bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustained BMP signaling induces the lens placode
Authors: GUNHAGA L , SJöDAL M , EDLUND T
Published: September 2008

Purpose Fate maps at late gastrula and head fold stages show that prospective olfactory and lens placodal cells are intermingled in a domain of the anterior border region between the neural plate and the future epidermis. During embryonic development Bone Morphogenetic Protein (BMP) signals represent one class of secreted signals that are implicated in lens specification. When and how BMP signals is involved in the initial specification of the lens placode remains to be defined.

Methods We have established explant and whole embryo assays of placodal cell differentiation in the chick embryo, and analyzed a panel of markers that are expressed in differentiated olfactory and lens placodal cells.

Results We provide evidence that cells in the anterior border region have become specified as olfactory and lens placodal cells at the late gastrula stage, and that BMP signals are required and sufficient to induce olfactory and lens placodal cells from these progenitor cells. We also provide evidence that time of exposure of progenitor cells to BMP signals plays a key role during the differential specification of olfactory and lens placodal cells. By the neural fold stage, the generation of lens cells requires continued exposure to BMP signals, whereas the generation of olfactory placodal cells has become independent of further exposure to BMP signals. Moreover, prolonged exposure of BMP signals promotes the generation of lens cells at the expense of olfactory placodal cells.

Conclusion Our results provide evidence that the specification of the lens placode requires sustained BMP signaling. Thus, our results support the emerging idea that time of exposure of progenitor cells to patterning signals play important roles during cell fate specification in different tissues in vertebrate embryos.
Is brimonidine better at stabilizing visual field than timolol?
Authors: KRUPIN T
Published: September 2008

Purpose Alpha‐2 adrenergic agonists are neuroprotective in animal models of focal cerebral ischemia. Brimonidine protects the retinal ganglion cell (RGC) from secondary degeneration following partial crush injury to the rat optic nerve and in an ocular hypertensive rat model. The mechanism for this effect is up‐regulation of brain‐derived neurotrophic factor in RGC and the retina. Brimonidine activates the alpha‐2 adrenoceptor at 2 nM. Topical administration of brimonidine produces pharmacologic drug concentrations in the vitreous (100‐170 nM) in humans that provides a drug delivery route to the RGCs sufficient to bind and activate the alpha‐2 adrenoceptor. In this way, brimonidine could function to maintain the health of the optic nerve independent of its ability to reduce intraocular pressure (IOP)

Methods The Low‐pressure Glaucoma Treatment Study (LoGTS) is a triple masked, randomized, multicenter clinical trial of the efficacy of monotherapy with brimonidine versus timolol eye drops to alter the course of low‐pressure (normal‐tension) glaucoma (untreated IOP < 22 mmHg). The primary outcome was visual field progression analyzed using point‐wise linear regression analysis. This methodology required a minimum of four visual fields to obtain and compared the slope of decibel sensitivity of each test location to all previous examinations. Field progression was defined as a negative slope > 1.0 decibel/year with a significance P£0.05 for the same three or more test locations on three consecutive examinations (i.e., over an 8 month interval).

Results Previously published articles contains a detailed description of the study methods and baseline patient characteristics and baseline visual field and IOP asymmetry. The current presentation will discuss LoGTS outcomes.

Commercial interest
Study of the role of P2Y6 receptors in the development of experimental autoimmune uveitis
Authors: JUDICE DE MENEZES RELVAS L
Published: September 2008

Abstract not provided
Advocating for research funding: The India experience
Authors: BALASUBRAMANIAN D
Published: September 2008

Abstract not provided
Papilledema due to cerebral venous thrombosis
Authors: BOSCHI A
Published: September 2008

Purpose Review the clinical features and the most effective method of diagnosis of cerebral dural venous sinus thrombosis (CDVT). Treatment procedure of the predisposing factors and of the cerebral thrombosis will be briefly discuss.

Methods Recent litterature is considered

Results CVDT is a challenging condition because the variability of clinical presentations. It might mimic many neurological disorders such as, meningitis, intracranial hypertension, encephalopathy and stroke. However, the most common pattern of presentation is with a pseudotumor cerebri like syndrome: headache, nausea, vomiting, papilledema, optic‐nerve related visual loss, and VI nerve palsies. CVDT can present at all ages, but is seen more in young and middle‐aged women. The most frequent predisposing factor is a hypercoagulable state, although contiguous infection, like mastoiditis or middle‐ear infections, and neoplasms should be excluded. MRI with gadolinium and MR venography are a safe and effective method for visualizing cerebral venous thrombosis. Treatment should be firstly direct toward any underlying medical condition, and any offending drug should be discontinued. Anticoagulation should be started with IV heparin, and usually followed by warfarin. Acetazolamide might be used to treat elevated intracranial pressure and mild field defect. Those with progressive or severe visual loss, despite medical therapy, should undergo optic nerve fenestration or other shunting procedure.

Conclusion One should keep in mind the possibility of CDVT in every patient with new‐onset headache of any type, particularly if worsening despite analgesic. Earlier the diagnosis, earlier the treatment, better is the outcome.
Pituitary apoplexy
Authors: KAWASAKI A
Published: September 2008

Hemorrhage or infarction of a pituitary tumor is termed pituitary apoplexy . Most patients experience abrupt onset of severe headache, altered mental status and visual changes. Visual loss may be unilateral or bilateral and the severity is variable. Ophthalmoplegia, usually due to compression of the ocular motor nerves in the cavernous sinus, may also be unilateral or bilateral. The 3rd nerve is most commonly affected. The clinical picture of acute 3rd nerve palsy associated with severe headache may be mistaken for aneurysmal subarachnoid hemorrhage Precipitating factors for pituitary apoplexy include hypotension, Valsalva maneuvers, malignant hypertension, pregnancy or exogenous estrogen administration and anticoagulation. Cranial MRI is the diagnostic test of choice. Morbidity and mortality are related to the abrupt onset of panhypopituitarism, particularly cortisol insufficiency. Acute management includes systemic corticosteroids in stress dosages (e.g., hydrocortisone 100 mg IV every 6‐8 hours), control of hemodynamic parameters (e.g.blood pressure) and correction of any metabolic derangements. Surgical decompression is usually performed as soon as the patient is stable.
Effect of different antioxidants in experimental alcoholic optic neuropathy
Authors: MENEZO ROZALEN JL , AVINO‐MARTINEZ JA , PERIS‐MARTINEZ C , ESPANA‐GREGORI E , ROMERO FJ
Published: September 2008

Purpose To establish the possible beneficial effects of three synthetic antioxidants: S‐adenosil‐L‐methionine (SAMe), N‐acetyl‐L‐cysteine (NAC) and Ebselen in optic nerve damage following chronic ethanol feeding in adult rats.

Methods Twenty male Sprague‐Dawley rats (five groups of four animals each) were fed a liquid, ethanol‐containing diet with littermates given isocaloric amounts of ethanol‐free diet serving as controls. Antioxidants were administered by dissolving them in the liquid diet at 0.4 mg/ml (SAMe), 0.163 mg/ml (NAC) and 5.33 mg/ml (Ebselen). After 6 weeks, optic nerves were obtained and parameters that are relevant for the modulation of oxidative stress, such as antioxidants ‐GSH content and Glutathione‐peroxidase (GSH‐Px) activity‐ and lipid peroxidation‐derived end products ‐malondialdehyde (MDA)‐ were determined. Comparisons between groups were done using Student´s t‐test for grouped data and one‐way ANOVA. Differences were considered significant at p<0.05.

Results N‐acetyl‐L‐cysteine and Ebselen were able to normalise MDA content and to restore GSH content and GSH‐peroxidase activity, to values not significantly different from those of controls (p>0.05). Treatment with SAMe slightly improved values of some parameters, although no statistically beneficial (p<0.05 versus control).

Conclusion These results support the use of NAC and Ebselen for the treatment of chronic alcohol‐induced optic nerve damage.
Limbal microenvironment can induce transdifferentiation of hair follicle stem cells into corneal epithelial‐like cells
Authors: BLAZEJEWSKA EA , SCHLOETZER‐SCHREHARDT U , KRUSE FE
Published: September 2008

Purpose To investigate the plasticity of murine vibrissa hair follicle (HF) stem cells regarding differentiation into corneal epithelial‐like cells through modulation by limbus‐specific microenvironmental factors.

Methods HFs were isolated and the dissociated bulge stem cells enriched by clonal expansion, and subcultivated on various extracellular matrices (collagen type IV, laminin‐1, laminin‐5, fibronectin) in DMEM/F12 medium supplemented with different conditioned media (CMs). CMs were derived from central and peripheral corneal fibroblasts and limbal stromal fibroblasts. Growth potential and cellular phenotype were evaluated by light and electron microscopy, real‐time‐PCR and immunohistochemistry using antibodies against stem cell (CK15, integrin α6) and differentiation markers (CK12) or (CK10).

Results Laminin‐5 and collagen IV promoted rapid cell adhesion, proliferation, and generation of confluent, regularly arranged epitheloid cell sheets, whereas laminin‐1 and fibronectin adversely affected these cell properties. Addition of CMs differentially influenced cellular phenotype and differentiation. Limbal fibroblast CM induced differentiation of cuboid cells showing ultrastructural characteristics of a corneal epithelial phenotype. Moreover, it markedly increased the number of CK12 immunopositive cells while decreasing expression of CK10 opposed to the other CMs.

Conclusion Hair follicle stem cells are capable of differentiating into corneal epithelial‐like cells in vitro when exposed to a limbus‐specific microenvironment. Therefore, the HF may be an alternative therapeutic source of multipotent stem cells for generation of autologous epithelial cell sheets for ocular surface reconstruction.
Bilateral internuclear opthalmoplegia in a patient with Devic’s neuromyelitis optica
Authors: GIL ARRIBAS L , PUEYO V , GARCIA‐MARTIN E , IDOIPE CORTA M , PINILLA I
Published: September 2008

Purpose To present a clinic case of Devic’s neuromyelitis optica (NMO) with bilateral ophtalmoplejia internuclear (OIN) , which is an extremely extraordinary association. To explain the reason why an episode of ophtalmoplejia internuclear appears in the context of a NMO case. To expose the visual involvement in NMO.

Methods We studied and observed the clinical evolution of a patient diagnosed of NMO. The profile started with headache and sudden loss of visual acuity in right eye (RE), counting fingers at 1metre. She related neurologic symptoms as paresthesias 18 months ago. At the evaluation with visual field, eye fundus, Ishihara test was diagnosed of retrobulbar neuritis RE. We treated the patient with metilprednisolone and immunosuppressant drugs. She got better. After the childbirth, new neurologic symptoms that remined to transverse myelitis appeared. After a new treatment with metilprednisolone and plasmapheresis, she got better but a sudden bilateral OIN appeared

Results The patient had a limitation in the movement of the eyes in addution and a bilateral nistagmus in abdution. The patient didn´t have a good reponse to the treatments. At present, she continues being admitted to hospital with paresis of legs and right arm. Double vision and OIN disappeared gradually. However, the patient has a residual exoforia in RE with nistagmus in abdution in left eye.

Conclusion The MNO prevalence is lower than a case for million inhabitants, and it is not used to affect the encephalon trunk. To diagnose NMO are required two major criteria and at least two of the three minor ones, and this patient fullfills the diagnosis criteria.
Summary of the findings of the RLBP1 mutations affecting the visual cycle known so far with extremely prolonged dark adaptation in the RP of Bothnia type
Authors: BURSTEDT MSI , SANDGREN O , GOLOVLEVA I , WACHTMEISTER L
Published: September 2008

Purpose The retinal diseases in the RP group associated with affected recycling of retinoids in the visual cycle is now being recognized in populations worldwide. The RLBP1 mutations are here summarized and the phenotype known so far is presented.

Methods A presentation of literature in the RLBP1 mutations and the phenotype of Bothnia Dystrophy (BD) with ophthalmologic findings and full‐field electroretinography (ERGs) findings after 24 hours of dark adaptation are presented.

Results The phenotype (BD) in this group is described, an early progressive maculopathy, retinitis punctata albescens (RPA) as well as peripheral retinal degenerative changes is found. An extremely prolonged dark adaptation (24h) in the BD disease is presented and the full‐field ERG (24h) show the rod b‐wave and the mixed rod‐cone a‐wave responses reached normal but delayed amplitudes in the ERGs, the increase of the oscillatory response up to normal level was found and no recovery of the cone response was found.

Conclusion The phenotypes of RLBP 1 mutations worldwide and in Sweden show similarities in the expression and may be represented by the phenotype of BD. The unique findings of extremely prolonged DA and a significant and additional capacity of recovery of rod function and activity in the inner retinal layer and a continuous but slow regeneration of rod photopigment seems to occur at least up to 24h. The visual process in the RPE is retarded but also the Müller cells of the retina seem to be involved. The findings support an extremely slow synthesis of photopigments and an irreversibly disturbed cone function early in BD.
Improvement of visual acuity and visual evoked patterned potentials done at different spatial frequencies after rehabilitation in 45 subjects affected by Cerebral Visual Impairment.
Authors: RUBERTO G , ANGELI R , PEZZOTTA S , BERTONE C , ANTONINI M , FAZZI E , TINELLI C , BIANCHI PE
Published: September 2008

Purpose To analyze improvement of visual acuity(VA) and visual evoked patterned potentials (pVEP) in children diagnosed by MR as cerebral visual impaired (CVI) after rehabilitation (refractive correction and occlusion terapy).

Methods In 45 CVI infants(mean age 5.6)we analysed VA and pVEPs improvement after 1 year of follow up. Teller Acuity Cards and/or optotype were used for decimal visual acuity. P‐VEPs were recorded at Oz,O1,O2, referenced to Fz. At least two spatial frequencies (among 300’,120’,60’,30’,15’).Statistical analysis were made between VA and pVEP improvement.

Results VEP and VA percentage of success was 100% and 89% respectively at the beginning; after 1 year VA percentage of success rised 100%. Mean VA before treatment was 2,29/10(0.2‐10); after treatment was 3,61/10(0.1‐10). VA improvement was statistically significant(z=0,00) VA improvement occurred in 68,89%, while 31,11% were unimproved. Improved VEP were 80% and unimproved 20%. We considered improved VEP when children were able to detect lower spatial frequencies or when, in the same spatial frequency, we found higher amplitudes and reduced latencies. Differences between VEP amplitude and latency were not statistically significant in all frequencies but in L60’ (T‐test L60':0.02). There was an association between VA improvement and therapy,(Pr = 0.02) There wasn’t association (Pr = 0.76) between VEP improvement and therapy. There wasn’t correlation between VA and VEP improvement.

Conclusion We found an improvement both in VA and VEP.VEP improvement is independent of therapy,VA improvement is correlated with therapy.
Flash vep anomalities in infants with delayed visual maturation (dvm)
Authors: SJÖSTROM A , KRAEMER M
Published: September 2008

Normally eye contact and responsive smile in infants develop within 3 to 8 weeks postnatally. Delays may be due to ocular/eye diseases, neurological conditions or have unknown etiology. The flash visual evoked potential (fVEP) shows a typical potential pattern development in infancy(Kraemer & Sjöström ISCEV 1996) reflecting maturation of the afferent visual pathways. The unspecific pathways develops first as the ’late potential’, eventually forming the P1 potential. The later retino‐geniculo‐cortical afferents development, i.e. the specific or primary pathway, is simultaneous with the development of conscious cortical vision. It is reflected in the VEP as development of the ’N1’‐potential and in behaviour as eye contact and responsive smile. We have followed infants referred to us due to lack of normal visual development. Besides traditional clinical examinations we also included fVEP and ERG examinations, preliminary first reported at ISCEV 1997 (Kraemer). The fVEP in DVM children were all pathologic at first session, except in those that had developed eye contact before visit. The main finding was lack of normal N1 potential, sometimes combined with latency increase of P1 and/or other wave form pathology. Many of the children later developed eye contact, some as late as a year postnatally, and simultaneously also a N1 potential in the fVEP. The DVM etiology most often was cerebral palsy conditions of various types and degrees, however other conditions also were found. Examples of these cases will be shown as well as possible neurophysiological explanations to the altered VEP activity.
Functional MRI of the superior colliculus in dissociated vertical deviation
Authors: LEYSEN I
Published: September 2008

Abstract not provided
Utility of FISH in diagnosis and therapy of ocular melanocytic lesions
Authors: SCHAUWVLIEGHE PP
Published: September 2008

Abstract not provided
Inflammatory cytokines in the tears of patients with vascularized corneas
Authors: VAN GRASDORFF S
Published: September 2008

Abstract not provided
Clinical variability in a three‐generation family with Duane’s syndrome
Authors: THOMAS S , ROBERTS E , AWAN M , GOTTLOB I
Published: September 2008

Purpose The majority of Duane syndrome cases are sporadic in origin with only 2‐5% patients showing a familial pattern. Only a few large families have been reported. The purpose of this study is to report the clinical presentations, abnormalities of ocular motility, and strabismus in 3 generations of a family with Duanes syndrome.

Methods 22 members of a family of three generations (age range 6 years to 70 years) were examined. Detailed ophthalmologic assessment included assessment of vision, binocularity, and video recordings of ocular motility.

Results Unilateral Duane syndrome type 1 was noted in the left eye of a lady in the first generation of the pedigree. In the second generation, of the 4 subjects examined, two females had esotropia with diplopia, one male had minimal bilateral abduction deficit with endpoint nystagmus and one sibling was normal. 12 subjects from the third generation were examined. Two of them had unilateral Duane’s syndrome. Two children had minimal abduction deficit with endpoint nystagmus. Three subjects had esotropia and diplopia requiring surgery. The mother of one of the affected subject had normal eye movements.

Conclusion This large family with Duane syndrome appears to have a dominant form of inheritance with variable penetrance and expressivity. The skipped generation indicates unaffected carrier state. The variable phenotypic expression seen in this family suggests that classical Duane syndrome could be one end of a spectrum of eye movement disorders comprising esotropia, abduction deficits and globe retraction; the other end being normal ocular motility.
MIC and clinical efficacy. From systemic to ocular breakpoints
Authors: PLEYER U
Published: September 2008

Abstract not provided
Eye and virus. What's new ?
Authors: BODAGHI B
Published: September 2008

Abstract not provided
Strabismus, epilepsy vs. motor & neurological disorders in quadriplegia
Authors: TIGANITA S , KOZEIS N , GOGAKI H , STOJANOVIC N , MOUTLIAS A , DIMOPOULOS A
Published: September 2008

Purpose To correlate strabismus and epilepsy with the severity of the motor and brain disorder in spastic quadriplegic children.

Methods 52 quadriplegic children (2‐9 years of age) participated in this study. Strabismus (Krimsky test), gross motor function (GMFCS) were estimated and EEG and brain MRI were also performed.

Results 29 children were premature and 23 were full terms. 30 out of 52 (57.69%) had epilepsy, 29 out of 52 (55.76%) had strabismus (19 (36.53%) esotropia & 10 (19.23%) exotropia). 73.07% of the children had moderate to very severe motor disorders. 32 children (61.53%) had periventricular leukomalacia and 20 (38.47%) had various brain damages.

Conclusion Epilepsy and strabismus are very common in quadriplegia and there is a statistically significant relationship between epilepsy, strabismus and neurological and brain damage.
Treatment of acquired periodic alternating nystagmus with memantine
Authors: MCLEAN RJ , THOMAS S , FAROOQ SJ , PROUDLOCK FA , GOTTLOB I
Published: September 2008

Purpose To report a patient with acquired periodic alternating nystagmus secondary to sarcoidosis successfully treated with memantine

Methods A 43 year old man had a four year history of acquired horizontal periodic alternating nystagmus (PAN) with oscillopsia secondary to sarcoidosis. Visual acuity (VA) was measured and eye movement recordings were performed with an infra‐red eye tracker (Eyelink I, 250 Hz) before and after treatment with 5 mg memantine per day

Results The visual acuity (VA) was 6/36 in the right eye and 6/24 in the left eye during maximum nystagmus amplitude. The duration of the right beating and left beating phases was 105‐110 seconds and of the quite phases was 4‐5 seconds. During the quiet phase the nystagmus was insignificant. On memantine the patient became significantly less symptomatic. The right visual acuity improved to 6/6 and the left to 6/4 during the entire cycle of PAN. Before treatment the nystagmus reached a maximum intensity of 11.9°/sec (frequency 3.6 Hz and amplitude 3.3°) during right beating periods and 14.0°/sec (frequency 3.5Hz and amplitude 4.0°) during left beating. Again the quiet phases in between were insignificant in terms of nystagmus. After treatment of 5mg of memantine per day the intensity was reduced to a maximum intensity of 0.41°/sec (frequency 1.54 Hz and amplitude 0.26°) during right beating period and 0.54°/sec (frequency 1.28 Hz and amplitude 0.42°) during left beating.

Conclusion We showed for the first time that memantine can reduce PAN dramatically (4% of the original amount). Treatment with memantine should be investigated systematically in PAN.
Biochemical markers in the vitreous
Authors: VAN AKEN E
Published: September 2008

Purpose Prealbumin is a 55kDa protein (transthyretin) which plays an important role in the plasma transport of retinol in complex with retinol‐binding protein. It is also synthesized by the retinal pigmentepithelium (RPE) but the functional significance of ocular prealbumin is still unclear. In this study, we wanted to explore the use of prealbumin as a biochemical marker in human vitreous fluid in various conditions.

Methods Prealbumin concentration was assayed in vitreous fluid using a BN II nephelometer (Dade Behring). Cadaver eyes (n =59) served as a reference. Vitreous fluid was investigated in 64 patients where therapeutic vitrectomy was indicated: 9 eyes were operated on for retinal detachment less than 1 week old, 25 eyes for longstanding retinal detachment (more than 1 week old), another 13 for proliferative diabetic retinopathy, 17 patients had vitreoretinal retraction at the macula, and in 1 case floaterectomy was performed.

Results In the reference group, median prealbumin value was 6.0 mg/l (IQR: 2‐19.8 mg/l); total protein: median 567 mg/l; IQR: 271‐996 mg/l). For patients operated for retinal detachment, prealbumin values were lowest in patients with retinal detachment less than 1 week old (median: 3 mg/l, IQR: 0‐12 mg/l) and highest for patients with longstanding retinal detachment (median: 17 mg/l, IQR: 1‐25 mg/l)(P<0.05).

Conclusion Prealbumin is abundant in human vitreous fluid. In pathological conditions, prealbumin values may vary. No correlation was found between prealbumin levels and total protein levels in vitreous fluid. In particular, patients with longstanding retinal detachment showed highest prealbumin values. This might be due to increased synthesis of prealbumin by RPE cells. Prealbumin concentrations in the vitreous may be used as a marker for retinal dysfunction.
Zonal differentiation of the epithelium including the lid wiper at the human lid margin
Authors: KNOP E , KNOP N , ZHIVOV A , KRAAK R , KORB D , GREINER JV , GUTHOFF R
Published: September 2008

Purpose The lid margin represent the “other end” of the tear film and appear critically important for ocular surface integrity, in addition to the glandular structures that produce the tears. It guarantees the thin expansion of the tear film with every blink and prevents the leakage of tears over the lid border. However, the differentiation of the lid margin zones is insufficiently known as yet.

Methods The upper and lower lid margin in human whole‐mount specimens from ten body donors was investigated in serial section histology and compared to the image by in‐vivo confocal microscopy in four eyes with a Heidelberg retina tomograph and Rostock cornea module (RLSM).

Results At the inner lid border, following the keratinised epidermis of the free lid margin, a narrow zone (100‐150µm) of para‐keratinised squamous epithelium represented the muco‐cutaneous junction (MCJ) corresponding to the line of Marx. This was followed by a much broader zone of epithelial thickening (50‐100µm) that formed a kind of cushion, reclined sharply at the inner lid border and represented the so called lid wiper which extended for about 1mm and finally transformed into the epithelium of the sub‐tarsal fold. MCJ and lid wiper extended all along the lid margin from nasal to temporal in upper and lower lid. Details of the epithelial structure as well as the underlying dermal papillae in these zones were also detectable by RLSM.

Conclusion Due to its location and structure, the lid wiper appears as the structure that actually spreads the tear film and is distinct from the MCJ/line of Marx. Better knowledge of the lid margin structure and its different zones appears important for the understanding of ocular surface disease, in particular the dry eye disease.
New surgical techniques for reconstruction of the lid margin
Authors: GICQUEL JJ
Published: September 2008

The lid margins are extremely important to the health of the ocular surface. They play a major role in the distribution of the tear film over the eye. It is therefore important that disease of the eyelid margins be controlled before significant scarring of the ocular surface occurs. Two or three rows of eyelashes are present in the upper eyelid margin and one or two rows of eyelashes in the lower one. The tarsal plates include the meibomian glands. The objectives of eyelid margin surgery are both functional and cosmetic. Structural eyelid margin defects should be corrected with surgical techniques that return the anatomy to as close to normal as possible. Upper eyelashes should be preserved during the surgical procedures because defects of eyelashes in the upper eyelid are very visible. Restoring normal three dimensional anatomy (good lid contour, continuity of the lashes, etc) allows the eyelid margins to keep their functions for ocular surface protection and tear film distribution and gives optimal cosmetic result. In the time we will have in this session, we will seek to focus on the up to date surgical techniques that can be employed to correct inherited or acquired eyelid margin structural defects.
Genetic epidemiology studies of cataract in a population‐based biobank
Authors: MCCARTY CA
Published: September 2008

Purpose To describe genetic epidemiology studies of cataract in the Marshfield Clinic Personalized Medicine Research Project (PMRP)

Methods The PMRP is the largest population‐based biobank in the US. Nearly 20,000 adults aged 18 years and older have participated, with stored DNA, plasma and serum samples, and access to the Marshfield Clinic medical records. Subjects complete a brief questionniare that includes questions about smoking and alcohol intake. Height and weight are measured and body mass index is calculated. A candidate gene study of age‐related cataract has been completed and a genome‐wide association study (GWAS) of age‐related cataract is currently underway. Cataract cases are identified through diagnostic codes for cataract and procedure codes for lens extraction. Exclusionary diagnoses and procedures include congenital cataract, after‐cataract, traumatic cataract and steroid‐induced cataract. Controls are identified by the absence of any of the inclusion diagnoses and procedures in the context of an eye exam in subjects aged 50 years and older in the previous five years. Cataract location (cortical, nuclear, PSC) is identified through manual chart abstraction and natural language processing of dictated notes.

Results In the candidate gene study of 1618 cataract surgery cases and 495 controls aged 60+, a SNP in the CRYGB gene proposed for study by Dr. Jochen Gray was found to be significantly associated with cataract surgery for females only. Electronic algorithms to accurately identify cases and controls for the GWAS study will be presented.

Conclusion It is possible to conduct scientifically rigorous genetic epdiemiology studies of cataract in the context of a group medical practice. Care needs to be taken to accurately classify case and control status.
Risk factors for cataract in India: the INDEYE study
Authors: CAMPARINI M , MARAINI G , MURTHY GVS , RAVINDRAN RD , CHAKRAVARTHY U , FLETCHER AE
Published: September 2008

Purpose To describe the prevalence of lens opacities and to assess risk factors in older people in India.

Methods People aged 60 years and older identified using random cluster‐sampling in 2 study centres in north and south India, attended an eye examination. Digital images of lens opacities were graded using the Lens Opacity Classification System III. To identify lifestyle and environmental factors associated with lens opacities, assessment of different potential risk factors was performed, with a focus on cooking fuels, tobacco and alcohol use, sunlight exposure, diet and antioxidant blood levels.

Results 2821 people in north India and 3079 in south India attended an eye examination. The prevalence of any cataract was 73.6% and similar in the two centres (p=0.2). Type of cataract differed in prevalence between the centres: nuclear 60.0% in north India, 48.0% in south India; posterior subcapsular 26.5% in north India, 21.7% in south India; cortical 9.6% in north India and 12.8 % in south India. Prevalence of any cataract rose with age (54.9%, age group 60‐64 years; 90.3%, age group 70 years and older, p<0.001) and was higher in women than in men (76.7%, women; 70.1%, men, p<0.001). Similar patterns with age and gender were observed for each type of cataract. Among risk factors, tobacco use, exposure to cooking fuels and antioxidants levels were significantly associated with cataract (p<0.001).

Conclusion Cataract prevalence, especially posterior subcapsular cataract, is very high in older Indians compared to comparable age groups in western populations. Factors as tobacco use, exposure to cooking fuels and low antioxidant blood levels may in part explain the high prevalence of cataract in this population.
Microperimetry, PERG and mfERG in patients with Stargardt dystrophy
Authors: JARC‐VIDMAR M , POPOVIC P , LENASSI E , BRECELJ J
Published: September 2008

Purpose The aim of our study was to evaluate retinal function in patients with genetically determined mutation in the ABCR gene by correlating retinal morphology with functional and electrophysiological tests.

Methods 12 patients (10F, 2M, VA: 0,2±0,2) were included in the study. The central 10º visual fields were tested with Octopus M2 TOP and microperimetry (MP1, Nidek technologies), that enables one to compare central retinal sensitivity and fixation patterns in relation to the fundus image. PERG and mfERG were recorded in all the patients according to the ISCEV standards.

Results mfERG showed reduced responses mostly in the inner three rings (ring 1: 33,9% of mean normal value, ring 2: 35,4%, ring 3: 57,5%, ring 4: 75,5%, ring 5: 84% of mean normal value). There was good correlation between mfERG and pattern P50 (r=0,7, p=0,0001) and N95 responses (r= 0,6, p=0,004). mfERG appears more sensitive for central retinal testing than pattern ERG. There was a high correlation found between microperimetry (MP) and static perimetry (MD, r = 0.6, p=0.008). Shift of fixation to the preferred retinal locus(seen on MP) was found in 8 out of 16 eyes tested with VA 0,2 and less. In patients with absolute central scotoma and shifting of fixation, scotoma may erroneously be interpreted as eccentric when seen only with static perimetry.

Conclusion In patients with visual acuity 0,2 and lower, the fixation shift to the preferred retinal locus was observed. Cautious interpretation of the static perimetry and mfERG as well as PERG is needed in patients with eccentric and nonstable fixation.
Ocular rigidity and hydrodynamics of the human eye
Authors: PALLIKARIS IG , GINIS HS , DASTIRIDOU AI , DE BROUWERE D , KYMIONIS G , TSILIMBARIS MK
Published: September 2008

Purpose The intraocular pressure (IOP) is the primary mechanical load to several ocular structures. It fluctuates over time as a result of a dynamic equilibrium between the systems of aqueous and blood flow. The purpose of this study is to characterize the eye’s pressure volume relationship and quantify hydro and haemodynamic parameters in the living human eye.

Methods An invasive manometric dynamic measurement procedure was developed and used in a series of healthy and pathological eyes measured intraoperatively before cataract surgery. Different measurement protocols involving injection of predetermined doses of saline and monitoring the IOP in a time‐resolved manner, allow the measurement of ocular rigidity, outflow facility and pulsatile ocular blood flow. In addition, a new non‐invasive ultrasound based technique enabled us to visualize and define the elastic properties of the ocular globe and periocular structures.

Results Measurements in humans indicate that the above techniques are safe and effective. A non‐linear pressure‐volume relationship is established. The ocular pulse amplitude (and therefore pulsatile ocular blood flow) is shown to correlate with IOP.

Conclusion A model that incorporates ocular rigidity is proposed in order to describe and quantify the relationship between hydrodynamic and hemodynamic parameters of the human eye. These measurements along with the use of new non invasive techniques may improve our understanding of the relationship between these parameters and their significance in health and disease.
Biomechanics of the eye tunic, especially the sclera and the cornea
Authors: SPOERL E , TERAI N , BOEHM AG , RAISKUP‐WOLF F , PILLUNAT LE
Published: September 2008

Purpose The biomechanics of the cornea is not only important for IOP‐measurement but also for the outcome of refractive surgery. In recent studies, a thin cornea was also identified as an independent risk factor for the onset and progression of glaucoma. Besides, the rigidity of the sclera was proposed to play an important role in glaucoma and myopia.

Methods An overview of biomechanical properties of the cornea and the sclera, based on own research results and on recent literature references, was performed.

Results A stiffer cornea led to an overestimation of true IOP measured by applanation tonometry. The stiffness of the cornea increased by age compared to a decreasing corneal thickness. The Ocular Response Analyzer (ORA) measures the viscosity of the cornea. Paradoxically, ORA measurement revealed a reduction of corneal hysteresis with age which may indicate that corneal hysteresis is not equal to stiffness. In glaucoma the scleral and corneal rigidity increased in contrast to a reduced corneal hysteresis (CH) which may indicate that a damping effect of these tissues is reduced in glaucoma patients. Conversely, a more flexible and distensible sclera, lamina cribrosa and cornea were proposed to be beneficial to protect against experimentally induced IOP‐spikes.

Conclusion A biomechanical concept of the eye tunic (cornea, sclera and lamina cribrosa) may further help to explain the relationship between IOP measurements, refractive surgery and glaucoma.
Cone electroretinograms to blue flashes on various backgrounds
Authors: SUSTAR M , BRECELJ J
Published: September 2008

Purpose To observe the S‐cone and LM‐cone responses of the photopic electroretinogram (ERG), to study their interactions, and to define under which stimulus conditions the ERG waveform reflect the function of the S‐cone as well as the L‐ and M‐cone systems.

Methods The photopic ERG was recorded from 10 control subjects in a full‐field stimulator (Diagnosys LLC, Littleton, MA). Responses were elicited with intensity series (0.004 to 1 cd*s/m2) of the blue (449 nm) stimuli on a 100 ph cd/m2 amber background (=40 sc cd/m2), as well as on a 100 ph cd/m2 green and a 40 sc cd/m2 red backgrounds.

Results The S‐cone response appeared at the implicit time of 43 ms, with lower stimulus intensities on the amber, green and red backgrounds. With higher stimulus intensities (0.028 cd*s/m2), it showed with a similar implicit time, but as a second peak subsequent to the LM‐cone response (b‐wave). With a further increase in intensity (0.15 cd*s/m2), the S‐cone response passed into the i‐wave of the LM‐cone system. The LM‐cone response appeared as a double peak (first peak: 24 ms; second peak: 28 ms) on an amber background at intensities from 0.028 cd*s/m2 and above. On a green background, the first peak was more prominent, while on a red background, the second peak dominated the LM‐cone response. This pattern of double‐peak appearance might indicate that the first peak originates mostly from the L‐cone system and the second peak from the M‐cone system.

Conclusion The S‐cone response can be elicited with various backgrounds as a single peak to a blue flash at lower intensities, while with brighter intensities it probably interacts with the LM‐cone system. The double peak of the LM‐cone response is an interesting finding, which might indicate selective monitoring the L‐ and M‐cone systems.
The EBO heritage: past, present and ... Concordia
Authors: KIVELÄ T
Published: September 2008

Abstract not provided
European network on education in ophthalmology
Authors: TASSIGNON MJ
Published: September 2008

Abstract not provided
Autofluorescence and microperimetry in clinically significant diabetic macular edema
Authors: BOTTEGA E , VUJOSEVIC S , PILOTTO E , BENETTI E , CASCIANO M , MIDENA E
Published: September 2008

Purpose Clinically significant diabetic macular edema (CSME) shows variable retinal structural and functional impairment. The aim of this study was to assess the correlation between different macular parameters, mainly fundus autofluorescence (FAF) and macular sensitivity, in diabetics with CSME.

Methods Sixty diabetic patients with untreated CSME (104 eyes) underwent: best corrected visual acuity determination (BCVA, logMAR), slit lamp biomicroscopy, fluorescein angiography, OCT, FAF and microperimetry.

Results Thirty eyes had normal FAF , whereas 74 increased (IFAF) pattern. Retinal sensitivity over areas with IFAF was significantly lower than over areas with normal FAF (p<0.001). Cystoid OCT‐pattern correlated to both presence and dimension of IFAF (p<0.05), whereas sponge‐like and subfoveal neuroretinal detachment did not. BCVA did not correlate either to FAF pattern or area of IFAF.

Conclusion Functional impact of CSME correlate with IFAF and is better determined with macular microperimetry rather than VA. Increased FAF seems to be a relevant characteristic of cystoid CSME. New structural and functional parameters should be used to better predict the prognosis of (treated and untreated) eyes affected by CSME.
Segmentation of spectral domain OCT volume scans of patients with no or minimal diabetic retinopathy
Authors: VAN DIJK HW , VAN VELTHOVEN MEJ , GRAVIN‐HAEKER M , KOK PHB , VERBRAAK FD , ABRAMOFF MD
Published: September 2008

Purpose A comparison of thickness measurements of segmented spectral domain optical coherence tomography (OCT) derived topographic maps of patients with no or minimal diabetic retinopathy (DR) versus healthy controls.

Methods Ninety‐nine patients, 44 with type 1 DM, and 36 with type 2 DM, with no or minimal DR underwent full ophthalmic examination, fundus photography and spectral domain OCT (3D OCT‐1000, Topcon). Following automated segmentation the mean thickness was calculated for 6 layers: 1/ Retinal Nerve Fibre Layer (RNFL), 2/ Ganglioncell layer (GCL) + Inner Plexiform Layer (IPL), 3/ Inner Nuclear Layer, 4/ Outer Plexiform Layer, 5/ Outer Nuclear Layer + Inner Segments (photoreceptor), 6/ Outer Segments (photoreceptor), in the ETDRS defined regions of the macula and compared to 76 age and sex matched healthy controls.

Results The total retinal thickness in the diabetic patients was reduced compared to the healthy controls. In the diabetic patients both the mean RNFL and the mean OPL were significantly (p<0.05) thinner.

Conclusion The decreased total retinal thickness in diabetic patients with no or minimal retinopathy may be due to a selective loss of thickness in several retinal layers and supports the concept of early DR as a neuro‐degenerative disease.
The extraocular muscles in Amyotrophic Lateral Sclerosis (ALS)?
Authors: PEDROSA DOMELLOF F , BRÄNNSTRÖM T , ANDERSEN PM , LIU JX
Published: September 2008

Purpose To investigate the morphology, fiber type composition, contractile proteins, extracelluar matrix (ECM), innervation and capillarisation, of the extraocular muscles (EOM) of patients deceased with ALS, in order to evaluate the possible involvement of EOMs in this disease.

Methods EOM and limb muscle samples obtained from 5 ALS patients and age matched controls at autopsy were processed for immunocytochemistry, with monoclonal antibodies against myosin heavy chain isoforms; laminin chains (Ln) α1, α2, α4, α5 and β2; etc. Hematoxylin and eosin, NADH‐TR, acetylcholinesterase and alpha‐bungarotoxin were also used.

Results The EOMs of ALS patients appeared remarkably unaffected, in strong contrast to the limb muscles. Wider variation in fiber diameter than normally seen in EOMs, including apparently atrophic and hypertrophic groups of fibers, was noted. MyHC embryonic was only present in sporadic fibers and the pattern of distribution of MyHC slow‐tonic was also affected. In most ALS cases, Ln α4, α5 and β2 isoforms were lost from the basement membrane of the EOM fibers . The laminin content of the neuromuscular junctions was altered, Ln α2 and β2 isoforms were missing in perineurium and endoneurium and Ln α5 was absent in endoneurium. In capillary and blood vessels, Ln α4, α5 were maintained whereas Ln β2 was absent.

Conclusion The changes observed in EOMs with ALS suggest that they are not completely spared in this motoneuron disease although they are significantly less affected that limb muscles. The altered contractile protein content and structure‐specific changes in the composition of the ECM are likely to be functionally relevant. Further studies are underway to determine the functional implications of our findings.
A comparison of clinical and eye movement characteristics between albinism and idiopathic infantile nystagmus with and without mutations in the FRMD7 gene
Authors: KUMAR AS , GOTTLOB I , PROUDLOCK FA , THOMAS S
Published: September 2008

Purpose Nystagmus consists of involuntary to and fro oscillations of the eyes. The differences between nystagmus associated with albinism and idiopathic infantile nystagmus (IIN) are unclear. Recently mutations in a novel gene called FRMD7 have been found to underlie a significant proportion of X‐linked IIN. Phenotypic variations in eye movements between FRMD7 and non‐FRMD7 types have also been recently described. We have compared clinical and eye movement characteristics between albinism and IIN with and without mutations in the FMRD7 gene.

Methods Clinical features and eye movement were recorded from 37 albino subjects, 83 subjects with the FRMD7 mutation and 45 subjects without the FRMD7 mutation.

Results Mean visual acuity was significantly worse in albinos compared to IIN patients (p<<0.0001). Although there was no significant differences between the groups (p>0.05) for nystagmus amplitude or foveation, the frequency of nystagmus was significantly slower in albinism (p<<0.0001). In addition, nystagmus associated with albinism was significantly more likely to be jerk nystagmus rather than pendular nystagmus compared to FRMD7 group (p<<0.0001). The most common waveform associated with albinism was pure jerk nystagmus, whereas non‐FRMD7 was more likely to be associated with jerk with extended foveation.

Conclusion Contrary to available literature, nystagmus associated with albinism shows distinct differences to IIN both with and without FRMD7 mutations. This suggests the possibility of different underlying mechanisms to albinism and IIN in generating eye oscillations although these are yet to be elucidated
Optical Coherence Tomography testing : possible biomarker value in multiple sclerosis?
Authors: RADOVIC N , PAVLOVIC D
Published: September 2008

Purpose To assess retinal nerve fiber layer thickness ( RNFLT ), macula volume (MV) and visual acuity (VA) in multiple sclerosis (MS) eye , with or without optic neuritis (ON).

Methods Optical coherence tomography ( OCT ) measures of the RNFLT and MV were studied in 14 patients with primary progressive multiple sclerosis ( 8 male / 6 female ‐ mean age 47 yrs ) and 12 patients with secondary progressive multiple sclerosis ( 5 male / 7 female ‐ mean age 41 yrs ). From the group with secondary progressive dissease 8 had history of ON. Control group consisted of 12 healthy control( 3 male / 9 female ‐ mean age 49 yrs ) underwent RNFLT and MV OCT testing.

Results Of the patients eyes not affected by ON, mean RNFLT and macula volume were reduced when compared with control values.The mean RNFLT and MV were significantly decreased in secondary progressive MS group, but not in primary progressive MS, when compared with controls. Decreased RNFL and MV significantly correlated with decreased VA and visual field mean deviation. RNFL loss was most evident in the tmeporal quadrant, where significant reduction was seen in secondary compared to primary progression MS, and primary progression MS versus control group.

Conclusion Progressive MS is manifesting more marked decrease in RNFLT and MV. OCT is promissing to detect subclinical changes in RNFL and MV, and could possibly considered as potential biomarker of reinal / brain involvement in MS.