Yves Uteza

Ophthalmologic findings in suspected child abuse victims with subdural hematomas

PURPOSE Shaken baby syndrome consists of intracranial and intraocular hemorrhages in young children in the absence of signs of direct head trauma. Because it has major medicolegal implications, it must be distinguished from accidental trauma. This study aimed to determine the ophthalmologic manifestations and their natural course in child abuse victims and whether ophthalmologic examination can help to distinguish shaken babies from children with accidental impact head trauma. DESIGN Prospective comparative observational case series. METHODS A prospective study was conducted from January 1996 to September 2001 on 241 consecutive infants hospitalized for a subdural hematoma to determine the frequency and the type of ocular abnormalities encountered. At admission, 186 children were highly presumed to have been shaken (group 1), 38 children had signs of direct head trauma without any relevant history of trauma (group 2), some of them having been possibly shaken, whereas 7 children had proven severe accidental head trauma (group 3). RESULTS Intraocular hemorrhages were the main finding. Their shape, laterality, and size were not significantly different in groups 1 and 2. However they were significantly more frequent in nonaccidental head trauma than in infants with head impact (77.5% versus 20%). None of the group 3 children had intraocular hemorrhage. Eighty-two percent of intraocular hemorrhages resolved within 4 weeks. CONCLUSIONS Intraocular hemorrhages are frequent in shaken babies but not specific of this syndrome. When associated with a subdural hematoma, they are strongly suggestive of shaken neglect. They are rare in pediatric accidental head trauma.

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.

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.

Congenital toxoplasma chorioretinitis transmitted by preconceptionally immune women

Editor,—During pregnancy primary toxoplasmic infection of the mother is a well known cause of congenital chorioretinitis due to fetal contamination by Toxoplasma gondii . It is generally thought that women infected before conception have no risk of transmitting the disease to the fetus unless they are severely immunocompromised.1 We report two children with severe ocular lesions due to congenital toxoplasmosis transmitted by preconceptionally immune mothers. ### CASE 1 A 1 year old girl presented with a convergent squint as a consequence of bilateral large macular scars. She was the first child of a healthy immunocompetent mother. Three months before conception, the systematic French prenuptial serological screening of the mother showed a recent toxoplasmic infection diagnosed by a high titre of specific immunoglobulin M (IgM) (IgM 5200, Biotrol Merck (normal <200), IgG= 40 IU/ml) (Table 1). She was treated with spiramycin 3 MIU per day for a month. At the time of referral, the mother’s titre of IgM had significantly decreased (IgM 200) and showed a slightly higher rate of IgG (140 IU/ml). Her daughter’s serological status showed a high titre of specific IgG (624 IU/ml), the presence …

Identification of novel PAX6 mutations in two families with bilateral aniridia

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. Hum Mutat 12:138, 1998.

Traumatismes oculaires et accouchement

Introduction Les traumatismes oculaires graves, lies a l’accouchement, sont rares et souvent dus a des manœuvres instrumentales. L’objectif de cette etude est d’exposer les differentes lesions oculaires graves pouvant survenir lors d’un accouchement et leurs eventuelles consequences. Patients et methodes Depuis 1984, nous avons examine dans le service onze cas de tels traumatismes. Pour chaque cas, les circonstances de l’accouchement, le cote atteint, les differentes lesions observees, oculaires, orbitaires, crâniennes, voire cerebrales, et les resultats des examens de suivi ophtalmologique ont ete notes. Resultats Dans la plupart des cas, les lesions etaient consecutives a des traumatismes par forceps. Elles etaient corneennes (vergetures verticales de la membrane de Descemet), retiniennes (hemorragies) voire orbitaires (nerf optique et nerf oculomoteur). Conclusion Ces atteintes, parfois graves, necessitent un examen precoce et exhaustif, eventuellement sous anesthesie generale, et une surveillance prolongee. Enfin, un examen neurologique (clinique et radiologique), pour depister des complications cerebrales, nous semble recommande.

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

A heterozygous deletion of exon 9 in the COL1A2 ‐ mRNA of a patient with symptoms of both the Ehlers ‐ Danlos ‐ Syndrome and the Osteogenesis Imperfecta is described. In the genomic DNA of the patient, exon 9 is homozygously present. We identified a novel heterozygous point mutation in the splice donor site of intron 9, leading to a G→A substitution in position +5. This mutation leads to heterozygous skipping of exon 9 in the COL1A2 ‐ mRNA of this patient. The deletion results in a shortened (by 18 amino acids) but in frame l2(1) chain, which probably leads to the formation of abberantly processed triple helices. Hum Mutat 12:138, 1998.

Diagnostic et traitement des glaucomes: Aide de l’informatique

Bien que peu familiers aux praticiens, des outils intellectuels dont l’algebre de Boole, l’analyse combinatoire et leurs techniques informatiques d’application proposent de nouvelles solutions aux problemes classiques du diagnostic. Quelle que soit la complexite de l’observation, la reponse provient toujours d’un ensemble de connaissances fini et le probleme devient des lors celui de l’exploitation d’un ensemble de donnees. Il n’y a pas d’invention dans l’etablissement du diagnostic. Les raisonnements traditionnels sont variables, personnels et fragiles, mais redondants et ils peuvent donner lieu a quatre sortes d’erreur par omission ou confusion, aux temps semeiologiques et dialectiques. Alors que les capacites physiologiques de l’esprit et de la memoire limitent les evocations a quelques parties du probleme des glaucomes, les solutions informatiques en apprehendent la totalite, soit 3 000 tableaux. A chaque interrogation, le programme examine chacun des 3 000 cas, ce qui elimine les quatre sortes d’erreur. Le caractere probabiliste des donnees qui obere la fiabilite des conclusions issues de raisonnements complexes est traite par les probabilites ajustee. Ces aides au diagnostic, dont le thesaurus est constamment actualise, ne peuvent etre utilisees que par un ophtalmologiste, seul capable de juger la pertinence des propositions. En retour, elles lui assurent que le patient beneficie de toutes les connaissances, y compris des plus recentes avancees de la science.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.