Synophthalmia and cyclopia: A histopathologic, radiographic, and organogenetic analysis

This paper presents the results of a detailed gross and histologic examination of the eyes and brain in a case of synophthalmia as well as radiographic studies of the skull. Data on 34 other cases of synophthalmia-cyclopia on file in the Registry of Ophthalmic Pathology, Armed Forces Institute of Pathology (AFIP), are also summarized. In synophthalmia-cyclopia, the median ocular structure is symmetrical and displays two gradients of ocular organization: (1) The anterior segments are usually paired and comparatively well differentiated, whereas, posteriorly, a single, more disorganized compartment is present; (2) the lateral components show more advanced differentiation than the medial. There is invariably a single optic nerve and no chiasm. The brain, the nose, and the bones and soft tissues of the upper facial region, while malformed, are symmetrical and show a similar gradient of organization in that the lateral parts are better developed than the medial. The constant occurrence of a profound cerebral malformation along with the ocular deformity suggests a widespread abnormality of the anterior neural plate from which both the eyes and brain emerge. The data indicate that the defect occurs at or before the time of closure of the neural folds when the neural plate is still labile. The probability of fusion of two ocular anlagen in synophthalmia-cyclopia seems less likely than the emergence of incomplete bicentricity in the ocular fields of the neural plate during the period when the eye primordia are initially induced by the mesoderm. Embryologic studies in experimental animals provide insight into possible mechanisms by which inperfect eye and brain primordia are established. Nonetheless, once established, the eye and brain primordia in synophthalmia-cyclopia are capable of and do complete each step of the usual sequence of ocular and cerebral organogenesis in an orderly manner. The resulting eyes and brain are organogenetically incomplete but histogenetically mature. Ancillary facial and osseous defects result from the faulty migration of neural crests and development of embryonic facial processes secondary to the abnormal ocular and cerebral rudiments. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. Presented in part at the annual meeting of the Association for Research in Vision and Ophthalmology in Sarasota, Florida, April 28, 1975, and at the biennial meeting of the AFIP-Ophthalmic Pathology Alumni Meeting in Washington, D.C., June 18, 1976.