Since its development in 2008, hand-held spectral domain optical coherence tomography (HHSD-OCT) has contributed to improve the management of paediatric ocular oncology cases, by allowing a non-invasive evaluation of the retina and optic nerve of the young children during the under anesthesia examination. In this session, emblematic cases will be presented, which illustrates its role in the differential diagnosis of paediatric tumors and its importance in the management (diagnostic and therapeutic) of retinoblastoma cases.

Purpose: We report the clinical features and phenotype‐genotype correlation in a large Tunisian family with granular corneal dystrophy type I. Methods: Twenty‐seven members of the Tunisian family underwent a complete ophthalmologic examination. A histopathological examination was performed on corneal specimens of four patients with advanced stage of corneal dystrophy. DNA extraction and direct Sanger sequencing of the exons 4 and 12 of TGFBI gene was performed for forty‐two members. Results: The diagnosis of granular corneal dystrophy type I was clinically and genetically confirmed. Sequencing of exon 4 of TGFBI gene revealed the p.Arg124Ser mutation in heterozygous and in homozygous status in patients with different clinical severity. Visual acuity was severely affected in the homozygous patients leading to a first penetrating keratoplasty at 20 years of age in 3 cases, and at 8 years in one case. Recurrence occurred rapidly, began in the seat the corneal stitches and remained superficial up to 40 years after the graft. In heterozygous cases, visual acuity ranged from 6/10 to 10/10. Corneal opacities were deeper and predominating in the stromal center. Conclusions: Our study describes for the first time phenotype‐genotype correlation in a large Tunisian family with granular corneal dystrophy type I and illustrates clinical presentation of homozygous p.Arg124Ser mutation. These results help to understand pathophysiology of the disease and profile of relapse after keratoplasty.

To evaluate the clinical phenotype of ten Tunisian families with non-syndromic retinitis pigmentosa (RP), to characterize genes and mutations causing these conditions, and to elaborate phenotype-genotype correlations.Descriptive clinical genetic study of 114 individuals, of whom 27 are affected by non-syndromic RP. Ophthalmic examination and various visual tests were performed. DNA was analyzed using single nucleotide polymorphism, microsatellite genotyping and direct sequencing to determine the genes and mutations involved.We identified seven mutated genes: RPE65, RDH12, USHER 2A, PDE6a, PDE6b, CRB1, and NR2E3. Analysis of phenotype-genotype correlation indicated that some genes were associated with specific phenotypes. In RPE65 mutations, we found early onset dystrophy, nystagmus, keratoconus, white dot deposits in earlier stages and clumped pigment in later stages. The RDH12-associated phenotype (juvenile RP) showed severe and early-onset dystrophy, diffuse spicule pigmentation, macular edema and thickening, and tomographic re-organization of retinal layers. The CRB1 mutation was characterized by preserved para-arteriolar retinal pigment epithelium and no hemeralopia.RP is clinically and genetically heterogeneous. The two ultimate goals of research are to provide efficient clinical diagnostic of affected gene by phenotype-genotype correlation and to design novel treatment regimens. Our goal is to create a specific chip for our population, and then future research will focus on the identification of the remaining causal genes, the elucidation of the molecular mechanisms of disease in the retina and the development of gene therapy approaches.

PURPOSE:To evaluate the clinical phenotype of ten Tunisian families with non-syndromic retinitis pigmentosa (RP), to characterize genes and mutations causing these conditions, and to elaborate phenotype-genotype correlations.METHODS:Descriptive clinical genetic study of 114 individuals, of whom 27 are affected by non-syndromic RP. Ophthalmic examination and various visual tests were performed. DNA was analyzed using single nucleotide polymorphism, microsatellite genotyping and direct sequencing to determine the genes and mutations involved.RESULTS:We identified seven mutated genes: RPE65, RDH12, USHER 2A, PDE6a, PDE6b, CRB1, and NR2E3. Analysis of phenotype-genotype correlation indicated that some genes were associated with specific phenotypes. In RPE65 mutations, we found early onset dystrophy, nystagmus, keratoconus, white dot deposits in earlier stages and clumped pigment in later stages. The RDH12-associated phenotype (juvenile RP) showed severe and early-onset dystrophy, diffuse spicule pigmentation, macular edema and thickening, and tomographic re-organization of retinal layers. The CRB1 mutation was characterized by preserved para-arteriolar retinal pigment epithelium and no hemeralopia.CONCLUSION:RP is clinically and genetically heterogeneous. The two ultimate goals of research are to provide efficient clinical diagnostic of affected gene by phenotype-genotype correlation and to design novel treatment regimens. Our goal is to create a specific chip for our population, and then future research will focus on the identification of the remaining causal genes, the elucidation of the molecular mechanisms of disease in the retina and the development of gene therapy approaches.

Retinoblastoma represents 11% of all cancers during the first year of life. New drugs and focal treatments have been developed in order to avoid the side effects of systemic chemotherapy and external radiotherapy. New targeted and local administration strategies such as periocular chemotherapy (topotecan) or direct ophthalmic artery delivery (carboplatin), are already used today in selected resistant cases. Radiotherapy, presently indicated only as a second-line treatment, is also subject to new techniques, targeting tumors more closely to avoid involving healthy tissue and reduce the risk of radio-induced nonocular tumors. Stereotactic conformal radiotherapy and proton therapy may thus be included in the new range of treatment methods in retinoblastoma.

Purpose: Complement factor H (CFH) Y402H SNP rs1063170 shows strong association with AMD. Phenotypical concordance of AMD is known from sibling and twin studies. Studies about genotype-phenotype associations showed inconsistent results. This study investigates the association of CFH Y402H SNP with AMD in a Swiss population, and the genotype-phenotype association, particularly in early stages of AMD. Methods: A total of 473 AMD patients and 69 control individuals were enrolled. Colour fundus photographs were graded according to the International Classification and Grading System for AMD. The SNP rs1063170 was evaluated for each patient. Statistical analysis was restricted to individuals with complete clinical data (420 AMD cases and 50 controls). Results: An OR of 3.0 was found for the presence of at least one risk C-allele, and OR 9.3 for the homozygous genotype. Individuals over the mean age of 76y and homozygous for the risk-allele C showed more frequently late forms of AMD. No phenotypic association was found for drusen size, drusen covered surface, drusen localisation nasal to the disc, and pigmentary changes. A trend for central drusen location was found in patients homozygous for the risk allele C [p=0.051]. Peripheral drusen were significantly more frequent in individuals with the risk allele C, particularly if homozygous [p=0.027]. Conclusions: This study confirms the risk association of the CFH Y402H polymorphism with AMD for the Swiss population. A genotype-phenotype association could be found for early forms of AMD, however only for some drusen features. Additional genetic factors are likely to influence the drusen phenotype. Further careful research is needed to better understand the genetic influence on AMD phenotypes.

Purpose: The mutations responsible for Best vitelliform macular dystrophy (BVMD) are found in a gene called VMD2. The VMD2 gene encodes a transmembrane protein named bestrophin-1 (hBest1) which is a Ca2+-sensitive chloride channel. This study was performed to identify disease-specific mutations in 27 patients with BVMD. Because this disease is characterised by an alteration in Cl− channel function, patch clamp analysis was used to test the hypothesis that one of the VMD2 mutated variants causes the disease. Methods: Direct sequencing analysis of the 11 VMD2 exons was performed to detect new abnormal sequences. The mutant of hBest1 was expressed in HEK-293 cells and the associated Cl− current was examined using whole-cell patch clamp analysis. Results: Six new VMD2 mutations were identified, located exclusively in exons four, six and eight. One of these mutations (Q293H) was particularly severe. Patch clamp analysis of human embryonic kidney cells expressing the Q293H mutant showed that this mutant channel is non-functional. Furthermore, the Q293H mutant inhibited the function of wild-type bestrophin-1 channels in a dominant negative manner. Conclusions: This study provides further support for the idea that mutations in VMD2 are a necessary factor for Best disease. However, because variable expressivity of VMD2 was observed in a family with the Q293H mutation, it is also clear that a disease-linked mutation in VMD2 is not sufficient to produce BVMD. The finding that the Q293H mutant does not form functional channels in the membrane could be explained either by disruption of channel conductance or gating mechanisms or by improper trafficking of the protein to the plasma membrane.

Background: Posterior microphthalmos is a rare autosomal recessive condition with normal anterior segment and small posterior segment resulting in axial hyperopia and retinal folding. History and Signs: The proband from a consanguineous Turkish family was clinically investigated at 5 months of age and followed for the next 8 years. At five months of age, refraction revealed a severe hyperopia of + 10 diopters in both eyes (OU) with a mean axial length of 16.5 mm. Fundus examination showed a dystrophic maculo-papillar bundle. Multiple whitish deep intraretinal linear lesions sparing the macula were present in the mid-periphery with no preferential orientation. Therapy and Outcome: By 8 years of age, visual acuity was 20/25 in the right eye (OD) and 20/30 in the left eye (OS) with S + 14 OU. The whitish linear lesions had disappeared and were replaced by retinal pigment epithelium alterations. Optical coherence tomography (OCT) revealed a thickened retina with normal appearance at the site of the linear lesions. Conclusions: This is the first report of long-term follow-up and OCT findings in this rare ocular developmental abnormality.

La maladie de Coats, ou télangiectasie rétinienne primaire, est une rétinopathie exsudative rare, généralement unilatérale, affectant le plus souvent des garçons dans la première décennie, non familiale, probablement congénitale, sans évidence de maladies systémiques associées, constituée de télangiectasies primaires et d'exsudats pouvant conduire à un décollement de rétine, à des hémorragies vitréorétiniennes, à un glaucome néovasculaire et finalement à la perte de la vision. La lésion primitive est vraisemblablement une anomalie localisée et évolutive de développement des vaisseaux rétiniens. L'origine précise n'est pas connue mais la maladie pourrait être liée à une mutation somatique du gène NDP (Norrie Disease Protein). Les télangiectasies idiopathiques juxtafovéolaires constitueraient une seconde forme clinique de télangiectasies primaires de la rétine limitée à la région maculaire. Il existe également des télangiectasies secondaires à des affections locales ou générales pouvant provoquer, comme dans la maladie de Coats, des exsudations rétiniennes importantes. C'est le cas par exemple d'une occlusion de branche veineuse, d'une rétinopathie actinique ou du diabète.

AIMS:To report the detailed clinical findings in a three generation pedigree with autosomal dominant cataract, microcornea, and coloboma resulting from mutation of the lens development gene, MAF.METHODS:Five members of a three generation pedigree with progressive cataracts underwent detailed ophthalmic examination to characterise associated ocular phenotypic features.RESULTS:The cataracts present in all affected individuals were cortical, and/or nuclear, pulverulent opacities. Corneal diameters of 10-10.25 mm were present in two family members. Axial lengths were in the normal range. Bilateral iris coloboma in the 6 o'clock position was present in one patient. Uveal melanoma was present in one patient, with uveal naevi in this and one other patient.CONCLUSION:The bZIP transcription factor MAF is a key lens development gene that regulates the expression of the crystallins. Individuals with a mutation in MAF may have pulverulent cataract alone or cataract in association with microcornea or iris coloboma.