[Accuracy of videokeratographic quantitative criteria for detection of keratoconus suspects in families with keratoconus]. / Efficience des critères vidéokératographiques quantitatifs dans l'analyse familiale de patients atteints de kératocône.

AIM: We statistically assessed the videokeratographic data obtained from families with keratoconus in order to determine reliable criteria for detecting keratoconus suspects. MATERIAL AND METHODS: Fourteen keratoconus patients from 12 families were enlisted. We investigated 55 relatives (110 eyes). Standard videokeratographic data were obtained by screening 30 individuals (60 eyes) with clinically normal eyes, with no history of ocular disorders, contact lens wear, or keratoconus individuals in their family. Videokeratographic qualitative and quantitative analyses were performed on every subject. The videokeratographic threshold values obtained from the control group were used as a reference. RESULTS: Two criteria based on the Klyce/Maeda indices proved their statistical significance in detecting keratoconus suspects. When considering the significant criteria ascertained by the statistical analysis, building pedigrees favored the autosomal dominant mode of inheritance. Two of the pedigrees corresponded to either a recessive mode of transmission or the potential occurrence of a de novo mutation. CONCLUSION: We have determined videokeratographic criteria of statistical significance for detecting keratoconus suspects. The knowledge of the status of each member of families with keratoconus is a prerequisite to performing genetic linkage analyses, which may allow a precise locus linked with this disorder to be refined.

[BIG-H3 protein: mutation of codon 124 and corneal amyloidosis]. / Protéine BIGH3: mutation du codon 124 et amylose cornéenne.

In 1997, a group of hereditary corneal dystrophies was related to mutations in the TGFBI (BIGH3) gene. Within this group, some corneal dystrophies present particular biochemical features in that they are characterized by corneal amyloid deposition. Contrary to clinical and genetic knowledge, the biochemical characteristics of the encoded protein (Big-h3) and the mechanisms of its amyloid conversion remain unclear. We review the current knowledge on the Big-h3 protein and focus on the behavior of the codon 124 region. We discuss this protein's mechanisms of amyloid conversion from our results and previous reports as well as from other types of amyloidosis. These data provide a better understanding of the putative processes leading to the phenotypic variations linked with their respective codon 124 mutation.

[Amiodarone and disk edema: physiopathological debate based on a case report]. / Amiodarone et oedème papillaire: problèmes physiopathogéniques à travers un cas.

We describe the case of a patient showing bilateral disk edema linked to amiodarone intake and discuss the controversial physiopathology of this condition. The clinical investigation as well as the follow-up of this case established the diagnosis of amiodarone-induced papillary disease. Pseudotumor cerebri and alteration of optic disk vascularization were also involved in the optic neuropathy displayed by this patient. This case illustrates the multifactorial character of this entity whose heterogeneous clinical expression is linked both to the direct toxic effect of amiodarone and the likely occurrence of pseudotumor cerebri, as well as to the disorders for which this type of medication is frequently used. Amiodarone is widely used and its implication as a cause of disk swelling should be systematically investigated.

[Spontaneous hyphema caused by Ginkgo biloba extract]. / Hyphéma spontané provoqué par l'extrait de Ginkgo biloba.

We report the first case of a patient in whom Ginkgo biloba extract proved to be the unique cause of spontaneous hyphema. Extensive ophthalmological and biological investigations were undertaken in order to assess the role of Ginkgo biloba: platelet numbering, hemostasis factors, Willebrand antigen, ristocetin cofactor, platelet glycoprotein immunophenotyping, glycoprotein expression after activation by thrombin, inflammatory markers, B-scan ultrasonography, and fluorescent iridography. No putative causes of hyphema were recorded other than Gingko biloba intake. The bleeding originated from the 12-o'clock position of the iris margin. Anamnesis identified Ginkgo biloba extract ingestion from 2 weeks before the appearance of the patient's visual trouble. Ginkgo biloba intake was stopped and the hemorrhage resolved with no recurrence during the 18 months of follow-up. Ginkgo biloba is known for platelet inhibition and is extensively used in the elderly because of its beneficial effects as a vascular protector. The clinical progression of the present case strongly suggests that Ginkgo biloba may cause hemorrhage and hyphema, even in the absence of any other predisposing factor.

[Clinically isolated Morning glory syndrome]. / Forme clinique de l'anomalie papillaire en fleur de liseron ou Morning glory syndrome.

The Morning glory syndrome is an uncommon congenital optic disk anomaly. It is characterized by a funnel-shaped and enlarged dysplasic optic disk with white tissue, and retinal vessels arising from the periphery of the disk and running an abnormally straight course over the peripapillary retina. We report here the case of a 7-year-old girl with a delayed diagnosis of Morning glory syndrome discovered at a regular examination that showed amblyopia. The optic disk anomaly was isolated. The search for other associated morphological and/or functional abnormalities is mandatory (retinal and/or cerebral malformation, frontonasal dysplasia, endocrine irregularities, neurofibromatosis type 2). Periodic ophthalmological examinations are recommended due to the frequency of retinal detachment.

Keratectasia induced by laser in situ keratomileusis in keratoconus.

PURPOSE: Corneal thinning disorders weaken the mechanical strength of affected corneas, suggesting that photorefractive procedures may be contraindicated in keratoconus. Few cases have been reported to confirm this hypothesis. METHODS: A 45-year-old man had two laser in situ keratomileusis (LASIK) procedures and one photorefractive keratectomy (PRK) performed on his left eye, and three LASIK procedures on his right eye. After these surgeries, a dramatic corneal ectasia and grade III haze occurred in both eyes, with a clinical diagnosis of keratoconus. The changes in his corneas were followed with videokeratography and slit-lamp microscopy. RESULTS: Preoperative videokeratograph of both eyes suggested keratoconus. After multiple refractive procedures, the best spectacle-corrected visual acuity was as low as 20/1200 bilaterally. Both eyes displayed dramatic corneal protrusion with corneal scarring. CONCLUSIONS: This case emphasizes the need for preoperative corneal thickness measurement and detailed analysis of videokeratographs. Thinning corneal disorders such as keratoconus, keratoconus suspects, or pellucid marginal degeneration are a contraindication for excimer laser ablative refractive procedures.

In vitro creation of amyloid fibrils from native and Arg124Cys mutated betaIGH3((110-131)) peptides, and its relevance for lattice corneal amyloid dystrophy type I.

BetaIGH3 protein has been recently involved in the pathogenesis of blinding corneal diseases, some of which have characteristic amyloid corneal deposits. The 124 codon of the betaig-h3 gene seems to be crucial for the amyloidogenicity of the protein product. We presently report an in vitro system that reproducibly forms amyloid fibrils from betaIGH3((110-131)) derived peptides. We also assessed the differences in fibril formation of two 22-amino acid peptides centered on the 124 residue: the native form and the Arg124Cys peptide (mutation linked to lattice corneal amyloid dystrophy type 1). After dialysis of Arg124Cys peptide against PBS 1/15 M pH 7.4 for 72 hours, Congo red staining and electron microscopy demonstrated the presence of abundant material fulfilling the criteria of amyloid. Quantitative analysis with thioflavine T fluorescence studies confirmed the high capacity of Arg124Cys peptide to form amyloid fibrils when compared to the native form.

BIGH3 exon 14 mutations lead to intermediate type I/IIIA of lattice corneal dystrophies.

PURPOSE: To screen the BIGH3 gene in three unrelated families with lattice corneal dystrophy (LCD), two of which disclosed a particular phenotype. METHODS: Genomic DNA was extracted from peripheral leukocytes of the affected patients and their family members. The entire coding sequence of the BIGH3 gene was screened for mutations by means of transcript analysis on total RNA isolated from peripheral leukocytes by reverse transcription-polymerase chain reaction performed with primers designed for this study. Each mutation was confirmed at the genomic level, by using published primers. RESULTS: One family that had a typical form of LCD, had the described R124C mutation in the BIGH3 gene. Two families with atypical forms of LCD were negative for the previously known mutations of the gene. Direct sequencing of the BIGH3 mRNA in the latter two families allowed us to identify two mutations located in exon 14. They consist of a 9-bp insertion at position 18851886 and one missense mutation at position 1877 of the BIGH3 gene. Three new polymorphisms were also observed. CONCLUSIONS: Two mutations different from those linked to LCD have been found in clinically distinguishable forms of this disease, intermediate between LCDs types I and IIIA. The DNA segment comprising both alterations normally encodes for a highly conserved region of the fourth internal domain of the Betaig-h3 protein, suggesting that this region may be of functional and/or structural importance. The identification of new mutations by screening of the complete BIGH3 gene and the comparative analysis of the induced modifications in betaig-h3 protein should shed light in the understanding of the molecular mechanisms underlying LCDs resulting from mutations in the BIGH3 gene, and may help to explain their phenotypic heterogeneity.

[Molecular genetics of pigmentary retinopathies: identification of mutations in CHM, RDS, RHO, RPE65, USH2A and XLRS1 genes]. / Génétique moléculaire des rétinopathies pigmentaires: identification de mutations des gènes CHM, RDS, RHO, RPE65, USH2A et XLRS1.

PURPOSE: To evaluate the occurrence and inheritance of various types of pigmentary retinopathy in patients followed at the outpatient clinic in the university hospital, Montpellier, France. To characterize genes and mutations causing these conditions. METHODS: Ophthalmic examination and various visual tests were performed. Mutations were sought from genomic DNA by PCR amplification of exons associated with single-strand conformation analysis and/or direct sequencing. RESULTS: Among 315 patients over an 8-year period, cases of retinitis pigmentosa (63.2%), Usher's syndrome (10.2%), Stargardt's disease (5.4%), choroideremia (3.2%), Leber's congenital amaurosis (3.2%), congenital stationary night blindness (2.9%), cone dystrophy (2.5%), dominant optic atrophy (1.9%), X-linked juvenile retinoschisis (1.6%), Best's disease (1.6%), and others (4.3%) were diagnosed. In retinitis pigmentosa, inheritance could be determined in 54.2% of the cases including dominant autosomic (26.6%), recessive autosomic (22.6%), and X-linked cases (5%) while it could not be confirmed in 45.7% of the cases (simplex cases in the majority). For the 6 examined genes, mutations were found in 22 out of 182 propositus (12.1%). Analysis of phenotype-genotype correlations indicates that in retinitis pigmentosa, RDS is more frequently associated with macular involvement and retinal flecks, RHO with regional disease, and RPE65 with the great severity of the disease with some cases of Leber's congenital amaurosis. CONCLUSIONS: Identification of genes may help in diagnosis and in genetic counseling, especially in simplex cases with retinitis pigmentosa. In this latter condition, molecular diagnosis will be necessary to rationalize future treatments.

[Ocular toxocariasis. Value of local immunodiagnosis]. / Toxocarose oculaire. Intérêt de l'immunodiagnostic local.

Toxocara canis is a nematode that may be involved in human ocular toxocariasis. Specific immunotesting is of importance but may be negative as toxocara antigens may localize exclusively in vitreous humor. We report here the case of one patient with optic disc toxocariasis granuloma negative for toxocara canis immunodiagnostic on serum. Clinical diagnosis was confirmed by toxocara canis specific enzyme-linked immunosorbent assay (ELISA) on aqueous humor showing elevated titers of antibodies. Systemic steroids associated to specific treatment of toxocariasis were initiated. Follow-up displayed regression of uveitis but development of vitreous bands leading to posterior retinal detachment. Toxocara posterior granuloma is of poor visual prognosis. Moreover, diagnosis may be of late setting, as clinical features are often unrecognized and specific immunodiagnostic on serum negative. Specific immunotesting on aqueous humor is of particular importance to rule out severe clinical differential diagnosis such as retinoblastoma in children. Ultrasound biomicroscopy (UBM) seems to be specific and sensitive in patients with a presumed diagnosis of peripheral toxocariasis. Granuloma surgery appears to yield good clinical results and allows histological confirmation of the diagnosis.

[Ocular trauma and caustic burns by air bags]. / Traumatisme oculaire et brûlure caustique par airbag.

We report two cases of ocular injuries caused by airbag inflation. These cases illustrate two main types of airbag-induced eye injuries: chemical and traumatic. In the first case, chemical keratitis was caused by the aerosol spray of alkaline particles produced by the airbag deployment system. In the second case, the high-speed deployment system caused mechanical injury to the anterior and posterior segments demonstrating the effect of the sudden deceleration when the individual hits the airbag. These two cases as well as others reported in the literature suggest that ocular injury should always be suspected because of the inherent traumatic effect of the airbag protection system.

[Clinical features and genetic analysis in a family with X-linked incomplete congenital stationary night blindness (CSNBi)]. / Particularités cliniques et analyse génétique dans une famille atteinte de cécité nocturne non progressive congénitale héréditaire liée au chromosome X dans sa forme incomplète (CSNBi).

PURPOSE: We describe particular clinical features in a three-generation family with X-linked CSNBi and present the genetic analysis. METHOD: The diagnosis of CSNBi was established on clinical and electrophysiological criteria. Polymorphic DNA markers of the Xp region were analyzed by fluorescent polymerase chain reaction. RESULTS: Clinical findings evidenced an atypical association of both myopia and hyperopia in the same brotherhood. The most interesting feature in this family was the observation of major worsening of the clinical shape between the first and the third generation of affected individuals. DNA analysis did not show significant linkage between the disease and markers of the Xp11-p21 region. Southern analysis did not show expansion of trinucleotide repeat CAG/CTG and CCG/CGG over the three generation. CONCLUSION: Haplotypic analysis together with clinical observations allow to exclude the existence of a myopia gene closely linked to the CSNB2 locus. The clinical anticipation observed in this family does not seem to be linked with trinucleotide repeat expansion CAG/CTG or CCG/CGG.

Rat messenger RNA for the retinal pigment epithelium-specific protein RPE65 gradually accumulates in two weeks from late embryonic days.

The RPE65 protein appears late during the retinal development. To study the basis for this regulation, the rat RPE65 cDNA was sequenced and the mRNA subsequently quantitated at various stages by competitive RT-PCR. RPE65 mRNA was detected as early as E18 (36 copies/ng of whole eye total RNA). It gradually accumulates up to P12 (27000 copies/ng) at which point it reaches a steady state level. This increase is interrupted for 3 days (P2-P4) during which the levels of mRNA remain stable. This timing and rate of accumulation parallels that of rat and mouse opsin mRNA and suggests that common factors may control the activation of genes in photoreceptors and retinal pigment epithelium cells.

Trauma after radial keratotomy and photorefractive keratectomy.

A 25-year-old man sustained bilateral ocular trauma from an explosion, which resulted in ocular injuries from the blast, mineral projections, and heat. Before the accident, the patient had eight-incision radial keratotomy in the left eye followed 1 week later by photorefractive keratectomy in the right eye. After the accident, the left cornea had a full-thickness rupture of four incisions; the fellow cornea had a full-thickness laceration from a mineral projection. Five months after the accident, the left eye had an uncorrected visual acuity of 20/25; the right eye did not achieve an acuity of 20/200 until 20 months after the accident.

[Bilateral ocular blast injury after refractive surgery by 2 current techniques. Comparative anatomo-clinical analysis of a case]. / Taumatisme oculaire bilatéral par blast après chirurgie réfractive selon les deux techniques courantes. Analyse anatomo-clinique comparative d'un cas.

Radial keratotomy reduces the strength of the cornea front of a trauma by blast. The authors present and analyze the case of a 25-year-old patient having been submitted to an ocular bilateral trauma by explosion. Twenty-two months earlier he had undergone radial keratotomy (RK) in the left eye followed 8 days later by photorefractive keratectomy (PKR) in the right eye for a -6,00 d. myopia RLE. Though the trauma by blast essentially reached the right eye, the corneal anatomical damages were more important in the left eye. This is according to us the first case report of trauma on eye subjected to PRK. We appreciate the clinical differences presented by each eye.

Bicoronal incision for nasal bone grafting.

The use of bicoronal incisions has been sufficiently described in neurosurgery and craniofacial surgery including osteotomies and injuries. This approach provides excellent surgical access for nasal reconstruction with a very low rate of morbidity. A series of 11 patients, together with three case reports, illustrates the advantages and possible complications of this type of incision.