developmental glaucoma/ juvenile onset glaucoma: axenfield rieger anomaly, peter's anomaly , aniridia, associated with other syndromes and chromosomal anomalies, mucopolysacharidosis , stickler syndrome etc..

1. DEVELOPMENTAL
GLAUCOMA
Dr. Nidhi Thaker

2. • Primary glaucomas with associated abnormalities
• All of the primary glaucomas that have associated
ocular abnormalities to be forms of anterior
segment dysgenesis.
• Neurocristopathies
• Anterior segment dysgeneses are attributed to
defects in neural crest migration or differentiation

3. 1. IRIDODYSGENESIS
a. Aniridiab
b. Congenital iris ectropion syndrome
c. Iridotrabecular dysgenesis (iris
hypoplasia)
2. CORNEODYSGENESIS
(IRIDOCORNEODYSGENESIS)
a. Axenfeld-Rieger anomaly
b. Peters anomaly
d. Sclerocornea
e. Congenital hereditary endothelial
dystrophy
f. Posterior polymorphous dystrophy
g. Megalocornea

4. AXENFELD-RIEGER
SYNDROME

5. Axenfeld-Rieger Syndrome
• Three Eponyms:
(A) Axenfeld Anomaly :
Limited to peripheral anterior segment defects
(B) Rieger Anomaly:
Peripheral abnormalities with additional
changes in the iris
(C) Rieger Syndrome:
Ocular anomalies plus systemic developmental
defects

6. 1. Partial retention of the primordial endothelium (e) on the iris (i)
and anterior chamber angle (aca);
2. Incomplete posterior recession of peripheral uvea from
trabecular meshwork (tm);
3. Abnormal differentiation between corneal and chamber angle
endothelium with a prominent, anteriorly displaced schwalbe
line (SL).
4. Development of tissue strands from retained endothelium
crossing the anterior chamber angle

7. • Anterior Chamber Cleavage Syndrome
• Mesodermal Dysgenesis Of The Cornea And
Iris

8. • Contraction of retained endothelium with iris changes of
corectopia (c), ectropion uvea (eu), and iris atrophy (ia), which may
continue after birth; a tissue strand (ts) can also be seen.
• Incomplete development of trabecular meshwork and Schlemm
canal (SC); continued traction on the iris with possible secondary
ischemia leads to hole formation (h).

9. General Features
• Bilateral
• Frequent family history of the disorder, with an
autosomal dominant mode of inheritance
• No sex predilection
• Frequent systemic developmental defects
• High incidence of associated glaucoma
• Age :birth to adulthood, with most cases recognized in
infancy or childhood

10. Ocular Features
CORNEA
• Prominent, anteriorly displaced
schwalbe line.
• White line on the posterior
cornea near the limbus.
• Incomplete, usually limited to
the temporal quadrant;
Sometimes 360 degree ; only
gonioscopic finding
• Occasional variation in the
overall size (i.e, Megalocornea
or, less often, microcornea) or
shape of the cornea
• Congenital opacities of the
central cornea

11. • Anterior Chamber Angle
• Gonioscopic examination;
1. Prominent schwalbe line
2. Iridocorneal adhesions
3. The anterior chamber angle is open and the trabecular
meshwork is visible, but the scleral spur is typically obscured
by peripheral iris, which inserts into the posterior portion of
the meshwork

12. •Iris
• Mild stromal thinning to
marked atrophy with hole
formation,
• Corectopia
• Ectropion uveae.
• When corectopia is present,
the pupil is usually displaced
toward a prominent
peripheral tissue strand the
atrophy and hole formation
typically occur in the
quadrant away from the
direction of the corectopia.

14. Other ocular abnormalities
• Strabismus
• Limbal dermoids
• Corneal pannus
• Cataracts
• Congenital ectropion uveae
• Congenital pupillary-iris-lens membrane
• Peripheral spokelike transillumination defects of the iris
• Retinal detachment
• Macular degeneration
• Chorioretinal colobomas
• Choroidal hypoplasia
• Hypoplasia of the optic nerve heads

15. • Glaucoma
• More than one half of the patients with the
axenfeld-rieger syndrome develop glaucoma.
• Childhood or young adulthood.
• The high insertion of peripheral iris into the
trabecular meshwork, appears to be more
pronounced in those eyes with glaucoma
• The proposed mechanism of glaucoma in
these cases relates to abnormalities of the
trabecular meshwork and schlemm canal

16. Systemic Features
• Dental anomalies:
Microdontia
Hypodentia
Oligodontia

17. Facial anomalies :
A receding upper lip and
prominent lower lip
Hypertelorism
Maxillary hypoplasia with
flattening of the midface
Telecanthus
A broad flat nose
Micrognathia
 mandibular prognathism

18. • primary empty sella
syndrome
• Congenital parasellar
arachnoid cyst
• Growth hormone
deficiency
• Others:
o Redundant periumbilical
skin
o Hypospadias
o Oculocutaneous albinism
o Heart defects
o Middle-ear deafness
o Mental deficiency

19. Genetic Linkage
• Chromosomes :4q25, 6p25, and 13q14.
• Type 1 :Pitx2 on 4q25
• Type 2: RIEG2 on 13q14
• Type 3: FOXC1 on 6p25

20. Differential Diagnosis
1. Iridocorneal Endothelial (ICE) Syndrom*
2. Posterior Polymorphous Corneal Dystrophy
3. Peters anomaly
4. Aniridia
5. Oculodentodigital Dysplasia
6. Ectopia Lentis et Pupillae
7. Congenital Microcoria and Myopia

21. Peters Anomaly
• Defect in the neural crest cell migration in the 6 – 8th
wk of fetal development
• Present at birth
• Usually bilateral
• Most cases are sporadic/autosomal recessive/
autosomal dominant transmission
• Defects of the ear and auditory system, orofacial
system, heart, genitourinary system, spine, and
musculoskeletal system
• Can be caused by mutation in the PAX6, PITX2,
CYP1B1, or FOXC1

22. Clinicopathologic Features
• Central corneal
abnormality : hallmark
1. Defect in the descemet
membrane and
corneal endothelium
with thinning and
opacification of the
corresponding area of
corneal stroma
2. Iris adhesions
3. Bowman layer absent
centrally

23. I. In Peters anomaly not associated with
keratolenticular contact or cataract
II. Peters anomaly associated with
keratolenticular contact or cataract
III. Peters anomaly associated with Axenfeld-
Rieger syndrome

26. Glaucoma
• 50% pts
• Infantile glaucoma
• Mechanism:
o Peripheral anterior synechiae formation
o Incomplete development of trabecular
meshwork and schlemm canal

27. Systemic association
• Craniofacial anomalies
• CNS anomalies
• Fetal alcohol syndrome
• Chromosomal abnormaalities
• ‘peter plus’ syndrome:
o Short-limbed dwarfism
o Cleft lip/palate
o Learning difficulties

28. D/D
o Other Causes of Central Corneal Opacities in
Infants:
• PCG
• birth trauma
• MPS
• congenital hereditary endothelial dystrophy.
o Posterior Keratoconus
o Congenital Corneal Leukomas and Staphylomas

29. ANIRIDIA
• Aniridia is a bilateral developmental disorder
characterized by the congenital absence of a normal
iris.
• Abnormal neuroectodermal development

30. Classification
AD
2/3rd
No systemic
complication
genotype+=
phenotype
sporadic
1/3rd
PAX6
MUTATION
WAGAR
SYNDROME/
Miller synd
AR
1%
Gillespie
syndrome
Cerebellar
ataxia + MR

31. Clinicopathologic Features
Iris
• Aniridia: variable
severity
• Iris and retinal
fluorescein : abnormal
iris vascular
remodeling that
resulted in incomplete
iris collarettes and
decreased retinal
foveal avascular zones

32. Lids:MGD
Cornea:
• Corneal pannus and
opacity begin in the
peripheral cornea
• Microcornea ,
sclerocornea
• Iridocorneal and
keratolenticular
adhesions
• High CCT
• Epibulbar dermoid

33. Lens
• Localized congenital
opacities
• progressive
• Subluxation
(superior)or
congenitally absent,
or it may be
reabsorbed

34. Fundus
• Foveal Hypoplasia, optic nerve hypoplasia, choroidal
coloboma
• Poor visual acuity and nystagmus
• Spectral-domain OCT can be used to confirm the presence of
foveal hypoplasia in eyes with aniridia, and this correlates well
with visual acuity independent of the iris rim width

35. Glaucoma
• 75% Pts
• late childhood and adolescence
Mechanism: synechial angle closure
secondary to the pulling of the rudimentary
iris tissue by contraction of pre exsisting
fibres
Glaucoma in aniridia usually develops after
rudimentary iris stump rotates anteriorly to
progressively cover the trabecular
meshwork

36. Other ocular and systemic association
• Choroidal colobomas
• Persistent pupillary membranes
• Sclerocornea
• Hallermann-streiff syndrome
• Small optic nerve heads
• Strabismus
• Ptosis
• Marfan syndrome with cervical ribs ,dental anomalies,
Tracheomalacia and delayed closure of the anterior
fontanelle
• Retinoblastoma

37. DEVELOPMENTAL GLAUCOMAS WITH
ASSOCIATED SYSTEMIC ANOMALIES
Sturge-Weber syndrome
Neurofibromatosis
Marfan Syndrome
Weill-Marchesani syndrome

38. STURGE WEBER SYNDROME
• Ancephalotrigeminal angiomatosis
• Unilateral
• Ipsilateral cavernous hemangioma/ facial cutaneous
hemangioma/ leptomeningeal angioma
• 30- 70%- Glaucoma
• Elevated episcleral venous presssure
• CNS symptoms

39. NEUROFIBROMATOSIS
• Most common phakomatosis
I. NF 1- von Recklinghausen or peripheral NF
– Most common
– 1: 3000- 5000
– AD, ch 17
• Ectropion uvea
• Lisch nodules
• Optic nerve glioma
• Eyelid neurofibroma
• Café au lait
• Axillary/inguinal freckling
• Cutaneous neurofibromas

41. II. NF2
• Central NF
• Chromosome 22
• Posterior subcapsular cataract in adolescence
• Not associated with glaucoma
• Bilateral acoustic neuroma
• Meningioma, schwannoma, ependymoma

42. OTHER SYNDROMES WITH
ASSOCIATED GLAUCOMA

43. Chromosomal Anomalies
• Trisomy 21
• Trisomy 13
• Trisomy 18
• Turner Syndrome

44. Trisomy 21:
Down Syndrome
• Mental retardation and
atypical facies.
• Ocular findings :epicanthus,
blepharitis, nystagmus,
strabismus, light-colored
and spotted irides,
keratoconus, cataracts, and
congenital glaucoma in
infancy, with the typical
findings of PCG

45. Trisomy 13-15: Trisomy D
Syndrome
• Mental retardation, deafness, heart disease,
and motor seizures
• Ocular findings: microphthalmia, coloboma
with cartilage, congenital cataracts, retinal
dysplasia, persistent fetal vasculature, and
dysembryogenesis of the anterior chamber
angle Glaucoma
Trisomy 18: Edwards Syndrome
• Anterior position of the iris obstructing the
anterior chamber angle

46. XO: Turner Syndrome
• short stature,
• postadolescent females with sexual
infantilism and multiple systemic anomalies.
• Ocular findings:
ptosis, epicanthus, cataract, strabismus, blue
sclera, corneal nebulae, and color blindness
Developmental glaucoma is rarely associated

47. GLAUCOMA ASSOCIATED WITH SYSTEMIC
CONGENITAL DISORDERS
 Lowe (Oculocerebrorenal) syndrome
 Stickler Syndrome
 Zellweger syndrome
 Hallermann-Streiff syndrome
 Rubinstein-Taybi (broad thumb) syndrome
 Oculodentodigital dysplasia
 Cockayne syndrome
 Fetal alcohol syndrome

48. Cystinosis
• Autosomal recessive metabolic disorder
• Characterized by widespread accumulation of
cystine crystals in ocular and nonocular tissues
• Mutation in the gene encoding cystinosin
(CTNS: 17p13)
• Pupillary block glaucoma caused by the
cystine accumulation in the iris stroma

49. Hepatocerebrorenal Syndrome:
Zellweger Syndrome
Multisystem congenital disorder characterized by
• central nervous system abnormalities
• Hepatic interstitial fibrosis
• Renal cysts
 Ocular findings :
• Nystagmus
• Corneal clouding
• Cataracts
• Retinal vascular and pigmentary abnormalities,
• Optic nerve head lesion
• Congenital glaucoma :iridocorneal adhesions may be the
mechanism of the glaucoma

50. Hallermann-streiff syndrome
• Micrognathia and dwarfism
• Ocular findings:
• Cataracts
• Microphthalmos.
• Glaucoma may also occur because of absorption of lens
material or associated aniridia or after cataract surgery
Kniest dysplasia
• Metatropic dwarfism
• Autosomal dominant inheritance
• Mutations in the COL2A1 gene
• Congenital glaucoma

51. Lowe syndrome
• Oculocerebrorenal syndrome
• Autosomal recessive/x-linked disorder
• Mental retardation, renal rickets, aminoaciduria,
hypotonia, acidemia,irritability.
• Cataract
• Glaucoma :secondary to removal of concurrent
congenital cataracts. Anterior insertion of the iris,
narrowing of the ciliary body band, and decreased
visibility of the scleral spur
• Microphthalmia, strabismus, nystagmus, miosis, and
iris atrophy.

52. 13-year-old boy with Lowe syndrome and glaucoma controlled
with medication use. He has aphakia in both eyes after
removal of congenital cataracts, and has small stature,
developmental delay, and esotropia.

53. Mucopolysaccharidoses
• The MPS constitute a group of inherited disorders
caused by deficiency of specific lysosomal enzymes
needed for the degradation of glycosaminoglycans,
or mucopolysaccharides
• The accumulation of partially degraded
glycosaminoglycans causes interference with cell,
tissue, and organ function.

54. • Hurler syndrome
• autosomal recessive disease with central nervous
system, skeletal, and visceral abnormalities
• ocular finding :
1. corneal clouding
2. Glaucoma has also been reported in Hurler
syndrome and was thought to result from
mucopolysaccharide-containing cells in the
aqueous outflow system
3. open-angle glaucoma
4. IOP returned to normal after bone marrow
transplantation

55. • Patients with mucopolysaccharidosis type
VI, the Maroteaux-Lamy syndrome
• Acute or chronic angleclosure glaucoma,
due to increased thickness of the peripheral
cornea than with pupillary block

56. Nail-Patella Syndrome
• dysplasia of the nails and absent or hypoplastic
patella as cardinal features, has been associated with
open-angle glaucoma.
Oculodentodigital Dysplasia
• hypoplastic dental enamel, microdontia, bilateral
syndactyly, and a characteristic thin nose.
• Glaucoma: mild developmental abnormalities of the
anterior chamber angle
• autosomal dominant mutation in the connexin-43
gene (CJA1, gene locus 6q21)

57. Prader-Willi Syndrome
• Muscular hypotonia, hypogonadism, obesity, and mental
retardation
• Abnormality of chromosome 15.
• Ocular findings: oculocutaneous albinism and congenital
ectropion uveae, which may be associated with open-angle
glaucoma
Rubinstein-Taybi Syndrome
• mental and motor retardation
• typical congenital skeletal deformities with characteristically
large, broad thumbs and first toes
• Ocular findings: bushy brows, hypertelorism, epicanthus,
antimongoloid slant of eyelids, and hyperopia,Infantile or
juvenile glaucoma(open angle)
• autosomal dominant

59. Stickler Syndrome
• Hereditary progressive arthroophthalmopathy
• An autosomal dominant connective tissue dysplasia,
• Characterized by ocular, orofacial, and generalized
skeletal abnormalities
• Ocular manifestations :
o High myopia
o Open-angle glaucoma
o Cataracts
o Vitreoretinal degeneration,
o Retinal detachment
o Numerous iris processes, suggestive of a developmental
abnormality of the angle neovascular glaucoma

61. • Three forms of Stickler syndrome
1. Type I :mutation in the COL2A1 gene
2. Type II :mutation in the a1-polypeptide of collagen
XI (COL11A1)
3. Type III :mutations in the collagen, type XI, alpha 2
gene (COL11A2)

62. • Wagner syndrome :mutation in the gene
encoding chondroitin sulfate proteoglycan-2
(CSPG2) a proteoglycan found in the
vitreous
• Marshall syndrome: mutations in the
COL11A1 gene
• Weissengacher-Zweymuller syndrome :
o also called Pierre Robin syndrome
o fetal chondrodysplasia mutation in the
COL11A2 gene (as in Stickler syndrome type
III).

64. Waardenburg Syndrome
• autosomal dominant disorder
• lateral displacement of the medial canthi;
• hyperplasia of the medial brows;
• a prominent, broad root of the nose;
• sectorial or complete iris heterochromia;
• congenital deafness and a white forelock
• defect of neural crest-derived tissues and is caused
by a mutation in the PAX3 gene (gene map locus
2q35,
• Open-angle glaucoma

65. Walker-Warburg Syndrome
• Hydrocephalus (H)
• Agyria (A)
• Retinal Dysplasia (RD)
• With or without Encephalocele (±E),
• Multiple eye abnormalities have been reported, including congenital
glaucoma
Cockayne Syndrome
• Autosomal recessive disorder
• Characterized by dwarfism and birdlike facies.
• Ocular manifestations
• “salt and pepper” retinopathy
• Cataracts
• Corneal ulcers or opacities
• Nystagmus
• Hypoplastic irides
• Irregular pupils