The 3rd European Conference Aniridia

Insights from the 3rd European Conference Aniridia

Insights from the 3rd European Conference Aniridia

Duisburg, Germany

27-28 August, 2016

 

Kelly Trout, BSN, RN

 

 

Image result for greek goddess iris

In Greek mythology, “Iris” was a goddess, the personification of the rainbow

 

 

Topics included:

 

Ocular Surface Disease

Aniridia-Associated Keratopathy

Artificial Iris

Glaucoma

Cataract

Aniridia Syndrome

Low Vison Care

The Role of the BDNF gene

Sleep Disturbances in Aniridia

Aniridia in WAGR syndrome

WAGR syndrome: clinical guide and Wilms tumor

 

 

 

 

Ocular Surface Disease (OSD)/Aniridia-Associated Keratopathy (AAK)

 

·         Ocular Surface Disease (OSD) occurs at some point in more than 90% of patients with aniridia

o       Often begins in first decade of life

o       Often worsens after ocular surgery or treatment for glaucoma

o       Caused by limbal (stem cell) deficiency

o       Extreme care should be taken to preserve the cornea

§         minimize number and extent of oculosurgical procedures whenever possible

§         minimize ptosis surgery (to decrease dry eye)

§         recognize ocular infections (“pinkeye”) promptly, treat with gentle antibiotics

§         use preservative-free, phosphate-free lubricants and eyedrops

§         avoid contact lenses unless therapeutic (scleral bandage lenses)

§         avoid VEGF antagonist eyedrops (bevacizumab, ranibizumab, pegaptamib)

 

·         Dry eye may be first symptom of OSD in patients with aniridia

o       Is a risk factor for progressive Aniridia-Associated Keratopathy (AAK)

 

·         Nonsurgical treatment

o       Goal of treatment is to avoid – or at least postpone – need for keratoplasty (cornea transplant)

o       Artificial tears

§         Should contain hyaluronic acid

§         semifluorinated alkanes (Novatears)

§         dexpanthenol ointment at night

o       Consider punctal occlusion (plug tear ducts), lid massage

o       Low-dose, unpreserved, phosphate-free steroid drops (Dexapos COMOD) or low-dose cyclosporine A (Ikervis)

o       Autologous serum drops

o       Amniotic membrane “patch”/Amniotic membrane extract eyedrops

o       Scleral bandage contact lens

 

·         Surgical treatment

o       Only if significant reduction of visual acuity

o       Stem cell transplant

o       Cornea transplant (must include limbal cells)

o       Boston Keratoprothesis (“K-Pro”) is alternative to cornea transplant

§         Artificial cornea

§         May be indicated if patient unable to tolerate immunosuppressive drugs

§         Increased risk of aniridia fibrosis syndrome

§         Requires contact lens and antibiotic eyedrops for life

§         If glaucoma occurs before/after K-pro, can be controlled in about 80% of patients

o       If patient has a drainage tube, may need to be repositioned

o       If patient does not already have a drainage tube, may need one after K-pro

 

§         Experimental/on the horizon: K-Pro with internal intraocular pressure sensor

 

 

Artificial Iris

 

·         Multiple speakers urged caution, citing high complication rates, including induced glaucoma (52%) and worsening keratopathy (47%)

 

·         One study compared the reasons parents and physicians give for considering artificial iris implants (decreased glare, improved appearance) and what patients with aniridia say about these concerns

o       The study found that patients’ priorities were not the same as parents/physicians:      

§         patients reported substantially less difficulty with glare/photophobia than assumed

·         Degree of photophobia in 49 patients

o       None: 7

o       Moderate: 36

o       Significant: 2

o       Severe: 4

§         patients felt strongly that improvements in cosmetic appearance did not warrant any risk to vision

 

·         Artificial iris implants remain an experimental and controversial procedure

 

 

 

 

 

 

 

 

Glaucoma

 

·         Occurs in up to 75% of patients with aniridia

 

·         May occur at any age (including at birth), but most commonly begins in childhood or early adulthood

 

·         Best way to measure intraocular pressure = applanation tonometry:

Image result for applanation tonometry

 

·         Corneal thickness can affect measurement of pressure

o       Increased corneal thickness is common in aniridia

 

·         Monitoring for glaucoma should be approximately every 6 months

o       If glaucoma develops, monitor more often

o       Glaucoma may develop after an initial exam with no evidence of glaucoma

 

·         Poorer visual outcome if

o       Familial aniridia

o       Greater number of surgeries

 

·         Treatment

o       Medical

§         eyedrops

o       Surgical

§         Trabeculotomy

§         Trabeculectomy

§         Drainage implants

§         Cyclodestructive procedures             

§         Laser procedures not useful

 

·         Some patients do not respond to medical or surgical treatment

 

·         Recent developments in surgical treatment of glaucoma:

o       “Minimally Invasive Glaucoma Surgery” (MIGS)

§         Early treatment is desirable

§         MIGS not as effective as traditional surgery but safer

§         Early (anecdotal) reports in aniridia are positive

 

 

Cataract

 

·         Incidence: 50-85% by age 20 years

 

·         Reserve surgical intervention until visual acuity is significantly impacted

o       Potential complications include: glaucoma, anterior fibrosis syndrome, ocular surface disease, retinal detachment

 

·         Intraocular lens implant recommended, generally well-tolerated

 

 

Aniridia Syndrome

 

·         May be the result of endocrine imbalance related to mutations of PAX6 gene

·         Includes:

o       Olfactory dysfunction (decreased or absent sense of smell)

o       Auditory Processing deficits

o       Sleep/Wake issues

o       Autism Spectrum disorder

o       Cognitive/learning difficulties

o       Diabetes

o       Obesity

o       Polycystic Ovary Syndrome

o       Eczema

 

·         Statistics on 83 patients with familial or sporadic aniridia

o       Dental abnormalities                          29 (35%)

o       Developmental delay                          14 (17%)

o       Musculoskeletal abnormalities          11 (13%)

o       Asthma                                                10 (12%)

o       Depression                                          10 (12%)

o       Infertility                                             9 (11%)

o       Gallbladder disease                            7 (8%)

o       Hypertension                                       6 (7%)

o       Diabetes                                              6 (7%)

o       Hyposmia (inability to smell)              4 (5%)

o       Pancreatitis                                         1 (1%)

 

                       

 

 

Low Vision Care

 

§         Vision challenges in Aniridia include:

o       photophobia/glare, decreased visual acuity, progressive visual impairment

 

§         Solutions:

o       Glare: sunglasses outdoors

§         Cold light sources indoors

o       Low Vision aids: magnifiers, telescopic spectacles, electronic reading devices

o       Orientation and Mobility: handheld telescopes, cane training

o       Early Intervention Services

o       Special Education

o       Vocational training and workplace equipment support

 

 

Role of the BDNF gene

 

·         Patients with BDNF haploinsufficiency (deletion of one copy of the BDNF gene) exhibit:

o       Hyperphagia (excessive hunger)

o       Childhood onset obesity

o       Intellectual disability

o       Impaired nociception (decreased response to pain)

 

·         Therapies (possibly medications) which increase BDNF signaling could be helpful for treating obesity and neurodevelopmental disorders, both in patients with rare disorders and in the general population

 

 

Sleep Disturbances in Aniridia

 

·         The PAX6 (aniridia) gene plays an important role in the development of the pineal gland (which produces the hormone melatonin). Patients with aniridia have:

o       Smaller pineal volume

o       Lower secretion of melatonin

o       Greater parental report of sleep disturbances in children

 

 

 

 

 

 

 

Aniridia in WAGR Syndrome

 

·         Observation of 20 patients with WAGR syndrome, ages 2-39yrs:

o       5 patients without intellectual disability (although 4 pts very young)

 

·         Compared to patients with PAX6 mutation, patients with WAGR syndrome may:

§         Require oculosurgical intervention at a younger age

§         Require ophthalmologic exam under anesthesia more often/later in life due to inability to cooperate

§         Have a higher rate of/degree of:

·         Corneal complications

·         Glaucoma

·         Refractive errors

o       3 patients with pathological myopia (extreme nearsightedness) and retinal detachment in one or both eyes

 

 

 

WAGR syndrome: clinical guide and Wilms tumor

 

·         WAGR is more than W-A-G-R

o       Absence of classic feature(s) does not exclude diagnosis. High level genetic testing required

o       Genital anomalies may be as frequent in females as in males, but are internal (ovaries, vagina, uterus) and may go undiagnosed

o       If abnormal ovaries, there is increased risk for gonadoblastoma/dysgerminoma

 

·         Hearing impairment: Auditory Processing Deficits (ASD) in >90%

o       Requires early identification and targeted interventions

 

·         Impaired pain perception in 50%

o       Parents/physicians may need to rely on symptoms of injury/illness other than pain

 

·         Autism Spectrum Disorder may be misdiagnosed

o       Behavioral symptoms may actually indicate some combination of Auditory Processing deficit, vision/cognitive impairment, Anxiety, and/or Attention Deficit Disorder/ADHD

o       Autism diagnosis may be helpful for obtaining wider range of educational

o       services

§         Targeting therapies to actual deficits is most effective

 

·         Late-onset renal failure affects 60% over age of 12

o       Lesion is focal segmental Glomerulosclerosis (FSGS)

o       Occurs in patients with WAGR who have not had Wilms tumor

o       Early diagnosis, aggressive treatment with ACE-inhibitor drugs slows progression

o       to end-stage renal failure (dialysis/transplant)

 

·         Propofol (medication commonly used for general anesthesia) should be used with caution in WAGR patients with hypertriglyceridemia

o       Associated with acute pancreatitis

 

·         Wilms tumor can occur in teens/adults with WAGR syndrome

o       Some level of surveillance is needed throughout life

o       No clear guidelines on type of imaging needed or frequency

 

·         Treatment for Wilms tumor with Adriamycin is associated with late-onset congestive heart failure

o       Lifelong periodic cardiac evaluation is needed

           

·         WAGR syndrome is extremely rare: more data is sorely needed

o       Patient registry is available to patients and physicians/researchers at

                           http://www.wagr.org

 

 

How Can We Better Understand Aniridia and WAGR Syndrome?

           

·         Increased collaboration between researchers, and between researchers – patients – and patient advocacy organizations

·         “Databases are crucial”

o                   Participate in A Patient Registry!