The NINA Study
The Northern Ireland
Nystagmus & Albinism Study
Dr. Natasha Healey PhD BSc (Hons) MCOptom
31st May 2014
Dr Julie McClelland, Dr Kathryn Saunders, Prof
Jonathan Jackson, Ms Eibhlin McLoone
Contents
 Albinism
- Background and subtypes
- Ocular Features
- Visual Symptoms
 Northern Ireland Nystagmus & Albinism (NINA) Study
- Background
- Results
Background
 Albinism term used to describe a group of disorders
with absent or reduced melanin production
 Results in hypopigmentation of the hair, skin and
eyes
 Prevalence:
1 in 20,000 worldwide
1 in 10,000 **N. Ireland
** NEW Results
Albinism
2 broad categories exist:
Albinism
Subtype
Category
Subcategory
OCA1A
OCA1
OCA
OCA1B
OCA2
OCA3
OCA4
OA
OA1
Several
others
OCA1A
OCA
Type
Cause
Pigment Birth
appearance
OCA1A
tyrosinase
negative
OCA
Nil
Mutation of
tyrosinase
gene
•Snow white
hair
Adult
appearance
No change
Skin does not
•white pale skin tan
•pale
blue/violet
irides
OCA1B
OCA
Type
Cause
OCA1B Reduced
functiontyrosinase
enzyme is
minimally
active
Pigment
Birth
appearance
Varies
Same as
(normal OCA1A
to
minimal)
Adult appearance
•Hair and iridies
can darken with
age
•Eyelashes
darker than
eyebrows/hair
•Skin may tan /
develop freckles
OCA2
OCA
Type
Cause
Pigment
Birth
appearance
OCA2
•Normal
tyrosinase
activity
Varies
•Hair / eyes
pigmented at
birth
•defective
transmembrane
protein
Adult
appearance
•Similar to
OCA1B but
in pigment is
less
•Hair colour at pronounced
birth can
range (light
•Pigment can
blonde-brown) remain
unchanged
OCA 3
 Common in African & Papua
New Guinean populations.
 Brick reddish skin, hair and iris.
OCA 4
 Mainly found in Japanese / Korean populations
 Physical appearance often indistinguishable from
OCA1B or OCA2.
Secondary OCA
 Blood clotting or immune disorders, more frequent in
Puerto Rico, Holland & Switzerland.
The Eye
Fovea
Eye muscle
Characteristic Ocular Features
• Iris transillumination*
The Eye
Fovea
Eye muscle
Iris Transillumination
Characteristic Ocular Features
• Iris transillumination*
• Foveal hypoplasia* **NEW FINDINGS
The Eye
Fovea
Eye muscle
Foveal Hypoplasia
‘typical’ fovea
Foveal Hypoplasia
‘absent fovea’
Characteristic Ocular Features
• Iris transillumination*
• Foveal hypoplasia*
• Fundal hypopigmentation*
Fundus Hypopigmentation
Typical fundus colour
fundus hypopigmention
Characteristic Ocular Features
• Iris transillumination*
• Foveal hypoplasia*
• Fundal hypopigmentation*
• Macular transparency
• Optic nerve hypoplasia
• Anomalous retinal vessel presence in the foveal avascular area
Fundus Hypopigmentation
Typical fundus colour
fundus hypopigmention
Characteristic Ocular Features
• Iris transillumination*
• Foveal hypoplasia*
• Fundal hypopigmentation*
• Macular transparency
• Optic nerve hypoplasia
• Anomalous retinal vessel presence in the foveal avascular area
• Abnormal misrouting of retinal ganglion cell axons at the optic
chiasm (VEP asymmetry)
‘Typical’ Visual Pathway: 60% fibres cross, 40% remain uncrossed
Typical Visual Pathway: 60% fibres cross, 40% remain uncrossed
Albinism: Higher percentage of fibres cross (95%), 5% uncrossed
Characteristic Visual Symptoms
• Reduced visual acuity
Characteristic Visual Symptoms
• Reduced visual acuity
• High refractive errors
No Refractive Error
•Eye that does not need glasses
No Refractive Error
•Eye that does not need glass
•Light / image rays focused perfectly on fovea / retina
Long Sighted Eye
•Hypermetropia
•Light/image focused behind retina
Long Sighted Eye
•Hypermetropia
•Eye needs PLUS lenses to focus light/image on retina
Short Sighted Eye
•Myopia
•Light / image is focused in front of the retina
Short Sighted Eye
•Myopia
•Eye needs MINUS lenses to focus light/image on retina
Short Sighted Eye
•Myopia
•Eye needs MINUS lenses to focus light/image on retina
Characteristic Visual Symptoms
• Reduced visual acuity
• High refractive errors
• Reduced contrast sensitivity
Characteristic Visual Symptoms
• Reduced visual acuity
• High refractive errors
• Reduced contrast sensitivity
• Nystagmus
Characteristic Visual Symptoms
• Reduced visual acuity
• High refractive errors
• Reduced contrast sensitivity
• Nystagmus
• Photophobia
Characteristic Visual Symptoms
• Reduced visual acuity
• High refractive errors
• Reduced contrast sensitivity
• Nystagmus
• Photophobia
• Reduced or absent stereoacuity
Characteristic Visual Symptoms
• Reduced visual acuity
• High refractive errors
• Reduced contrast sensitivity
• Nystagmus
• Photophobia
• Reduced or absent stereoacuity
• Amblyopia
Characteristic Visual Symptoms
• Reduced visual acuity
• High refractive errors
• Reduced contrast sensitivity
• Nystagmus
• Photophobia
• Reduced or absent stereoacuity
• Amblyopia
• Strabismus
The Northern Ireland
Nystagmus & Albinism
(NINA) Study
The NINA Study
Autumn 2008- Spring 2012
Location:
Royal Group of Hospitals
Altnagelvin Area Hospital
Recruited:
105 participants (age range 4.5 months-47 years)
Albinism n=73
ICN n=32 (control group)
Retrospective analysis (n=147 medical files, 1986-2010)
Control Group
Idiopathic congenital nystagmus (ICN)
 Nystagmus may also occur in isolation
 Onset prior to 6 months of age
 Normal ocular and neurological anatomy
Method
 Refractive Error:
strict cycloplegic protocols
Method
 Refractive Error:
strict cycloplegic protocols
 Visual acuity:
age appropriate tests
Method
 Refractive Error:
strict cycloplegic protocols
 Visual acuity:
age appropriate tests
 Nystagmus assessment : video recorded/graded
Method
 Refractive Error:
strict cycloplegic protocols
 Visual acuity:
age appropriate tests
 Nystagmus assessment : video recorded/graded
 Corneal curvature:
Nidek Hand-held keratometer
Fovea
Eye muscle
Method
 Refractive Error:
strict cycloplegic protocols
 Visual acuity:
age appropriate tests
 Nystagmus assessment : video recorded/graded
 Corneal curvature:
Nidek Hand-held keratometer
 Axial Length:
IOL Master (NC) Biometer
Fovea
Eye muscle
Method
 Refractive Error:
strict cycloplegic protocols
 Visual acuity:
age appropriate tests
 Nystagmus assessment : video recorded/graded
 Corneal curvature:
Nidek Hand-held keratometer
IOL Master (NC) Biometer
 Axial Length:
 Contrast Sensitivity & Straylight:
-Pelli Robson Chart
- Straylight meter
Method
 Refractive Error:
strict cycloplegic protocols
 Visual acuity:
age appropriate tests
 Nystagmus assessment : video recorded/graded
 Corneal curvature:
Nidek Hand-held keratometer
 Axial Length:
IOL Master (NC) Biometer
 Contrast Sensitivity:
Pelli Robson Chart
 Foveal imaging:
SD-OCT
Fovea
Eye muscle
Main
NINA Study
Results
Prevalence of Albinism
In N. Ireland
Prevalence of Albinism in N. Ireland
•Worldwide prevalence 1 in 20,000
•N. Ireland prevalence 1 in 10,000
•New NINA Study Results albinism prevalence in N. Ireland
1 in 4,500 – 6,000
•published March 2014, British Journal of Ophthalmology
Prevalence of Albinism in N. Ireland
1 in 4,500 – 6,000
NINA Study has highlighted:
• Public health issue- with higher numbers than services are planned for
•Numbers need taken into consideration when planning future serviceeye appointments, funding for benefits, classroom assistants etc
•NINA suggest this underestimation of albinism prevalence is not an
isolated case, suspecting worldwide figures to be erronous
The Significance of Foveal Hypoplasia
Fovea
Eye muscle
Normal
Retinal Development
•Fovea begins @ 25 weeks gestation
•Continues to develop until 15-45 months of age
•During this time the foveal cells change shape and mature
SD-OCT Imaging
typical fovea
Foveal hypoplasia:
OCA/OA
Foveal Morphology Results
 Spectrum of foveal hypoplasia occurred
Examples of Foveal Hypoplasia
Foveal Morphology Results
 Spectrum of foveal hypoplasia occurred
 Grade of foveal hypoplasia was statistically significantly
related to Visual Acuity (Agreement with Thomas et al., (2011)
 Poorest VA (mean VA 6/36) was associated with the
severest foveal hypoplasia
NEW NINA Findings:
 Highest refractive error (highest hypermetropia) was
associated with the severest foveal hypoplasia
Foveal Morphology Results
Spectrum of foveal hypoplasia occurred
Grade of foveal hypoplasia was statistically significantly
related to Visual Acuity (Agreement with Thomas et al., (2011)
Poorest VA (mean VA 6/36) was associated with the
severest foveal hypoplasia
NEW NINA Findings:
 Highest refractive error was associated with the severest
foveal hypoplasia
- published April 2013, Investigative Ophthalmology & Visual Science
Refractive Error
Previous studies of refractive error in albinism
Author
Location
Subject
numbers
Age range (years)
Most prevalent type
of refractive error
Wildsoet et al 200027
Boston
25
3-51
Long sighted
Edmunds 194932
New York
16
7-45
Long sighted
Mvogo et al 199933
Cameroon
42
Not available
Short sighted with
astigmatism
Loshin and Browning
1983 34
Not available
8
Not available
Long sighted
Nathan et al 198535
Australia
35
1-16
Long sighted
Perez-Carpinell et al
198231
Spain
9
7-39
Short sighted
Sampath and Bedell
200236
USA
19
10-35
Long sighted
Kasmann et al 199637
Germany
68
0.5-78
Link between short
sight and OCA1
Refractive Error
 Long sighted
 Eye length typical
 Large range of refractive errors existed
 High horizontal astigmatism
Why are the high levels of
refractive error present?
 Typically at birth babies have high levels of long
sightedness and astigmatism
Why are the high levels of
refractive error present?
 Typically at birth babies have high levels of long
sightedness and astigmatism
 Typically these levels decrease over the first 8 years
of life
Why are the high levels of
refractive error present?
 Typically at birth babies have high levels of long
sightedness and astigmatism
 These levels decrease over the first 8 years of life
 Process is called ‘Emmetropisation’
Why are the high levels of
refractive error present?
 Typically at birth babies have high levels of long
sightedness and astigmatism
 These levels decrease over the first 8 years of life
 Process is called ‘Emmetropisation’
New: NINA study has found that the high levels
found at birth do not appear to decrease as much
as we would expect over the first 8 years of life.
Another important feature the NINA Study has found is:
 That some element of astigmatism in albinism is
congenital (higher at birth than typical baby eye)
 Therefore are not solely a mechanical consequence
of nystagmus
 Recommend, if have astigmatism to wear glasses as
early as possible, don’t wait and to wear full time.
Another important feature the NINA Study has found is:
That some element of astigmatism in albinism is
congenital (higher at birth than typical baby eye)
Therefore are not solely a mechanical consequence of
nystagmus
Future Research
 NINA Study Findings currently in process for
publication:
1. Corneal Astigmatism
2. Questioning SSI and SI Categories for Albinism
- worldwide call for further research
3. Advanced Clinical Guidelines for Eye care in
Albinism
4. **Need for future research in genetics, and foveal
hypoplasia during gestation and infancy
NINA Study Summary
 Prevalence of Albinism is greater than expected in NI, and
also possibly worldwide
 Need to look at public spending in this area
 Role of Foveal Hyoplasia in Visual Acuity and Refractive Error
 Longsighted with horizontal astigmatism most common,
suggesting glasses from a very early age
 Astigmatism generally corneal and some already there before
birth
 Re-diagnosed some of those participating in the ‘control group’
NINA Outcomes
 Clinical recommendations
 Provided answers to worldwide questions
 Increased awareness
 Increased awareness of support parents require
 Increased awareness of Albinism Fellowship and
Angel Eyes Charities (NI)
 Highlighted need for future research
 Further publications pending
 Last thing to say is a huge.....
Thank You
Acknowledgements
 Children, adults and parents
 Ms. E. McLoone
 Mr. C.E. Willoughby
 Ms. R.Brennan
 Dr. G. Mahon
 Dr. D. Burns
 The Low Vision Clinic, RGH
 Dayward, RGH
 Optometry Clinic, AAH
 Charities (AE/AF)
 University of Ulster
 Department of Education & Learning
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