Congenital glaucoma and other ocular abnormalities associated with pericentric inversion of chromosome 11.

Pericentric inversion of chromosome 11 occurred in consecutive generations of family members with congenital glaucoma. Affected persons were characterized by unilateral or bilateral congenital glaucoma, bilateral corneal disease, and a lack of appreciable dysmorphism. Previous reports of inversions of chromosome 11 are rare, and no ocular abnormalities have been noted. Chromosomal abnormalities may be the cause of some forms of congenital glaucoma and should be included in the genetic heterogeneity of this disease.

Clinicopathological findings in a growing optic nerve melanocytoma.

We present an unusual case of a melanocytoma of the optic disc that showed documented progressive growth over a period of six years. It reached the largest size of any reported optic nerve melanocytoma and the eye was enucleated because of the possibility of malignant degeneration. Optic nerve melanocytomas are locally invasive but are not known to undergo transformation into malignant melanoma. Follow-up should remain the primary approach in the management of patients with optic nerve melanocytomas, as previously advocated by Zimmerman.

Ring stromal opacity in lens-corneal adhesion.

Severe congenital corneal clouding may be associated with abnormal anterior segment development (dysgenesis). Often, congenital corneal opacities preclude visualization of intraocular anatomy. In this report, five eyes of four patients with congenital corneal clouding and lens-corneal adhesion (LCA) are described. All had a ring- or doughnut-shaped haze within the stroma surrounding a central clear corneal zone delineating the adhesion. Recognition of LCA is pivotal in planning surgical therapy for eyes with congenital corneal clouding. As a clue to recognition of this anomaly, the ring-shaped stromal opacity may aid in diagnosis of this phenomenon and in avoidance of surgical complications.

Learning disabilities: update comment on the visual system.

The role of the eye in vision and its relationship to learning disabilities is discussed in this very timely article. A historical overview is included, as well as a consideration of the more recent neuroanatomic research in this area.

Re-recession of the medial rectus muscles in patients with recurrent esotropia.

PURPOSE: Retrospective evaluation of changes in ocular motility after surgical re-recession of the medial rectus (MR) muscles as treatment of recurrent esotropia (ET). METHODS: We describe 115 patients (age, 11 months-77 years; median, 11.1 years; 83 children and 32 adults) with an average amount of non-accommodative ET before surgery of 18.7 PD (SD = 8.8 PD). Preoperative alignment, amount of re-recession, distance from insertion to the limbus, and postoperative alignment and versions were collected. RESULTS: In most cases, MR muscles were re-recessed to a fixed distance of 12 mm from the limbus, with unilateral re-recessions in cases with relatively small ET (typically < 20 PD) and bilateral re-recessions in cases with larger amounts of ET (typically > 20 PD). No clear relation was found between the amount of re-recession and the change in alignment in prism diopters. The success rate (esotropia [ET] < or = 10 PD or exotropia [XT] < or = 8 PD) 4 weeks to 8 months after surgery was 85%, with 4 patients still showing ET and 13 patients showing XT. Incidence of XT was higher for bilateral than for unilateral re- recessions. Significant underaction of the MR muscles was noted in 7% of the patients. None of the undercorrected patients and only 1 of the overcorrected patients were adults. Among adults, incidence of MR underaction was 4%. Long-term follow-up (8-120 months; median, 25 months) data from 59 patients indicated that good stability in alignment can be expected. CONCLUSION: The results support the notion that MR re-recession to 12 mm from the limbus successfully corrects recurrent ET up to 35 PD and that it is particularly effective in adults.

Anterior segment dysgenesis keratolenticular adhesion and aniridia.

Three additional cases of keratolenticular adhesion and aniridia have been reported. A review of the embryology and terminology in the description of complex lesion of the anterior segment might suggest the more general phrase, anterior segment dysgenesis, to have advantage. Finally, the simultaneous occurrence of anterior segment anomalies and hemophilia is reported.

Blepharophimosis and cardiopathy.

A 2 1/2-year-old girl with blepharophimosis and ventriculoseptal defect is described. Blepharophimosis is rare, and this complex more so. Yet, the clinical implications of its recognition are potentially important.

Pediatric keratoplasty: problems in management.

A summary of experience in pediatric keratoplasty is given by adding ten recent cases to a previous report. A review of keratoplasty in infants and children from the literature generally recommends the procedure as safe and effective. Recent reports, however, cast some doubt on the effectiveness of the procedure for certain conditions. An update of experience is given as a focal point for a discussion of problems in clinical management of children who undergo keratoplasty. These problems are arbitrarily separated by pre-, intra-, and postoperative time frames.

Terrien's marginal corneal degeneration.

Terrien's disease is an uncommon (Terrien himself saw only three cases in thirty years of practice) corneal condition characterized by vascularization, opacification, lipid deposition, and thinning. With progression, large degrees of astigmatism occur and perforation is a threat. One-third of cases exhibit an inflammatory component. While typically described as a disease of middle to late age, these four cases indicate the full spectrum of clinical disease may be seen by an ophthalmologist who cares for children.

An alternative hypothesis for iris maldevelopment (aniridia).

Two principal hypotheses for the pathogenesis of hypoplastic iris development ("aniridia") have been proposed: 1) the ectodermal theory, positing incomplete elaboration of the cup, resulting in an absence of framework for further development; and 2) the "mesodermal" theory, wherein inadequate migration or proliferation of mesenchymal elements is proposed. Two eyes of two patients with persistent "anterior leaf" iris strand remnants which traverse the pupillary space are reported. They are differentiated from the previously described persistent tunica vasculosa lentis. The presence of a persistent pupillary iris strand suggests portions of the iris may have formed and inappropriately regressed. Recent work in cell biology highlights the importance of remodeling and cell death in revealing ultimate phenotypic expression. This alternative hypothesis suggests that aniridia may be explained in part on the basis of excessive remodeling and cell death.

Retinal vascular and optic nerve abnormalities in albinism.

Albinism is a condition in which the pigment melanin may not be synthesized from tyrosine. The fundus photographs of 24 eyes of 12 patients with the clinical diagnosis of either ocular or oculocutaneous albinism were reviewed. We observed two findings that to our knowledge have not been reported previously. Eighteen eyes of ten patients had prominent retinal vessels coursing through the putative macular area instead of arching around it. Large noncilioretinal vessels extended from the disc to the dysplastic "foveal zone" in eight eyes of five patients. Typical optic nerve hypoplasia (ONH) was seen in six eyes of four patients; features suggestive of ONH were present in an additional ten eyes of six patients. The cross-over (sharing) of clinical features between albinism and aniridia is striking and raises questions about pathophysiologic mechanisms.

Collagen maturation defects in Ehlers-Danlos keratopathy.

Ehlers-Danlos syndrome is one of many inherited abnormalities of connective tissue, specifically collagen. A 16-year-old caucasian female with Type VI Ehlers-Danlos syndrome had five unusual corneal findings, four of which have not been reported in association with Ehlers-Danlos syndrome: micro-cornea (previously reported), cornea plana, keratoconus posticus, stromal haze at the level of Bowman's layer and a peripheral ring opacity suggestive of anterior embryotoxon. Type VI Ehlers-Danlos syndrome is associated with deficient activity of lysyl hydroxylase which ultimately is responsible for cross-linking collagen chains, the source of its tensile strength. Genetic regulation of procollagen formation is believed to be mediated by mRNA. Aggregation and maturation in the extracellular matrix is probably influenced and mediated by its evolving biochemical environment, particularly by complex carbohydrate moieties. An understanding of collagen maturation, and the pathophysiologic and biophysical consequences of abnormalities at this level of biochemical organization, permits more specific understanding of ocular dysmorphology and collagen diseases.

Role of the neural crest in anterior segment development and disease.

Certain eye and associated systemic developmental anomalies are apparently related by virture of a common neural crest origin. The development of the anterior segment is extremely complex and is dependent upon the presence or absence of certain local factors (including extracellular matrices and glycoproteins), inductors, receptors, and specific time sequencing. Understanding anterior segment anomalies and their systemic associations requires an understanding of neural crest proliferation and migration patterns; and they may be unified under the designation of neurocristopathies. Goldenhar's syndrome, not previously considered a neurocristopathy, may be considered one on the basis of the relationship between clinical findings and neural crest embryology.

Glycoconjugates, cellular differentiation, and congenital glaucoma.

Studies of congenital glaucoma have described and debated the disease process in cellular and structural terms, yet the functional aspects of the disease remain poorly understood. This paper presents an attempt to look at the disease from a different perspective: the role of glycoconjugates and their influence on morphogenesis of the corneoscleral angle. Extracellular and cell-surface complex carbohydrates and trabecular meshwork development were observed in normal C-57 BL/6J mice with light and electron microscopy. Lectin-stained fixed tissues were evaluated by fluorescein light microscopy and with computer-controlled scanning microspectrophotometry. The appearance and type of specific glycoconjugates was related to morphogenesis and differentiation, with specific reference to the development of the trabecular meshwork. Our results suggest that glycoconjugates are: (1) important in the morphogenesis of the corneoscleral angle, and (2) provide some of the required signals for the differentiation of the cells of the trabecular meshwork. These findings emphasize the possibility that a complex series of morphological and biological events in the normal development of the trabecular meshwork ultimately leads to a functionally competent trabecular meshwork, that is, capacitation.

Phlyctenular keratoconjunctivitis.

There is growing evidence that a variety of corneal disorders may be expressions of altered immune mechanisms. Phlyctenular keratoconjunctivitis is probably such a condition. Typically described as arising from hypersensitivity to tuberculin protein, other antigens clearly may participate, particularly staphylococcus products. When corneal involvement occurs, it need not be confined to the peripheral cornea. The symptoms of the process may be disproportionate to obvious findings and so exaggerated as to suggest a psychiatric disorder. Resultant visual deficits, if the disease is corneal, progressive, unrecognized, and untreated may be profound. Representative examples of this disease are cited. Immune mechanisms are reviewed. The importance of recognizing the characteristic sign and symptom complex is stressed. Appropriate diagnostic studies and treatment regimens are presented.

Brown's syndrome in twins.

Monozygotic twin girls concordant for Brown's syndrome with reversed asymmetry are presented. This appears to be the first report of concordance for the presence of Brown's syndrome in twins. Embryological factors and a possible explanation for the etiology of this condition in the form as presented are discussed.

Photophobia, epiphora, and torticollis: a masquerade syndrome.

Three young children presented with photophobia, epiphora, and torticollis as the initial manifestation of a posterior fossa tumor. In each case there was a delay in treatment due to the presumptive diagnosis of a local ocular inflammatory condition. We recommend that children with unexplained photophobia, epiphora, and torticollis undergo an imaging technique to evaluate the posterior fossa.

Congenital glaucoma and retinal dysplasia.

The differential diagnosis of leukocoria (pseudoglioma) in the neonate includes multiple conditions, including malformations with retinal dysplasia as a component. Typically bilateral, retinal dysplasia is characteristically seen in microphthalmic eyes. Certain chromosomal defects have been described. The case reported herein presented in the first month of life with an enlarged eye, elevated intraocular pressure, prominent iris vasculature, and leukocoria. Family history was positive in one respect: this is the second child of a Viet Nam veteran exposed to Agent Orange. The first child, from a different mother, also had birth defects. Other than his left eye, the child is completely normal. Ultrasonography showed posterior vitreous opacities of indeterminate configuration. CT scan suggested a posterior intraocular mass. Histologically, the principal features were an anomalous, largely unformed corneoscleral angle, intraocular hemorrhage, and retinal dysplasia. Light microscopic studies were performed. The corneoscleral angle revealed an anteriorly inserted iris with an absence of trabecular meshwork and Schlemm's canal. This case is considered unique on the basis of the association of retinal dysplasia with congenital glaucoma and larger-than-normal eye. The significance of reported paternal exposure to Agent Orange in this instance is unknown.

Neurofibromatosis type 1 in children.

OBJECTIVE: To document ophthalmic and general characteristics of Neurofibromatosis Type 1 (NF1) in children; and to characterize the iris changes of NF1 including their variability and reliability. DESIGN AND PATIENTS: One hundred and ninety-six patients with NF1 were evaluated for general characteristics; 156 patients underwent prospective eye evaluations; and 151 NF1 patients and controls had iris photography in accordance with a protocol. Masked evaluation of photographs compared to a known diagnosis, and interobserver reliability tests were performed. MAIN OUTCOME MEASURES: Incidence of iris changes consistent with NF1 (Lisch nodules, plus) by age group; spectrum of iris changes found; correlation of iris findings to known diagnosis and Kappa coefficients for interobserver reliability. RESULTS: Iris changes were common in children over age 5, and increased with age; masked evaluation of photographs compared to a known diagnosis yielded fair to poor correlation (Kappa = -.02 to .50); interobserver reliability was poor (Kappa = -.02 to .24, overall .174); iris changes found in NF1 are more diverse than classic descriptions of Lisch nodules, and including a broader spectrum probably increases the sensitivity and decreases the specificity of their diagnostic value. CONCLUSION: Iris changes as a diagnostic marker for NF1 may need rethinking; this study calls to question their reliability and validity.

A value analysis model applied to the management of amblyopia.

PURPOSE: To assess the value of amblyopia-related services by utilizing a health value model (HVM). Cost and quality criteria are evaluated in accordance with the interests of patients, physicians, and purchasers. METHODS: We applied an HVM to a hypothetical statistical ("median") child with amblyopia whose visual acuity is 20/80 and to a group of children with amblyopia who are managed by our practice. We applied the model to calculate the value of these services by evaluating the responses of patients and physicians and relating these responses to clinical outcomes. RESULTS: The consensus value of care for the hypothetical median child was calculated to be 0.406 (of 1.000). For those children managed in our practice, the calculated value is 0.682. Clinically, 79% achieved 20/40 or better visual acuity, and the mean final visual acuity was 0.2 logMAR (20/32). Value appraisals revealed significant concerns about the financial aspects of amblyopia-related services, particularly among physicians. Patients rated services more positively than did physicians. CONCLUSIONS: Amblyopia care is difficult, sustained, and important work that requires substantial sensitivity to and support of children and families. Compliance and early detection are essential to success. The value of amblyopia services is rated significantly higher by patients than by physicians. Relative to the measured value, amblyopia care is undercompensated. The HVM is useful to appraise clinical service delivery and its variation. The costs of failure and the benefits of success are high; high-value amblyopia care yields substantial dividends and should be commensurately compensated in the marketplace.