Place des implants pseudophaques toriques dans la prise en charge du kératocône

OBJECTIFS : Evaluer l'efficacité, la sécurité et la prédictibilité des implants pseudophaques toriques implantés chez des patients atteints de kératocône. METHODES : Une étude rétrospective, bicentrique, a été réalisée sur dossier médical de patients atteints de kératocône traités par exérèse du cristallin et mise en place d'un implant Acrysof TM Totic SN60TT (Laboratoire Alcon) dans le sac capsulaire. Les données réfractives et topographiques pré et postopératoiores : MAVC, réfraction subjective, kératométries, astigmatisme cornéen et astigmatisme chirurgical induit ont été analysées. RESULTATS : 31 yeux de 19 patients (moyenne d'âge de 54 +- 18,28 ans) incluant 20 yeux atteints de kératocônes avérés, stables et 11 yeux kératoconiques ayant bénéficié d'un traitement cornéen préalable par kératoplastie et/ou anneaux intracornéens ont été évalués. La moyenne de cylindre subjectif préopératoire était de -3,91 +- 0,53 D et la moyenne postopératoire de -1,5 +- 0,5 D soit une réductrion de 61,5 %. Les moyennes pré et postopératoires de la sphère étaient de -3,32 +- 1,36 D et -0,23 +- 0,22 D (diminution de 93 %). L'équivalent sphérique moyen de -5,28 +- 1,34 D en préopératoire était de -0,98 +- 0,32 D en postopératoire soit 81,5 %. Un gain d'acuité visuelle a été constaté chez 72,4 % des patients. La moyenne de MAVC est passée de 0,39 +- 0,04 Logmar (4/10) à 0,15 +- 0,04 Logmar (7/10) soit un gain moyen de 2,44 +- 0,57 lignes d'acuité visuelle. L'astigmatisme chirurgicalement induit, calculé par analyse vectorielle, était de 0,21 D à 32. Aucune rotation d'implant, évolution du kératocône ou autre complication n'a été constatée. CONCLUSION : L'implantation torique pseudophaque sur l'astigmatisme irrégulier de haut degré, tel que dans les kératocônes ou post-kératoplastie, semble être une option thérapeutique efficace, sûre et prédictible. L'étude de plus grandes séries serait nécessaire pour confirmer ces premiers résultats encourageants.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Structural Variant Disrupting the Expression of the Remote <i>FOXC1</i> Gene in a Patient with Syndromic Complex Microphthalmia

Ocular malformations (OMs) arise from early defects during embryonic eye development. Despite the identification of over 100 genes linked to this heterogeneous group of disorders, the genetic cause remains unknown for half of the individuals following Whole-Exome Sequencing. Diagnosis procedures are further hampered by the difficulty of studying samples from clinically relevant tissue, which is one of the main obstacles in OMs. Whole-Genome Sequencing (WGS) to screen for non-coding regions and structural variants may unveil new diagnoses for OM individuals. In this study, we report a patient exhibiting a syndromic OM with a de novo 3.15 Mb inversion in the 6p25 region identified by WGS. This balanced structural variant was located 100 kb away from the FOXC1 gene, previously associated with ocular defects in the literature. We hypothesized that the inversion disrupts the topologically associating domain of FOXC1 and impairs the expression of the gene. Using a new type of samples to study transcripts, we were able to show that the patient presented monoallelic expression of FOXC1 in conjunctival cells, consistent with the abolition of the expression of the inverted allele. This report underscores the importance of investigating structural variants, even in non-coding regions, in individuals affected by ocular malformations

Identification of PITX3 mutations in individuals with various ocular developmental defects

International audienceBackground: Congenital cataract displays large phenotypic (syndromic and isolated cataracts) and genetic heterogeneity. Mutations in several transcription factors involved in eye development, like PITX3, have been associated with congenital cataracts and anterior segment mesenchymal disorders. Materials and methods: Targeted sequencing of 187 genes involved in ocular development was performed in 96 patients with mainly anophthalmia and microphthalmia. Additionally, Sanger sequencing analysis of PITX3 was performed on a second cohort of 32 index cases with congenital cataract and Peters anomaly and/or sclereocornea. Results: We described five families with four different PITX3 mutations, two of which were novel. In Family 1, the heterozygous recurrent c.640_656dup (p.Gly220Profs*95) mutation cosegregated with eye anomalies ranging from congenital cataract to Peters anomaly. In Family 2, the novel c.669del [p.(Leu225Trpfs*84)] mutation cosegregated with dominantly inherited eye anomalies ranging from posterior embryotoxon to congenital cataract in heterozygous carriers and congenital sclereocornea and cataract in a patient homozygous for this mutation. In Family 3, we identified the recurrent heterozygous c.640_656dup (p.Gly220Profs*95) mutation segregating with congenital cataract. In Family 4, the de novo c.582del [p.(Ile194Metfs*115)] mutation was identified in a patient with congenital cataract, microphthalmia, developmental delay and autism. In Family 5, the c.38G>A (p.Ser13Asn) mutation segregated dominantly in a family with Peters anomaly, which is a novel phenotype associated with the c.38G>A variant compared with the previously reported isolated congenital cataract. Conclusions: Our study unveils different phenotypes associated with known and novel mutations in PITX3, which will improve the genetic counselling of patients and their families

Identification of <i>PITX3</i> mutations in individuals with various ocular developmental defects

<p><b>Background</b>: Congenital cataract displays large phenotypic (syndromic and isolated cataracts) and genetic heterogeneity. Mutations in several transcription factors involved in eye development, like <i>PITX3</i>, have been associated with congenital cataracts and anterior segment mesenchymal disorders.</p> <p><b>Materials and methods</b>: Targeted sequencing of 187 genes involved in ocular development was performed in 96 patients with mainly anophthalmia and microphthalmia. Additionally, Sanger sequencing analysis of <i>PITX3</i> was performed on a second cohort of 32 index cases with congenital cataract and Peters anomaly and/or sclereocornea.</p> <p><b>Results</b>: We described five families with four different <i>PITX3</i> mutations, two of which were novel. In Family 1, the heterozygous recurrent c.640_656dup (p.Gly220Profs*95) mutation cosegregated with eye anomalies ranging from congenital cataract to Peters anomaly. In Family 2, the novel c.669del [p.(Leu225Trpfs*84)] mutation cosegregated with dominantly inherited eye anomalies ranging from posterior embryotoxon to congenital cataract in heterozygous carriers and congenital sclereocornea and cataract in a patient homozygous for this mutation. In Family 3, we identified the recurrent heterozygous c.640_656dup (p.Gly220Profs*95) mutation segregating with congenital cataract. In Family 4, the <i>de novo</i> c.582del [p.(Ile194Metfs*115)] mutation was identified in a patient with congenital cataract, microphthalmia, developmental delay and autism. In Family 5, the c.38G>A (p.Ser13Asn) mutation segregated dominantly in a family with Peters anomaly, which is a novel phenotype associated with the c.38G>A variant compared with the previously reported isolated congenital cataract.</p> <p><b>Conclusions</b>: Our study unveils different phenotypes associated with known and novel mutations in <i>PITX3</i>, which will improve the genetic counselling of patients and their families.</p

First evidence of SOX2 mutations in Peters' anomaly: Lessons from molecular screening of 95 patients

International audiencePeters' anomaly (PA) is a rare anterior segment dysgenesis characterized by central corneal opacity and irido-lenticulo-corneal adhesions. Several genes are involved in syndromic or isolated PA (B3GLCT, PAX6, PITX3, FOXE3, CYP1B1). Some copy number variations (CNVs) have also been occasionally reported. Despite this genetic heterogeneity, most of patients remain without genetic diagnosis. We retrieved a cohort of 95 individuals with PA and performed genotyping using a combination of comparative genomic hybridization, whole genome, exome and targeted sequencing of 119 genes associated with ocular development anomalies. Causative genetic defects involving 12 genes and CNVs were identified for 1/3 of patients. Unsurprisingly, B3GLCT and PAX6 were the most frequently implicated genes, respectively in syndromic and isolated PA. Unexpectedly, the third gene involved in our cohort was SOX2, the major gene of micro-anophthalmia. Four unrelated patients with PA (isolated or with microphthalmia) were carrying pathogenic variants in this gene that was never associated with PA before. Here we described the largest cohort of PA patients ever reported. The genetic bases of PA are still to be explored as genetic diagnosis was unavailable for 2/3 of patients. Nevertheless, we showed here for the first time the involvement of SOX2 in PA, offering new evidence for its role in corneal transparency and anterior segment development