bluuebunny/crossref_metadata_2025 huggingface dataset:
Disruption of binocular vision following cataract surgery
Authors: WHITE JES
Published: October 2007

Purpose: The aim of this study was to assess the incidence of disruption of binocular vision following cataract surgery and to re‐evaluate the role of Orthoptists in pre‐assessment clinics for cataract surgery.

Methods: A retrospective study was carried out of all patients who attended the hospital for cataract surgery between January 2003 and December 2003. The incidence of ocular motility disorders and diplopia which had been recorded in the case notes was noted pre‐operatively, two weeks post operatively and if it was still persisting more than six weeks post operatively. All patients with persistent diplopia/symptoms related to disruption of binocular vision had been referred for Orthoptic assessment.

Results: In the period from January‐December 2003 2147 patients had cataract surgery, 93% of whom had surgery under local anaesthesia. There was a total of 17 (0.8%) cases with persistent disruption of binocular vision post cataract surgery. The aetiology of the binocular problems was divided into three groups 1)refractive, 2)pre‐existing deviation and 3)induced deviation. Treatment was by means of prisms, refractive correction, occlusion, Botulinum toxin and surgery.

Conclusions: The incidence of disruption of binocular vision in those patients undergoing cataract surgery is not high. However the symptoms that they have can be very difficult for the Orthoptist to eliminate despite a range of treatment modalities. The Orthoptist therefore has an important role in pre‐assessment cataract surgery clinics in highlighting those patients in which there are potential binocular complications.
Non‐melanocytic conjunctival epithelial lesions ‐ overview
Authors: ROSNER M
Published: October 2007

Purpose: To give an overview on the clinical presentation, differential diagnosis and treatment of non‐melanocytic conjunctival epithelial lesions.

Methods: The current literature on non‐melanocytic conjunctival epithelial lesions was reviewed.

Results: The non‐melanocytic conjunctival premalignant and malignant epithelial lesions include actinic keratosis, dysplasia, intraepithelial neoplasia and squamous cell carcinoma. The traditional management was by surgical excision with clear margins and cryotherapy was added to ensure the complete destruction of tumor cells. During the last decade new approaches were suggested using topical chemotherapy with mitomycin C, 5‐fluorouracil and interferon alpha‐2b as well as photodynamic therapy.

Conclusions: New data is accumulating regarding the long and short‐term follow‐up after traditional and newer treatment modalities for non‐melanocytic conjunctival, epithelial lesions. Based on this data, the common practice of the management of these lesions is changing from almost only surgery towards increased use of the different topical chemotherapy treatments.
Clinicopathologic analysis in nasolacrimal canal obstruction
Authors: ALTAN‐YAYCIOGLU R , CANAN H , BAL N , SIZMAZ S , PELIT A , AKOVA YA
Published: October 2007

Purpose: To analyze the histopathological results of lacrimal sac biopsies in primary acquired nasolacrimal canal obstruction.

Methods: 150 consecutive patients who were diagnosed as primary acquired nasolacrimal canal obstruction were included in this prospective non‐comparative study. Previous history of trauma and surgery to the periorbital area was accepted as exclusion criteria. Patients were evaluated for age, gender, history, and presenting symptoms. Lacrimal drainage system abnormalities were assessed. Lacrimal system irrigation, dacryocystography, and in selected cases dacryoscintigraphy was performed. All patients underwent external dacryocystorhinostomy. Biopsy specimens were obtained from the posterior inferior flap and examined by the same pathologist.

Results: The results of 27 male and 123 females with age ranging from 6 to 80 years (mean 47.7 ± 15.8 years) were analyzed. None of the patients had preexisting history of systemic disease. Ninteen patients had grossly abnormal or infectious appearing sac at the time of surgery. Of these, one patient had granulomatous inflammation of the lacrimal sac and was diagnosed with sarcoidosis during postoperative examination. One patient with normal appearing sac had basosquamous cell carcinoma and underwent dacryocystectomy. The remaining specimens showed chronic inflammation (n= 124), fibrosis (n= 19), normal mucosa (n= 4), or lymphoid hyperplasia (n= 1).

Conclusions: Pathological examination of the lacrimal sac in primary nasolacrimal canal obstruction revealed chronic inflammatory changes in most of the patients. Although rare, granulomatous inflammation or tumour of the lacrimal sac might be observed in such cases. We recommend to biopsy all cases with nasolacrimal canal obstruction.
The EVI‐genoret phenotype / genotype patient data base: a pan‐European tool for retinal dystrophies and age related macular degeneration
Authors: ZRENNER E , WILKE R , TROEGER E , AYUSO C , VALLESPIN E , SILVA E , SCHOLL HP , BELLMANN C , RIPP R , POCH O , CUNHA‐VAZ J , SAHEL JA , CHAKRAVARTHY U , MOORE T
Published: October 2007

Purpose: Supported by EVI‐Genoret (EU LSHG‐CT‐512036)

To build a patient registry that provides comprehensive, well standardized and high quality information on the phenotype and genotype of patients with hereditary and age related retinal diseases. To foster international collaboration by providing easy access to this resource of uniformly phenotyped patients for researchers worldwide.

Methods: Within the EU funded project EVI‐Genoret standards for comprehensive phenotyping of patients with ARMD and hereditary retinal dystrophies (HRD) have been developed. These standards are implemented as electronic Case Report Form (CRF) in the patient registry. SOPs for clinical procedures assure high level of data quality. A 3 level system of datasets ensures comprehensive data acquisition and protection of sensible data. Data accessibility tags are used in order to establish and share data between collaborators. The database is SQL based and uses Java‐script as a platform independent user interface. Legal and ethical questions that arise in different countries are addressed by a professional project management.

Results: The registry can be easily accessed by Internet after a registration process. The user interface enables simple access irrespective of the operating system, no special software must be installed. The electronic CRF guides through the examination. An intelligent system checks in real‐time for plausibility of entered data, supports consequent entries and automatically hides non‐relevant fields, thus facilitating time effective work.

All entries are stored based on a 3 level system. Level1 as basic catalogue of entries is accessible to all users, only after one to one cooperation agreement mandatory level2 can be accessed.

So far 4 European centres (Coimbra, London, Paris, Madrid, Tübingen) and one in the US contribute to the registry with more than 2000 entries for AMD and HRD in the first year since its implementation.

Conclusions: We preset the first international patient registry for patients with HRD and ARMD based on widely accepted CRFs and clinical SOPs. This registry will serve as a valuable resource for clinical trials in both ARMD and HRD and for basic research in this field and is open for collaborators to join.
A previously undescribed autosomal recessive retinal dystrophy
Authors: HOLDER GE , BURGESS R , MILLAR ID , LEROY BP , URQHART JE , FEARON IM , DE BAERE E , BROWN PD , ROBSON AG , WRIGHT GA , KESTELYN P , WEBSTER AR , MANSON FDC , BLACK GC
Published: October 2007

Purpose: To report a previously undescribed autosomal recessive retinal dystrophy

Methods: Seven patients from five families in two countries were ascertained with progressive visual loss and punctate retinal flecks. All patients received full ophthalmic examination, ERGs, PERG, EOG and fundus autofluorescence imaging, and gave DNA for mutational screening. They had previously received a variety of diagnoses, including “Goldmann‐Favre syndrome”, “fundus flavimaculatus” and “unrecognised dystrophy”.

Results: All patients had reduced visual acuity, were hyperopic and had irregularity of the RPE reflex with widespread subretinal deposits. A maculopathy was associated with intra‐retinal or subretinal fluid in four cases. Autofluorescence imaging was particularly useful in demonstrating these signs. Angle‐closure glaucoma was present in two cases. All patients had abnormality of both rod and cone full‐field ERG responses, with delay in the cone flicker ERG. All had abnormal EOG light‐rise. Progression in ERG abnormality was documented in three families. The results of genetic analysis will be discussed.

Conclusions: A novel retinal disorder is described. The distinctive clinical and electrophysiological features enable directed mutational screening.
Accuracy of scanning laser polarimetry, scanning laser tomography in a glaucoma screening trial
Authors: HOLLO G , TOTH M , KOTHY P
Published: October 2007

Purpose: To compare the usefulness of scanning laser polarimetry (GDx‐VCC), scanning laser tomography (HRT) and their combined evaluation in glaucoma screening.

Methods: In a non‐population‐based pre‐publicized trial, self‐recruited Caucasian participants were screened for glaucoma with GDx‐VCC, HRT, and by independent clinical examination. Cases with possible glaucoma as found with any of the screening methods underwent a detailed clinical investigation to verify or exclude glaucoma.

Results: Of the 136 attendees 118 participants (218 eyes) successfully underwent the GDx‐VCC and HRT II measurements. Twenty‐three eyes of 13 participants had glaucoma. Seventeen glaucomatous eyes had early damage. Evaluated separately, the GDx‐VCC screening test (borderline=normal) performed best with 7.5 positive likelihood ratio (PLR). PRL for all HRT parameters was <3.7. Combining different threshold criteria, for GDx‐VCC PLR increased to 14.0‐17.7, but no useful increase was seen for HRT (PRL<4.7 for all combinations). Combination of the best HRT and GDx‐VCC criteria resulted in PRL increase compared to the HRT combinations, but PRL decrease compared to the GDx‐VCC combinations (PRL<12.7 for all combinations).

Conclusions: In this population with relatively high risk for mild glaucomatous damage, a combination of different GDx‐VCC criteria but not HRT criteria or combinations containing HRT criteria were useful for glaucoma screening.
The localisation of erythropoietin and erythropoietin‐receptor in the retinas of Goto‐Kakizaki rats using immunohistochemical methods
Authors: DEAK G , SZABO A , SERES A , NEMETH J , SZEL A
Published: October 2007

Purpose: A number of data indicates that erythropoietin (EPO) exhibits neuroprotective and neurotrophic properties in the brain and in the retina. EPO has been recently described to be elevated in the vitreous fluid of patients with proliferative diabetic retinopathy or diabetic macular edema. The aim of our study was to describe the cellular localisation of EPO and its receptor (EPO‐R) in the mammalian retina and to evaluate whether it is altered under diabetic conditions.

Methods: Retinas of eight 10 weeks old type‐2 diabetic Goto‐Kakizaki (GK) and eight age‐matched non‐diabetic control (Wistar) rats were analyzed by immunohistochemistry in the study. Sections were cut from each specimen and stained with EPO and EPO‐R specific antibodies. The labelling was visualized by the ABC method or by fluorescent antibodies.

Results: Although the retinas of both groups showed similar and diffuse distribution of immunolabels, the intensity of staining was variable among the specimens. The EPO specific staining resulted a strong label in the ganglion cell layer and a less intense staining in the inner nuclear and pigment epithelium layers. The receptor specific antibody labelled the same layers and structures, but the staining intensity was more robust. There was no significant difference regarding the staining pattern of either EPO or EPO‐R between the diabetic and non‐diabetic retinas.

Conclusions: Erythropoietin and erythropoietin‐receptor are present in the retinas of GK rats although there is no significant difference in this early age as compared to non‐diabetic rat retinas. Further evaluation is necessary to assess the role of erythropoietin in diabetic retinopathy.
Intracorneal bevacizumab for treating corneal neovascularization in an experimental rabbit model
Authors: PERIS‐MARTINEZ C , ALCOCER‐YUSTE P , SANCHO‐TELLO M , AVINO‐MARTINEZ J , MARTINEZ‐BELDA R , MENEZO JL , ROMERO FJ , BOSCH‐MORELL F
Published: October 2007

Purpose: To evaluate the safety and efficacy of intracorneal and subconjunctival bevacizumab in treating corneal neovascularization in an experimental rabbit model.

Methods: Eighteen eyes of 9 animals (New Zealand‐female rabbits) participated in this study. For assessment of corneal neovascularization we use an alkali solution (NaOH 1 M). All rabbit eyes developed features of limbal stem cell deficiency like corneal neovascularization, pesistent epithelial defects, etc...The right eye of the animal received 2 injections of bevacizumab (one under conjunctiva and another intracorneal) and left eye will receive two injections of a placebo solution (made of physiological serum) as a control group.

Results: One month of follow‐up. All control corneas were revascularized to the center. Partial regression of newvessels was observed in 7 out of nine rabbit eyes treated with bevacizumab.

Conclusions: On the basis of the results, we suggest that bevacizumab can be effective in reducing corneal neovascularization in this experimental model.
Support for the idea that light is a risk factor in optic neuropathies, like glaucoma
Authors: OSBORNE NN
Published: October 2007

Purpose: Retinal ganglion cell (RGC) axons in the globe contain many mitochondria and it has been hypothesised that light can interact with these organelles to affect RGC survival in glaucoma. Studies on different cell‐types were conducted to support such a proposition.

Methods: Near confluent cultures of RGC‐5 cells, primary rat retinal cultures, fibroblasts with normal (BJhTERT) or mitochondria depleted of mtDNA (rho0) were transferred to incubators containing light (400‐760nm; 800‐2000 lux; generally 2 days). Some of the cultures were covered with white paper to exclude the light. The cultures were then analysed for cell viability, generation of free radicals (ROS) and for death by apoptosis.

Results: Oxidative status and mitochondrial dehydrogenase activity in retinal cultures (‐40±5%), RGC‐5 cells (‐20±4%) and BJhTERT cells (‐13±3%) was reduced significantly by light. Light reduced the number of GABA‐positive neurones (‐42±6%) in retinal cultures. Light caused a 3‐5 fold increase in TUNEL‐positive cells in primary retinal, RGC‐5 and BJhTERT cultures, than in the dark. ROS staining was also clearly elevated by light. The light‐induced toxic effect on the different cell types was significantly blunted by antioxidants like vitamin E and lipoic acid. Moreover, light‐induced apoptosis was caspase independent but PARP dependent. In contrast, rho0 cells that lacked functional mitochondria were unaffected by light.

Conclusions: The present study shows that light can directly affect mitochondrial function to induce apoptosis. This supports the view that light can interact with the many RGC axon mitochondria to affect the viability of GCs and that this may be of significance in the progression of glaucoma.
Monitoring individual compliance in glaucoma patients used to topical therapy
Authors: BRON AM , HERMANN M , CREUZOT‐GARCHER C , DIESTELHORST M
Published: October 2007

Purpose: Individual compliance with Brimonidine eye drops was studied in glaucoma patients and ocular hypertensives.

Methods: Conventional Brimonidine vials were equipped with a microprocessor‐controlled monitoring device capable to record date and time of each eye drop application including ambient temperature. After written informed consent, glaucoma and ocular hypertensive patients used to eye drop therapy were randomly assigned to Brimonidine therapy b.i.d or t.i.d daily for 4 weeks.

Results: Twenty six males and fourteen females aged 69 ± 11 years [42‐89] were enrolled in this study. According to the monitoring devices all patients were non‐compliant with regard to total dose and coverage. Electronic records revealed a mean of 1.5 (range: 1.1‐2.0) applications per day for patients assigned to Brimonidine 2x daily with a mean treatment interval of 16.8 hours (range: 12.1‐22.2 h). Patients on Brimonidine 3x daily showed a mean rate of 1.9 (range: 1.8‐2.7) applications per day and a mean treatment interval of 11.9 h (range: 9.1‐13.9 h). One patient discontinued therapy after day 7 (12 applications) and one after day 1 (1 application only). No difference was observed between IOP at baseline and after one month (p=0.16).

Conclusions: The monitoring devices permit to detect individual non‐compliance with regard to missed doses, non‐treatment intervals. Our data confirm the need for larger studies on individual compliance with topical ocular therapy in glaucoma.
Spontaneous choroidal haematomas: differential diagnosis with uveal melanoma: a retrospective review of 95 cases
Authors: DESJARDINS L , LUMBROSO‐LEROUIC L , LEVY‐ GABRIEL C , GERBER S , BERGES O , IBA ZIZEN MT
Published: October 2007

Purpose: Introduction : Patients with peripheral choroidal melanoma are often misdiagnosed as uveal melanoma

Methods: We have reviewed the clinical , MRI and ultrasonographic characteristics of patients sent to Curie institute for suspected uveal melanoma between 1998 and 2006 and of whom final diagnosis was choroidal hematoma

Results: 95 patients were seen with this diagnosis ( for 2357 patients treated for uveal melanoma during the same period); the age varies between 54 and 92 years with a median age of 77 years; there was a history of macular degeneration in 27 cases and posterior pole drusen in 3 cases.11 patients were taking anticoagulant or antiaggregant medications .There was sudden loss of vision in 35 cases and a vitreous haemorrhage in 18 cases. The lesion was located in the posterior pole in 28 cases and in the periphery in 67 cases. The thickness measured by B scan ultrasonography varied between 1 mm and 7, 8 mm with a mean thickness of 2, 86 mm.

MRI was necessary in 27 cases and color doppler ultrasonography in 10 cases. These exams usually show peripheral enhancement with gadolinium (compared to full thickness gadolinium enhancement in melanomas) and no vessels with doppler (compared to visible vascularisation in melanomas)

A follow up was performed in 42 patients showing progressive fibrin scarring

Conclusions: These peripheral hematomas can be due to peripheral exsudative chorioretinopathy or to ruptured retinal macroanevrysm; they are more frequent in elderly patients with vascular diseases . The diagnosis of choroidal hematoma is generally made by fundus examination but MRI and color doppler imaging can be usefull
Intravitreal bevacizumab in the treatment of refractory uveitic macular edema‐A one year follow up observational study
Authors: GALLAGHER MJ , CERVANTES‐CASTANEDA RA , YILMAZ T , FOSTER CS
Published: October 2007

Purpose: To evaluate the long term outcome of intravitreal bevacizumab in the treatment of refractory uveitic macular edema (UME).

Methods: Retrospective, non comparative, interventional case series.

SETTING: Massachusetts Eye Research and Surgery Institute.

PATIENT POPULATION: All uveitic patients with macular edema who were refractory to conventional therapy and who were treated with intravitreal bevaclizumab were identified and assessed. MAIN OUTCOME MEASURES: Best corrected distance visual acuities (VA) and optical coherence tomography (OCT) central macular thickness measurements. Correlative statistical analysis includes the use of the student's t‐paired test, Kaplan‐Meier, and linear regression analysis.

Results: 29 eyes of 27 patients with diverse uveitic etiologies were analyzed and followed up for a period of one year. Thirteen patients received a single intravitreal bevacizumab injection. Six patients required a second intravitreal bevacizumab injection, while ten patients received combination therapy of intravitreal bevacizumab and triamcinolone acetonide. Baseline mean LogMAR VA was –0.59. At one year the mean LogMAR VA was ‐0.42± 0.36 (P=0.0045). Baseline mean OCT central macular thickness was 383.66 microns. At one year the mean thickness value was 294.32±110.87. (p=0.0007).

Conclusions: Intravitreal bevacizumab is a useful and therapeutically beneficial agent in the treatment of refractory UME. Some patients will require adjunctive intravitreal bevacizumab injections or the use of combination therapy with intravitreal triamcinolone acetonide.
Optical inhibition of axial myopia progression
Authors: PHILLIPS JR , ANSTICE NS
Published: October 2007

Purpose: The Dual‐focus Inhibition of Myopia Evaluation in New Zealand (DIMENZ) clinical trial tests the efficacy of myopic retinal defocus in slowing myopia progression.

Methods: Dual‐focus (DF) soft contact lenses have a central correction zone and peripheral zones that cause 2.00D of simultaneous myopic retinal defocus during distance and near viewing. Children (12‐14 yrs, n=40, mean refractive error: ‐ 2.70D) were fitted with a DF lens in one eye and a single vision distance (SVD) lens in the fellow eye. After 10 mo. wear, lens assignment was swapped between eyes and the lenses worn for a further 10 mo. Accommodation was measured using an open‐field autorefractor. Myopia progression was monitored using cycloplegic autorefraction and partial coherence interferometry every 5 mo.

Results: Visual acuity and contrast sensitivity of eyes wearing DF & SVD lenses were not different (p=0.209 & 0.157). When the DF lens was worn with either a single vision near (effective add = +2.50D) or a SVD lens in the fellow eye, children accommodated normally to a target at 40 cms. Preliminary results for 10 children after 10 mo. showed that the mean (± 1 SE) increase in myopia and axial length in eyes wearing the DF lens (‐0.45 ± 0.40D & 0.08 ± 0.079mm) were significantly less (p<0.0001 & 0.00002) than in eyes wearing the SVD lens (‐0.79 ± 0.41D & 0.21 ± 0.11 mm). Thus, DF lenses had a 12 mo. adjusted treatment effect of 0.40D & 0.15 mm.

Conclusions: DF lenses provide normal acuity and contrast sensitivity. They do not alter accommodative response, so provide myopic retinal defocus at distance and near. Myopia progression is slowed significantly in eyes wearing DF lenses, suggesting that myopic defocus acts as an anti‐myopiagenic stimulus.
Cup reversal protects from glaucoma progression
Authors: HARJU M , SAARI J , KURVINEN L , VESTI E
Published: October 2007

Purpose: Reversal of optic disc cupping after reduction in intraocular pressure (IOP) is well documented. The effect of cup reversal on the risk of progression of glaucoma was investigated.

Methods: All 80 consecutive patients referred to the Helsinki University Eye Hospital between May 1995 and May 1997 because of exfoliation glaucoma were included. They were treated medically, with laser trabeculoplasty, or surgically. Fifty‐six patients (mean age ±SD at study entry, 70 ± 7 years) were followed for 5.9 ± 0.8 years. Scanning laser opthtalmoscopy (Heidelberg Retina Tomograph, HRT) of the optic nerve head was performed before treatment and at follow up visits. A decrease of more than 5% in the HRT parameter cup volume (CV) after change in treatment was considered to be a sign of cup reversal. The effect of cup reversal on progression of glaucoma was modelled in multiple logistic regression.

Results: Of 56 patients, 24 showed progression of glaucoma in visual fields or optic discs. The other 32 remained stable. IOP reduced from 21 ± 5 mmHg to 16 ± 4 mmHg (P < 0.001). Presence of cup reversal was related to decreased risk of progression of glaucoma (Odds ratio [OR], 0.226; 95% CI, 0.055‐0.917, P = 0.037). The risk of progression increased with higher MD at study entry (OR, 1.158 for each dB; 95% CI, 1.034‐1.296; P = 0.011), and higher final IOP (OR, 1.216 for each mmHg; 95% CI, 1.000‐1.479; P = 0.050). The change in IOP from study entry to final IOP was not associted with progressio progression (OR, 0.964 for each mmHg; 95% CI, 0.850‐1.092, P = 0.561).

Conclusions: Optic disc cupping can be reversed and sustained for years after IOP reduction. Cup reversal seemed to be an independent protective factor against progression of glaucoma.
Matrix metalloproteinase‐2 (MMP‐2) is expressed in melanoma associated spongiform scleropathy (MASS)
Authors: ALYAHYA GA , KOLKO M , PRAUSE JU , HEEGAARD S
Published: October 2007

Purpose: To correlate the expression of matrix metalloproteinase 2 (MMP‐2) with the occurrence of

melanoma associated spongiform scleropathy (MASS) and tumour extension in eyes with

uveal melanoma.

Methods: Twenty‐two specimens of human eyes with choroidal melanoma were selected for this study. Eleven were MASS positive with tumour extension and eleven were MASS negative without tumour extension. Sections were examined for MMP‐2 expression by in situ hybridization.

Immunohistochemical study of the same specimens was conducted. For double labelling, primary MMP‐2 antibodies directed against fibroblasts and macrophage were applied.

Results: Distinct hybridization signals with MMP‐2 were seen in fibroblast‐like cells located in the sclera in 14 out of 22 melanoma eyes.

MMP‐2 mRNA expression was detected in ten eyes with MASS and tumour extension. In eight the signals were seen in numerous cells. In melanoma cases without MASS, MMP‐2 signals were detected in four cases and only one case showed numerous positive cells. The expression of MMP‐2 was further demonstrated at protein level by immunostaining, confirmed by double labelling experiment.

Tumour macrophages were also found to harbour MMP‐2.

Conclusions: MASS which is considered as scleral degradation process, may be mediated by MMP‐2 produced by scleral fibroblasts under the influence of tumour cells and/or tumour macrophages. This is manifested by the significantly higher expression of MMP‐2 in MASS areas indicating that MMP‐2 is involved in the development of MASS.

MASS changes may represent a step in the invasion of uveal melanoma. This association between MASS and MMP‐2 could be considered as a new prognostic marker in uveal melanoma.
A mutation in a novel connexin‐like gene affects early lens development in the mouse
Authors: PUK O , LOESTER J , GRAW J
Published: October 2007

Purpose: Aim of the study was the morphological and genetical characterization of Aey12, a novel dominant mouse mutant suffering from microphthalmia, lens and corneal opacities.

Methods: A genome wide linkage analysis was performed using micro‐satellite markers. The Aey12 mutation was identified by sequence analysis of positional candidate genes. Histological analysis and in‐situ hybridizations were performed at the stages E10.5 ‐ E17.5.

Results: Aey12 (abnormality of the eye) is a new dominant mouse mutant, which was recovered in an ENU mutagenesis program at the GSF. Aey12 animals are characterized by small eyes with cornea opacities and lenses with cataracts and vacuoles. Both, heterozygotes and homozygotes, are viable and fully fertile. As major histological defect, the elongation of the primary lens fibres is blocked resulting in the stop of lens development at this stage. Genome‐wide linkage analysis mapped the Aey12 mutation on mouse chromosome 10 between the markers D10Mit206 and D10Mit189. Among the positional candidate genes, one EST (D230044M03Rik) encodes a connexin‐like protein, which is similar to Connexin 43.4. A G‐T point mutation was identified at cDNA position 96 resulting in an R32Q amino acid exchange in a transmembrane domain. D230044M03Rik is expressed in the posterior part of the lens vesicle exactly at the position where the primary fiber elongation starts. Furthermore, an additional expression was observed in many other tissues like brain, lung, heart, liver and kidney.

Conclusions: The new mouse mutant Aey12 is characterized by an early block of the eye development caused by a point mutation in a novel connexin‐like gene.
Disturbed vascular response of the central retinal artery during hypercapnia in normal tension glaucoma
Authors: PLANGE N , KAUP M , HARRIS A , AREND KO , REMKY A
Published: October 2007

Purpose: Altered blood flow regulation might contribute to the pathogenesis of glaucoma. The purpose of the study is to investigate retrobulbar flow velocities during hypercapnia in patients with normal tension glaucoma (NTG) without systemic vasospasm and healthy controls.

Methods: Sixteen NTG patients (mean age 58 +/‐ 14 years) and sixteen control subjects (mean age 50 +/‐ 13 years, p=0.10) were enrolled in this clinical study. Blood flow velocities (peak systolic velocity (PSV), end‐diastolic velocity (EDV)) and resistive indices (RI) of the ophthalmic (OA) and central retinal artery (CRA) were assessed using colour Doppler imaging (CDI). Blood flow velocities were measured under normocapnic and hypercapnic conditions (increasing the end‐tidal pCO2 by 15%). Blood pressure, ventilation rate and oxygen saturation were monitored simultaneously.

Results: During hypercapnia, the increase of the PSV (p=0.044) and EDV (p=0.037) of the CRA was significanlty reduced in NTG patients compared to healthy controls. Flow velocities of the OA increased significantly in all subjects (PSV: p=0.039, EDV: p=0.003) during hypercapnia. Blood pressure, oxygen saturation and intraocular pressure changed similarly in both study groups with carbon dioxide provocation.

Conclusions: Vascular response to hypercapnia was reduced in the CRA of NTG patients compared to controls. This may indicate a faulty vasodilatory response in NTG patients without vasospastic disease.
Topical beta‐blockers and the risk of cardiovascular mortality
Authors: JANSONIUS NM , WOLFS RCW , WITTEMAN JC , HOFMAN A , DE JONG PTVM , STRICKER BHC , MUSKENS RPHM
Published: October 2007

Purpose: Recently, the Blue Mountains Eye Study reported an association between the use of topical timolol and cardiovascular mortality (Lee et al. Ophthalmology 2006). The purpose of the present study was to confirm or falsify this clinically very important finding, using data from the population‐based Rotterdam Study.

Methods: 6971 participants of the Rotterdam Study, a longitudinal population based study of all residents aged 55 years and older from a district of Rotterdam, The Netherlands, were followed from 1991 onwards. Medication use and morbidity were recorded continuously during follow‐up. For the current analysis, baseline use of topical beta‐blockers and systemic cardiovascular medication as well as baseline cardiovascular morbidity were used, aiming to follow the design of the Blue Mountains Eye Study as close as possible. Cause of death was registered up to 1‐1‐2005. Data were analysed using Cox regression; Hazard ratios of topical beta‐blocker use were adjusted for age, sex, cardiovascular morbidity and use of systemic cardiovascular medication.

Results: Mean age at baseline was 69 years (SD 9 years); 146 participants were using topical beta‐blockers at baseline. 2726 participants died during follow‐up (all cause mortality 40.1%), 611 (9.0%) had a cardiovascular cause of death. Hazard ratio of topical beta‐blocker use was 0.80 (95% confidence interval 0.63‐1.02; P=0.07) for all cause mortality and 0.78 (0.46‐1.29; P=0.32) for cardiovascular mortality.

Conclusions: In our data, the use of topical beta‐blockers at baseline was not associated with either all cause mortality or cardiovascular mortality during follow‐up.
Aldose Reductase Inhibition Counteracts Diabetes‐Induced Retinal Oxidative Injury, Glial Activation, and Apoptosis
Authors: OBROSOVA IG , SHIN J , ALI TK , JULIUS U , EL‐REMEZZY A , DREL VR
Published: October 2007

Purpose: To access the role for increased aldose reductase (AR) activity in oxidative injury, glial activation, and apoptosis in retinae of diabetic rats and high glucose‐exposed cultured retinal pericytes and endothelial cells.

Methods: Control (C) and STZ‐diabetic (D) rats were treated with/without the AR inhibitor fidarestat (F, 16 mg/kg/g, for 10 wks after 2 wks without treatment). The rate of apoptosis was assessed in flat‐mounted retinas by TUNEL assay with immunoperoxidase staining, and nitrotyrosine (NT), poly(ADP‐ribose) [PAR, a marker of poly(ADP‐ribose) polymerase activation] and glial fibrillary acidic protein (GFAP) expression in retinal sections by immunohistochemistry. Primary bovine retinal pericytes and endothelial cells were cultured in 5 mM or 30 mM glucose with/without F (10 microM) for 3‐14 d. Apoptosis was assessed by TUNEL assay, NT and PAR by immunocytochemistry, and Bax and Bcl‐2 expression by Western blot analyses.

Results: The number of TUNEL‐positive nuclei (Mean ± SEM) was increased ~4‐fold in D (207 ± 33 vs 49 ± 4 in C, p < 0.01), and this increase was partially corrected in D+F (106 ± 34, p < 0.05 vs D). The apoptotic cell number increased with prolongation of exposure of both pericytes and endothelial cells to high glucose. F counteracted high glucose‐induced apoptosis, and NT and PAR accumulation in both cell types. Antiapoptotic effect of F in high glucose‐exposed retinal pericytes was not associated with inhibition of Bax or increase in Bcl‐2 expression (endothelial cell studies are in progress).

Conclusions: AR inhibition with fidarestat conteracts diabetes‐associated retinal oxidative injury, glial activation, and apoptosis.
External dacryocystorhinostomy
Authors: DUCASSE A
Published: October 2007

Purpose: Indications, techniques and complications of external DCR.

Methods: Indications are lacrimonasal stenosis with clinical symptoms : epiphora, dacryocystitis . The external approach is more specifically interesting in case of canalicular stenosis associated, when a skin approach is necessary or in case of lacrimal tumor . The endonasal approach is the best way in case of nasal or sinusal pathology, failure of DCR or lacrimal abscess and for us in case of bilateral DCR. Technique is always the same, under general or local anaesthesia with nasal vasoconstriction. After disinfection, probing, the skin incision is short and rectilinear inside or outside the angular vessels. Marking is the anterior lacrimal crest. After section of the medial canthal tendon, an osteotomy is performed ; it must be wide with or without anterior ethmoidectomy. We make two anterior mucosal flaps which are sutured and fixed at the periosteum. We do not use systematically a bicanalicular intubation ; we put an intubation in case of canalicular stenosis, or for a second DCR or in case of surgical difficulties. The main complications are haemorrhages, cribrosal plate fracture with cerebrospinal leakage, infection, pain and in a few case, a bad scar.

Results: The results are good. Anatomical and functional success are found in 88 to 96%, for us 91.2% . The failures occur during the three first months.

Conclusions: Conclusion: To compare internal or endonasal DCR, the advantages for the external way are cost, rapidity and usual practise. Endonasal DCR needs a lot of material, an apprenticeship and usually a scanner before the surgery and systematically a bicanalicular intubation. In conclusion, external DCR remains an easy technique, which is quick, with high success rate and few complications.
Radiologic diagnostic of the lacrimal system. Meassurements of the bony lacrimal canal in a european population
Authors: LACHMUND U , JAVDANI Z , PILAT Y , COOLEN C , VALAVANIS A , WILHELM K
Published: October 2007

Purpose: To examine the bony anatomical structures and dimensions of the nasal lacrimal duct.

Methods: Patients who underwent a routinely multislice Spiral CT examination of the nasal sinus were retrospectively reexamined.

The original data set with thin slices in 0.75mm was used to reconstruct the nasal lacrimal duct in 3 dimensions (axial, coronal, sagital).

Results: We found a spectrum of the diameter of the bony canal from 3.0‐4.0mm.

There was no significant difference in sex and also in the population based on typical swiss names and more foreign names.

Conclusions: Measurements of the bony canal are very important if lacrimal interventions like balloondilatation or stentimplantation is performed. Our results of the bony canal were similar results to Janssen et. al. (2001). This population based study proved no difference in between the races.
Oxidation damage repair in the lens: Thioltransferae and Thioredoxin systems
Authors: LOU MF
Published: October 2007

Purpose: Oxidative stress can modify/damage protein thiols to protein‐S‐S‐glutathione (PSSG) or protein‐protein disulfides, leading to high molecular weight aggregation and cataract formation. The two thiol/disulfide regulatory systems of thioltransferase (TTase) and thioredoxin (TRx) are examined for their roles in oxidation damage repair in lens proteins/enzymes and protection of lens clarity.

Methods: Human lens epithelial (HLE) B3 cells were examined for their resistance to oxidative stress of H2O2 by monitoring PSSG level, glyceraldehyde 3‐phosphodehydrogenase (G‐3PD) and GSH peroxidase (GPx) activities among groups of control (vector), TTase /TRx overexpressed or cadmium treated (inhibitor to both) cells. Exodgenous TTase or TRx were used to enrich the cellular TTase or TRx for the similar studies. TTase knockout (KO) mouse model was used to examine the effect of TTase deletion on lens clarity.

Results: TTase or TRx transfectants showed 2‐fold expression over the control. These cells displayed a faster and complete recovery of G‐3PD or GPx activity and lowered PSSG formation. Cadmium suppressed G‐3PD re‐activation in cells exposed to H2O2. TRx showed similar ability to repair and reactivate these oxidatively damaged enzymes. Cells enriched with overexpressed TRx gene or treated with exogenous TRx induced upregulation of several oxidation defense enzymes. Lenses from TTase KO mice were less resistant to oxidative stress, and showed age‐dependent increase in PSSG and accumulation of high molecular weight aggregates sooner than that of the age‐matched wild type mice.

Conclusions: TTase and TRx systems can repair oxidation damage and restore protein/enzyme functions in the lens. TTase is essential to lens clarity.
A model for corneal endothelium specular microscopy images
Authors: SÖDERBERG PG , BUCHT C
Published: October 2007

Purpose: As a part of an ongoing project on corneal endothelium morphometry by diffraction, a model for corneal endothelium specular microscopy (CSM) images has been developed. The simulator has been developed to as realistically as possibly emulate real CSM images. Development of the simulator was anticipated to be valuable in examining the impact of varying quality of CSM images on different methods of corneal endothelium morphometry.

Methods: The model was written with the mathematical programming language MATLAB. An earlier version of the simulator was used to find theoretical functional relationships between cell density and cell size variation of the corneal endothelium and identifiable characteristics in the diffraction pattern, simulated using a numerical Fourier transform. Further development has added realism to the created images as well as ways of altering illumination profiles, image noise and contrast.

Results: Currently, the simulation model allows creation of realistic clinical CSM images and variation of; CSM image size, cell size and density, regularity of cell shape, variation in cell size, frequency of illumination profile, weight of illumination profile, level of image distortion, and level of cell barrier contrast.

Conclusions: There are several different CSM instruments on the market providing CSM images of varying quality. There are also a number of, often instrument specific, tools for analysis of CSM images resulting in measurement variation depending on instrument, patient and operator. It is anticipated that a simulation model that allows standardized variation of important characteristics in CSM images will be an important tool for evaluation of existing tools for analysis of CSM images and for creation of new improved alternatives.
Dose dependence of alpha‐tocopherol protection against in vivo ultraviolet radiation and associated alterations in lens redox balance
Authors: JING W , LÖFGREN S , DONG X , ZHANG Y , MODY V , AYALA M , MEYER L , GALICHANIN K , SÖDERBERG PG
Published: October 2007

Purpose: To investigate the dose dependence of alpha‐tocopherol protection against in vivo ultraviolet radiation (UVR) induced light scattering and associated alterations in the redox balanced in the albino rat lens.

Methods: Five groups of twenty, six‐week‐old female albino Sprague Dawley rats were supplemented with 0, 5, 25, 50, and 100 IU/day alpha‐tocopherol orally depending on group belonging for 4 weeks. Then, each rat was unilaterally exposed in vivo to 8 kJ/m2 UVR‐300 nm for 15 min. At 1 week after exposure to UVR, the rats were sacrificed, the lenses were extracted and homogenized. Lens total reduced (GSH) and oxidized (GSSG) glutathione; glutathione‐ reductase (GR) and oxidase (GPx) were determined colorimetrically by enzyme reactions.

Results: Alpha‐tocopherol caused a dose‐dependent protection against UVR induced light scattering with a rate constant (1/e) of 4.8 IU/day. The exposure to UVR caused a depletion of total lens GSH at low alpha‐tocopherol supplementation that recovered towards higher alpha‐tocopherol supplementation. The UVR exposure did not cause any alteration of total lens GSSG at any level of alpha‐tocopherol supplementation. The UVR exposure did not cause any alteration of total lens GR‐ or GPx activity at any level of alpha‐tocopherol supplementation.

Conclusions: Alpha‐tocopherol dose dependently protects against UVR induced light scattering. The protection of UVR induced light scattering is associated with a reduction of GSH depletion due to UVR exposure without any effect on total lens GSSG or GR‐ or GPx activity
Methods for quantifying diplopia
Authors: HOLMES JM , HATT SR , LESKE DA , ADAMS WE
Published: October 2007

Purpose: Methods for quantifying diplopia include 1) the Goldmann diplopia field, 2) the Cervical Range of Motion (CROM) method, evaluating 10 specific positions of gaze and 3) a Diplopia Questionnaire addressing 7 positions of gaze (rating diplopia as always, sometimes or never). We investigated how patients’ subjective perception of the severity of their diplopia (percent impact) related to scores obtained using each of these methods.

Methods: 28 patients with acquired binocular diplopia due to strabismus were asked to rate the percent impact of their diplopia, based on all daily activities. Diplopia was also quantified using the Goldmann perimeter, CROM method and Diplopia Questionnaire. Scores were scaled from 0 to 100, where 0 was no diplopia and 100 was diplopia in all measured positions. Correlations between percent impact and diplopia measures were assessed using intra‐class correlation coefficients (ICC) and mean values compared using t‐tests.

Results: Across all patients, the mean self‐rated percent impact was 40% (range 0 to 100%). Mean scores using the CROM and Questionnaire were similar to percent impact (39% and 38% respectively), whereas Goldmann scores significantly overestimated severity when compared to perceived impact (51%, p<0.05). Percent impact was most closely correlated to the Questionnaire score (ICC=0.75). The most frequent reason for a higher Goldmann diplopia score was scoring of diplopia beyond 30 degrees.

Conclusions: Quantifying diplopia using the CROM method and Diplopia Questionnaire better represents the perceived impact of patients’ diplopia than scores obtained on the Goldmann perimeter. The CROM method and Diplopia Questionnaire may prove useful instruments for clinical evaluation of diplopic patients and in future clinical trials.
In vivo GFP imaging of dormant liver metastasis in a human uveal melanoma mouse model
Authors: FERNANDES BF , LOGAN P , DI CESARE S , ANTECKA E , MARSHALL JC , BURNIER MN
Published: October 2007

Purpose: We previouly demonstrated the feasibility of a human uveal melanoma GFP model in nude mice. We were able to monitor the preferential colonization of the liver by malignant cells during a 20‐day period. In this study we extended the observation period in order to observe disease progression and metastatic growth.

Methods: Five hundred thousand, GFP transfected, human primary uveal melanoma cells (92.1) were injected into the tail vein of 30 nude mice at time zero. Starting at day one, five mouse per week was imaged, using an abdominal incision to expose the liver, for up to 60 minutes before sacrifice. The liver was imaged in vivo and post mortem, while the lungs, spleen, and kidney were all examined post‐mortem for GFP expression. Histopathological examination of all organs was performed to ensure that the GFP signal was arising from malignant cells.

Results: In vivo imaging of the liver revealed positive GFP signal in all mice throughout the experiment. Malignant cells seeded the liver after injection, but there was no apparent tumor growth upon completion of the experiment. The micrometastatic foci remained viable without changes in size or intensity of the signal. No tumors were seen in any other organ at the end of the experiment. Histopathology confirmed that the cells emitting GFP were malignant cells.

Conclusions: The results of this uveal melanoma model show great promise for understanding the previously unobservable interactions between single human uveal melanoma cells and native liver tissue. The fact that our cells successfully colonize the liver yet remain dormant for six weeks should actually mirror the disease in humans; metastases in patients takes roughly five to ten years to develop.
Changed retinal capillary flow in patients with disc haemorrhages
Authors: KURVINEN L , HARJU M , SAARI J , VESTI E
Published: October 2007

Purpose: Vascular pathogenesis in glaucoma has been recognized and optic disc haemorrhages (DH) may pre‐cede nerve fiber damage in glaucoma. The change in peripapillary retinal capillary flow after resorbtion of DH was investigated.

Methods: Included were 25 eyes of 25 patients with DH. 17 eyes had glaucoma. Peripapillary retinal capillary flow was measured with the Heidelberg Retina Flowmeter in arbitrary units (AU). The first measure‐ment was made right after diagnosis of DH and the second six months later. Automatic full field perfu‐sion image analyser was used for analysis. Mean flow (MF), peak systolic flow (SF), and minimum dia‐stolic flow (DF) were measured, and pulsation index (PI) calculated. Flow values are reported from the whole temporal peripapillary retina (Area 1), the same horizontal level as the DH (Area 2), and from the area specifically around the DH (Area 3).

Results: A significant increase in MF after resorbtion of DH was detected in Area 1 (median 263 AU, range 188 – 561 AU, vs. 328 AU, 199 – 462 AU; P = 0.008), and Area 2 (255 AU, 166 – 386 AU, vs. 330 AU, 198 – 646 AU; P=0.04). The increase in MF in Area 3 was of borderline significance (342 AU, 230 – 513 AU, vs. 402 AU, 200 – 629 AU; P = 0.10), as was the increase in SF in Area 2 (334 AU, 187 – 486 AU, vs. 400 AU, 227 – 690 AU; P = 0.07). No significant changes in DF or PI were found.

Conclusions: Increase in retinal capillary flow after resorbtion of DH suggests a generalized decrease in retinal flow at the time DH is detected, or a compensatory increase after ischemia.