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.

Paraneoplastic optic neuropathy in a patient with a non-small cell lung carcinoma: a case report.

PURPOSE: To report a case and describe the clinical approach to a patient with a non-small cell lung carcinoma and paraneoplastic optic neuropathy. METHODS: Case report. RESULTS: A 79-year-old woman with known non-small cell lung carcinoma was admitted with a swollen optic disc in the right eye. After detailed clinical, laboratory, and imaging studies, the authors diagnosed paraneoplastic optic neuropathy, excluding other possible diagnosis. CONCLUSIONS: Paraneoplastic optic neuropathy is a clinical challenge and should be considered as a possible diagnosis in every cancer patient with optic disc edema.

Immunohistochemical study of extracellular matrix components in epiretinal membranes of vitreoproliferative retinopathy and proliferative diabetic retinopathy.

PURPOSE: The migration, proliferation, differentiation, and adhesion of cells and other cellular functions are influenced by the surrounding extracellular matrix in normal and wound healing conditions. The formation of epiretinal membranes, a wound healing process, is a serious complication of retinal diseases, the most important being proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). In the present study, the authors investigated the expression of various extracellular matrix components and in particular tenascin, fibronectin, laminin, collagen IV, and MMP-3 glycoprotein as well as the expression of glial fibrillary acidic protein in each type of epithelial membrane in order to elucidate the role of these molecules in the formation of these two types of membranes. METHODS: The authors performed immunohistochemistry in 14 PVR and 14 PDR membranes, using antibodies against the above mentioned extracellular matrix components. Tenascin and fibronectin were observed as major components in the extracellular matrix, while laminin and collagen type IV were detected as minor components in both types of membranes. A higher fibronectin expression in PVR compared with PDR membranes was found (p=0.0035). A positive relationship of its expression with the proliferative activity (p=0.15) and collagen type IV expression (p<0.0001) was also observed. RESULTS: Tenascin expression was positively correlated with glial fibrillary acidic protein positive cells in PDR membranes (p=0.04). Collagen type IV localized around vessels was observed with high levels in PDR membranes (p=0.0031). CONCLUSIONS: The results indicated that the extracellular matrix components seem to be involved in PVR and PDR, contributing to tissue remodeling and perhaps by different pathogenetic pathways, which could reflect different stages of development in these two types of membranes.

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.

Repeated melting of corneal grafts in a patient with rheumatoid arthritis and Sjögren's syndrome.

We present a case of corneal melting in a patient with severe rheumatoid arthritis and Sjögren's syndrome. The melting appeared in the area of a bacterial corneal ulcer that healed after treatment with antibiotics. No signs of scleritis were present. Repeated melting of two corneal grafts was seen after surgery.

Silicone intubation as an alternative to dacryocystorhinostomy for nasolacrimal drainage obstruction in adults.

Silicone tubing was used to repair the patency of the nasolacrimal drainage system in 115 patients (four bilaterally) with chronic nasolacrimal duct obstruction. The patients were over 20 years old and 16 were men and 99 women; 46% presented an uncomplicated obstruction with epiphora and 54% presented additional signs of chronic dacryocystitis. We used the technique of Quickert and Dryden with modifications. The silicone tube remained for a mean of 5.5 months (+/- 2.5 SD). After removal of the tube the follow-up ranged from 6 to 42 months (mean +/- SD: 16 +/- 9). Patency was maintained in 89% of cases with uncomplicated obstruction and in 69% of those with chronic dacryocystitis (total success rate 78%). We can therefore recommend silicone intubation of the lacrimal drainage system as an alternative to dacryocystorhinostomy (DCR), in adults with obstruction of the nasolacrimal duct. In addition, unlike DCR this technique is bloodless and the operation takes less time.

Vitrectomy results for diffuse diabetic macular edema with and without inner limiting membrane removal.

PURPOSE: To determine whether vitrectomy for diffuse diabetic macular edema with and without internal limiting membrane (ILM) peeling is equally effective in reducing edema. METHODS: The authors retrospectively analyzed the surgical outcomes in 73 eyes of 52 patients with diffuse diabetic macular edema. Eighteen eyes (Group A) underwent three-port pars plana vitrectomy with posterior hyaloid membrane (PHM) removal, while 55 eyes (Group B) had pars plana vitrectomy with additional ILM peeling after PHM removal. RESULTS: Intraoperatively, the posterior hyaloid was found to be attached to the macula in all eyes. In Group A, macular edema resolved completely in 8 eyes (44.4%) with improvement of visual acuity (VA). In Group B, VA improved in 38 eyes (69.1%) with complete resolution of edema. The results of this study indicated that vitrectomy effectively reduced macular edema but eyes with ILM peeling (Group B) presented better results than those without ILM peeling. Another important factor related to the outcome seems to be the level of glycosylated hemoglobin (HbA1c). CONCLUSIONS: In eyes with diffuse diabetic macular edema vitrectomy seems to be effective, but additional ILM peeling presented better results.

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.

[Treatment of toxoplasmosis. The treatment of toxoplasmic chorioretinitis]. / Traitement de la toxoplasmose. Le traitement de la chorio-rétinite toxoplasmique.

Toxoplasmosis is the commonest cause of inflammatory disease of the posterior segment of the eye. We treated 23 patients with acute toxoplasma chorioretinitis with sulfonamides, pyrimethamine and corticosteroids for a period of 4 weeks. All patients with acute disease had characteristic foci and a positive titer on the Sabin-Feldman dye test. In all patients, we observed clinical improvement within 2 weeks, but one patient with a lesion larger than 2 disc diameters improved after the third week. During the follow-up period ranging from 6 months to 6 years (mean 2.5 years), there have been four recurrences (17%). No serious side effects of treatment were observed in our patients.

[A case of secondary ghost cell glaucoma with pseudohypopyon after cataract extraction]. / Un cas de glaucome secondaire par "cellules fantômes" (ghost cell) avec pseudohypopyon, après extraction de cataracte.

A 75 year woman with chronic vitreous hemorrhage underwent extraction of a senile cataract. Surgery was complicated by the flow of brown fluid from the vitreous to the anterior chamber, which was not entirely removed. Post-operatively there was pain, 2 mm of brown hypopyon and intraocular pressure elevation to 60 mm Hg with the preoperative diagnosis of endophthalmitis, a pars plana vitreous tap and instillation of intravitreal antibiotics was performed. Bacterial cultures were negative and the presence of erythrocyte "ghost cells" established the diagnosis of hemolytic glaucoma. As medical management proved ineffective, a pars plana vitrectomy was performed. One year post-operatively the patient had a visual acuity of 0.4-0.5, normal intraocular pressure without medication and evidence of an old branch retinal vein occlusion. The mechanism of hemolytic "ghost-cell" glaucoma in this case is discussed.

[An example of dominant heredity in the transmission of primary open-angle glaucoma in a northwestern region of Greece]. / Un exemple d'hérédité dominante our la transmission du glaucome primitif à angle ouvert dans une région du nord-ouest de la Grèce.

The authors have accomplished an epidemiological clinical and genetic study on primary open-angle glaucoma among 411 persons in the North Western district of Greece (Epirus), belonging to 4 genealogical trees. 112 of the 411 persons were offsprings aged 30 years or more, alive or dead, and they had direct blood-relation to the propositus. 35 of these offsprings were suffering from primary open-angle glaucoma. The classification and the number of the affected subjects suggested that one major gene, expressed by the autosomal dominant character, is the main factor for the heredity of primary open-angle glaucoma in Epirus-Greece.

[Antigen HLA-B5 in Adamantiadès-Behçet syndrome (author's transl)]. / Le HLA-B5 antigène dans le syndrome d'Adamantiadès-Behçet, sa valeur diagnostique à propos de 4 cas atypiques).

Among 16 cases clinicaly diagnosed as Adamantiadès-Behçet syndrome coming from various areas of Northern Greece, antigen HLA-B5 was found on 12, i.e. 75% instead of 18,5% in the normal population of the same areas (200 subjects were examined by Dr. Z. Polymenidis in this thesis). On 3 other cases the antigen found was HLA-BW35 (belonging to group C4), while on the last one the antigen was HLA-B27. 4 cases, suspicious for atypical Adamantiadès-Behçet syndrome, are reported in which the discovery of antigen HLA-B5 inhanced the clinical diagnosis of the syndrome and made possible the early application of suitable treatment (steroids, immunosupressors).

[Familial coexistence of the association: Fabry's syndrome and congenital ptosis]. / Coexistence familiale de l'association: syndrome de Fabry et ptosis congénital.

The authors undertook a clinical and genetic study in a large family with the aim of identifying the mode of inheritance of Fabry syndrome and congenital ptosis. These two types of pathology were present to varying extents. The family pedigree consisted of 95 individuals, spanning 5 generations. Three individuals (males) were found to have Fabry syndrome and 14 (males and females) congenital ptosis. The patients with Fabry syndrome also had congenital ptosis. According to these results, Fabry syndrome is inherited by an X-linked recessive mode and congenital ptosis by an autosomal dominant mode.

[Hereditary juvenile dystrophy of the macula in a large family from Epirus]. / Dystrophie héréditaire juvénile de la macula chez une famille nombreuse d'Epire.

The authors present a clinical, epidemiologic and genetic study of juvenile macular dystrophy (Stargardt's disease) in a large kindred from Epirus in Greece. The family tree consists of 372 individuals spanning six generations over more than a century. 257 are direct descendants of the founding couple. Nineteen individuals were found to suffer from Stargardt's disease, thirteen of whom are still alive today. Segregation analysis of the data showed that in this pedigree, the disease is transmitted with the autosomal dominant mode of inheritance.

[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.