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TRANSLATIONAL GENOMICS
Keratoconus – Genes and Risk Factors
Tuesday 11th November 2014
A/Professor Paul Baird
Ocular Genetics Unit
• Keratoconus – the disease
• Families
• Gene studies
• Other risk factors
Treatment options and severity of
Keratoconus
Disease severity
mild
Treatment options
Glasses
Contact lenses
moderate
Toric IOLs
X-linking
Keratoplasty
severe
Corneal transplantation
 We would like to identify risk factors that influence the disease
process
- Pre-diagnosis
- Disease progression
- Response to treatment
Aetiology
Keratoconus is a Complex disease
Non genetic factors
Genetic factors
Eye rubbing
 Twin studies
 Allergy
 Familial aggregation studies
 Connective tissue
dysfunction
 Genetic studies
Contact lens wear
Keratoconus study
Eye Exam
Questionnaire
Demographics, Birth history,
Ethnicity, Educational
Background, Ocular &
Medical History, Family
history Smoking &
Alcohol consumption
details
Economic
burden
questionnaire
VA, Refraction, Axial
Length, Slit Lamp,
Keratometry, OCT,
Pentacam
DNA Sample
Venepuncture
2 x 9ml samples
Saliva
Participants
Biometric
Measurement
Quality of life
questionnaire
Height, Weight
Hip : Waist
Keratoconus study – Genetic studies
Eye Exam
Questionnaire
Demographics, Birth history,
Ethnicity, Educational
Background, Ocular &
Medical History, Family
history Smoking &
Alcohol consumption
details
Economic
burden
questionnaire
VA, Refraction, Axial
Length, Slit Lamp,
Keratometry, OCT,
Pentacam
DNA Sample
Genetic studies
Venepuncture
Participants
Saliva
Biometric
Measurement
Quality of life
questionnaire
Height, Weight
Hip : Waist
Family studies in Keratoconus
Families help us to track down keratoconus disease genes
We want to recruit more families where
keratoconus is found in multiple family
members
Identifying Genes in Keratoconus
Multiple genes implicated
Eg: VSX1, SOD1, ILIB, COL4A3,
COL4A4, LOX
Few of these replicated (small
sample size, different
methodologies)
More robust findings for:
Hepatocyte Growth Factor (HGF) gene
Genes involved with central corneal thickness (CCT)
Currently identifying other genes using a genome wide approach
Risk Factor Questionnaire
Age (years)
BMI
Gender (male)
Eye Rubbing
Ethnicity
Cigarette Smoking
Alcohol consumption
Diabetes
Hypertension
Sleep disorder
Connective tissue disorder
Arthritis
Migraine
Allergy
Hayfever
Asthma
Eczema
Identify genetic variants/other risk factors of interest associated
with disease
Incorporate data from patient records
- Bioinformatic integration of these data
Future Directions
• Keratoconus appears to have multiple genes and risk
factors
• Collecting more individuals and families with keratoconus
• Exploring the role of the immune system in disease
• Put these risk factors together to better understand
disease and help improve patient care