Sectoral Ciliary Body Agenesis Complicated with Cataract Formation Diagnosed by Ultrasound Biomicroscopy

We aimed to present a novel case of sectoral ciliary body agenesis and complicated cataract as an embryogenic defect of eye development diagnosed by ultrasound biomicroscopy. A 20-year-old male patient presented with a complaint of visual impairment in his left eye since childhood. Slit-lamp examination of the left eye revealed pigment precipitation and focal lens opacities extending from the temporal quadrant through the posterior lens capsule, blocking the central optical axis. On ultrasound biomicroscopy examination, there was a hyperechoic reflection belonging to the rudimentary ciliary body structures between 2-5 o'clock in the temporal quadrant. The zonules could not be visualized in the same location. At all other quadrants of the anterior chamber angle, the ciliary body and zonules were normal. This is a very rare case of sectoral ciliary body agenesis complicated by cataract. Ultrasound biomicroscopy may be useful for detecting rare congenital anomalies of the anterior segment, anterior chamber angle, and ciliary body.

Effect of primary iris and ciliary body cyst on anterior chamber angle in patients with shallow anterior chamber.

OBJECTIVE: To evaluate the prevalence of primary iris and/or ciliary body cysts in eyes with shallow anterior chamber and their effect on the narrowing of the anterior chamber angle. METHODS: Among the general physical check-up population, subjects with shallow anterior chambers, as judged by van Herick technique, were recruited for further investigation. Ultrasound biomicroscope (UBM) was used to detect and measure the cysts located in the iris and/or ciliary body, the anterior chamber depth (ACD), the angle opening distance at 500 µm (AOD500), and the trabecular-iris angle (TIA). A-scan ultrasonography was used to measure the ocular biometry, including lens thickness, axial length, lens/axial length factor (LAF), and relative lens position (RLP). The effect of the cyst on narrowing the corresponding anterior chamber angle and the entire angle was evaluated by the UBM images, ocular biometry, and gonioscopic grading. The eye with unilateral cyst was compared with the eye without the cyst for further analysis. RESULTS: Among the 727 subjects with shallow anterior chamber, primary iris and ciliary body cysts were detected in 250 (34.4%) patients; among them 96 (38.4%) patients showed unilateral single cyst, 21 (8.4%) patients had unilateral double cysts, and 42 (16.8%) patients manifested unilateral multiple and multi-quadrants cysts. Plateau iris configuration was found in 140 of 361 (38.8%) eyes with cysts. The mean size of total cysts was (0.6547 ± 0.2319) mm. In evaluation of the effect of the cyst size and location on narrowing the corresponding angle to their position, the proportion of the cysts causing corresponding angle narrowing or closure among the cysts larger than 0.8 mm (113/121, 93.4%) was found to be significantly higher than that of the cysts smaller than 0.8 mm (373/801, 46.6%), and a significant higher proportion was also found in the cysts located at iridociliary sulcus (354/437, 81.0%) than in that at the pars plicata (131/484, 27.1%). In evaluating the effect of the cyst on the entire anterior chamber angle, the eyes with multiple and multi-quadrants cysts manifested significant narrowing of the entire anterior chamber angle as compared with the eyes without cysts, based on the data analysis in comparison of TIA, AOD500, and gonioscopic grading evaluation. The unilateral single or double cysts in the eyes had no significant effect on narrowing of anterior chamber angle as compared with eyes without cysts. The iris and/or ciliary body cysts did not seem to affect the axial length, ACD, lens thickness, RLP, LAF. CONCLUSIONS: The prevalence of primary iris and ciliary body cyst was 34.4% in the subjects with shallow anterior chamber. The cysts larger than 0.8 mm, locating at iridociliary sulcus, or multiple and extensive cysts were inclined to cause the angle narrowing or closure.

Síndrome de Joubert: a propósito de cuatro hermanos adultos afectados / Joubert syndrome: report of four adult siblings affected

Introducción. El síndrome de Joubert es una rara enfermedad de transmisión genética autosómica recesiva. Hasta el momento se han descubierto 10 genes asociados. Todos ellos codifican para proteínas ciliares primarias, de ahí que seconsidere al síndrome de Joubert dentro de las ‘ciliopatías’. Las cilias primarias están implicadas en la proliferación celular neuronal y migración axonal en el cerebelo y el tallo cerebral, siendo indispensables para su correcto desarrollo. La primera descripción fue realizada por Joubert et al en 1968, comunicando cuatro casos de individuos con agenesia parcial o total del vermis cerebeloso, síndrome de apnea-hiperapnea episódica neonatal, movimientos oculares anormales, ataxia y retraso mental. Uno de ellos presentaba también meningoencefalocele occipital. Casos clínicos. Se describen cuatro individuos adultos afectados por la enfermedad, hermanos biológicos entre sí, de 24 a 35 años de edad, presentando la evolución clínica y neuroimágenes con el ‘signo del molar’ del mesencéfalo, característico de la entidad, imagen formada por la agenesia o hipoplasia del vermis cerebeloso, pedúnculos cerebelosos superiores estrechos, horizontalizados, engrosados y elongados con falta de decusación, y fosa interpeduncular profunda en losistmos y puentes superiores. Conclusiones. Se pone de manifiesto la necesidad de un diagnóstico precoz de la enfermedad para lograr un correcto seguimiento, abordaje terapéutico y consejo genético familiar, así como también el papel del cerebelo en funciones cognitivasy desarrollo de la inteligencia (AU)

Introduction. Joubert syndrome is a rare, autosomal recessive genetic transmission illness, with ten associated genes discovered at the time. They code for primary ciliary proteins; that is why Joubert syndrome is considered a ‘ciliopathie’.The primary cilia are involved in cell proliferation and neuronal migration in cerebellum and axonal brain, being essential for their proper development. The first description was made in 1969 by Marie Joubert and colleagues. They reportedfour cases with partial or total agenesis of the cerebellar vermis, apnea-hyperpnea neonatal episodic, abnormal eye movements, ataxia and mental retardation. One of them also showed occipital meningoencephalocele. Case reports. Four adult individuals affected by the disease are described. All of them biological siblings, within 24-35 yearsold, and presenting the ‘sign of the molar’ midbrain in their clinical and neuroimaging. It is an entity characteristic, with the image formed by agenesis or hypoplasia of the cerebellar vermis, superior cerebellar peduncle narrow, flatten, thickened and elongated with a lack of decussation and deep interpeduncular fossa at the level of the isthmus and upper bridges. Conclusions. This study shows the need for early disease diagnosis to ensure proper monitoring, therapeutic approach and family genetic counseling, as well as the role of the cerebellum in cognitive functions and intelligence development (AU)

[Bilateral ciliary zonule defect]. / Beidseitiger Zonulafaserdefekt.

Anterior segment colobomas can be found isolated or in combination with changes in the posterior segment. A coloboma of the ciliary zonule leads to alteration of the lens profile with myopia and astigmatism. Amblyopia and cataract development may also occur. We present two cases with a coloboma of the zonule with different degrees of expression and the most important differential diagnoses are discussed.

[Persistent fetal vasculature syndrome--clinical image and diagnostic difficulties]. / Zespól przetrwalego unaczynienia plodowego--obraz kliniczny i trudnosci diagnostyczne.

PURPOSE: The aim of this review is to present cases of clinically differentiated picture of persistent fetal vasculature syndrome--PFVS (also called persistent hyperplastic primary vitreous body--PHPVB) observed in group of infants and children. MATERIAL AND METHODS: Case records of four children with characteristic changes of posterior form of persistent fetal vasculature syndrome, which were observed on fundus of the eyes, were analyzed retrospectively. Routine ophthalmological examination, genetic, cytogenetic and laboratory tests towards coexisting bacterial, viral and parasitic diseases and congenital anomaly of the eye or chorioretinal neoplastic changes of neonatal period were performed. Ophthalmological changes were archived using Ret-Cam II apparatus (Clarity Medical Systems). Measurement of the axial diameter of the eyes and exclusion coexisting ocular disease by ultrasonography (A-scan US i B-scan US and color Doppler ultrasonography--CDU), were performed. RESULTS: Different clinical image of posterior form of persistent hyperplastic primary vitreous body was observe in ophthalmological examination. Changes such as fibrovascular tissue connecting optic disc (n. II) with ora serrata of the retina coexisting with retinoschisis, retrolental mass or persistent hyaloid artery were observed. Additionally concomitant features in pathological eyes were: iris hypoplasia, corectopia, microphthalmia, congenital cataract, secondary glaucoma, degeneration or retinoschisis and intrvitreous haemorrhage. Strabismus, nystagmus and heart disease in the form of persistent fetal circulation were associated with ophthalmological changes. Inflammatory and genetically determined diseases were excluded in differential diagnosis. CONCLUSIONS: The diagnosis of persistent hyperplastic primary vitreous body (PHPVB) was confirmed by characteristic clinical symptoms and results of the additional research. Suggestion of recognition of this syndrome (PHPVB) as well as persistent fetal vasculature syndrome (PFVS) should be implemented diagnostics towards other optic and systemic development defects.

Heparan sulfate deficiency in periocular mesenchyme causes microphthalmia and ciliary body dysgenesis.

The heparan sulfate (HS) is a component of proteoglycans in the extracellular matrix and on cell surfaces, modulating developmental processes. The aim of this study is to investigate whether the defect of HS in the periocular mesenchyme impairs ocular morphogenesis. First, using Protein 0-Cre transgenic mice, we ablated Ext1, which encodes an indispensable enzyme for HS synthesis, in the developing periocular mesenchyme. The expression of Ext1 messenger RNA (mRNA) and HS were observed by RT-PCR and immunohistochemistry, respectively. The phenotypes in the mutant were evaluated by light microscopy and immunohistochemistry for cellular makers. Second, the distribution of the mutant periocular mesenchymal cells was tracked using a Rosa26 Cre-reporter gene. No mutant embryos (Protein 0-Cre;Ext1(flox/flox)) were identified after embryonic day 14.5 (E14.5). RT-PCR showed that an intense band amplified from Ext1 was observed in cDNAs from the control periocular mesenchymal cells at E13.5; however, the band for Ext1 was hardly detectable in cDNA from the mutant embryo, indicating that the mRNA was missing in the mutant periocular mesenchyme at E13.5. The HS expression was disrupted in the periocular mesenchyme of the mutant ocular tissues. The HS deficiency resulted in microphthalmia with reduced axial lengths, lens diameters, and vitreous sizes compared with the littermate eyes. The mutant embryos showed agenesis of the anterior chamber, where cells expressing Cre recombinase were distributed. Moreover, the mutants showed phenotypic alterations in the neural ectoderm including dysgenesis of the presumptive ciliary body and agenesis of the optic nerve head. These findings demonstrate that HS in the periocular mesenchyme plays a critical role in normal ocular morphogenesis, indicating reciprocal interactions between the periocular mesenchyme and the neural ectoderm.

Acute angle closure after implantable contact lens insertion unresponsive to surgical peripheral iridectomy.

We present a case of acute angle closure that occurred after insertion of an implantable contact lens (ICL). The apparent papillary-block angle closure did not resolve after 2 patent iridotomies and a surgical iridectomy, but did respond to pupil dilation (not constriction). Ultrasound biomicroscopy revealed abnormally large and irregular ciliary processes that may have contributed to the unusual behavior of the ICL-iris complex. The condition resolved after the ICL was replaced by one with a smaller haptic diameter. Routine ultrasound biomicroscopic assessment of the ciliary body anatomy preoperatively and ICL haptic positioning postoperatively may identify risk factors that could predispose ICL patients to acute angle closure.

Genotype and phenotype correlations in congenital glaucoma: CYP1B1 mutations, goniodysgenesis, and clinical characteristics.

PURPOSE: To determine whether there is a correlation among mutations in the cytochrome P4501B1 gene (CYP1B1), the degree of angle dysgenesis observed histologically, and disease severity in congenital glaucoma. DESIGN: Interventional case series. METHODS: Direct DNA sequencing was used to screen six unrelated children with congenital glaucoma, each set of parents, and all siblings for CYP1B1 mutations. Specimens of the anterior chamber angle obtained at trabeculectomy were examined histologically to identify abnormalities of the aqueous outflow pathway. CYP1B1 mutations were correlated with both the degree of angle dysgenesis and the patients' disease severity (age at diagnosis, difficulty in achieving intraocular pressure [IOP]) control. RESULTS: Four (66.7%) of the six patients were compound heterozygotes for mutations in the CYP1B1 gene. Seven of the eight CYP1B1 mutations were identified, including two novel mutations (R117P, C209R) and five others previously described (G61E, R368H, R390H, E229K, 4340delG). The cases were divided on the basis of histological phenotype into categories of (1) severe goniodysgenesis highlighted by the agenesis of the canal of Schlemm (two patients), (2) moderate goniodysgenesis characterized by the presence of a band of collagenous tissue (CT) in the trabecular meshwork (TM) and/or the juxtacanalicular tissues (JXT) (three patients), and (3) mild goniodysgenesis with deposition of a mucopolysaccharide material in the JXT (one patient). CYP1B1 mutations were identified in both cases of severe angle dysgenesis and two of three cases of moderate dysgenesis. Disease severity closely correlated with the degree of angle dysgenesis. CONCLUSIONS: Most patients in our cohort had compound heterozygous CYP1B1 mutations. Specific CYP1B1 mutations may be associated with severe or moderate angle abnormalities.

[Persistent hyperplastic primary vitreous--developmental anomaly of the eye in children]. / Pierwotnie przetrwale cialo szkliste--wada rozwojowa galki ocznej u dzieci.

Persistent hyperplastic primary vitreus in children continues to be a diagnostic and therapeutic challenge for ophthalmologists. It can occur in isolation, in association with other ocular disorders and rarely as a part of systemic disorder. Characteristic features include microphthalmic eye, white vascularized retrolental tissue with or without a persistent hyaloid artery, centrally dragged ciliary processes, an anteriorly shifted and (or) swollen lens, and varing degrees of lenticular opacification. PHPF is the most common associaton with unilateral cataracts. Differential diagnosis and functional effect of treatment are discussed.

Genotype and phenotype correlations in congenital glaucoma.

PURPOSE: To determine whether there is a correlation among mutations in the cytochrome P450 1B1 gene (CYP1B1), the degree of angle dysgenesis observed histologically, and disease severity in congenital glaucoma. METHODS: Direct DNA sequencing was utilized to screen six unrelated children with congenital glaucoma, each set of parents, and all siblings for CYP1B1 mutations. Specimens of the anterior chamber angle obtained at trabeculectomy were examined histologically to identify abnormalities of the aqueous outflow pathway. CYP1B1 mutations were correlated with both the degree of angle dysgenesis and the patient's disease severity (age at diagnosis, difficulty in achieving intraocular pressure control). RESULTS: Four of the six patients (66.7%) were compound heterozygotes for mutations in the CYP1B1 gene. Seven of the eight CYP1B1 mutations were identified, including two novel mutations (R117P, C209R) and five others previously described (G61E, R368H, R390H, E229K, 4340delG). The cases were divided based on histological phenotype into categories of (1) severe goniodysgenesis highlighted by the agenesis of Schlemm's canal (two patients), (2) moderate goniodysgenesis characterized by the presence of a band of collagenous tissue in the trabecular meshwork and/or the juxtacanalicular tissues (three patients), and (3) mild goniodysgenesis with deposition of a mucopolysaccharide material in the juxtacanalicular tissue (one patient). CYP1B1 mutations were identified in both cases of severe angle dysgenesis and two of three cases of moderate dysgenesis. Disease severity closely correlated with the degree of angle dysgenesis. CONCLUSION: The majority of cases in the cohort had compound heterozygous CYP1B1 mutations. Specific CYP1B1 mutations may be associated with severe or moderate angle abnormalities.

Bilateral complete isolated cryptophthalmos: a case report.

Cryptophthalmos is a condition of congenital eyelid malformation most commonly accompanied by syndactyly, urogenital anomalies, and cognitive impairments as in Fraser syndrome. We report on a patient with characteristic features consistent with autosomal dominant bilateral complete isolated cryptophthalmos. This patient represents only the sixth documented case of bilateral complete isolated cryptophthalmos. Defining characteristics of this variety are discussed, including bilateral central dimpling over the globes, normal eyebrow growth, and the absence of cognitive impairment. We introduce phenotypic features that distinguish bilateral isolated cryptophthalmos from other forms and discuss its relatively favorable prognosis.

Ultrasound biomicroscopic findings in aniridia.

PURPOSE: To describe the ultrasound biomicroscopic features of eyes with aniridia. DESIGN: Observational case series. METHODS: Nineteen eyes of 10 patients with aniridia (six males and four females) ranging in age from 3 months to 53 years (21.0 +/- 16.4, mean +/- SD), and 50 normal subjects (30 men and 20 women) ranging from 16 to 56 years (31.1 +/- 13.2) were evaluated. Ultrasound biomicroscopic findings were recorded in the 3-, 6-, 9-, and 12-o'clock directions. Adult patients (aged 16 years or older) with aniridia were compared with the age-matched controls. RESULTS: Ultrasound biomicroscopy (UBM) detected extremely tiny irises in all eyes with aniridia. The eyes with aniridia showed significantly smaller values than the controls in ciliary body length (4.49 +/- 0.63 versus 5.79 +/- 0.44 mm, P <.001, unpaired Student t test), ciliary body thickness (0.75 +/- 0.17 versus 1.24 +/- 0.22 mm, P <.001), iris root thickness (0.47 +/- 0.14 versus 0.61 +/- 0.07 mm, P <.001), scleral-ciliary process angle (31.7 +/- 3.26 versus 43.1 +/- 4.48 degree, P <.001), and anterior chamber depth (1.99 +/- 0.43 versus 2.94 +/- 0.34 mm, P <.001). In the aniridia eyes, there was a significantly positive correlation between iris thickness and ciliary body thickness (Pearson r = 0.829, P =.001). CONCLUSION: Ultrasound biomicroscopic imaging demonstrated that not only iris hypoplasia but also ciliary body hypoplasia exist in aniridia. Anterior inclination of the ciliary process was also found, which was thought to be at least partly responsible for the shallow anterior chamber.

Lack of type XVIII collagen results in anterior ocular defects.

Mice lacking type XVIII collagen have defects in the posterior part of the eye, including delayed regression of the hyaloid vasculature and poor outgrowth of the retinal vessels. We report here that these mice also have a fragile iris and develop atrophy of the ciliary body. The irises of Col18a1-/- mice can be seen to adhere to the lens and cornea. After the pupils begin to function, the double layer of epithelial cells separates at the apical cell contacts, leading to defoliation of its posterior pigment epithelial cell layer, and extracellular material begins to accumulate in the basement membrane zones of the iris. In contrast to the iris epithelia, where no clear signs of cellular atrophy were detected, the lack of type XVIII collagen resulted in atrophy of the pigmented epithelial cells of the ciliary body, and there were also ultrastructural abnormalities in the basement membrane zones. These changes did not lead to chronically elevated intraocular pressures, however. Our results indicate that type XVIII collagen is needed for the integrity of the epithelial basement membranes of the iris and the ciliary body and that its gene should therefore be taken into account as a new potential cause of anterior segment disorders in the eye.

Age-dependent iris abnormalities in collagen XVIII/endostatin deficient mice with similarities to human pigment dispersion syndrome.

PURPOSE: Collagen XVIII is expressed in ocular basement membranes (BMs) and inactivating mutations cause Knobloch syndrome, with several ocular abnormalities. In this study we investigated ocular structures in collagen XVIII/endostatin (Col18a1(-/-))-deficient mice to elucidate the role of this extracellular matrix component in the eye. METHODS: Eyes of Col18a1(-/-) and control mice were examined by light and transmission electron microscopy, laser scanning ophthalmoscopy, and fluorescence angiography. Immunohistochemical analysis of neuronal, epithelial, and immune cells in the eye was performed with antibodies against established cell markers. RESULTS: Col18a1(-/-) mice showed a disruption of the posterior iris pigment epithelial (IPE) cell layer with release of melanin granules. The BM of the posterior IPE was attached to the lens and the nonpigmented epithelium of the ciliary body, which was flattened in mutant mice. In aged mutant mice a severe thickening of the stromal iris BM zone was found, and pigmented cells migrated out of the iris and covered the retina along the inner limiting membrane (ILM), sometimes penetrating into the retina. These cells resembled iris clump cells, and immunohistochemistry demonstrated that they were macrophage-like cells. Furthermore, morphologically abnormal retinal vasculature was seen by fluorescence angiography. CONCLUSIONS: The abnormalities in the iris and ciliary body of Col18a1(-/-) mice demonstrate an important role of collagen XVIII for the function of ocular BMs. The absence of this collagen alters the properties of BMs and leads to severe defects in the iris, showing striking similarities to human pigment dispersion syndrome. In addition, loss of collagen XVIII creates changes that allow clump cells to migrate out of the iris. These cells have not been well characterized previously. In the current study we showed that they are macrophage-like cells and are able to penetrate the ILM in mutant mice. The disease mechanism of human pigment dispersion syndrome is not well understood, but Col18a1(-/-) mice may serve as a model and demonstrate the potential importance of alterations in extracellular matrix components in this disease.

[Complications of a voluminous congenital ciliary body cyst]. / Komplikationen einer grossen kongenitalen Ziliarkörperzyste.

BACKGROUND: Multiple cysts of iris and ciliary body may cause many complications such as acute or chronic angle closure glaucoma. PATIENT: We present a boy with multiple congenital cysts of the iris pigment epithelium and a voluminous cyst of the unpigmented ciliary body epithelium of the right eye. This resulted in lenticular astigmatism, concomitant strabismus divergens and subsequently to anisometropia. The voluminous cyst (8 x 12 mm in diameter) was folded around the lens, reached the optic axis and resulted in displacement of the lens and contact between the iris and the corneal endothelium from 6.30 to 11. After puncture and partial resection of the cyst at the age of 8 months the boy developed a subcapsular multivesicular cataractic clouding of the temporal lens and a progredient myopia (up to - 14.0/- 2.0/0 degrees ); in contrast the left eye was hyperopic (+ 3.5/- 3.75/0 degrees ). The lens was subluxated superonasally due to congenital damage of the zonular fibres. Because development of visual acuity seemed limited by these determinants (20/200 at the right eye), cataract surgery with posterior capsulorhexis, anterior vitrectomy, and implantation of a capsular tension ring and posterior chamber intraocular lens was performed at the age of nearly five. Actually, there is an orthotropia, best corrected visual acuity in the distance of 20/32 in the right and 20/20 in the left eye; binocular vision is somewhat restricted. CONCLUSION: Usually congenital cysts are clinically not very relevant; occasionally surgical intervention is required to ensure adequate development of visual acuity.

High-frequency ultrasonography findings in persistent hyperplastic primary vitreous.

PURPOSE: To identify anatomic correlates in eyes with persistent hyperplastic primary vitreous (PHPV) by using high-frequency ultrasonography. METHOD: Three main groups of patients were studied by means of high-frequency ultrasonography over a 19-month period. Group I included 9 eyes of 9 patients with newly diagnosed unilateral PHPV. Group II included 4 eyes of 4 patients with unilateral PHPV that had been previously surgically treated. Group III included 22 eyes and was a control group of patients without PHPV. This group consisted of the 5 contralateral normal eyes of 5 patients with unilateral PHPV in the fellow eye, both eyes of one patient with uncomplicated unilateral cataracts, the affected eye of one patient with unilateral uncomplicated cataract, the affected eye of one patient with isolated retinal coloboma, and 13 normal eyes of 7 young adults. Group I and II patients also had B-scan ultrasonography performed and had any intraoperative findings noted. RESULTS: Characteristic features of PHPV, such as centrally dragged ciliary processes and swollen anteriorly displaced lens, were observed only in those eyes with PHPV. A new echographic finding of a double linear echo was observed in the region of the pars plana or plicata only in eyes with PHPV. This finding was confirmed intraoperatively to be consistent with a thickened adherent anterior hyaloid face and not to be an anteriorly inserted peripheral retina. CONCLUSION: High-frequency ultrasound can be reliably used to distinguish characteristic features of PHPV. To our knowledge this is the first such description of the use of high-frequency ultrasonography in PHPV eyes. Furthermore, the presence of a thickened adherent anterior hyaloid face may help explain the well-recognized complications of peripheral retinal tears and retinal detachments during and after surgical intervention.

Haploinsufficiency of the transcription factors FOXC1 and FOXC2 results in aberrant ocular development.

Anterior segment developmental disorders, including Axenfeld-Rieger anomaly (ARA), variably associate with harmfully elevated intraocular pressure (IOP), which causes glaucoma. Clinically observed dysgenesis does not correlate with IOP, however, and the etiology of glaucoma development is not understood. The forkhead transcription factor genes Foxc1 (formerly Mf1 ) and Foxc2 (formerly Mfh1 ) are expressed in the mesenchyme from which the ocular drainage structures derive. Mutations in the human homolog of Foxc1, FKHL7, cause dominant anterior segment defects and glaucoma in various families. We show that Foxc1 (+/-)mice have anterior segment abnormalities similar to those reported in human patients. These abnormalities include small or absent Schlemm's canal, aberrantly developed trabecular meshwork, iris hypoplasia, severely eccentric pupils and displaced Schwalbe's line. The penetrance of clinically obvious abnormalities varies with genetic background. In some affected eyes, collagen bundles were half normal diameter, or collagen and elastic tissue were very sparse. Thus, abnormalities in extracellular matrix synthesis or organization may contribute to development of the ocular phenotypes. Despite the abnormalities in ocular drainage structures in Foxc1 (+/-)mice, IOP was normal in almost all mice analyzed, on all genetic backgrounds and at all ages. Similar abnormalities were found in Foxc2 (+/-)mice, but no disease-associated mutations were identified in the human homolog FKHL14 in 32 ARA patients. Foxc1 (+/-)and Foxc2 (+/-)mice are useful models for studying anterior segment development and its anomalies, and may allow identification of genes that interact with Foxc1 and Foxc2 (or FKHL7 and FKHL14 ) to produce a phenotype with elevated IOP and glaucoma.