Aniridia

[Family Ties Forever!]

I got this idea from one of the other threads here. I have what is called Aniridia. It's a rare eye condition. In my case, the Aniridia was not hereditary. It was sparadic. Onset was at birth. While some individuals have Wilms Tumor as well, I do not, thankfully. Also some suffer neurological defects such as mental retardation. I do not have any such defects. My Aniridia is the type that is complete non-existant. I do not have an iris at all in either eye. My vision loss is complicated by Glaucoma, Cataracts, Cornea Scarring, Stignatism, in addition to the Aniridia. Onset of the Glaucoma and Cataracts was eight years after the onset of the Aniridia. Current visual acuity for me is 20/800 at best. Aniridia causes severe sensitivity to light, esp. sunlight.

Here's information about it:

Below information can be found:
http://www.emedicine.com/oph/topic43.htm

Aniridia

Synonyms and related keywords: absence of iris, partial or complete absence of iris, congenital aniridia, iridemia, iris hypoplasia, panocular disorder, cataract

INTRODUCTION

Background
Aniridia is a congenital, hereditary, bilateral, extreme form of iris hypoplasia that may be associated with other ocular defects. It describes an extreme form of iris hypoplasia in which the iris appears absent on superficial clinical examination. However, gonioscopy shows the presence of the iris root. Aniridia is not just an isolated defect in iris development but is a panocular disorder with macular and optic nerve hypoplasia, cataract, and corneal changes that are other anomalies that lead to decreased vision and nystagmus. Visual acuity is generally low but is unrelated to the degree of iris hypoplasia. Glaucoma is a secondary problem causing additional visual loss over time.

Patients with aniridia usually lack a foveal reflex, indicating poor macular development. True aplasia of the optic nerve also can occur. All these patients need specialized management of each individual problem. Because of poor visual acuity and nystagmus, low vision aids are very helpful. Lifelong regular follow-up care is necessary for the early detection of any new problems, especially glaucoma, lens, and systemic problems, so that timely treatment is given. Since the condition has a dominant transmission, proper genetic counseling should be obtained.

Clinical manifestation

Aniridia alone
Aniridia in association with systemic defects

Wilms tumor (20% of cases)
Genitourinary abnormalities
Mental retardation
Aniridia in association with ocular defects

Albinism
Ectopia lentis (50%)
Spontaneous lens dislocation
Arcus juvenilis
Keratoconus
Cataract (50-85%)
Glaucoma (30-50%)
Nystagmus
Strabismus
Optic nerve hypoplasia (75%)

Pathophysiology
The pathogenesis of aniridia is attributed to a primary developmental arrest of the neuroectoderm and a secondary alteration of all 3 neural crest waves of the mesenchyme. The functional development of the anterior segment is a complex interrelationship between the neural ectoderm and the neural crest waves of the mesenchyme. The pathogenesis may involve defective formation or excessive regression of various layers of the anterior segment caused by cellular or biochemical aberrations. This explains the combined anterior and posterior segment neural ectodermal and mesenchymal defects. The iris stroma is hypoplastic, indicating an altered third neural crest wave of mesenchyme.

Aniridia occurs as the following:

Autosomal disorder
An identifiable chromosome deletion of the short arm of chromosome 11, including band p13
Sporadic case
The exact defect in iris morphogenesis giving rise to aniridia is unknown. Because the iris pigment epithelium, the iris musculature, the retina, and the optic nerve are derived from neuroectoderm, there may be a common embryologic origin for these anomalies. As an isolated ocular malformation, aniridia is an autosomal dominant disorder, which is caused by a mutation in the PAX6 (paired box gene family) gene.

Patients with aniridia who have a positive family history are not at an increased risk for Wilms tumor. Two genetic loci for aniridia have been identified: one (AN1) on chromosome arm 2p and one (AN2) on chromosome 11.

Patients with aniridia without a positive family history have a 30% chance of developing Wilms tumor, and they represent new mutations for the autosomal dominant gene. About one third of such patients have a mutation that affects the WT and AN2 loci, causing the patient to develop Wilms tumor; the other two thirds of patients have a mutation of just the AN2 locus. Because of the high mortality from Wilms tumor, those patients with the WT and AN2 mutations have a low probability of reproducing, whereas those with just AN2 mutations have normal fertility and, hence, a 50% risk to pass the aniridia gene mutation to each child.

Frequency
United States

At present, aniridia strikes 1 in 60,000 individuals; in Canada, this would represent only 475 individuals based on a present population of 28.5 million. In the United States, studies have shown the incidence to be 1 in 90,000. Based on a population of 265 million, this would represent 2945 people.

International
Aniridia is rare and has an incidence of 1 per 64,000 to 1 per 96,000 live births. About two thirds of these cases are familial.

Mortality/Morbidity
All patients with aniridia are visually handicapped for a lifetime. This already reduced vision is threatened further by such complications as cataract and glaucoma. Those patients with Wilms tumor have a reduced span of life.

Race
No racial predisposition exists.

Age

Congenital glaucoma and aniridia usually are not associated at birth. The glaucoma develops at either the preteen or the teenage level.
Significant cataracts may occur before puberty. The risk for cataract increases with age, with lens opacities observed in 50-85% of patients during the first 2 decades of life.

History

The history is straightforward. The condition is discovered early in life, especially in whites. In blacks, the condition might remain undiscovered for a long time until an ophthalmologist examines the eyes for visual problems. The patient presents with the following problems:

Absence of iris
Nystagmus
Strabismus
Reduced vision
Thorough family history

Specific inquiry about any ocular abnormality and/or low vision
Dental anomaly
Protruding umbilicus
Genitourinary abnormalities (Wilms tumor)
Mental retardation
Thorough systemic examination of the patient

Physical

A detailed ocular examination is sometimes difficult because of photophobia and nystagmus. If slit lamp flash pictures are taken, they can provide detailed information on corneal opacities and blood vessels, the depth of the anterior chamber, the edge of a transparent dislocated lens, the presence or absence of zonular fibers, and the presence of lenticular opacities. Photographs are useful to observe changes in the tissues with the passage of time. A picture session is especially important in children.

The patient might show the following findings:

Nystagmus
Strabismus
Photophobia
Cornea

Pannus
Epithelial ulcers
Aniridic keratopathy
Arcus juvenilis
Microcornea
Anterior chamber

Best judged with a slit lamp microscope
Configuration dependent upon the position of the crystalline lens
Iris

Complete absence of iris on oblique illumination
Hypoplasia with irregular pupillary margins (atypical coloboma of pupil)
Root of the iris visible on gonioscopy
Angle of the anterior chamber - Trabecular meshwork may be partially or completely covered by the iris stump.
Crystalline lens

Transparent or opaque
Ectopia lentis
Completely dislocated lens
Vitreous - Usually normal
Fundus

Optic nerve hypoplasia
Macular reflex dull
Glaucomatous cupping
Intraocular pressure

Normal
Increased
Vision - Usually about 20/200 or less

Causes
Aniridia is caused by the following:

An identifiable chromosome deletion of the short arm of chromosome 11, including band p13.
Patients with aniridia who have a positive family history: Two genetic loci for aniridia have been identified, one (AN1) on chromosome arm 2p and one (AN2) on chromosome 11.
As an isolated ocular malformation, aniridia is an autosomal dominant disorder, which is caused by a mutation in the PAX6 (paired box gene family) gene.

Other Problems to be Considered

Rieger syndrome with iridocorneal dysgenesis
Congenital coloboma of the iris
Hereditary iris hypoplasia
Traumatic iris injury
Surgical iris coloboma
Bilateral congenital mydriasis
AGR triad - Sporadic (bilateral or unilateral) aniridia, genitourinary abnormalities, and mental retardation

Lab Studies

Chromosomal deletion is detected by cytogenetic testing with the use of high-resolution banding.
Submicroscopic deletions of the Wilms tumor gene are recognized with a fluorescent in situ hybridization (FISH) technique.
High-resolution chromosome studies are obtained in sporadic cases to determine if there is a deletion of band 11p13.
Serial renal ultrasound examinations are indicated in patients through age 7 years, especially for those with a deletion of band 11p13 or for those with a negative family history of aniridia and normal chromosomes.

Histologic Findings
Histologically, small portions of the iris are always present; the ciliary body is usually hypoplastic; and the anterior chamber angle may be normal, immature (ie, incompletely developed), or malformed. In eyes enucleated from older patients, extensive peripheral anterior synechiae that cause the iris stump to adhere to the posterior corneal surface have been observed.

Medical Care

Prophylaxis is directed toward the prevention of glaucoma, which includes the following:

Medical treatment with miotics
Surgical separation of the iris from the trabecular meshwork in selected cases
The medical treatment is directed toward control of intraocular pressure, which includes the topical use of the following:

Miotics
Beta-blockers
Sympathomimetics
Carbonic anhydrase inhibitors
Prostaglandin analogues
The chances of failure with local antiglaucoma treatment are high.
Treatment of photophobia and nystagmus

Tinted or iris contact lenses
Tinted spectacle lenses
Tinted intraocular lenses (IOLs)
By the above measures, reducing the amplitude and frequency of nystagmus is possible.
Treatment of refractive errors - Careful refraction and complete correction
Treatment of amblyopia and strabismus

Usually, the potential visual acuity in both eyes should be symmetrical.
When the vision is unequal without structural difference, vigorous amblyopia exercises should be performed in the worst eye.
Binocularity can be achieved if macular hypoplasia is not severe.
Strabismus surgery is indicated at an early age.

Surgical Care

Management of corneal opacification

Keratoplasty
Keratoprosthesis
Management of cataract

In-the-bag lens implantation in cases without lens dislocation
Use of opaque intracapsular rings to produce an artificial pupil or use of a large intraocular lens with a clear central optic and an opaque periphery
In-the-bag IOL placement with intracapsular rings, when there is slight lens displacement
Lens extraction followed by contact lens correction, if the lens is grossly out of place
Management of glaucoma

Goniotomy

Prophylactic
Early surgical therapy - Some risk to the crystalline lens and the zonules exists because the surgery is performed from the anterior approach.
Trabeculotomy is safer than goniotomy. The tissues can be defined more clearly, and accurate surgery can be performed. However, failures are common.
Filtering procedures - Greater danger of injury to the crystalline lens and disturbance of the vitreous exists because the iris is absent.

Nonperforating filtration surgery techniques are safer, because the anterior chamber remains undisturbed. Since glaucoma develops in young patients with aniridia, the intraoperative use of mitomycin is justified.

Fugo blade can be used to produce a transconjunctival microfiltration track of 200-300 µm in any part of the angle, away from the lens and the vitreous.
Laser therapy to angle abnormalities
Cyclocryotherapy - Endocyclophotocoagulation in selected cases
Glaucoma valve procedure - The choice of the techniques and the order in which they are used depends upon the peculiarities of the case and the perception of the surgeon.

Consultations

Banded chromosome analysis on the patient and both parents
Linkage analysis when large families are available
Genetic counseling

Further Outpatient Care

Lifelong, regular, and careful follow-up care is essential.

Deterrence/Prevention

Patients should have proper genetic counseling.
Patients should have thorough lifelong follow-up care to determine whether glaucoma is present.

Complications

Aniridia can be complicated by the presence or association of other problems, mainly cataract and glaucoma.

Prognosis

Prognosis varies from patient to patient.
Unmonitored and untreated elevated intraocular pressure may damage vision.
Cataract may require surgery.
Progressive corneal opacification may need corneal grafting.

Patient Education

Thoroughly educating the patient and parents about this condition and the associated ocular anomalies and systemic problems is mandatory.

Medical/Legal Pitfalls

Failure to detect glaucoma
Failure to educate the patient regarding all aspects of the disease, including the genetic aspects
Failure to refer for a thorough systemic checkup

Special Concerns

Structural iris defects: These defects may present as full-thickness holes through the iris with or without sphincter involvement. A more extensive defect with most of the iris absent is seen in aniridia.
Other associated ocular anomalies and systemic problems are as follows:

Wilms tumor
Mental retardation
WAGR (Wilms tumor, aniridia, genitourinary abnormalities, mental retardation) syndrome

Photos 1-11 (see website) eyes with Aniridia.

References:

Akpek EK, Harissi-Dagher M, Petrarca R, Butrus SI, Pineda R 2nd, Aquavella JV, et al. Outcomes of Boston keratoprosthesis in aniridia: a retrospective multicenter study. Am J Ophthalmol. Aug 2007;144(2):227-231. [Medline].
Dharmaraj N, Reddy A, Kiran V, Mandal A, Panicker S, Chakrabarti S. PAX6 gene mutations and genotype-phenotype correlations in sporadic cases of aniridia from India. Ophthalmic Genet. Sep 2003;24(3):161-5. [Medline].
Elsas FJ, Maumenee IH, Kenyon KR, Yoder F. Familial aniridia with preserved ocular function. Am J Ophthalmol. May 1977;83(5):718-24. [Medline].
Fantes JA, Bickmore WA, Fletcher JM, Ballesta F, Hanson IM, van Heyningen V. Submicroscopic deletions at the WAGR locus, revealed by nonradioactive in situ hybridization. Am J Hum Genet. Dec 1992;51(6):1286-94. [Medline].
François J, Coucke D, Coppieters R. Aniridia-Wilms' tumour syndrome. Ophthalmologica. 1977;174(1):35-9. [Medline].
Friedman AL. Wilms' tumor detection in patients with sporadic aniridia. Successful use of ultrasound. Am J Dis Child. Feb 1986;140(2):173-4. [Medline].
Glaser T, Walton DS, Maas RL. Genomic structure, evolutionary conservation and aniridia mutations in the human PAX6 gene. Nat Genet. Nov 1992;2(3):232-9. [Medline].
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[Yooch]

I hadn't heard anything about this condition. Thanks for the information.

I've had something called iritis twice, (it's nothing compared to what you describe), but is insidious in its own way. It doesn't go away on it's own and they give you a prescription cortisone eye drop, and in my case another drop for eye pressure. You have to take it for weeks on end.

Our eyes--how vulnerable they are, and how we take our vision for granted.

I hope you are ok.

[Family Ties Forever!]

I'm pretty sure I know what medicine you are referring to. In 2002 I had several reoccuring eye infections in one eye and had to use a special eye drop solution for weeks. It burned BIG time.

Thank you. I am ok. My vision is progressive, meaning, that my vision continues to worsen over time.

[Janice]

Originally Posted by Family Ties Forever!

My vision is progressive, meaning, that my vision continues to worsen over time.

That's the part of your condition that really concerns me, Jenny. It's terrible all around, but I wish it would stabilize. You do very well, online, and from what you've told me, in your regular life. I'm sure it's not easy. I'm glad you have SO, as I'm sure you spent a lot of time indoors. It's a nice distraction for you. It's also great to have you around.

[Family Ties Forever!]

Originally Posted by Janice

That's the part of your condition that really concerns me, Jenny. It's terrible all around, but I wish it would stabilize. You do very well, online, and from what you've told me, in your regular life. I'm sure it's not easy. I'm glad you have SO, as I'm sure you spent a lot of time indoors. It's a nice distraction for you. It's also great to have you around.

Thanks Janice. It would be nice if it would stabilize. I hope that I never completely lose my vision. I depend so much on the vision I do have. That is true, I spend most of my time inside. SO is a nice distraction and I enjoy it here. My eye doctor always seems impressed with how I do and the fact that I use a computer and am able to get online. Of course with special large print software. Even still though. I guess I've never really felt that it's impressive that I can do that, but I guess that's because I expect that of myself. It's kind of cool though that he's impressed by that.

[Janice]

Jenny, I heard of a program that allows a person to speak, and it will type out what is dictated. Have you ever heard of that?

[dawsongirl]

Did your schools growing up do special things for you, like print assignments in bigger type? I think even back when we were in school, there wasn't as many accomidations for disabilities as there is now. I assume you were able to be in regular classrooms with minimal adjustments; you were/are obviously smart enough.

[Family Ties Forever!]

Originally Posted by dawsongirl

Did your schools growing up do special things for you, like print assignments in bigger type? I think even back when we were in school, there wasn't as many accomidations for disabilities as there is now. I assume you were able to be in regular classrooms with minimal adjustments; you were/are obviously smart enough.

Yes, assignments had to be enlarged. The teachers had to take the assignment and tests and make it larger by using the photocopier and enlarging the size of what was on the paper. They used paper that was larger than the standard 8 1/2 X 11. They used 11 X 17 size paper to make it fit. Each year the print had to be larger and larger in order for me to see it. I was in regular classes except for two classes in third grade and one class in fourth grade. Other than that all my classes K-12 were regular level. In third grade the resource classes were for math and reading. In fourth grade just reading. They realized quickly that I really didn't need to be in the resource level math class. I was on level. Basically I was somewhat behind in reading, but managed to catch up, and was back in all regular classes including reading by fifth grade. My textbooks also had to be larger so that I could see the print in them. Toward the end of high school the teachers were having to enlarge materials significantly larger than the standard 10 or 12 font size.