4.2 Examples of Genetic Disorders of the Anterior Segment

•Almost no or very little pigment of the trabecular meshwork. The surface glistens like cellophane.

•Schwalbe’s ring and the scleral spur are not as white as in adults.

•The recess is (much) smaller than in adults.

•The peripheral anterior stroma of the iris is thin, and the pigmented layer shines through.

4.2Examples of Genetic Disorders of the Anterior Segment

4.2.1Primary Congenital Glaucoma, Hydrophthalmus, Buphthalmus, Childhood Glaucoma (Birth

to the 10th Year of Life)

The simplest developmental disorder is dysgenesis of the trabecular meshwork and Schlemm’s canal (trabeculodysgenesis) that leads to hydrophthalmus or buphthalmus. The globe has a larger diameter than the age percentile values. The cornea has a diameter of more than 12 mm at birth and shows Haab’s striae. There are breaks in Descemet’s membrane running horizontally or parallel to the limbus (Fig. 4.2).

The chamber angle is open and it is not possible to differentiate the structures in detail. It is often combined with an anterior insertion of the iris with many iris processes. The neural crest cells have not developed properly to form the trabecular meshwork structures. Sometimes even Schlemm’s canal is missing. The stroma of the peripheral iris is very hypoplastic and forms garlands, so you can easily detect the dark pigmented posterior layer of the iris (Fig. 4.3). An impermeable membrane, formerly called Barkan’s membrane, coating the chamber angle, cannot be found histologically.

The onset of the disease differs. It occurs bilaterally in 70%. In 80% it is diagnosed within the first year of life. If onset is later (after 3 or 4 years of age), the disease does not lead to a larger diameter of the globe because of the higher stiffness of the collagens of the sclera and cornea.

Besides sporadic cases, hereditary congenital glaucoma is associated with mutations in the genes CYP1B1 (coding for cytochrome P 450

Fig. 4.2 Breaks in Descemet’s membrane called Haab’s striae in the cornea of an eye with buphthalmus (regredient light)

Fig. 4.3 Chamber angle in an eye with primary congenital glaucoma showing a scalloped appearance, prominent vessels on the iris, and a fine white membrane over the iris (special wide angle goniolens for goniotomy; courtesy P. Khaw)

1B1) and LTBP2 (latent transforming growth factor beta binding protein 2).

An eye with a megalocornea has a diameter larger than usual, but the anterior segment (cornea, iris and iris insertion, chamber angle) and all other parameters (IOP, optic disc, length of the globe) are within the normal ranges.

4.2.2More Complex Dysgeneses: Secondary Childhood Glaucomas

Axenfeld described a prominent Schwalbe’s ring and called it embryotoxon corneae posterius. It does not increase the risk for glaucoma. This white line often has connections to the anterior layer of the iris composed of fine thin fibers (Figs. 4.4, 4.5, and 4.6).

Rieger described the dysgenesis mesodermalis corneae et iridis with atrophy of the iris and an ectopic pupil due to adhesions or bridging tissue bands between the iris and (the prominent) Schwalbe’s ring (Fig. 4.7).

Axenfeld-Rieger syndrome (autosomal dominant) shows developmental disorders of the anterior segment of the eye. Systemic disorders are dental and maxillary hypoplasia and failure of involution of the periumbilical skin. There are three types according to the pathological gene map locus: type 1 (RIEG1) with the locus on chromosome 4q25–q26, type 2 (RIEG2) with the locus on chromosome 13q14, and type 3 (RIEG3) with the locus on chromosome 6p25 (with cardiac defects).

Peters described congenital defects of Descemet’s membrane presenting as a central corneal leucoma with circular synechiae around the center

Fig. 4.4 Embryotoxon posterius is seen as a thin white line in the nasal and temporal parts of the peripheral cornea (arrows) and represents a prominent Schwalbe’s ring. It is of no pathological concern in relation to glaucoma

Fig. 4.6 Gonioscopic findings of the eye in Fig. 4.5 showing tissue bridges from the iris to the prominent Schwalbe’s ring (embryotoxon posterius)

Fig. 4.5 Slitlamp photograph of a prominent Schwalbe’s ring temporally

Fig. 4.7 Rieger anomaly with white line in the nasal periphery of the cornea with bridging tissue bands decentering the pupil (korectopia)