University of Edinburgh

Eye conditions and case studies

Presented on 28 October 2011

Dr Andrew Blaikie
Consultant Ophthalmologist

Childhood Visual Impairment: Ocular Conditions

Purpose of Talk

  • Discuss the most common conditions that you are likely to see in your job
  • Opportunity to ask questions and pick my brains
  • Lots to talk about - can't cover everything

NOT the Purpose of Talk

  • Tell you how to manage child from an educational point of view
  • Suggest low vision management
  • Although I am familiar with some of the issues I am not an expert in that field
  • Hopefully I can learn from you?

References: VIS or SSC website Dutton & Bowman book Taylor and Hoyt book

Anatomical Sites

  1. Whole Globe
  2. Cornea
  3. Lens
  4. Uvea (Iris, Ciliary Body and Choroid)
  5. Retina
  6. Optic Nerve
  7. Brain


anatomical site

Whole Globe 73
Albinism 44
Coloboma 11
Microphthalmia 7
Glaucoma 3
Refractive error 2
Stickler's Syndrome 2
CHARGE Syndrome 1
Peter's Anomaly 1
Persistent Hyperplastic Vitreous 1
Marfan's Syndrome 1

Whole Globe


Characteristic ocular changes associated with albinism

  • Nystagmus
  • Reduced visual acuity
  • Strabismus
  • Absent or reduced iris pigment
  • Absent or reduced melanin pigment in the retinal pigment peithelium
  • Foveal hypoplasia*
  • Misrouting of the optic fibres at the chiasm*

*Constant features of albinism

Glasses in Albinism (n=35)

  • Median refractive correction was 1.875 D spherical equivalent (range: -9.75 to +8.88 D)
  • Glasses wear was initiated at a median age of 14 months (range: 3 months to 14 years)
  • Compliance 'excellent' in 29/35, 'fair' in 4
  • Mean binocular VA at distance was 20/80.9 corrected and 20/107.6 uncorrected ( P < 0.001)
  • Mean VA at near was 20/28.4 corrected and 20/41 uncorrected
  • No great benefit to stereoacuity

Tinted glasses

  • Tint - reduce photodysphoria
  • UV filters - reduce ageing damage to retina
  • Polarisation - glare
  • Photochromatic lenses only change colour to UV light so will not go dark in the car


  • Chromosomes
  • Autosomes
  • Sex
  • Inheritance patterns
  • Dominant
  • Recessive
  • X-linked

46 pairs of chromosomes

  • 22 pairs of autosomes
  • (numbered by size)
  • 1 pair of 'sex' chromosomes
  • (X or Y named by shape)


  • Only requires one copy of a misprinted gene for the condition to be expressed
  • Males and females equally affected
  • 1 in 2 children of affected parent will also be affected
  • 1 in 2 will be normal and not carriers
  • Don't really get carriers (but you can if disease is only weakly expressed)

Recessive Inheritance

  • A 'recessive' condition to be 'manifest' requires both copies of the gene to be misprinted
  • Affects male and females equally
  • If only one copy misprinted then they are a 'carrier'
  • If both parents carriers then 1 in 4 chance child will be affected
  • 1 in 2 chance child will be carrier
  • 1 in 4 chance neither affected or a carrier


  • Males XY Females XX
  • Most x-linked conditions recessive so mainly boys affected
  • Affected male will always pass on misprinted gene on X to daughters
  • None of his sons will get his X and so none will be affected or carriers


  • Confused?
  • Draw out the diagrams and stare at them and it makes sense


  • Congenital
  • Acquired (usually adults)
  • Sensory (eye problem)
  • Motor Congenital (brain problem)


  • Acquired: Oscillopsia and Reduced VA
  • Congenital: only reduced VA
  • Null point
  • Abnormal Head Posture (AHP)


  • Glasses
  • Prisms
  • Contact lenses
  • AHP Surgery

Coloboma & Microphthalmia


  • Part of eye missing
  • Infero-nasal part
  • Closure of embryological cleft
  • Iris, retina, optic nerve



  • How much vision
  • Anything else wrong
  • Retinal Detachment
  • Orbit growth and facial symmetry
  • Environmental cause?
  • Genetic Counselling


  • Increasingly uncommon cause of childhood VI
  • Early diagnosis
  • Preventative treatment


Peter's Anomaly




  • 'Itis' means inflammation
  • Uvea is coloured part of eye
  • Anterior: Iris
  • Intermediate: Ciliary Body
  • Posterior: Choroid



Retina 57
Retinopathy of prematurity


Leber's Congenital Amaurosis


Macular Dystrophy 7
Retinitis Pigmentosa 7
Cone Dystrophy 6
Rod-cone Dystrophy 4
Chorioretinal Atrophy 2
Coloboma 2
Retinoblastoma 2
Rod Monochromatism 2
Toxoplasmosis 2
Retinoschisis 1



  • No colour (because only one type)
  • Poor acuity
  • Work well in dark
  • Movement


  • Colour (because 3 different types)
  • Fine detail
  • Daylight
  • Still

Macular Dystrophies

Stargardt's Disease

Retinitis Pigmentosa

  • Description of appearance
  • Disease of any part of the retina
  • Progressive rod and cone dystrophy
  • Inherited
  • Isolated ocular condition
  • Associated with other conditions
  • A syndrome


  • Poor night vision: 'Night Blindness'
  • Loss of peripheral visual field: 'Ring Scotoma'
  • Gradual loss of visual acuity
    • Cataract
    • Macular Oedema

Gene Therapy

Ophthalmology Leading the Way

Many visually impairing eye conditions have an underlying genetic cause

  • AMD
  • Glaucoma
  • Retinopathy of prematurity
  • Range of inherited retinal dystrophies
  • Cone dystrophies
  • Stargardt's disease
  • Retinitis Pigmentosa

Several ways gene therapy can help treat a condition

  • Replace mutated gene (recessive)
  • Inactivate or neutralise an aberrant gene (dominant)
  • Alter function of genes that are indirectly involved in the pathogenesis (ischaemic NV)
  • New genes that express a therapeutic protein (neuroprotection)

Find a suitable condition

  • Many inherited retinal dystrophies
  • Only a minority do we know the mutation (misprint)
  • Leber's Congenital Amaurosis
  • LCA2 caused by a mutation in RPE65 gene leaves the cells relatively intact even though function has stopped

LCA2 – early and late appearances


Retinal Gene Therapy

  • Put 'working' gene into a virus
  • Inject suspension of virus under the retina
  • Virus infects the cell and the cells normal workings reads the new gene and makes the missing gene product

Big Questions

  • Will this do harm to the eye or the rest of the body?
  • Will the cell start functioning again?
  • Will this lead to vision improving?

Start with animal models

  • Briard Dog - spontaeneous RPE65 mutation
  • Mouse model - both spontaeneous and induced mutations
  • Used Adeno-associated virus vector (AVV) with working RPE 65 gene

How do you monitor success?

  • Nystagmus
  • ERG
  • Pupillometry
  • Visual behaviour studies; obstacle course in different lighting conditions
  • 11 years (human) follow-up and doing well

Briar dogs are now man's best friend - race to the moon starts

3 centres

  • London, Moorfields
  • Children's Hospital of Philadelphia (CHOP)
  • University of Florida/Pennsylvania

Similar Approach from each group

  • AAV vector
  • 3 adults in each centre (17-26)
  • VA range 20/115 to 20/2000
  • Vitrectomy
  • Injection of virus under retina (150ul to 1000ul)



  • Pupillometry
  • Nystagmus
  • ERG



  • VA - 3/9 improved (all from CHOP)
  • Perceived light sensitivity - 7/9 improved
  • Pupillometry -4/9 improved
  • ERG - all stayed the same



Side effects

  • 1/9 developed a macular hole
  • No wider immune response to the virus or systemic infection measured

The future for LCA2

  • Animal studies suggest earlier treatment greater the response
  • Paediatric population with minimal retinal degeneration

Retinopathy of Prematurity

  • Blood system immature
  • Parts of retina have no blood supply
  • 'Ischaemic': leads to release of growth hormones (VEGF)
  • Causes Damage: Retinal Detachment

Screening programme

  • <32 weeks
  • <1500 g
  • If ROP reaches a bad stage then treat


  • Laser or cold 'cryo' therapy
  • Kills peripheral retina
  • Switches off VEGF release
  • Reduces risk of detachment by 90%

Survivors with no ROP may still have VI

Later problems

  • Myopia
  • Squint
  • Amblyopia
  • CVI (25% of premature babies have PVL)


Knudson 2-hit hypothesis

He noticed that there were 2 groups of patients: Those patients with a family history of retinoblastoma and those without (the majority).

Familial form

  • Those with a family history tended to present earlier in childhood and often had bilateral disease and within an eye could be multi-focal.


  • Those without a family history presented later and only had a single eye involved.


Interpretation of epidemiology

For a tumour to develop a gene was involved and that mutations were needed in this gene (called the retinoblastoma gene).

Normal people have two copies of this gene, one inherited from the father and one from the mother.

In the sporadic form of retinoblastoma a mutation had to occur in each copy. If a single mutation could occur in one in a 106 cells in a given period of time then the probability of a mutation occurring in both copies would be one in 1012, that is, very rare. Obviously the longer the period of time that elapses the more likely this is, but it is unlikely to occur more than in one cells. Hence tumours occur late and are unilateral.

In contrast in the familial form of the disease, the child inherits from a parent one mutant copy of the retinoblastoma gene. Since it still requires mutations in both copies for a tumour to develop then the probability of this is one in a 106.  This is a million times more likely than in the sporadic form. Hence the disease occurs earlier and also there is a high probability of it occurring in more than one cell, and thus tumours may be multi-focal and bilateral.

Took 17 years to prove: Hypothesis was proposed in the early 1970s: the identification of the retinoblastoma gene occurred in 1987 and confirmed Knudson's hypothesis.



Optic Nerve

Optic Nerve Hypoplasia

Optic nerve hypoplasia is a condition present from birth in which the eye does not have all the usual wiring between the eye and brain to transfer information about the visual world. The loss of wiring can sometimes be only very small but sometimes can be complete with no information being transferred from the eye to the brain at all. One or both eyes can be affected.

Septo-Optic Dysplasia

Optic Atrophy

  • Loss of retinal ganglion cells

Different forms of the condition

  • Inherited (genetic)
  • Acquired (secondary to glaucoma, brain injury, maternal drug use)

Lots of different Ocular VI conditions in children

  • Variable manifestations
  • Variable vision
  • Variable prognosis
  • Huge challenge to have a working understanding - probably only comes with experience.