Ocular ochronosis in alkaptonuria patients carrying mutations in the homogentisate 1,2-dioxygenase gene.
AIMS: To assess the involvement of the recently identified human homogentisate 1,2-dioxygenase gene (HGO) in alkaptonuria (AKU) in two unrelated patients with ochronosis of the conjunctiva, sclera, and cornea. METHODS: A mutation screen of the entire coding region of the HGO gene was performed using single stranded conformational analysis after polymerase chain reaction with oligonucleotide primers flanking all 14 exons of the HGO gene. Fragments showing aberrant mobility were directly sequenced. RESULTS: Two homozygous missense mutations, L25P and M368V, were identified, each of which leads to the replacement of a highly conserved amino acid in the HGO protein. CONCLUSIONS: The authors describe a novel mutation, L25P, in the German population and bring to 18 the total number of known HGO mutations. (+info)
A clinical and molecular genetic study of a rare dominantly inherited syndrome (MRCS) comprising of microcornea, rod-cone dystrophy, cataract, and posterior staphyloma.
AIM: To phenotype and genetically map the disease locus in a family presenting with autosomal dominant microcornea, rod-cone dystrophy, cataract, and posterior staphyloma. METHODS: Six affected and three unaffected members of the pedigree were examined. All individuals provided a history and underwent a full clinical examination with A-scan and B-scan ultrasonography and electrophysiological testing where appropriate. PCR based microsatellite marker genotyping using a positional candidate gene approach was then performed on DNA samples extracted from venous blood provided by each subject. RESULTS: The disorder is inherited as an autosomal dominant trait with variable expressivity and has a complex phenotype. Affected individuals had bilateral microcornea, pulverulent-like lens opacities, a rod-cone dystrophy and posterior staphyloma (MRCS). Using a positional candidate gene approach, the authors have evidence suggestive of linkage of this disorder to a region on 11q13 within the nanophthalmos 1 (NNO1) genetic interval. The small family size militates against achieving a LOD score of 3, but the haplotype data and the position of the putative MRCS locus within a known nanophthalmos locus are suggestive of linkage. A candidate gene within this region (ROM1) was screened and no mutations were found in affected members of the family. CONCLUSION: This rare developmental disorder has some phenotypic similarities to nanophthalmos and possibly maps to a locus within the genetic interval encompassing the NNO1 locus. Screening of candidate genes within this region continues. (+info)
Corneoscleral cyst treated with distilled water injection.
To describe the first case of the treatment of a corneoscleral cyst by distilled water injection into a corneal cyst. The anterior wall of a cyst of the limbal communication was punctured with a surgical blade. Aspiration and irrigation of the contents of the cyst with a 27-gauge anterior chamber cannula were performed repeatedly, three times. Distilled water, instead of balanced salt solution, was injected into the collapsed cyst, and was then aspirated completely after 5 minutes. The injection and aspiration of distilled water was repeated once more. The scleral cyst was surgically excised. Twelve months after surgery, several small white granular opacities, presumably epithelial cell nests, were observed on the interface of the collapsed cyst cavity, but there was no recurrence of the cyst. The best spectacle-corrected visual acuity (BSCVA) was 1.0 with a correction of +1.25-2.00 X 45. No significant change in central corneal endothelial cell density was noted. We suggest that this simple technique may represent an alternative method for the management of corneal cysts, and may have less risk of developing a corneal opacity or causing other serious damage to surrounding tissues. (+info)
Ocular and scleral alterations in gene-targeted lumican-fibromodulin double-null mice.
PURPOSE: To elucidate the role of leucine-rich proteoglycans lumican and fibromodulin in the sclera. METHODS: Lumican- and fibromodulin-null heterozygous mice were intercrossed to obtain wild-type (Lum(+/+)Fmod(+/+)), lumican-null (Lum(-/-)Fmod(+/+)), fibromodulin-null (Lum(+/+)Fmod(-/-)), and double-null (Lum(-/-)Fmod(-/-)) littermates. Axial length was measured on enucleated whole eyes, and ocular structural changes were examined by histology. The morphology of collagen fibrils in the sclera was examined by transmission electron microscopy (TEM). RESULTS: Compared with the ocular axial length in wild type mice, the axial length was increased by 10% in Lum(-/-)Fmod(-/-) (P = 0.02) mice. Retinal detachment was frequent in the double-null and rare in the lumican-null animals. Compared with the wild-type sclera, the sclera in all null mutants was significantly thinner with fewer lamellae (P < 0.05). The double-null sclera contained abnormally large-diameter (120-160 nm) and small-diameter (30-60 nm) collagen fibrils, whereas the fibromodulin-null sclera was enriched for the small-diameter fibrils. The collagen fibril diameter distribution in the lumican-null sclera was similar to that of the wild-type. CONCLUSIONS: An increase in small-diameter fibrils in the fibromodulin-null sclera suggests a key role for fibromodulin in the maturation and assembly of scleral collagen fibrils. That fibril diameter distribution in the lumican-null sclera was comparable to that in the wild type, but severely disrupted in the double null, suggests a role for lumican that is crucial in the absence of fibromodulin. The eyes of Lum(-/-)Fmod(-/-) mice show certain features of high myopia: increased axial length, thin sclera, and retinal detachment. Mutations or altered expression of these proteoglycans may contribute to myopia in humans. (+info)
Juvenile xanthogranuloma as an isolated corneoscleral limbal mass: a case report.
A case of a juvenile xanthogranuloma of the corneoscleral limbus was encountered in a 5-year-old oriental boy, who presented with a 5-month history of a lump in the right eye. The lesion extended from the inferior limbus. This yellow-orange mass was vascular and firmly fixed to the underlying tissue. The lesion was diagnosed preoperatively as an atypical dermolipoma and an uneventful excisional biopsy was performed. The pathologic diagnosis showed the characteristic picture of a juvenile xanthogranuloma with numerous Touton giant cells. Dermoid and lipodermoid tumors, as a corneoscleral limbal mass, are the most frequently encountered in childhood. A juvenile xanthogranuloma is a rare and usually benign skin disease with an unknown cause, which occurs in infants and young children. However, it can occur also as a corneoscleral limbal mass in young children. (+info)
Results of a prospective study for the treatment of retinoblastoma.
BACKGROUND: The objectives of this prospective study were to avoid adjuvant treatment for patients with intraocular disease and patients with postlaminar optic nerve invasion (PL-ONI) without full choroidal or scleral invasion. Adjuvant chemotherapy (Regimen 1) was given to patients with scleral invasion, PL-ONI without cut section, and full choroidal and/or scleral invasion. A more intensive regimen of higher dose intravenous chemotherapy (Regimen 2) and local radiotherapy was given to patients with PL-ONI and compromise at the cut end and to patients with overt extraocular disease. METHODS: Six-month intravenous chemotherapy included carboplatin plus etoposide alternating with cyclophosphamide plus vincristine (Regimen 1) and the same drugs at higher dosage plus idarubicin (Regimen 2). Chemoreduction with carboplatin and vincristine with or without etoposide was given to selected patients (n = 39 patients). RESULTS: From 1994 to 2001, 169 patients were evaluable at the Hospital Garrahan (Buenos Aires, Argentina). One hundred eighteen patients with intraocular disease had a 5-year disease free survival (DFS) rate of 0.98, including 54 patients with choroidal invasion. None of 22 patients with isolated PL-ONI developed recurrent disease, whereas 2 of 8 patients with concomitant risk factors had tumor recurrences and died. Three of 5 patients with scleral invasion survived, and 7 of 10 patients with cut-end ONI survived. The only patient with metastatic disease that survived (n = 6) had only lymph node invasion. CONCLUSIONS: Adjuvant therapy can be avoided in patients with intraocular and isolated PL-ONI. Patients with PL-ONI who also had other risk factors required intensive adjuvant therapy, such as patients with cut-end and overt extraocular disease. Metastatic disease was not found to be curable with this approach. (+info)
Scleral plaque is a commonly occurring change in older individuals. We report a case of bilateral scleral plaques seen in an elderly female patient. This current case report describes a common but often missed benign scleral change in the elderly individual. (+info)
Osteogenesis imperfecta of the temporal bone: CT and MR imaging in Van der Hoeve-de Kleyn syndrome.
We report the progressive otic capsule demineralization around the membranous labyrinth and facial nerve in an adult patient with osteogenesis imperfecta tarda. Whereas the initial CT scan showed bandlike, undermineralized pericochlear areas, 2 years later, repeat CT performed because of hearing deterioration showed progression of these findings to the promontory, the round window niche, and the labyrinthine and tympanic segments of the facial nerve canal. MR imaging demonstrated enhancement of the abnormal otic capsule and of the intratemporal and canalicular facial nerve. The differential diagnosis of osteogenesis imperfecta tarda affecting the temporal bone includes otosclerosis, Paget disease, otosyphilis, and Camurati-Engelmann disease. (+info)