Good Hope, Heartlands, and Solihull Eye Clinics

Macular dystrophies & related

David Kinshuck notes from a lecture given by Prof T Moore, 2008


  • RPE=Retinal Pigment epithelium
  • FFA=retinal fluorescein angiogram
  • OCT=laser scan of retina
  • CNV= choroidal neovasularisation
  • AF= Autofluorescence




Foveal hypoplasia

North Carolina/Sorsby's

  • See
  • excellent photos
  • also called Sorsby's (initially these were thought to be separate disease, but now NC and Sorsby's are believed to be the same condition
  • North carolina..macula colobomas appearance.
  • may get cnv
  • findings
    • Big hole in centre of macula
    • Drusen cluster in a circle in the foveal area
    • small compact drusen
  • None progressive unless cnv

Vitelliform macular dystrophy, Bests disease

This is primarily an RPE disease, with secondary damage of photoreceptors. It has a reasonable prognosis. It is often called Best disease, especially in younger people. Separate page


  • the large gene codes for chloride channels in the RPE cells
  • the disease is modified by other genes
  • VMD2 gene 11q13
  • novel gene, encodes 585 aa protein (bestrophin), mainly missence mutations   Genes Eye 2012



  • stage 1...dark central angiogram as light obstructed
  • reduced EOG; ERG normal
  • small % develop CNV
  1. stage 1 (angiogram changes only)
  2. stage 2a? central yellowish blob
  3. stage3 scrambled egg
  4. scar
  5. Look out for cnv as well, need ffa as well

Juvenile x linked retinoschisis

x linked juvenile retinoschisis

patient age 6y enlarge

another age ~30y

  • photos google
  • males only
  • hyperopic with squints
  • visible with green light of ophthalmoscope
  • foveal schisis...seen easily with OCT
  • 50% peripheral retinal changes, silvery, scars
  • 'negative wave' ERG muller cell disease
  • dorzolamide drops help a few
  • RS1 gene, identifies carriers (tested in Cambridge)
  • genotype and phenotype correlation, very variable
  • case with photos
  • vitrectomy may help...before detachment/vitreous haem AJO 12

Stargardt disease

  • AR recessive  ABCA4 gene  Eye 13
  • 51 exons, expressed in rods and cones, ABC transporter removes all-transretinal from outer segment discs..defective ATP transport in photoreceptors
  • retina is damaged by the toxic effect of the A2E and lipofuscin waste products
  • white flecks at level of RPE, macular atrophy, dark choroid
  • abnormal autofluorescence in RPE
  • lipofuscin accumulates (a waste product), later get geographic atrophy
  • abnormal pattern ERG, normal ERG early
  • theoretically reducing light will reduce waste products
  • RNIB
  • affects cones first, then rods
  • some adults lose peripheral vision first, as the RPE may die first
  • Occult macular dystrophy may be a type of stargarts Retina14
  • selectice choriocapillaris loss: flecks withperipapillary sparing
  • show on oct: atrophy...choroid...different from geographic.
  • "ELOVL4: best-corrected visual acuity ranged from 20/25 to 20/200. Early pathologic changes included thickening of the external limiting membrane and outer nuclear atrophy followed by retinal pigment epithelium loss in later stages. Photoreceptor loss present in early stages with good visual acuity.
    PROM1 patient also had similar central vision loss with significant outer nuclear atrophy, with more diffuse and patchy retinal pigment epithelium loss throughout the macula."Retina16
  • Athens needed BJO16

Andrew Webster 2011, some notes

  • 1/50 carriers
  • generally autosomal recessive, very variable penetrance
  • only a small% look like typical Stragradts
  • very large 50 exon gene, 400 mutatioins.

A  case

  • age 17, recent vision 6/12, now 6/36
  • EOG / ERG / retinal appearance normal
  • passed as normal
  • OCT: no neurosensory retina

Another case

  • flashes when reverising ca
  • lecks in retina
  • reeduces patern ERG
  • late onset Stargardts, ABCA4, should never get much worse in this patients
  • google photos
  • photos... dark angiogram in early stages
  • Mutations in Elovl4 cause Stargardt disease-3,


Rod-cone dystrophy incuding retinits pigmentosa
(thanks to Antonio Calcagnia)

Rod-cone dystrophy is a general term used for inherited conditions in which rods and cones (rods more than cones) do not function and as a result usually (but not always) die. By far the most common rod-cone dystrophy is retinitis pigmentosa which presents in different ways. However, there are other rarer conditions like Leber’s congenital amaurosis which come under the same definition.

So all RPs are rod-cone dystrophies but not all rod-cone dystrophies are RP, many authors however use RP and rod-cone dystrophy  interchangeably.

Symptoms are very variable, especially early in the condition.

Retinal examination (looking for bone-spicule pigmentation and/or arterial attenuation and/or disc pallor), visual field testing, and electrodiagnostics identify the condition. Gene analysis is still in its infancy and not generally available, but has a better prognostic value; the problem with labelling it as retinitis pigmentosa implies we are looking at 40+ known genes (and increasing: see

Prognosis depends a lot on the gene: if a very young patient has significant symptoms, then the outlook is not fantastic; OCT may be helpful in these cases to establish the extent of photoreceptor loss at the posterior pole. Patients may get support from the RP society, as the symptoms of rod-cone dystrophy will be similar to those of “typical” RP.

RP RNIB     RP Fighting Blindness (The British Retinitis Pigmentosa Society) PO Box 350, Buckingham MK18 1GZ Tel: 01280 821 334 RP Helpline 0845 123 2354


Genes in macular dystrophy 2011


dominant drusen  fibulin pR354w
Sorsby TIMP 3 xon 5
RDS RDS, dominant
Best Best 1 dominant, recessice
Stargardts ABCA4
MIDI (deaf, diabetes) mitochondrial 3243 g-> a
x linked RPGR, RP2, XLRG Look for macular oedema, diamox and trusopt can help


Cone Dystrophies

Review BJO 16. "The cone dysfunction syndromes (CDS) are a collection of heterogeneous inherited conditions, with inherited retinal disorders being the second commonest cause of legal blindness in childhood and the leading cause among the working-age population in England and Wales.1 CDS have varying modes of genetic inheritance and have been classically described as stationary conditions in contrast to the progressive cone dystrophies.

Clinically, CDS are characterised by

  • presentation at birth/early infancy with visual loss and variable degrees of colour vision abnormalities, nystagmus and photophobia,
  • These reflect the dysfunction of the foveally concentrated cone cells that constitute approximately 5% of human photoreceptors. Given that these disease characteristics have an early onset and severely impair important behaviours of daily living such as facial recognition, reading and daylight vision, the consequent debilitating impact on patients’ lives is considerable.
  • colour vision defects not discussed in the review BJO 16
  • In this review
    • complete and incomplete achromatopsia (ACHM),
    • blue-cone monochromatism (BCM),
    • oligocone trichromacy (OT),
    • bradyopsia and
    • Bornholm eye disease (BED)."


General & support 2011

It is becoming increasingly important to kame a diagnosis, now so much is know about the respective conditions. Mr Andrew Webster at Moorfields is one of the UK's experts. Counselling can be more appropriate It is very important to workout the pedigree and draw a map of the family. As a guide..if the grandparents are no affected, then the gene may not bepassed on. But if the parents ar related then the condition is likely to be recessive. Electro diagnosistic tests are usful..the dystrophy may be

  • cone only (periphery may stay ok)
  • affect rods (peripheral vision may be lost later
  • There may be other eye problems depending on the condition, eg
    • cataract
    • CNV
    • macular oedema
    • schisis etc
    • Autofluorescence is very helpful
  • Support
  • advice
    • no smoking
    • healthy diet, low fat, low saltdiet, with lots of fibre, green vegetables etc
    • Vitamin A supplement may be harmful in ABCA4
  • Light
    • may not be that good in some types of RP
    • dark light is toxic GUCY20, GUCA1A


  • Table top mountain appearance with oct

Familial dominant drusen

  • adjacent to optic  nerve

Gyrate atrophy


Malattia leventinese, doynes honeycomb

  • Nasal drusen, radially arranged, with atrophy


  • Maternally inherited diabetes and deafness
  • Like gyrate atrophy
  • Mitochondrial; 3 different phenotypes
  • May depend on % of defect in mitochomrdria

Pattern dystrophy

  • formerly rds 2
  • submacular deposit
  • Collection of conditions, various phenotypes
  • butterfly, pulverulentis, etc
  • if severe : choroiretinal arrophy, dark choroid,