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Iridogoniodysgenesis with Cataract
I R I D O G O N I O D Y S G E N E S I S W I T H CATARACT PAUL H E N K I N D , M.D.,
AND ALAN H. FRIEDMAN,
M.D.
Bronx, New York Ocular examination—Visual acuity was RE: 20/400 (-5.50 sph. C +2.50 cyl. ax. 90°) and LE: 20/40 (-8.00 sph. C +2.50 cyl. ax. 90°). Color vision (AO-HRR plates) was normal in the left eye. Ocular rotations were full and the eyelids and conjunctivae normal. Both corneas were nor mal and each measured 12 mm in diameter. Keratomer readings were: RE: 40.00 mer 5°, 40.75 mer 95°, and LE: 39.75 mer 5°, 41.75 mer 95°. Schwalbe's line was not evident on slit-lamp ex amination. Corectopia was present with each slightly oval pupil displaced superonasally (Fig. 2). Both irides were greyish-blue, showed scant stroma, and lacked a colarette. The pupillary ruff was absent superonasally. The periphery of each iris transilluminated. Gonioscopy revealed deep, heavily pigmented, abnormal angles (Fig. 3). A veil of pigmented tissue of varying density lined the angle from the angle recess to schwalbe's line. Normal CASE REPORTS angle structures could not be visualized. A heavily This family is of Italian origin (Fig. 1). pigmented ciliary body band was apparent behind the more diaphanous portions of the abnormal angle There is no history of consanguinity. The tissue. Radial and circumferential angle vessels were eyes of the two affected boys (IIIi and III 2 ) present bilaterally. A moderately cataractous lens and their parents (II 2 and II 3 ) were exam with wrinkled anterior lens capsule was present in the right eye. The left lens showed prominent corti ined. Data concerning other family members cal spokes and pigment stars on the anterior lens were obtained from the parents. capsule. The right fundus was not visualized. The left fundus had an optic disk with myopic crescent Case 1—This 21-year-old truck driver (IIIi) was and early posterior staphyloma. seen in consultation for evaluation of a cataract in The intraocular pressures (applanation) were his right eye and elevated intraocular pressure in RE: 20 mm Hg and L E : 31 mm Hg, while tonoghis left eye. He stated that he always had poorer raphy revealed a coefficient of outflow of RE: 0.18 sight in his right eye and that recently he noted a and LE: 0.19. Perimetry (Goldmann) showed a rapid decrease in its vision. The patient denied ocu full left field with normal blind spot. lar trauma or exposure to physical or chemical During a three-week observation period, the agents. Family history revealed that an older right lens rapidly matured and the capsular wrin brother (IIIi) had undergone cataract surgery at the kling increased. Follow-up tonometry showed nor age of 23 years and the mother had had repair of a mal intraocular pressures in both eyes. An intracapretinal detachment at the age of 45 years. Medical sular cataract extraction with sector iridectomy was evaluation revealed the patient to be a healthy man performed and although alpha chymotrypsin (in 1: with a mild erythematous, scaly skin rash over his 5000 dilution) was utilized, direct zonulysis was re cheek bones. He was the product of a full-term quired. Firm adhesions between vitreous and poste pregnancy without history of maternal infection, rior lens capsule were present and were severed and his growth and development were normal. Lab during delivery of the lens. There was no vitreous oratory studies, including chromosomal analysis and loss. x-rays, were normal. Case 2—This 26-year-old man (III2) had worn glasses since early childhood. He was the product From the Department of Ophthalmology, Albert of a full-term pregnancy without history of mater Einstein College of Medicine and Montefiore Hos nal infection, and his growth and development were pital and Medical Center. This work was supported normal. He stated that at the age of 15 years his by Public Health Service Grant EY 00613 01 from left eye was struck with a lead pencil. This necessi the National Eye Institute, and a grant from the tated patching for a day. At the age of 23 years, Seeing Eye, Inc., Morristown, New Jersey. while serving in the US Navy, he noted a sudden Reprint requests to Paul Henkind, M.D., Depart decrease in vision in his left eye. A cataract was ment of Ophthalmology, Albert Einstein College of found and after cataract surgery he was advised Medicine and Montefiore Hospital and Medical Cen that the lens "broke" during the operation. ter, 111 East 210th Street, Bronx, New York 10467. Examination showed the patient to be well-devel949
A variety of heritable disorders may affect the anterior segment of the eye. This report describes two brothers who show identical abnormalities of the anterior segment. These patients have anomalies of the iris and ante rior chamber angle (iridogoniodysgenesis) and cataracts which developed and pro gressed to maturity in early adulthood. We have been unable to find reports of similar associated ocular abnormalities in the litera ture. The relationship of this syndrome to other inherited anterior segment anomalies is discussed.
AMERICAN JOURNAL OF OPHTHALMOLOGY
950
NOVEMBER, 1971
IRIDOGONIODYSGENESIS (IDG) WITH CATARACT
87
81
87
3 brothers -(1 with myopia) 2 sisters
n 60
III
7children all normal
L-Sl 2 i
2L_126
>L_I S
H B /
X
myopia cataract and I D G retinal detachment
glaucoma ?
Fig. 1 (Henkind and Friedman). Pedigree of patients with iridogoniodysgenesis with cataract. The affected family members are IIL and III>. oped with no gross abnormalities except an ortho dontic problem which was being corrected by braces. Ocular examination—The eyes of this patient were strikingly similar to those of his brother (IIIi). Visual acuity was RE: 20/25 (piano spli. Z +1.00 cyl. ax. 90°) and LE: 20/30 (+6.75 sph.). Color vision (AO-HRR plates) and Amsler Grid testing were normal in each eye. The intra ocular pressures (applanation) were 11 mm Hg. Ocular motility, eyelids and adnexae were normal. Both corneas were clear except for peripheral scar-
Fig. 2 (Henkind and Friedman). Case 1. Top: Right eye with iris hypoplasia, deficient pupillary ruff (arrow) corectopia and cataract. Bottom: Left eye with iris hypoplasia and cataract.
Fig. 3 (Henkind and Friedman). Case 1, right eye. Goniophotograph of angle at six o'clock (Goldmann gonioprism). Arrow 1 points to line of iris insertion. Arrow 2 points to Schwalbe's line. The area between 1 and 2 is lined by a veil of pigmented tissue of varying density. Note the diapha nous areas between the arrows.
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IRIDOGONIODYSGENESIS
ring superiorly and a superficial central scar in the left eye. In the right eye, Schwalbe's line was barely visible nasally on slit lamp examination. Horizontal corneal diameters were R E : 12 mm, and L E : 11 mm. Keratometer readings were: R E : 40.75 mer 5°, 43.00 mer 95°, and L E : 41.50 mer 180°, 41.75 mer 90°, with irregular mires. Corectopia was present with each slightly oval pupil displaced superonasally (Fig. 4 ) . Both irides were greyish-blue, showed scant stroma, and lacked a collarette. There was absence of the pupillary ruff superonasally in both eyes. The periphery of each iris transilluminated. In the left eye, a basal iridectomy was present at 10 o'clock and a slit-like open ing at 12 o'clock. Gonioscopy was virtually identi cal to that seen in his brother. Both angles were deep, heavily pigmented, and lined by a veil of ab normal tissue (Fig. 5 ) . There were prominent radial and circumferential angle vessels in both eyes. After iris dilatation, the right lens was noted to have numerous pigment stars on the anterior capsule and a relatively dense posterior subcapsular opacity. Vitreous floaters were present in the right eye. The right fundus appeared normal. Examina tion of the left fundus revealed an optic disc with myopic conus. Case 3—This 61-year-old housewife is the mother of both patients (Ilia and I l k ) . She has worn a myopic correction since childhood. In Janu ary, 1956, she underwent surgery for a retinal de tachment in her right eye. There is no history of
Fig. 5 (Henkind and Friedman). Case 2, right eye. Goniophotograph of angle at six o'clock (Goldmann gonioprism). Arrow 1 points to line of iris insertion. Arrow 2 points to Schwalbe's line. As in Figure 3, the area between 1 and 2 is lined by a veil of pigmented tissue. Note the diaphanous zones between the arrows. ocular trauma or infection and her general health is excellent. Ocular examination—Visual acuity was R E : hand motion only (—4.25 sph.), and L E : 2 0 / 4 0 + (—5.50 sph.). Color vision ( A O - H R R plates) was normal. The intraocular pressures (applanation) were 12 mm H g . Ocular rotations were full and the eyelids and conjunctivae normal. The corneas were normal and both diameters measured 11 mm. Both irides were hazel and displayed a normal collarette and pupillary ruff. T h e pupils were cen tric, reactive to light and 4 mm in diameter. Goni oscopy revealed wide open angles ( 3 + ) with a normal configuration. Slight pigment speckling was present overlying the meshwork especially inte riorly. The lenses showed early cortical changes, more so in the right eye. Vitreous floaters were seen in the right eye. The right fundus displayed a number of pigmented chorioretinal scars in the inferotemporal quadrant and a retinal band nasally. The left fundus was normal. Case 4—This 60-year-old man is the father of both patients ( I I I i and I l i a ) . H e denies any ocular complaints and is in excellent health. Ocular examination—Visual acuity was R E : 20/25 ( - 2 . 0 0 sph. Z - 0 . 5 0 cyl. ax. 160°) and L E : 2 0 / 6 0 + ( - 2 . 7 5 sph. Z - 0 . 5 0 cyl. ax. 165°). The intraocular pressures (applanation) were 14 mm Hg. Ocular motility, eyelids and conjunctivae were normal. The corneas were normal and both cor neal diameters measured 10 mm. Both irides were hazel and displayed normal markings; the pupils were centric, reactive to light and 4 mm in diam eter. Gonioscopy revealed open angles ( 3 + ) with a normal architecture. A prominent circular vessel was seen in the right chamber angle. The lens showed early cortical opacities inferonasally in each eye. The fundi were normal.
Fig. 4 (Henkind and Frieman). Case 2. T o p : Right eye with iris hypoplasia and corectopia. Bot tom: Left eye with peripheral iridectomy at 10 o'clock, iris hypoplasia and corectopia.
DISCUSSION
These two brothers display an unusual
AMERICAN JOURNAL OF OPHTHALMOLOGY
952
combination of ocular findings: iridogoniodysgenesis and rapidly maturing cataracts. Three major points are to be considered: the genetic aspects of the condition, the relation of this syndrome to other anterior segment anomalies, and the early appearance of cata racts. The occurrence of an almost identical clin ical picture in two brothers suggests an he reditary etiology. Both were healthy from birth without stigmata or prenatal infection. The normal appearance of the parents' ante rior ocular segments, and the absence of a family history of cataract during the preced ing two generations, are strong evidence against autosomal dominant inheritance. Sex-linked recessive inheritance is doubtful because the maternal grandfather presum ably had normal eyes and the mother's eyes are unlike those of her affected sons. We must consider, therefore, that iridogoniodysgenesis and early cataract formation is an expression of autosomal recessive inheri tance. Further evidence for this is the strik ing similarity of the affected brothers' eyes. In this regard, recessive conditions often present a limited range of expressivity while dominant ones have a variable phenotype.1 The relation between the present condition and other anterior segment anomalies is summarized in Table 1. The posterior embryotoxon of Axenfeld2 consists of a prominent Schwalbe's line which can be seen by direct observation without gonioscopy. A prominent Schwalbe's
NOVEMBER, 1971
line is present in about 15% of all individu als.3 In more pronounced cases of posterior embryotoxon, the iris may be hypoplastic and adhesions between the corneal opacity and the peripheral iris stroma may occur. Such cases probably represent variants of Rieger's anomaly. Dominant pedigrees, particularly where there is involvement of the iris, have been reported, but autosomal recessive inheritance has also been docu mented.4 Cataract formation is not a feature of this condition. One of our patients (HI 2 ) has an externally visible posterior embryo toxon in his right eye, but we do not feel that it is a characteristic of this syndrome. Mesodermal dysgenesis of the iris and cornea is an anomaly that was clearly delin eated by Rieger.5 Its primary features are hypoplasia of the anterior iris stroma, iris strands bridging the angle and posterior em bryotoxon. Glaucoma is common in the first few decades of life and a variety of lens opacities have been noted, but early onset of cataract has not been described.6 Rieger's anomaly is inherited as an autosomal domi nant and a wide range of expressivity is evi dent in affected families. When associated with dental or skeletal anomalies, the condi tion has been termed Rieger's syndrome. Our affected patients can be separated from those with Rieger's anomaly both by the dif ferent clinical appearance of the eyes and by the presumably different mode of inheri tance. Peters' anomaly,7 considered a mesoder-
TABLE 1 COMPARISON OF THE HERITABLE ANTERIOR SEGMENT ANOMALIES
Condition Posterior embryotoxon8~4 Mesodermal dysgenesis of iris and cornea6,8 Peters anomaly'-* Goniodysgenesis with glaucoma10,11 Iridogoniodysgenesis and cataract (present cases)
Heredity
Ocular Abnormalities Cornea
Recessive (?) Common dominant (?) Autosomal dominant Common
Iris
Angle
Lens
Glaucoma
Other Findings
Occasional* Occasional* None
Occasional* None
Common
Common
Occasion al*
Common
Recessive (?) Common Common Autosomal dominant Occasional* Common
Common Common
Common None
Common Common
May have den tal or skele tal abnor malities None None
Autosomal recessive
Common
Common
?
None
* Involvement has been noted.
None
Common
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IRIDOGONIODYSGENESIS
mal dysgenesis of the cornea,8 is a congenital disorder in which there is a central corneal opacity with abnormalities of the deep stroma and a local absence of Descemet's membrane. Though the anomaly may be lim ited to the cornea, various defects in the an terior segment, including corectopia, iris hypoplasia, persistant pupillary membranes, and anterior polar cataract have been re corded.8 While there are human pedigrees with combinations of Rieger's and Peters' anomalies, the latter is generally considered to involve recessive inheritance.8 On the other hand, Reese and Ellsworth 9 have clas sified the various anterior segment conditions together under the broad title, anterior chamber cleavage syndrome, and have noted that mothers of a number of their patients had rubella or other presumably viral infec tions during the first trimester of pregnancy. Goniodysgenesis and hereditary juvenile glaucoma10 is characterized by an abnormal iridocorneal angle, iris hypoplasia, and glau coma which develops in the first few decades of life. Inheritance is autosomal dominant in nature. The iris hypoplasia, corectopia, and appearance of the angles in this condition are very similar to that found in our pa tients. One of our patients ( U l i ) had sev eral elevated intraocular pressure readings in his left eye, but tonography, visual fields, and repeat applanation tonometry failed to confirm the presence of glaucoma. It is con ceivable that elevated ocular tensions will be manifest as glaucoma at a later date. In the large pedigree reported by Jerndal 10 and that of Weatherill and Hart 11 a number of family members had "minor" dysgenesis of the an gle and normal ocular pressure. Early onset of cataract was not noted in either of these pedigrees, nor is it a feature of congenital glaucoma, with the possible exception of that seen with rubella. While our patients resem ble those with goniodysgenesis and juvenile glaucoma, the presence of cataracts, lack of glaucoma, and different mode of inheritance are significant distinguishing characteristics. We presume that the early appearance and maturation of cataracts in our cases are re
lated to the anterior segment abnormality. The possibility does exist, however, that the lens changes are unrelated to the iris and an gle changes. A number of heritable condi tions are characterized by the early appear ance of rapidly progressive cataracts. Wer ner's syndrome12 is one such disorder, with cataracts developing between the ages of 20 and 35 years and rapidly progressing to in tumescence. The premature senility and en docrine disturbances of Werner's syndrome were not present in our cases. The cataracts found in Rothmund's syndrome develop in the first few years of life. Neither Werner's nor Rothmund's syndromes have associated angle anomalies. Rapidly maturing cataracts are also seen in association with diabetes mellitus. Neither of our affected patients manifested chemical or clinical evidence of diabetes. Patient IIIj had a very mild eczematoid eruption overlying his malar promi nences. There were no other skin lesions and therefore one cannot relate the cataracts to a dermatologic disorder. Neither affected pa tient was ever treated with x-radiation nor were they exposed to the wide variety of chemical agents which have been reported to induce cataracts.12 Conradi's syndrome (dysplasia epiphysealis punctata) has re cently been reported to have an anterior chamber angle anomaly similar to that found in mesodermal dysgenesis.13 Patients with this condition also have cataracts. Our pa tients lack the typical clinical appearance of patients with this syndrome. Pigmented lens capsule stars were present on the anterior capsule of the less cataractous lens of each affected brother and represents remnants of a persistant pupillary membrane. Such rem nants are not usually associated with cataract formation and are commonly seen in other wise normal eyes.14 SUMMARY
Two brothers manifested abnormalities of the iris and anterior chamber angle (iridogoniodysgenesis) and cataract. The cataracts developed in early adulthood and rapidly progressed to maturity. The absence of a
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AMERICAN JOURNAL OF OPHTHALMOLOGY
family history of cataract during the preced ing two generations, and the normal appear ance of the parents' anterior ocular seg ments, provided strong evidence against autosomal dominant inheritance. ACKNOWLEDGMENTS
We thank Dr. Herbert Vogel for referring his patient for our observation. We also thank Miss Leslie Rosenberg for typing the manuscript and Mr. Henrick Malpica for the photographs. REFERENCES
1. Siegel, I.: Personal communication. 2. Axenfeld, T.: Embryotoxon corneae posterius. Ber. Deutsch. Ophth. Ges. 42:301, 1920. 3. Burian, H. M., Braley, A. E., and Allen, L.: Enternal and gonioscopic visibility of the ring of Schwalbe and the trabecular zone. Tr. Am. Ophth. Soc. 52:389, 1954. 4. Forsius, H., Eriksson, A., and Fellman, J.: Embryotoxon corneae posterius in an isolated popu lation. Acta Ophth. 42:42, 1964. 5. Rieger, H.: Beitrage zur Kenntnis seltener Missbildungen der Iris; 2. Ueber Hypoplasie des Irisvorderblattes mit Verlagerung und Entrundung
NOVEMBER, 1971
der Pupille. Graefe's Arch. Ophth. 133:602, 1935. 6. Henkind, P., Siegel, I. M., and Carr, R. E.: Mesodermal dysgenesis of the anterior segment: Rieger's anomaly. Arch. Ophth. 73:810, 1965. 7. Peters, A.: Ueber angeborene Defektbildung der Descemetschen Membran. Klin. Mbl. Augenheilk. 44:27, 1906. 8. Alkemade, P. P. H.: Dysgenesis Mesodermalis of the Iris and the Cornea. A Study of Rieger's Syndrome and Peters' Anomaly. Assen, Van Gorcum, 1969. 9. Reese, A. B., and Ellsworth, R. M.: The ante rior chamber cleavage syndrome. Arch. Ophth. 75: 307,1966. 10. Jerndal, T.: Goniodysgenesis and hereditary juvenile glaucoma. Acta. Ophth. Suppl. 107, 1970. 11. Weatherill, J. E., and Hart, C. T.: Familial hypoplasia of the iris stroma associated with glau coma. Brit. J. Ophth. 53:433, 1969. 12. Duke-Elder, S. and Jay, B.: System of Oph thalmology, vol. 11. Diseases of the Lens and Vitre ous, Glaucoma and Hypotony. London, Kimpton, 1969, pp. 20, 105. 13. Hammond, A.: Dysplasia epiphysialis punctata with ocular anomaly. Brit. J. Ophth. 54:755, 1970. 14. Duke-Elder, S.: System of Ophthalmology, vol. 3. Normal and abnormal development. London, Kimpton, 1964, part 2, p. 775.
AND ALAN H. FRIEDMAN,
M.D.
Bronx, New York Ocular examination—Visual acuity was RE: 20/400 (-5.50 sph. C +2.50 cyl. ax. 90°) and LE: 20/40 (-8.00 sph. C +2.50 cyl. ax. 90°). Color vision (AO-HRR plates) was normal in the left eye. Ocular rotations were full and the eyelids and conjunctivae normal. Both corneas were nor mal and each measured 12 mm in diameter. Keratomer readings were: RE: 40.00 mer 5°, 40.75 mer 95°, and LE: 39.75 mer 5°, 41.75 mer 95°. Schwalbe's line was not evident on slit-lamp ex amination. Corectopia was present with each slightly oval pupil displaced superonasally (Fig. 2). Both irides were greyish-blue, showed scant stroma, and lacked a colarette. The pupillary ruff was absent superonasally. The periphery of each iris transilluminated. Gonioscopy revealed deep, heavily pigmented, abnormal angles (Fig. 3). A veil of pigmented tissue of varying density lined the angle from the angle recess to schwalbe's line. Normal CASE REPORTS angle structures could not be visualized. A heavily This family is of Italian origin (Fig. 1). pigmented ciliary body band was apparent behind the more diaphanous portions of the abnormal angle There is no history of consanguinity. The tissue. Radial and circumferential angle vessels were eyes of the two affected boys (IIIi and III 2 ) present bilaterally. A moderately cataractous lens and their parents (II 2 and II 3 ) were exam with wrinkled anterior lens capsule was present in the right eye. The left lens showed prominent corti ined. Data concerning other family members cal spokes and pigment stars on the anterior lens were obtained from the parents. capsule. The right fundus was not visualized. The left fundus had an optic disk with myopic crescent Case 1—This 21-year-old truck driver (IIIi) was and early posterior staphyloma. seen in consultation for evaluation of a cataract in The intraocular pressures (applanation) were his right eye and elevated intraocular pressure in RE: 20 mm Hg and L E : 31 mm Hg, while tonoghis left eye. He stated that he always had poorer raphy revealed a coefficient of outflow of RE: 0.18 sight in his right eye and that recently he noted a and LE: 0.19. Perimetry (Goldmann) showed a rapid decrease in its vision. The patient denied ocu full left field with normal blind spot. lar trauma or exposure to physical or chemical During a three-week observation period, the agents. Family history revealed that an older right lens rapidly matured and the capsular wrin brother (IIIi) had undergone cataract surgery at the kling increased. Follow-up tonometry showed nor age of 23 years and the mother had had repair of a mal intraocular pressures in both eyes. An intracapretinal detachment at the age of 45 years. Medical sular cataract extraction with sector iridectomy was evaluation revealed the patient to be a healthy man performed and although alpha chymotrypsin (in 1: with a mild erythematous, scaly skin rash over his 5000 dilution) was utilized, direct zonulysis was re cheek bones. He was the product of a full-term quired. Firm adhesions between vitreous and poste pregnancy without history of maternal infection, rior lens capsule were present and were severed and his growth and development were normal. Lab during delivery of the lens. There was no vitreous oratory studies, including chromosomal analysis and loss. x-rays, were normal. Case 2—This 26-year-old man (III2) had worn glasses since early childhood. He was the product From the Department of Ophthalmology, Albert of a full-term pregnancy without history of mater Einstein College of Medicine and Montefiore Hos nal infection, and his growth and development were pital and Medical Center. This work was supported normal. He stated that at the age of 15 years his by Public Health Service Grant EY 00613 01 from left eye was struck with a lead pencil. This necessi the National Eye Institute, and a grant from the tated patching for a day. At the age of 23 years, Seeing Eye, Inc., Morristown, New Jersey. while serving in the US Navy, he noted a sudden Reprint requests to Paul Henkind, M.D., Depart decrease in vision in his left eye. A cataract was ment of Ophthalmology, Albert Einstein College of found and after cataract surgery he was advised Medicine and Montefiore Hospital and Medical Cen that the lens "broke" during the operation. ter, 111 East 210th Street, Bronx, New York 10467. Examination showed the patient to be well-devel949
A variety of heritable disorders may affect the anterior segment of the eye. This report describes two brothers who show identical abnormalities of the anterior segment. These patients have anomalies of the iris and ante rior chamber angle (iridogoniodysgenesis) and cataracts which developed and pro gressed to maturity in early adulthood. We have been unable to find reports of similar associated ocular abnormalities in the litera ture. The relationship of this syndrome to other inherited anterior segment anomalies is discussed.
AMERICAN JOURNAL OF OPHTHALMOLOGY
950
NOVEMBER, 1971
IRIDOGONIODYSGENESIS (IDG) WITH CATARACT
87
81
87
3 brothers -(1 with myopia) 2 sisters
n 60
III
7children all normal
L-Sl 2 i
2L_126
>L_I S
H B /
X
myopia cataract and I D G retinal detachment
glaucoma ?
Fig. 1 (Henkind and Friedman). Pedigree of patients with iridogoniodysgenesis with cataract. The affected family members are IIL and III>. oped with no gross abnormalities except an ortho dontic problem which was being corrected by braces. Ocular examination—The eyes of this patient were strikingly similar to those of his brother (IIIi). Visual acuity was RE: 20/25 (piano spli. Z +1.00 cyl. ax. 90°) and LE: 20/30 (+6.75 sph.). Color vision (AO-HRR plates) and Amsler Grid testing were normal in each eye. The intra ocular pressures (applanation) were 11 mm Hg. Ocular motility, eyelids and adnexae were normal. Both corneas were clear except for peripheral scar-
Fig. 2 (Henkind and Friedman). Case 1. Top: Right eye with iris hypoplasia, deficient pupillary ruff (arrow) corectopia and cataract. Bottom: Left eye with iris hypoplasia and cataract.
Fig. 3 (Henkind and Friedman). Case 1, right eye. Goniophotograph of angle at six o'clock (Goldmann gonioprism). Arrow 1 points to line of iris insertion. Arrow 2 points to Schwalbe's line. The area between 1 and 2 is lined by a veil of pigmented tissue of varying density. Note the diapha nous areas between the arrows.
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IRIDOGONIODYSGENESIS
ring superiorly and a superficial central scar in the left eye. In the right eye, Schwalbe's line was barely visible nasally on slit lamp examination. Horizontal corneal diameters were R E : 12 mm, and L E : 11 mm. Keratometer readings were: R E : 40.75 mer 5°, 43.00 mer 95°, and L E : 41.50 mer 180°, 41.75 mer 90°, with irregular mires. Corectopia was present with each slightly oval pupil displaced superonasally (Fig. 4 ) . Both irides were greyish-blue, showed scant stroma, and lacked a collarette. There was absence of the pupillary ruff superonasally in both eyes. The periphery of each iris transilluminated. In the left eye, a basal iridectomy was present at 10 o'clock and a slit-like open ing at 12 o'clock. Gonioscopy was virtually identi cal to that seen in his brother. Both angles were deep, heavily pigmented, and lined by a veil of ab normal tissue (Fig. 5 ) . There were prominent radial and circumferential angle vessels in both eyes. After iris dilatation, the right lens was noted to have numerous pigment stars on the anterior capsule and a relatively dense posterior subcapsular opacity. Vitreous floaters were present in the right eye. The right fundus appeared normal. Examina tion of the left fundus revealed an optic disc with myopic conus. Case 3—This 61-year-old housewife is the mother of both patients (Ilia and I l k ) . She has worn a myopic correction since childhood. In Janu ary, 1956, she underwent surgery for a retinal de tachment in her right eye. There is no history of
Fig. 5 (Henkind and Friedman). Case 2, right eye. Goniophotograph of angle at six o'clock (Goldmann gonioprism). Arrow 1 points to line of iris insertion. Arrow 2 points to Schwalbe's line. As in Figure 3, the area between 1 and 2 is lined by a veil of pigmented tissue. Note the diaphanous zones between the arrows. ocular trauma or infection and her general health is excellent. Ocular examination—Visual acuity was R E : hand motion only (—4.25 sph.), and L E : 2 0 / 4 0 + (—5.50 sph.). Color vision ( A O - H R R plates) was normal. The intraocular pressures (applanation) were 12 mm H g . Ocular rotations were full and the eyelids and conjunctivae normal. The corneas were normal and both diameters measured 11 mm. Both irides were hazel and displayed a normal collarette and pupillary ruff. T h e pupils were cen tric, reactive to light and 4 mm in diameter. Goni oscopy revealed wide open angles ( 3 + ) with a normal configuration. Slight pigment speckling was present overlying the meshwork especially inte riorly. The lenses showed early cortical changes, more so in the right eye. Vitreous floaters were seen in the right eye. The right fundus displayed a number of pigmented chorioretinal scars in the inferotemporal quadrant and a retinal band nasally. The left fundus was normal. Case 4—This 60-year-old man is the father of both patients ( I I I i and I l i a ) . H e denies any ocular complaints and is in excellent health. Ocular examination—Visual acuity was R E : 20/25 ( - 2 . 0 0 sph. Z - 0 . 5 0 cyl. ax. 160°) and L E : 2 0 / 6 0 + ( - 2 . 7 5 sph. Z - 0 . 5 0 cyl. ax. 165°). The intraocular pressures (applanation) were 14 mm Hg. Ocular motility, eyelids and conjunctivae were normal. The corneas were normal and both cor neal diameters measured 10 mm. Both irides were hazel and displayed normal markings; the pupils were centric, reactive to light and 4 mm in diam eter. Gonioscopy revealed open angles ( 3 + ) with a normal architecture. A prominent circular vessel was seen in the right chamber angle. The lens showed early cortical opacities inferonasally in each eye. The fundi were normal.
Fig. 4 (Henkind and Frieman). Case 2. T o p : Right eye with iris hypoplasia and corectopia. Bot tom: Left eye with peripheral iridectomy at 10 o'clock, iris hypoplasia and corectopia.
DISCUSSION
These two brothers display an unusual
AMERICAN JOURNAL OF OPHTHALMOLOGY
952
combination of ocular findings: iridogoniodysgenesis and rapidly maturing cataracts. Three major points are to be considered: the genetic aspects of the condition, the relation of this syndrome to other anterior segment anomalies, and the early appearance of cata racts. The occurrence of an almost identical clin ical picture in two brothers suggests an he reditary etiology. Both were healthy from birth without stigmata or prenatal infection. The normal appearance of the parents' ante rior ocular segments, and the absence of a family history of cataract during the preced ing two generations, are strong evidence against autosomal dominant inheritance. Sex-linked recessive inheritance is doubtful because the maternal grandfather presum ably had normal eyes and the mother's eyes are unlike those of her affected sons. We must consider, therefore, that iridogoniodysgenesis and early cataract formation is an expression of autosomal recessive inheri tance. Further evidence for this is the strik ing similarity of the affected brothers' eyes. In this regard, recessive conditions often present a limited range of expressivity while dominant ones have a variable phenotype.1 The relation between the present condition and other anterior segment anomalies is summarized in Table 1. The posterior embryotoxon of Axenfeld2 consists of a prominent Schwalbe's line which can be seen by direct observation without gonioscopy. A prominent Schwalbe's
NOVEMBER, 1971
line is present in about 15% of all individu als.3 In more pronounced cases of posterior embryotoxon, the iris may be hypoplastic and adhesions between the corneal opacity and the peripheral iris stroma may occur. Such cases probably represent variants of Rieger's anomaly. Dominant pedigrees, particularly where there is involvement of the iris, have been reported, but autosomal recessive inheritance has also been docu mented.4 Cataract formation is not a feature of this condition. One of our patients (HI 2 ) has an externally visible posterior embryo toxon in his right eye, but we do not feel that it is a characteristic of this syndrome. Mesodermal dysgenesis of the iris and cornea is an anomaly that was clearly delin eated by Rieger.5 Its primary features are hypoplasia of the anterior iris stroma, iris strands bridging the angle and posterior em bryotoxon. Glaucoma is common in the first few decades of life and a variety of lens opacities have been noted, but early onset of cataract has not been described.6 Rieger's anomaly is inherited as an autosomal domi nant and a wide range of expressivity is evi dent in affected families. When associated with dental or skeletal anomalies, the condi tion has been termed Rieger's syndrome. Our affected patients can be separated from those with Rieger's anomaly both by the dif ferent clinical appearance of the eyes and by the presumably different mode of inheri tance. Peters' anomaly,7 considered a mesoder-
TABLE 1 COMPARISON OF THE HERITABLE ANTERIOR SEGMENT ANOMALIES
Condition Posterior embryotoxon8~4 Mesodermal dysgenesis of iris and cornea6,8 Peters anomaly'-* Goniodysgenesis with glaucoma10,11 Iridogoniodysgenesis and cataract (present cases)
Heredity
Ocular Abnormalities Cornea
Recessive (?) Common dominant (?) Autosomal dominant Common
Iris
Angle
Lens
Glaucoma
Other Findings
Occasional* Occasional* None
Occasional* None
Common
Common
Occasion al*
Common
Recessive (?) Common Common Autosomal dominant Occasional* Common
Common Common
Common None
Common Common
May have den tal or skele tal abnor malities None None
Autosomal recessive
Common
Common
?
None
* Involvement has been noted.
None
Common
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IRIDOGONIODYSGENESIS
mal dysgenesis of the cornea,8 is a congenital disorder in which there is a central corneal opacity with abnormalities of the deep stroma and a local absence of Descemet's membrane. Though the anomaly may be lim ited to the cornea, various defects in the an terior segment, including corectopia, iris hypoplasia, persistant pupillary membranes, and anterior polar cataract have been re corded.8 While there are human pedigrees with combinations of Rieger's and Peters' anomalies, the latter is generally considered to involve recessive inheritance.8 On the other hand, Reese and Ellsworth 9 have clas sified the various anterior segment conditions together under the broad title, anterior chamber cleavage syndrome, and have noted that mothers of a number of their patients had rubella or other presumably viral infec tions during the first trimester of pregnancy. Goniodysgenesis and hereditary juvenile glaucoma10 is characterized by an abnormal iridocorneal angle, iris hypoplasia, and glau coma which develops in the first few decades of life. Inheritance is autosomal dominant in nature. The iris hypoplasia, corectopia, and appearance of the angles in this condition are very similar to that found in our pa tients. One of our patients ( U l i ) had sev eral elevated intraocular pressure readings in his left eye, but tonography, visual fields, and repeat applanation tonometry failed to confirm the presence of glaucoma. It is con ceivable that elevated ocular tensions will be manifest as glaucoma at a later date. In the large pedigree reported by Jerndal 10 and that of Weatherill and Hart 11 a number of family members had "minor" dysgenesis of the an gle and normal ocular pressure. Early onset of cataract was not noted in either of these pedigrees, nor is it a feature of congenital glaucoma, with the possible exception of that seen with rubella. While our patients resem ble those with goniodysgenesis and juvenile glaucoma, the presence of cataracts, lack of glaucoma, and different mode of inheritance are significant distinguishing characteristics. We presume that the early appearance and maturation of cataracts in our cases are re
lated to the anterior segment abnormality. The possibility does exist, however, that the lens changes are unrelated to the iris and an gle changes. A number of heritable condi tions are characterized by the early appear ance of rapidly progressive cataracts. Wer ner's syndrome12 is one such disorder, with cataracts developing between the ages of 20 and 35 years and rapidly progressing to in tumescence. The premature senility and en docrine disturbances of Werner's syndrome were not present in our cases. The cataracts found in Rothmund's syndrome develop in the first few years of life. Neither Werner's nor Rothmund's syndromes have associated angle anomalies. Rapidly maturing cataracts are also seen in association with diabetes mellitus. Neither of our affected patients manifested chemical or clinical evidence of diabetes. Patient IIIj had a very mild eczematoid eruption overlying his malar promi nences. There were no other skin lesions and therefore one cannot relate the cataracts to a dermatologic disorder. Neither affected pa tient was ever treated with x-radiation nor were they exposed to the wide variety of chemical agents which have been reported to induce cataracts.12 Conradi's syndrome (dysplasia epiphysealis punctata) has re cently been reported to have an anterior chamber angle anomaly similar to that found in mesodermal dysgenesis.13 Patients with this condition also have cataracts. Our pa tients lack the typical clinical appearance of patients with this syndrome. Pigmented lens capsule stars were present on the anterior capsule of the less cataractous lens of each affected brother and represents remnants of a persistant pupillary membrane. Such rem nants are not usually associated with cataract formation and are commonly seen in other wise normal eyes.14 SUMMARY
Two brothers manifested abnormalities of the iris and anterior chamber angle (iridogoniodysgenesis) and cataract. The cataracts developed in early adulthood and rapidly progressed to maturity. The absence of a
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family history of cataract during the preced ing two generations, and the normal appear ance of the parents' anterior ocular seg ments, provided strong evidence against autosomal dominant inheritance. ACKNOWLEDGMENTS
We thank Dr. Herbert Vogel for referring his patient for our observation. We also thank Miss Leslie Rosenberg for typing the manuscript and Mr. Henrick Malpica for the photographs. REFERENCES
1. Siegel, I.: Personal communication. 2. Axenfeld, T.: Embryotoxon corneae posterius. Ber. Deutsch. Ophth. Ges. 42:301, 1920. 3. Burian, H. M., Braley, A. E., and Allen, L.: Enternal and gonioscopic visibility of the ring of Schwalbe and the trabecular zone. Tr. Am. Ophth. Soc. 52:389, 1954. 4. Forsius, H., Eriksson, A., and Fellman, J.: Embryotoxon corneae posterius in an isolated popu lation. Acta Ophth. 42:42, 1964. 5. Rieger, H.: Beitrage zur Kenntnis seltener Missbildungen der Iris; 2. Ueber Hypoplasie des Irisvorderblattes mit Verlagerung und Entrundung
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der Pupille. Graefe's Arch. Ophth. 133:602, 1935. 6. Henkind, P., Siegel, I. M., and Carr, R. E.: Mesodermal dysgenesis of the anterior segment: Rieger's anomaly. Arch. Ophth. 73:810, 1965. 7. Peters, A.: Ueber angeborene Defektbildung der Descemetschen Membran. Klin. Mbl. Augenheilk. 44:27, 1906. 8. Alkemade, P. P. H.: Dysgenesis Mesodermalis of the Iris and the Cornea. A Study of Rieger's Syndrome and Peters' Anomaly. Assen, Van Gorcum, 1969. 9. Reese, A. B., and Ellsworth, R. M.: The ante rior chamber cleavage syndrome. Arch. Ophth. 75: 307,1966. 10. Jerndal, T.: Goniodysgenesis and hereditary juvenile glaucoma. Acta. Ophth. Suppl. 107, 1970. 11. Weatherill, J. E., and Hart, C. T.: Familial hypoplasia of the iris stroma associated with glau coma. Brit. J. Ophth. 53:433, 1969. 12. Duke-Elder, S. and Jay, B.: System of Oph thalmology, vol. 11. Diseases of the Lens and Vitre ous, Glaucoma and Hypotony. London, Kimpton, 1969, pp. 20, 105. 13. Hammond, A.: Dysplasia epiphysialis punctata with ocular anomaly. Brit. J. Ophth. 54:755, 1970. 14. Duke-Elder, S.: System of Ophthalmology, vol. 3. Normal and abnormal development. London, Kimpton, 1964, part 2, p. 775.