Kozo Ikeda

Anomalies associated with Axenfeld-Rieger syndrome

Abstract · Background: To detect the associated anomalies in patients with Axenfeld-Rieger syndrome is clinically important, because early treatment for such anomalies is crucial to both visual and systemic development. This study was conducted to clarify the associated anomalies in the syndrome. · Methods: We evaluated 21 patients with Axenfeld-Rieger syndrome encountered at Nagoya City University Hospital over a 16-year period. Patients who presented with a prominent Schwalbe’s line accompanying the iris strands were diagnosed as having Axenfeld-Rieger syndrome. · Results: The series consisted of 9 males and 12 females, ranging in age from 1 month to 41 years, mean 15.4±12.7 (SD) years. The syndrome was bilateral in 17 cases and unilateral in 4 cases. Hypoplasia of the iris was observed in 10 eyes of 6 patients. The associated ocular anomalies included sclerocornea in 6 eyes of 3 patients, developmental glaucoma in 5 eyes of 3 patients, persistent pupillary membrane in 4 eyes of 2 patients, microphthalmos in 3 eyes of 2 patients, and typical iris coloboma in 1 eye. Of 10 eyes with hypoplasia of the iris, 5 exhibited glaucoma. The accompanying systemic anomalies included 9 cases of dental anomalies, 5 of facial anomalies, and 3 of Alagille syndrome. · Conclusions: All of the associated ocular and systemic anomalies appeared to arise from the maldevelopment of the neural crest cells. Patients with Axenfeld-Rieger syndrome should therefore be examined for the presence of anomalies in the tissues of neural crest origin. Patients with hypoplasia of the iris should be checked for glaucoma.

Maldevelopment of neural crest cells in patients with typical uveal coloboma.

PURPOSE To clarify the pathogenesis of ocular and systemic anomalies associated with typical uveal coloboma. METHODS The records of 72 patients with typical uveal coloboma (35 males and 37 females) treated at Nagoya City University Hospital during a 16-year period were reviewed. RESULTS Typical uveal coloboma was bilateral in 33 patients and unilateral in 35 patients; 4 patients were unclassified because of severe contralateral microphthalmos. Uveal coloboma was an isolated defect in 23 (37%) patients. Other ocular anomalies were present in 19 (31%) patients, systemic anomalies were found in 7 (11%) patients, and both other ocular and systemic anomalies were noted in 13 patients (21%). The associated ocular anomalies included microphthalmos in 28 eyes of 23 patients, persistent pupillary membrane in 28 eyes of 18 patients, and posterior embryotoxon in 20 eyes of 15 patients. The accompanying systemic anomalies included ear anomalies, retarded growth, and retarded development in 18 patients; heart anomalies in 13 patients; genital hypoplasia in 12 patients; and congenital facial palsy in 10 patients. The collection of malformations known as the CHARGE association was diagnosed in 14 (19%) patients. CONCLUSION Abnormal development of neural crest cells appeared to be responsible for the majority of associated ocular and systemic anomalies in patients in the present series, suggesting that typical uveal coloboma may be related to maldevelopment of the neural crest cells. The present findings indicated that ophthalmologists should be aware of the possible association of typical uveal coloboma with systemic anomalies.

Clinical Evaluation of Posterior Embryotoxon in One Institution

To elucidate the pathogenesis of posterior embryotoxon, we estimated its incidence in our clinic and evaluated its associated ocular and systemic anomalies. Slit-lamp and gonioscopic examinations were performed on 440 randomly selected patients at Nagoya City University Hospital over a 10-month period. Posterior embryotoxon was detected in 107, 50 bilateral and 57 unilateral, cases (24.3%). Twelve (11.2%) of the 107 cases had open-angle glaucoma. Accompanying ocular anomalies included six cases of sclerocornea, two each of persistent pupillary membrane and familial exudative vitreoretinopathy, and 1 each of melanocytoma of the optic nervehead, choroidal nevus and subconjunctival dermoid cyst. Associated systemic anomalies included three cases of Alagille syndrome, two of congenital biliary atresia, and one each of congenital facial palsy with microtia, congenital adrenal hyperplasia, empty sella syndrome, Hirschsprung disease and Wilson disease. Many of these ocular and systemic anomalies were caused by the maldevelopment of neural crest cells. Patients with posterior embryotoxon should be examined for the possible presence of open-angle glucoma and for ocular and systemic anomalies related to maldevelopment of neural crest cells.

Histochemical studies on the separation of the lens vesicle

We studied histologically the changes and distribution patterns of glycosaminoglycan molecular species during the separation of the lens vesicle in the mouse. Embryos were obtained by sacrificing pregnant mice of the Jcl: ICR strain on day 10.5 and 11 of pregnancy. Serial frontal sections were stained with hematoxylin-eosin and a sensitized high iron diamine method. To identify glycosaminoglycan molecular species in tissues, enzyme digestion (double digestions with chondroitinase B and testicular hyaluronidase) and chemical modification (nitrous acid treatment) were performed in combination with the sensitized high iron diamine method. Before separation of the lens vesicle, the glycosaminoglycan molecular species, identified in the basement membrane of the presumed corneal epithelium and intercellular matrices between the presumed corneal epithelium and lens vesicle, were chondroitin sulfate A/C and B, and those in the lens capsule were chondroitin sulfate A/C. After separation of the lens vesicle, heparan sulfate emerged in the basement membrane of the presumed corneal epithelium and intercellular matrices between the presumed corneal epithelium and lens vesicle. These results are thus taken to indicate that the changes and distribution patterns of glycosaminoglycan molecular species play an important role during separation of the lens vesicle.

Histochemical studies of glycosaminoglycans in the developing eyelids of experimental microphthalmic (Cts) mice

PURPOSE The Cts mouse is a mutant strain which induces congenital cataract and small eyes in homozygotes. The process of eyelid development in Cts mice was examined histochemically. MATERIALS AND METHODS Prenatal (from day 14 of gestation) and postnatal (to day 14) animals of unaffected and homozygous mice were examined. Sensitized high iron diamine staining was done after chondroitinase B/testicular hyaluronidase double digestion, and sensitized low iron diamine staining was done after Streptomyces hyaluronidase digestion. RESULTS The main chondroitin sulfate isomer in the dermis of the eyelid changed from chondroitin sulfate A/C to chondroitin sulfate B at birth in the unaffected mice. In the homozygotes, the same change took place 4 days after birth. In the dermis of the eyelid, hyaluronic acid was first detected on day 14 of gestation and gradually increased until birth in both unaffected and homozygous mice. There was slightly more hyaluronic acid in homozygous mice until 4 days after birth. CONCLUSION The present study showed that the maturation of glycosaminoglycan molecular species in the eyelid was retarded in Cts homozygotes.