Voxel-based morphometry and diffusion tensor imaging of the optic pathway in primary open-angle glaucoma: a preliminary study.

BACKGROUND AND PURPOSE: Neuropathologic studies in experimental and human glaucoma have demonstrated degenerative changes in the optic pathway. The purpose of this study was to assess the optic pathway in POAG by using VBM and DTI. MATERIALS AND METHODS: Eighteen patients 57.05 ± 11.38 years of age with POAG of 8.30 ± 5.14 years' duration and 18 control subjects underwent a complete ophthalmologic examination, including quantification of the RNFLT by using Stratus OCT 3, and brain imaging. The imaging protocol consisted of a T1-weighted high-resolution 3D spoiled gradient-echo sequence and a multisection spin-echo- planar diffusion-weighted sequence. Data preprocessing and analysis were performed by using Matlab 7.0 and SPM 5. RESULTS: Left temporal and right nasal RNFLTs were significantly thinner than right temporal and left nasal RNFLTs. In patients, VBM revealed a significant reduction in the left visual cortex volume, the left lateral geniculate nucleus, and the intracranial part of the ONs and the chiasma. In addition, a significant decrease of FA was observed in the inferior fronto-occipital fasciculus, the longitudinal and inferior frontal fasciculi, the putamen, the caudate nucleus, the anterior and posterior thalamic radiations, and the anterior and posterior limbs of the internal capsule of the left hemisphere (P < .05). CONCLUSIONS: Neurodegenerative changes of the optic pathway and several brain areas associated with the visual system can be observed by using VBM and DTI in patients with POAG, suggesting that glaucoma is a complex neurologic disease.

Perimetric and peri-papillary nerve fibre layer thickness findings in multiple sclerosis.

BACKGROUND AND PURPOSE: Several previous studies have employed optical coherence tomography (OCT) of the optic disc and 'white-on-white' automated perimetry to evaluate optic neuritis (ON) associated with multiple sclerosis (MS). This study employed OCT, white-on-white automated perimetry as well as 'blue-on-yellow' automated perimetry to evaluate MS patients with or without episodes of ON. METHODS: The MS group consisted of 56 patients with MS (27 patients with no history of ON in both eyes and 29 patients with at least one ON attack in one or both eyes), whereas the control group consisted of 56 age- and sex-matched healthy subjects. All patients underwent a complete neurological and ophthalmological examination. Peri-papillary retinal nerve fibre layer thickness (RNFLT) was evaluated using OCT. The mean defect and pattern standard deviation for both white-on-white and blue-on-yellow perimetry were also recorded. RESULTS: RNFLT and perimetric scores were significantly lower in MS group without a history of ON and in the unaffected eyes of MS group with unilateral ON, compared with controls. MS group with more than one ON episodes had significantly compromised blue-on-yellow perimetric indices, compared with patients with one ON episode, whereas respective differences for white-on-white perimetry were not statistically significant. CONCLUSIONS: The significantly lower RNFLT and perimetric scores in MS group patients without ON, compared with control group, may possibly be attributed to sub-clinical episodes of ON or to retrograde degeneration of nerve cells from sub-clinical post-chiasmal lesions. Blue-on-yellow perimetry may be advantageous over white-on-white perimetry in evaluating MS-associated functional defects.

Characterization of 23 small supernumerary marker chromosomes detected at pre-natal diagnosis: The value of fluorescence in situ hybridization.

Small supernumerary marker chromosomes (sSMCs) cannot be identified or characterized unambiguously by conventional cytogenetic banding techniques. Until recently, the large variety of marker chromosomes, as well as the limitations in their identification, have presented a diagnostic problem. In order to determine the origin of sSMCs, we used a variety of fluorescence in situ hybridization (FISH) methods, including centromere-specific multicolor FISH, acrocentric specific multicolor FISH, subcentromere-specific multicolor FISH and multicolor FISH with whole chromosome paint probes. Moreover, uniparental disomy testing was in all cases attempted. From a total of 28,000 pre-natal samples from four diagnostic genetics laboratories in Greece, 23 (0.082%) supernumerary marker chromosomes were detected. The mean maternal age was 36.2 years (range 27-43) and the mean gestational age at which amniocentesis was performed was 18.5 weeks (range 16-23). Eighteen markers were de novo and 5 markers were inherited. Molecular cytogenetic methods were applied to determine the chromosomal origin and composition of the sSMC. In total, 17 markers were derived from acrocentric chromosomes (14, 15, 21 and 22) and 6 markers were non-acrocentric, derived from chromosomes 9, 16, 18, 20 and Y. Uniparental disomy was not detected in any of the cases studied. With regard to pregnancy outcome, 13 pregnancies resulted in normal healthy neonates, while 10 pregnancies were terminated due to ultrasound abnormalities. A total of 23 marker chromosomes from 28,000 pre-natal samples (0.082%) were identified. Molecular cytogenetic techniques provided valuable information on the chromosomal origin and composition of all the sSMCs. Especially in cases with normal ultrasound, the FISH results rendered genetic counseling possible in a category of cases previously considered a diagnostic problem. Abnormal outcome was observed in 10 cases (43,5%), 7 of which showed abnormal ultrasound findings. New technologies, such as array-comparative genomic hybridization, should be used in future genotype-phenotype correlation studies, although the high mosaicism rate poses a problem.

Conventional MRI and magnetisation transfer imaging of the brain and optic pathway in primary open-angle glaucoma.

Neuropathological studies in experimental and human glaucoma have shown degenerative changes in the optic pathway. The purpose of the study was to evaluate, with conventional MRI and magnetisation transfer imaging, the brain and the optic pathway of patients with primary open-angle glaucoma (POAG). 26 patients, aged 67.4+/-8.6 years, and 26 control subjects were studied. The presence of white matter hyperintensities (WMH) was evaluated on fluid-attenuated inversion recovery images of the brain. The area of the optic nerves was assessed on coronal short tau inversion recovery images. Magnetisation transfer ratio (MTR) was measured in the chiasm and in the grey and white matter (CGM and CWM) of the calcarine fissure. More WMH were observed in patients (total 261, mean 10.8, standard deviation 12.7) than in control subjects (total 127, mean 4.7, standard deviation 5.7; p<0.001). The area (mm(2)) of optic nerves (10.7+/-5.7) and the MTR (%) of the chiasm (53.7+/-8.4), the CWM (60.9+/-4.2) and the CGM (53.6+/-5.6) were all lower in patients than in control subjects (13.6+/-4.3, 62.1+/-6.2, 67.6+/-8.6 and 57.0+/-4.6, respectively; p<0.05). The area of optic nerves showed significant correlation with the MTR of the chiasm (R = 0.41), the MTR of the CGM (R = 0.33), the MTR of the CWM (R = 0.34) and the cup to disc ratio (R = -0.46). POAG leads to optic nerve atrophy and degeneration of the optic pathway. The finding of an increase in the number of WMH suggests that cerebrovascular disease may play a role in the pathogenesis of POAG.

A novel locus on 19q13 associated with autosomal-dominant macular dystrophy in a large Greek family.

OBJECTIVE: To describe the clinical features of and genetic locus associated with autosomal-dominant macular dystrophy (MCDR5) in a large Greek family. METHODS: 26 members of a single family underwent clinical examinations and venepuncture. A genomewide linkage scan using 400 microsatellite markers distributed with an average spacing of 10 cM throughout the human genome. RESULTS: 14 members of the study family exhibited clinical features of the disease including decreased central vision and macular abnormalities in the posterior pole of the retina. Analysis of loci known to be associated with macular dystrophy did not show positive linkage. A genomewide linkage scan showed linkage to chromosome 19q, with a two-point maximum LOD score of 5.809 at theta = 0 between the disease and marker locus D19S412. On the basis of recombination events, the disease interval was localised between markers D19S420 and D19S540 on chromosome 19q, at a span of about 3.8 cM, in an area known to contain 120 known genes/transcripts. Eleven of these genes/transcripts were sequenced, and no disease-causing mutation was identified. CONCLUSIONS: This study describes a new locus on 19q associated with autosomal-dominant macular dystrophy, designated as MCDR5. Additional study of other family members will be necessary to further narrow the interval and identify the responsible gene. The study of MCDR5 will aid in elucidation of the underlying pathogenic mechanisms for this and other macular diseases, including age-related macular degeneration.

Consumo de alcohol y problemas relacionados con el alcohol en Grecia / The situation of alcohol use and abuse in Greece

Objetivo: Este artículo analiza los datos del recientemente creado Sistema Nacional Griego de Vigilancia del Alcohol, desarrollado por el Punto Focal Griego, instituto de salud mental. El objetivo de este artículo es presentar una revisión y visión de conjunto de la situación del alcohol en Grecia. Material y métodos: La recogida de datos se ha realizado por el Punto Focal Griego en colaboración con las agencies y fuentes de información relacionadas con el alcohol en Grecia. Éstas incluyen: a) la base de datos electrónica sobre aspectos legales NOMOS; b) las encuestas nacionales a población general y escolar; c) los organismos y centros que desarrollan actividades asistenciales y de prevención, y e) el Laboratorio Toxicológico Nacional. Resultados: La información sobre la situación del alcohol y los problemas relacionados con el alcohol en Grecia es limitada. Sin embargo, existe un creciente interés y preocupación gubernamental por este tema, como lo muestra las acciones legislativas llevadas a cabo y la mayor disponibilidad de recursos asistenciales. Conclusiones: El sistema de vigilancia existente debe mejorarse e incrementarse. Con el fin de tener una mejor visión de conjunto del fenómeno, es necesaria una mayor colaboración con otras agencias y fuentes de información, así como una mejor información procedente de las fuentes individuales de información

Objective: This paper presents data from the newly established national alcohol monitoring system in Greece, developed by the Greek REITOX Focal Point ­ University Mental Health Research Institute. The objective of the paper is to give an overview of the situation of alcohol-related issues in Greece. Material and methods: Collection and/or compilation of data have been carried out by the Greek Focal Point in collaboration with the agencies and sources of information that deal with alcohol in Greece. These include: a) the NOMOS electronic legal database; b) the general population and student population nationwide epidemiological surveys; c) preventive and treatment agencies; d) Traffic police; and e) General State Chemical Laboratory. Results: The approach to the situation of alcohol-related issues in Greece is piecemeal. However, there is a growing government concern over alcohol issues as demonstrated by actions taken within the framework of legislation and treatment facilities. Conclusions: The existing monitoring system must be extended. In order to have the full picture of the phenomenon, close collaboration with more agencies/sources of information is needed, as well as a synthesis of results from individual sources

Refining the primary open-angle glaucoma GLC1C region on chromosome 3 by haplotype analysis.

The GLC1C locus for primary open-angle glaucoma (POAG) is inherited as an autosomal dominant trait. This region on chromosome 3 is 11 cM long. DNA samples from members of a Greek and an American GLC1C family were obtained to determine whether additional typing of microsatellite markers in family members might narrow the region. GLC1C family members were evaluated clinically for POAG on the basis of open angles, intraocular pressures, cupping of discs, and visual fields. DNA samples from the Greek and Oregon GLC1C families were used to further refine the GLC1C region using microsatellite markers. A total of 22 affected members were identified in the two families. Common alleles for D3S3637 and D3S3612 were present in the disease haplotype from both families, suggesting that they may have a common founder. A newly diagnosed patient in the American family had a recombination in the distal portion of the GLC1C haplotype. This recombination narrows the GLC1C region from 11 to 4 cM.

Oral pilocarpine for the treatment of ocular symptoms in patients with Sjögren's syndrome: a randomised 12 week controlled study.

OBJECTIVE: To evaluate the efficacy and side effects of oral pilocarpine for the treatment of ocular symptoms in patients with primary Sjögren's syndrome (SS). METHODS: A 12 week, single centre, randomised controlled study was performed. Twenty nine patients were randomly assigned to receive oral pilocarpine (5 mg twice a day), 28 only artificial tears, and 28 inferior puncta occlusion. Patients receiving oral pilocarpine and those with inferior puncta occlusion also received artificial tears. Patients were evaluated at baseline and throughout the study for their subjective global assessment of dry eyes and for their objective assessment of dry eyes (Schirmer's-I test, rose bengal test, and imprint test). RESULTS: Patients taking oral pilocarpine had significant improvement in subjective global assessment of dry eyes, as was evaluated by improvement of >55 mm on a visual analogue scale (VAS) for responses to the eye questionnaire, compared with patients treated with artificial tears (p<0.001) and those with inferior puncta occlusion (p<0.05). Furthermore, patients receiving oral pilocarpine also showed greater objective improvement, as measured by the rose bengal test (p<0.05), while Schirmer's-I test showed no differences between the treated groups. Commonly reported adverse events were headache, increased sweating, nausea, and vomiting in the pilocarpine group, while one patient in the inferior puncta occlusion group had blepharitis and was withdrawn from the study. CONCLUSION: 10 mg of pilocarpine daily given to patients with SS for 12 weeks had a beneficial effect on subjective eye symptoms, as evaluated by improvement >55 mm on a VAS. Additionally, an improvement of rose bengal staining was noted, but an increase in tear production, as measured by the Schirmer-I test, was not substantiated.

Tele-ophthalmology and conventional ophthalmology using a mobile medical unit in remote Greece.

We evaluated the quality of medical services delivered to remote glaucoma patients from a mobile unit. A four-wheel-drive vehicle containing the necessary equipment visited five different remote locations in Greece. During a three-year prospective study, 1205 patients were examined, of whom 230 had glaucoma. The majority of the subjects were examined by the unit's medical staff using the available instrumentation (e.g. slit-lamp and tonometer), while 56 glaucoma subjects were telemedically examined by consultants at the Patissia General Hospital, in Athens. Control data were obtained from a random sample of 260 urban glaucoma patients. A significantly greater proportion of the remote patients had an inadequate awareness of glaucoma (77%) compared with the urban patients (20%). Significantly more remote patients had poorer compliance (68%) in comparison with urban patients (23%). A significantly larger proportion of the remote patients had high intra-ocular pressure (21%) compared with the urban patients (5%). Technical difficulties occurred in the 13 of the 56 telemedical examinations. Mobile medical units can enhance access to medical services and contribute to the health-care of under-served populations.

Our experience with perfluorohexyloctane (F6H8) as a temporary endotamponade in vitreoretinal surgery.

PURPOSE: To evaluate the use of F6H8 as a temporary endotamponade for complicated and special cases of retinal detachment instead of silicone oil. METHODS: We have used F6H8 with 14 patients since February 1999. Eight suffered from rhegmatogenous retinal detachment (RRD) with multiple tears located inferiorly. Three presented inferior traction retinal detachment (TRD) under silicone oil, two suffered from ocular trauma with inferior TRD, and one had idiopathic macular hole. The substance was introduced into the eye after pars plana vitrectomy and membrane peeling if needed, and we tried to introduce as much as possible. RESULTS: With F6H8 the retina was easily reattached in all cases, like with perfluorocarbon liquids. The postoperative view was very good. F6H8 was removed in all cases after 3-8 weeks. Anatomical success was achieved in 12 out of 14 eyes. Two eyes presented severe PVR. F6H8 entered the anterior chamber in 4 cases, but no corneal complications occurred. In one case there was a marked IOP rise due to an anterior block, treated with superior iridotomy. In two cases retinal detachment (RD) occurred in the upper part and was treated with additional surgery, F6H8 removal and silicone oil injection. CONCLUSIONS: F6H8 seems to be a promising tamponade agent for special cases of RD.

Retinopathy of prematurity and other ocular problems in premature infants weighing less than 1500 g at birth.

PURPOSE: To estimate the incidence of retinopathy of prematurity and other ocular problems in a population of preterm infants. METHODS: This retrospective study included all infants with gestational age (GA) <32 weeks and birth weight (BW) <1500 g cared for in the neonatal intensive care unit (NICU) over a period of nine years (1992-2000). Ophthalmological examination was started the 4th week of life and included refractive examination, examination of the cornea and funduscopy under mydriasis. An ocular motility test was done after the 2nd month. RESULTS: The study included 194 infants. Stage I and II retinopathy occurred in 51 infants but regressed spontaneously. Five of the 194 (2.5%) had to undergo cryopexy. Optic disc atrophy was observed in association with peri-intraventricular hemorrhage (PIIVH) (grade IV) in seven infants. Fifteen infants (7.7%) had retinal hemorrhages which were absorbed by three months of age. Almost 20% of the study infants developed high refractive errors and 13.4% strabismus. CONCLUSIONS: Not only retinopathy of prematurity, but other serious ocular problems were observed in this population of preterm infants. The role of PIIVH III-IV in the pathogenesis of certain ocular problems needs further elucidation.

Genetic linkage of autosomal dominant primary open angle glaucoma to chromosome 3q in a Greek pedigree.

A locus for juvenile onset open angle glaucoma (OAG) has been assigned to chromosome 1q in families with autosomal dominant inheritance (GLC1A), due to mutations in the TIGR/MYOC gene. For adult onset OAG, called primary open angle glaucoma or POAG, five loci have so far been mapped to different chromosomes (GLC1B-GLC1F). Except for the GLC1B locus, the other POAG loci have so far been reported only in single large pedigrees. We studied a large family identified in Epirus, Greece, segregating POAG in an autosomal dominant fashion. Clinical findings included increased cup to disc ratio (mean 0.7), characteristic glaucomatous changes in the visual field, and intraocular pressure before treatment more than 21 mmHg (mean 31 mmHg), with age at diagnosis 33 years and older. Linkage analysis was performed between the disease phenotype and microsatellite DNA polymorphisms. Linkage was established with a group of DNA markers located on chromosome 3q, where the GLC1C locus has previously been described in one large Oregon pedigree. A maximal multipoint lod score of 3.88 was obtained at marker D3S1763 (penetrance 80%). This represents the second POAG family linked to the GLC1C locus on chromosome 3q, and haplotype analysis in the two families suggests an independent origin of the genetic defect.

Metabolic abnormalities in patients with primary open-angle glaucoma.

PURPOSE: Although there are few data on the underlying mechanisms of primary open-angle glaucoma (POAG), it has been suggested that metabolic diseases may play a role in the evolution of the disease. We carried out the present study to investigate the involvement of metabolic disturbances in POAG pathogenesis. MATERIAL/METHODS: Serum metabolic parameters were evaluated in 49 POAG patients without a known history of diabetes mellitus and 72 age and sex matched individuals without glaucoma (control group). RESULTS: Among the metabolic parameters examined, only fasting serum glucose and uric acid levels were found significantly higher in patients with glaucoma compared to the control population (117+/-17 mg/dl vs 105+/-11 mg/dl, p=0.05 and 6.2+/-1.9 mg/dl vs 5+/-1.2 mg/dl, p=0.006, respectively). Additionally, a considerably greater proportion of patients had disturbances of the carbohydrate metabolism and hyperuricemia. CONCLUSION: We conclude that disturbances of carbohydrate and uric acid metabolism could play a role in glaucoma damage and pathogenesis.

Partial trisomy 17q22-qter and partial monosomy Xq27-qter in a girl with a de novo unbalanced translocation due to a postzygotic error: case report and review of the literature on partial trisomy 17qter.

Partial trisomy 17q22-qter is a rare but well-recognized clinical entity. We present a case of partial trisomy for the long arm of chromosome 17, which was detected in a female infant with severe psychomotor and somatic retardation, Stargardt disease, short limbs, and numerous minor anomalies. Differential chromosomal staining demonstrated an excess of genetic material on the long arm of the late replicating X chromosome. FISH and DNA polymorphism analysis showed that the extra material belonged to the distal part of the long arm of chromosome 17 and that there was a partial monosomy of the distal part of the long arm of the derivative X chromosome. The breakpoint regions of this translocation were identified by molecular analysis using polymorphic microsatellite markers on human chromosomes 17 and X. The origin of the abnormal X chromosome was found to be paternal, whereas the origin of the duplicated part of chromosome 17 was maternal. The unbalanced translocation between the paternal X and the maternal chromosome 17 is, therefore, suggested to be due to a postzygotic error.

Exclusion of one pedigree affected by adult onset primary open angle glaucoma from linkage to the juvenile glaucoma locus on chromosome 1q21-q31.

A locus for autosomal dominant juvenile onset primary open angle glaucoma (POAG) was recently assigned to chromosome region 1q21-q31. In the present study, a large Greek family with autosomal dominant adult onset POAG was investigated using microsatellite markers. Exclusion of linkage of the adult onset POAG gene to the region D1S194-D1S191 was obtained in this pedigree. Therefore, the data provide evidence that juvenile and adult onset POAG are genetically distinct disease entities.

Juvenile open-angle glaucoma: a report of a pedigree.

Six patients with juvenile open-angle glaucoma have been studied clinically and genetically in a family pedigree consisting of 17 members. This study revealed that juvenile open-angle glaucoma has an autosomal dominant mode of inheritance and the detected patients showed incipient to severe disturbances of visual function.

[Association of progressive external ophthalmoplegia and lattice corneal dystrophy]. / Association d'une ophtalmoplégie externe progressive et d'une dystrophie grillagée de la cornée.

The authors conducted a study in a family pedigree comprising 33 patients (men 16, women 17). In this pedigree there coexisted patients with progressive external ophthalmoplegia and corneal lattice dystrophy. Two patients with progressive external ophthalmoplegia and ten with lattice corneal dystrophy were found. One of our patients (propositus) suffered from both diseases. Our study proves that, in this pedigree, progressive external ophthalmoplegia and corneal lattice dystrophy have an autosomal dominant mode of inheritance.

[Sterile corneal ulcers in dry eye. Incidence and factors of occurrence]. / Les ulcères cornéens stériles de l'oeil sec. I. Fréquence et facteurs de leur apparition.

Sterile corneal ulceration is a serious complication in patients with keratoconjunctivitis sicca. The records of 134 patients, 19 males and 115 females, who presented with dry eyes in the Ophthalmologic Clinic were reviewed. Over a period of 6 years, 33 eyes of 23 (17%) patients developed a sterile corneal ulcer. The etiologies of dry eyes in these patients were: Primary Sjogren's syndrome: 10 cases, rheumatoid arthritis: 5 cases, ocular pemphigoid 6 cases, atopy: 1 case, local irradiation: 1 case. Patient's age and sex were not significantly associated with ulcer development (p greater than 0.05). The presence of a major underlying disease was the major contributing factor. Appropriate local treatment and patient compliance were also contributing factors. Blepharitis was found in 90% of patients.

[Sterile corneal ulcers in dry eye. II. Treatment, complications and course]. / Les ulcères cornéens stériles de l'oeil sec. II. Traitement, complications et évolution.

Over a period of 6 years, 23 patients (4 males and 19 females: mean age 56 years) who presented dry eyes developed 33 sterile corneal ulcers. Treatment included occlusion of the eyes or bandage soft contact lenses, prophylactic topical administration of antibiotics, punctal occlusions and currently available tear substitutes. Seventeen eyes healed completely without any corneal opacity and 10 eyes healed with opacity. Nine of the 33 eyes developed microbial keratitis. The causes of microbial keratitis were Staphylococcus aureus in 7 cases, beta-hemolytic Streptococcus in one and Pseudomonas aeruginosa in one case. The microbial keratitis was treated with intensive topical antibiotics. In 6 eyes, corneal perforation occurred. Rheumatoid arthritis coexisted in four cases.