothelial cell density were assessed before and immediately after preparation as well as after 48 hours of organ culture storage using light microscopy following 0.15% trypan blue and 0.9% sucrose treatment.

Results Immediately after the preparation, on average 4.9 % and 5.2 % of dead cells were found in group 1 and group 2, respectively. The percentage of dead cells decreased significantly during subsequent storage in organ culture in both groups (to 1.5 % and 1.7 % for group 1 and 2). There was no significant decrease in live endothelial cell density in group 1 during 48 hours of culturing; however, there was a significant decrease in group 2.

Conclusion The decrease in endothelial cell density during organ culturing depends on the original values. We suggest that the minimal acceptable live endothelial cell density of corneas intended for preparation should be 2500 cells/mm2 to ensure the best clinical outcomes.
Planar patch‐clamping in human corneal endothelial cells: a new tool for clinical application?
Authors: MERGLER S , PLEYER U
Published: November 2010

Purpose Identification of apoptotic or damaged human corneal endothelial cells (HCECs) is limited to morphological evaluation such as phase contrast microscopy and vital staining. The molecular mechanisms of corneal endothelial cell loss are not fully understood. Special investigations in cellular signalling and ion channel research are necessary to elucidate the mechanisms of corneal cell loss. In this context, it is known that this cell loss is often caused by apoptosis in oxidative stress.

Methods Automated planar patch‐clamp has become common in drug development and safety programs because it enables efficient and systematic testing of compounds against ion channels during voltage‐clamp. A particularly successful automated approach is based on planar patch‐clamp chips and this is the basis for the technology used here. Routine intracellular or extracellular perfusion opens possibilities for studying the regulation and pharmacology of ion channels. Previously, these studies were available only to highly skilled and dedicated experimenters.

Results Notable, definite ion channel activities could be demonstrated by conventional as well as by planar patch‐clamp in HCECs for the first time. In particular, temperature‐sensing transient receptor potential (TRP)‐like non‐selective cation channel currents as well as capsaicin‐sensitive ion channel currents could be detected. The expression of TRPV1‐3 ion channels in HCEC could also be confirmed by RT‐PCR, Western blot analysis and fluorescence cell imaging.

Conclusion The administration of this novel measuring technology opens new perspectives in the investigation of the physiology of HCEC. The findings may have direct clinical implication (eye banking procedures, keratoplasty).
Cataract formation after incorporation of radioactive iodine
Authors: DALKE C , ROSEMANN M , PUK O , GRAW J
Published: November 2010

Purpose The ocular lens is one of the most radiosensitive organs in mammals and a pathological sign after exposure to ionising radiation is the formation of cataracts. We generated a mouse model to mimic the situation after the accident in the Chernobyl power plant.

Methods Pregnant and nursing FBV‐mice were treated with iodine131 for diaplacentar and galactogen transfer to the litter. The offspring which incorporated the radioiodine were examined for lens opacities at the age of 6 and 12 months. Iodine131 is a beta radiation emitting nuclide with a short half live of 8 days. Mothers were injected twice with 100 kBq I‐131, on day 14 post conception and day 6 post natal. Cataracts were investigated at 6 and 12 months of age using a slit lamp.

Results Depending on the litter size and weight, a single progeny incorporates between 8 to 14 % of entire activity. More than 50% of the injected activity is transmitted from the mother to the entire offspring. Iodine is accumulated in the thyroid and an average thyroid dose of 3.7 Gy was calculated. Because of the short distance between the thyroid and the eye, a lens dose of 0.5 Gy was estimated. In the FBV mice, we observed at the age of 6 months two cataracts among 15 irradiated lenses (13%), but none among 7 unirradiated controls. At the age of 12 months, almost all lenses showed cortical cataracts in both groups. However, there were 17 nuclear cataracts among 66 irradiated lenses (25%), but only 1 among 16 controls (6%).

Conclusion These preliminary data indicate that this method is sensitive enough to detect the cataract‐causing potential of low‐dose ionizing radiation in the mouse. However, for detailed analysis larger cohorts and quantification of the data are necessary.