[Computer-assisted diagnosis and therapy for glaucoma]. / Diagnostic et traitement des glaucomes.

Boolean algebra, or combinatory analysis and their related computer routines, can provide invaluable help in resolving classic diagnostic problems. However complex each case may be, the diagnosis is always made from a finite set of data, and the fundamental problem is thus how to exploit this data. Invention no longer has a place in ascertaining a diagnosis. Traditional ways of reasoning are numerous, personal, and fragile, but fortunately redundant. They may give rise to four types of error: omission or mistake (an error of judgment), either during the semiotic or the dialectic stages. Whereas the physiological capacity of the human brain and memory only enables it to make a limited number of hypotheses concerning certain aspects of glaucoma, computer programs can take the total number of hypotheses into account, i.e., 3000. For every input the program explores each of the 3,000 items, thus eliminating the four types of error. The probabilistic nature of data, which compromises the confidence one can have in conclusions resulting from such complex reasoning, is treated by the adjusted probabilities. The use of such diagnostic aids, whose thesaurus is updated regularly, is reserved for ophthalmologists, the only authority capable of assessing the pertinence of the computer responses. Consequently, the specialist can rest assured that the patient has benefited from the most comprehensive and updated knowledge in medical science.

Ocular cell transfection with the human basic fibroblast growth factor gene delays photoreceptor cell degeneration in RCS rats.

Based on the K8/JTS-1-mediated transfection technique, we developed an in vivo protocol for an efficient transfer of plasmid DNA to ocular cells. As determined with condensed plasmids containing reporter genes for either beta-galactosidase (pcDNA-lacZ) or enhanced green fluorescent protein (pREP-EGFP), the immortalized human retinal epithelial cells RPE D407 and human embryonic kidney 293 cells can be transfected with typical efficiencies of 11 and 19%, respectively. Unlike 293 cells, RPE D407 cells had a reduced viability on transfection with both plasmids. In vivo, subretinal injections of DNA-K8/JTS-1 complexes revealed reporter gene expression in choroidal and RPE cells of normal pink-eyed Royal College of Surgeons (RCS) rats. The validity of this transfection technique in terms of retinal cell survival in RCS rats was then examined by using pREP-hFGF2 plasmid, which encodes the human basic fibroblast growth factor isoforms (hFGF2). Subretinal injection of pREP-hFGF2-K8/JTS-1 complexes into 3-week-old dystrophic RCS rat eyes reveals a delayed photoreceptor cell degeneration 60 days postinjection. In this case, the average analyzed field points with delayed cell dystrophy represent 14 to 17% of the retinal surface as compared with 2.6 and 4% in pREP5beta and vehicle-injected eyes, respectively. Peptide-mediated in oculo transfection thus appears to be a promising technique for the treatment of retinal cell and photoreceptor degenerations.

Identification of novel VMD2 gene mutations in patients with best vitelliform macular dystrophy.

ABSTRACT We report five novel VMD2 mutations in Best's macular dystrophy patients (S16F, I73N, R92H, V235L, and N296S). An SSCP analysis of the VMD2 11 exons revealed electrophoretic mobility shifts exclusively in exons 2, 3, 4, 6 and 8. Direct sequencing indicated that these shifts are caused by mono-allelic transition in exons 2, 4, 6, 8 and transversion in exons 3 and 6. Five novel "silent" polymorphisms are also reported: 213T>C, 323C>A, 1514A>G, 1661C>T, and 1712T>C. Hum Mutat 17:235, 2001.

Absent lacrimal ducts, distichiasis, dysmorphic features, and brachydactyly: a case report.

We report a male patient presenting with the association of absent lacrimal ducts, distichiasis, dysmorphic facial features and limb abnormalities. Extensive chromosomal studies showed normal chromosomes. We discuss differential diagnoses such as Setleis, Char and Lacrimo-Auriculo-Dento-Digital (LADD) syndromes. This may represent a novel entity for which parental consanguinity would support an autosomal recessive mode of inheritance.

[Ocular injuries and childbirth]. / Traumatismes oculaires et accouchement.

INTRODUCTION: Severe ocular traumatisms related to childbirth are rare and often subordinate to maneuvers with instruments. The aim of this study was to report on the different severe ocular injuries that might occur during childbirth and their possible consequences. There can be several of these ocular injuries. PATIENTS AND METHODS: Since 1984, we have examined 11 cases of this type of traumatism. For each case, the childbirth circumstances, the affected side, the different injuries observed such as ocular, orbital, cranial and even cerebral lesions, and the results of the ophthalmological follow-up examinations were recorded. RESULTS: In most cases, lesions resulted from forceps traumatisms, and the injuries were corneal (vertical tears in the Descemet's membrane), retinal (hemorrhages), and orbital (e.g., the optical nerve and oculomotor nerve). CONCLUSION: These injuries, sometimes severe, must benefit from early and complete examination, possibly with general anesthesia, and long-term follow-up. Furthermore, a radiographic and clinical neurological examination is recommended to prevent any cerebral complication.

[Retraction nystagmus of vascular origin]. / Nystagmus retractorius d'origine vasculaire.

We report a case of a 42-year-old woman who was referred for diplopia. She appeared to have a convergence retraction syndrome and loss of vertical gaze. The clinical course led to a diagnosis of thromboembolic cerebrovascular event in the region of the posterior commissure on the basis of risk factors such as smoking and oral contraceptive use. The final outcome was rapidly favorable.

[Congenital megalocornea]. / La mégalocornée congénitale.

Congenital megalocornea is a bilateral enlargement of the cornea's diameter that can be associated with trabecula and/or iris dysgenesis. This condition predisposes the patient to glaucoma. The physiopathology is poorly understood and may be related to lens induction during embryological development of the anterior of the eye. X-linked genetic transmission is found in 50% of cases, autosomal transmission in 40%, and sporadic transmission in the remaining 10%. Diagnosis is based on a thorough examination of the child's eye, often with general anesthesia. Different clinical aspects can be observed: simple megalocornea without ocular or systemic anomalies, megalocornea with ocular and/or systemic anomalies as well as multiple malformation syndromes, dermatological diseases, skeletal diseases, and genetic or chromosomic diseases. A systematic general pediatric examination is therefore necessary. Congenital megalocornea must be considered, first of all, as a differential diagnosis of primary congenital glaucoma and all of its etiologies. Treatment of associated ocular diseases, the search for an association with systemic diseases, and follow-up for the rest of the patient's life are indispensable.

[Characteristics of retinal detachment in children]. / Particularités du décollement de rétine chez l'enfant.

INTRODUCTION: Pediatric retinal detachments differ from adult retinal detachments in their etiologies, prognosis and treatment. The aims of this study were the analysis and long-term follow-up of a group of pediatric retinal detachment patients. PATIENTS AND METHODS: All the cases of juvenile retinal detachments treated in our department between 1987 and 1999 were retrospectively studied. The age at the time of diagnosis, etiology, initial topography of the detachment, treatments undertaken, follow-up, and final results were recorded. RESULTS: The study investigated 64 eyes of 53 children. The follow-up was longer than 6 months for 31 eyes, with a mean follow-up of 39.5 months. The main etiologies were traumatism, high myopia, and affections leading to an exudative retinal detachment such as retinoblastoma and Coats disease. Circular scleral buckling was often used because of the vitreous cohesiveness in children. A vitrectomy was frequently associated to treat severe proliferative vitreoretinopathy. The final visual acuity was higher than 0.05 in 32% of the cases. DISCUSSION: The etiological features, late diagnosis and frequency of proliferative vitreoretinopathy are responsible for the greater severity of retinal detachments in children. These factors associated with amblyopia lead to poor visual prognosis. CONCLUSION: Retinal detachment in children remains a severe pathology. However the prognosis seems to be improving with progress in examination techniques and surgery methods.

Renal coloboma syndrome.

OBJECTIVE: To characterize the ocular features of renal coloboma syndrome. DESIGN: Prospective, observational case series. PARTICIPANTS: Twelve patients referred by the pediatric nephrology clinic and the ophthalmic records of five additional patients. METHODS: For each patient, age at the time of examination, gender, renal function, and presence of a mutation in the PAX2 gene were noted. All patients underwent measurement of visual acuity and anterior and posterior segment examination with fundus photography. Goldmann visual fields were tested in four cases. MAIN OUTCOME MEASURES: Visual acuity, optic disc abnormalities, and mutation in the PAX2 gene. RESULTS: Mean age was 21.5 years. Renal failure was mild in 6 patients and severe in 11 patients. A mutation in the PAX2 gene was identified in nine patients, without correlation to the ocular phenotype. Ocular features could be divided into five groups: optic disc dysplasia limited to an unusual pattern of retinal vessels without functional consequence; optic disc pit with normal visual acuity and blind spot enlargement; large optic disc coloboma; large coloboma of the optic disc and adjacent retina; morning glory anomaly (these last three conditions were accompanied by poor visual acuity). Fundus abnormalities were symmetrical in most cases and unrelated to renal status. CONCLUSIONS: Ophthalmic and renal characteristics of the renal coloboma syndrome are highly variable. The need for dialysis or renal transplantation can occur early in life or several years later. A wide range of ocular abnormalities located in the posterior segment can be observed. Mild optic disc dysplasia or pit have no functional consequence and can be underdiagnosed. More severe colobomas or related abnormalities, such as morning glory anomaly, often lead to poor visual acuity. Molecular biology allows detection of the mutations in the PAX2 gene, but can be negative in approximately 50% of cases. The observation of an optic disc coloboma or related abnormality stimulates the ophthalmologist to propose simple nephrologic investigations to check for renal hypoplasia, a potentially life-threatening disease. Conversely, renal hypoplasia stimulates the nephrologist to ask for a fundus examination to confirm the diagnosis and check for complications such as retinal detachment.

Intravitreous transplantation of encapsulated fibroblasts secreting the human fibroblast growth factor 2 delays photoreceptor cell degeneration in Royal College of Surgeons rats.

We developed an experimental approach with genetically engineered and encapsulated mouse NIH 3T3 fibroblasts to delay the progressive degeneration of photoreceptor cells in dark-eyed Royal College of Surgeons rats. These xenogeneic fibroblasts can survive in 1. 5-mm-long microcapsules made of the biocompatible polymer AN69 for at least 90 days under in vitro and in vivo conditions because of their stable transfection with the gene for the 18-kDa form of the human basic fibroblast growth factor (hFGF-2). Furthermore, when transferred surgically into the vitreous cavity of 21-day-old Royal College of Surgeons rats, the microencapsulated hFGF-2-secreting fibroblasts provoked a local delay of photoreceptor cell degeneration, as seen at 45 days and 90 days after transplantation. This effect was limited to 2.08 mm2 (45 days) and 0.95 mm2 (90 days) of the retinal surface. In both untreated eyes and control globes with encapsulated hFGF-2-deficient fibroblasts, the rescued area (of at most 0.08 mm2) was significantly smaller at both time points. Although, in a few ocular globes, surgical trauma induced a reorganization of the retinal cytoarchitecture, neither microcapsule rejection nor hFGF-2-mediated tumor formation were detected in any treated eyes. These findings indicate that encapsulated fibroblasts secreting hFGF-2 or perhaps other agents can be applied as potential therapeutic tools to treat retinal dystrophies.

Identification of novel PAX6 mutations in two families with bilateral aniridia. Mutations in brief no. 167. Online.

We report two novel PAX6 mutations in aniridia patients of two Swiss pedigrees (We, Sc) which give rise to different phenotypes. An SSCP analysis of the PAX6 14 exons reveals electrophoretic mobility shifts exclusively in exons 5 and 12 of aniridia patients. As determined by bidirectional sequencing and restriction digest analysis, these shifts are caused by mono-allelic base transitions in exon 5 (c.547C-->T; R44X; We) and intron 12 (IVS12+5G-->A; Sc). Each mutation co-segregates with the trait in the affected family with complete penetrance. The Sc mutation in the splicing donor site of intron 12 may result in either intron inclusion or exon skipping, both giving rise to a truncated PAX6 protein which may retain a residual transactivating activity. In contrast, the We genetic alteration is a loss-of-function mutation leading to a more severe phenotype than that observed in the Sc pedigree.