Journal of Pediatric Ophthalmology and Strabismus

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Rieger's Syndrome: A Form of Iridocorneal Mesodermal Dysgenesis

H Dunbar Hoskins, Jr, MD; Robert N Shaffer, MD

Abstract

In 1935, Rieger1 described a syndrome in which the primary ocular features are hypoplasia of the anterior stromal leaf of the iris, filaments or bands of iris tissue bridging the iridocorneal angle, a marked prominence of Schwalbe's line (posterior embryotoxon), and a frequent association with glaucoma. He postulated that this was a hereditary disorder of the development of the mesodermal structures of the anterior segment, and termed the anomaly dysgenesis mesodermalis cornea et iridis. Subsequent investigations have confirmed the specific syndrome whose diagnostic criteria include variations of the features mentioned above.

In 1920, Axenfeld2 described a markedly prominent, thickened, and centrally displaced Schwalbe's line which he labeled posterior embryotoxon. This was felt to be a form of Rieger's syndrome, and, thus, Axenfeld's name is used to describe those variations of Rieger's syndrome which have only posterior embryotoxon and iris filaments or bands bridging the angle with or without glaucoma.3'4 These phenomena may represent variations in expression of the same genetic defect.

The findings in Rieger's syndrome present in diverse forms, which indicates the variability of expression of the syndrome, and will be described in some detail in this paper.

Inheritance Pattern

Genetic studies have indicated that Rieger's syndrome is a dominantly transmitted defect with a high penetrance. Alkemade, in his comprehensive monograph,5 calculated the penetrance rate as 95 per cent, and, although a wide variance in phenotypic expression is found, he feels that the diagnosis is always clinically obvious. Other investigators,3,6 however, suggest that mild forms of the disease can be difficult to differentiate from the extremes of variations in normal angle structure.

Description of Abnormalities

Although the four features mentioned in the first paragraph are the most frequent findings in this disorder, various other ocular and systemic abnormalities have been described.5'7'* Emmetropia occurs in less than 10 per cent of patients, while high degrees of myopia, hyperopia and astigmatism are common. Exotropia occurs more frequently than esotropia. The strabismus is not always related to ametropia and may be associated with cranial anomalies.

Sclera and Cornea

Although blue scleras have been described in iridocorneal mesodermal dysgenesis, they have not been found more frequently than in other developmental defects of the anterior segment. Microcornea, which may be illusional due to a poorly defined timbal border, has been described in a small number of patients, while macrocornea, even in the absence of glaucoma, occurs more often. The majority of patients have normal corneal measurements. Prominent posterior embryotoxon, usually visible without gonioscopy, is almost universally present in this syndrome, although Henkind3 described a case in which it was absent, and feels it is not essential to the diagnosis. It is a re lucent line commonly located 0.5 to 2.0 mm anterior to the limbus on the posterior surface of the cornea. It often forms a complete circle and is semitransparent, although opacities may be present at the sites of iris adhesions (Fig. 1 ). Portions of it may be detached into the anterior chamber* Central corneal opacities are not common, which makes this syndrome different from the anterior chamber cleavage syndrome of Reese 10 (Peter's anomaly, congenital anterior staphyloma).

Comment

Most investigators agree that the sine qua non of iridocorneal mesodermal dysgenesis is hypoplasia of the anterior mesodermal layer of the iris. When this is accompanied by posterior embryotoxon and bridging filaments, the diagnosis is obvious.

Rieger's syndrome has occasionally been confused with the anterior chamber cleavage syndrome of Reese (Peter's anomaly, congenital anterior staphyloma)." This anomaly has a central corneal opacity and thus differs from Rieger's syndrome (Fig. 4). The opacity is usually in the posterior corneal layers and is surrounded by…

In 1935, Rieger1 described a syndrome in which the primary ocular features are hypoplasia of the anterior stromal leaf of the iris, filaments or bands of iris tissue bridging the iridocorneal angle, a marked prominence of Schwalbe's line (posterior embryotoxon), and a frequent association with glaucoma. He postulated that this was a hereditary disorder of the development of the mesodermal structures of the anterior segment, and termed the anomaly dysgenesis mesodermalis cornea et iridis. Subsequent investigations have confirmed the specific syndrome whose diagnostic criteria include variations of the features mentioned above.

In 1920, Axenfeld2 described a markedly prominent, thickened, and centrally displaced Schwalbe's line which he labeled posterior embryotoxon. This was felt to be a form of Rieger's syndrome, and, thus, Axenfeld's name is used to describe those variations of Rieger's syndrome which have only posterior embryotoxon and iris filaments or bands bridging the angle with or without glaucoma.3'4 These phenomena may represent variations in expression of the same genetic defect.

The findings in Rieger's syndrome present in diverse forms, which indicates the variability of expression of the syndrome, and will be described in some detail in this paper.

Inheritance Pattern

Genetic studies have indicated that Rieger's syndrome is a dominantly transmitted defect with a high penetrance. Alkemade, in his comprehensive monograph,5 calculated the penetrance rate as 95 per cent, and, although a wide variance in phenotypic expression is found, he feels that the diagnosis is always clinically obvious. Other investigators,3,6 however, suggest that mild forms of the disease can be difficult to differentiate from the extremes of variations in normal angle structure.

Description of Abnormalities

Although the four features mentioned in the first paragraph are the most frequent findings in this disorder, various other ocular and systemic abnormalities have been described.5'7'* Emmetropia occurs in less than 10 per cent of patients, while high degrees of myopia, hyperopia and astigmatism are common. Exotropia occurs more frequently than esotropia. The strabismus is not always related to ametropia and may be associated with cranial anomalies.

Sclera and Cornea

Although blue scleras have been described in iridocorneal mesodermal dysgenesis, they have not been found more frequently than in other developmental defects of the anterior segment. Microcornea, which may be illusional due to a poorly defined timbal border, has been described in a small number of patients, while macrocornea, even in the absence of glaucoma, occurs more often. The majority of patients have normal corneal measurements. Prominent posterior embryotoxon, usually visible without gonioscopy, is almost universally present in this syndrome, although Henkind3 described a case in which it was absent, and feels it is not essential to the diagnosis. It is a re lucent line commonly located 0.5 to 2.0 mm anterior to the limbus on the posterior surface of the cornea. It often forms a complete circle and is semitransparent, although opacities may be present at the sites of iris adhesions (Fig. 1 ). Portions of it may be detached into the anterior chamber* Central corneal opacities are not common, which makes this syndrome different from the anterior chamber cleavage syndrome of Reese 10 (Peter's anomaly, congenital anterior staphyloma).

Fig. i: Hypoplasia of iris stroma with axially displaced and thickened Schwalbe's line (posterior embryotoxon).

Fig. i: Hypoplasia of iris stroma with axially displaced and thickened Schwalbe's line (posterior embryotoxon).

Iris and Pupil

Hypoplasia of the iris stroma to a varying extent is present in all patients with iridocorneal mesodermal dysgenesis (Rieger's syndrome). The anterior mesodermal leaf may be absent, in which case the sphincter appears prominent, and there are no iris folds or crypts. The deeper mesodermal layer with its radial pattern may be thinned, and transillumination through the pigmented epithelium is occasionally possible. This hypoplasia may involve the entire iris surface or only a small segment, and usually both eyes are affected to a similar degree.

Pupillary abnormalities, including corectopia, polycoria, dyscoria, and ectropion uveae have been described in over two thirds of the reported cases (Fig. 2). Persistent pupillary membranes have been noted occasionally.

Iridocorneal Angle

Adhesions between peripheral iris and the corneal angle wall are a constant finding in this syndrome. They range from fine threadlike filaments to broad membranes which insert into the trabeculum and the area of Schwalbe's line (Fig. 3). These are frequently quite obvious and can be large enough to cause distortion of the pupil by traction. In other patients they take on the appearance of prominent iris processes. Occasionally blood vessels are seen to bridge the angle in the filaments of iris tissue. Deeper in the angle, a yellow to gray membrane may sometimes be seen in the area between the trabeculum and iris root. This membrane appears to be a continuation of the anterior stroma of the iris. The trabeculum itself may have a thickened translucent appearance.

The iris insertion is not displaced anteriorly, and the chamber angle is always wide open. Schlemm's canal, when visible (some have such extensive processes that the angle is largely concealed), retains its normal position, although pathological specimens have revealed that portions of it may be absent or posteriorly displaced*

Fig. 2: Typical pupillary anomalies, corectopia, polycoria. Note hypoplasia of iris and absence of collarette allowing the sphincter muscle to be easily seen. Reprinted with permission from Shaffer RN and Weiss, DI: The Congenital and Pediatric Glaucomas. St Louis, CV Mosby, i970.

Fig. 2: Typical pupillary anomalies, corectopia, polycoria. Note hypoplasia of iris and absence of collarette allowing the sphincter muscle to be easily seen. Reprinted with permission from Shaffer RN and Weiss, DI: The Congenital and Pediatric Glaucomas. St Louis, CV Mosby, i970.

Fig. 3, A and B: Iris filaments bridging angle to insert in thickened posterior embryotoxon. Filaments have varied shapes. Reprinted with permission from Shaffer RN and Weiss DI: The Congenital and Pediatric Glaucomas. St. Louis, 1970.

Fig. 3, A and B: Iris filaments bridging angle to insert in thickened posterior embryotoxon. Filaments have varied shapes. Reprinted with permission from Shaffer RN and Weiss DI: The Congenital and Pediatric Glaucomas. St. Louis, 1970.

Lens

Pigmented star-shaped opacities of the anterior capsule of the lens are the most commonly mentioned lenticular change, although cataracts as well as colobomata and various degrees of subluxation have all been reported.

Retina and Choroid

Although various disc and retinal vascular anomalies have been reported in isolated instances in Rieger's syndrome, there is apparently no constantly associated neuroretinal anomaly other than cupping of the optic disc if glaucoma should occur.

Choroidal hypoplasia has been described in several patients and suggested histologically in one.1* Since the choroid arises from the same embryonal mesoderm as the iris, it is not unreasonable to expect a defect in the choroid which may be evident in lightly pigmented eyes.

Glaucoma

Glaucoma may be present at birth and resemble any other form of congenital glaucoma with enlarged cloudy corneas, epiphora, and photophobia. More commonly, it has its onset in later childhood or early adult life, and occurs, usually bilaterally, in 50 per cent of affected individuals who have undergone ophthalmological evaluation. The degree of visible anomalous development of the angle does not correlate with the presence of glaucoma. Certainly the bridging filaments, even though they may be quite dense, are not the obstructing element. In all likelihood, a developmental defect within the trabeculum is responsible for the decreased aqueous outflow.

Systemic Anomalies

Absent and malformed teeth are the most consistent nonocular manifestation of iridocorneal mesodermal dysgenesis. Hypoplasia of the mandible and maxilla and hypertelorism are frequently mentioned. Other reported systemic anomalies occur so infrequently as to be coincidental rather than true manifestations of the syndrome.

Therapy

Unless glaucoma occurs, the only therapy required is correction of refractive errors and strabismus surgery if indicated. In the presence of glaucoma, a trial of medical therapy is advisable. Should this fail to control the tension, and disc and field changes are present, external filtration surgery must be performed. In those few patients who present in infancy with hydrophthalmos, goniotomy has seldom been found to be of value. This might be explained in part by the aplasia of Schlemm's canal which has been previously noted in some pathology-specimens.

Standard external filtration procedures are hazardous in these young, distensible eyes because subsequent increase in intraocular pressure can result in staphylomata at the operative sites. Recently, external trabeculectomy has been used in three of these eyes; however, it is too soon to know if this will prove to be the best mode of therapy for these patients.

Fig. 4: Peter's anomaly. The central opacity may undergo gradual clearing.

Fig. 4: Peter's anomaly. The central opacity may undergo gradual clearing.

Fig. 5: Goniophotograph of father of patient in Fig. I. Note abundant iris processes inserting anterior to scleral spur. None reached Schwalbe's line. The patient's mother had similar angles.

Fig. 5: Goniophotograph of father of patient in Fig. I. Note abundant iris processes inserting anterior to scleral spur. None reached Schwalbe's line. The patient's mother had similar angles.

Comment

Most investigators agree that the sine qua non of iridocorneal mesodermal dysgenesis is hypoplasia of the anterior mesodermal layer of the iris. When this is accompanied by posterior embryotoxon and bridging filaments, the diagnosis is obvious.

Rieger's syndrome has occasionally been confused with the anterior chamber cleavage syndrome of Reese (Peter's anomaly, congenital anterior staphyloma)." This anomaly has a central corneal opacity and thus differs from Rieger's syndrome (Fig. 4). The opacity is usually in the posterior corneal layers and is surrounded by a zone of clear cornea. Adhesions in the form of bands or filaments arise from the surface of the iris to attach to the posterior surface of the corneal defect. Complete resolution of this opacity is uncommon but gradual clearing is often seen. Glaucoma is frequently present. Although sporadic cases have been reported in families with Rieger's syndrome, Peter's anomaly is also seen as a pure familial trait or as a spontaneous occurrence in normal families. Phenotypically, it appears to be an extreme form of Rieger's syndrome; however, genotypically, they seem to be different entities.

The significance of bridging filaments in the form of iris processes has been recently investigated. Lichter " evaluated 340 normal eyes gonioscopically and found that only eight contained an abundance of iris processes inserting anterior to the scleral spur, and that four of these had a positive steriod provocative test. A subsequent evaluation 13 revealed that anteriorly inserting iris processes were abundantly present in 25 per cent of 70 glaucomatous and hypertensive eyes, and six of eight eyes (75 per cent) with pigmentary glaucoma. Since only 0.25 per cent of normal eyes have large numbers of iris processes, the authors suggested that the prominence of anteriorly displaced iris processes was a presumptive sign of a developmental defect in the angle.

We have recently studied four generations of the family of a child with frank iridocorneal mesodermal dysgenesis. Although none of the members showed the full-blown syndrome, several demonstrated varying degrees of iris stromal hypoplasia with prominent iris processes inserting into the trabecular band (Fig. 5). There was no evidence, demonstrable or historical, of posterior embryotoxon, pupillary abnormalities, or glaucoma in any of the ancestors. Although spontaneous cases are usually attributed to gene mutation it is appealing to speculate that mild forms of the syndrome may be passed as variants of normal and thus escape classification. Careful observation of the quantity and positioning of iris processes and their relationship to other anterior segment anomalies and glaucoma may help clarify this subject.

Summary

A review of the terminology, heredity, pathogenesis, and clinical findings of iridocorneal mesodermal dysgenesis has been presented. Its relationship with glaucoma and the therapeutic requirements resulting from this assocation have been mentioned. It is suggested that mild forms of the syndrome may be manifested by subtle changes in the positioning and quantity of iris processes associated with minor degrees of stromal abnormalities of the iris.

References

1. Rieger H: Dysgenesis mesodermalis cornea et iridis. Z Augenheilk 86:333, 1935.

2. Axenfeld TH: Embryotoxon cornea posterius Klin Monastbl Augenheilkd 65:381, 1920.

3. Henkind P, Siegel IM, Carr RE: Mesodermal dysgenesis of the anterior segment; Riegers anomaly. Arch Ophthalmol 73:810, 1965.

4. Duke-Elder S: System of Ophthalmology. Vol XI. London, Klimpton, 1969, p 635.

5. Alkemade PPH: Dysgenesis mesodermalis of the iris and cornea. Netherlands, Royal VanGorcum Ltd.

6. Burian HM, Braley AE, Allen L: Visibility of the ring of Schwalbe and the trabecular zone. Arch Ophthalmol 53:767, 1955.

7. Kolker A, Hetherington J: Becker-Shaffer's Diagnosis and Therapy of the Glaucomas. 3rd ed. St Louis, CV Mosby, 1970, p 284.

8. Shafer RN, Weiss DI: Congenital and Pediatric Glaucomas. St Louis, CV Mosby, 1970.

9. Wolter JR, Sandall G. Fralick FB: Mesodermal dysgenesis of the anterior eye, J Ped Ophthalmol 4:41, 1967.

10. Busch G, Weiskopf J, Busch K: Dysgenesis mesodermalis et ectodermalis. Riegeroder Riegersche Krankheit. Klin. Monastbl Augenheilkd 136:512, 1960.

11. Reese AB, Ellsworth RM: The anterior chamber cleavage syndrome. Arch Ophthalmol 75:307, 1966.

12. Lichter PR: Iris processes in 340 eyes. Am J Opthalmol 68:872, 1969.

13. Lichter PR, Shaffer RN: Iris processes and glaucoma. Am J Ophthalmol 70:905, 1970.

10.3928/0191-3913-19720201-08

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