Miscellaneous Retinopathies

Photoreceptor dystrophies

Retinitis pigmentosa (see dedicated chapter)

Stargardt’s

• Most common macular dystrophy

• AR most common: ABCA4 (or ELOVL4, PROM1), which is found on chromosome 1

  • (also AD types)

• Caused by accumulation of lipofuscin in the RPE

• VA drops to 6/60 usually and can present in childhood

• Features

  • Beaten-bronze, mottled macula
  • Yellow-white, pisciform lesions at the RPE: more elongated than drusen
  • Bull’s eye appearance may progress to geographic atrophy
  • CNV
  • ERG: normal/subnormal photopic, normal scotopic
  • EOG: subnormal
  • FFA: dark choroid (masking of the background choroid by diffuse RPE abnormality

• Fundus flavimaculatus: adult-onset form, may have normal vision

Achromatopsia

• Rod monochromatism: lack of cone function

• Complete vs incomplete forms: better VA and some preserved colour vision in incomplete form

  • Most patients have the complete form all three cone populations are deficient

• Genes: CNGA3, CNGB3, GNAT2

• Features

  • Reduced VA (6/60) and colour vision from birth
  • Pendular nystagmus
  • Photophobia
  • Normal fundus appearance: or mild RPE changes (which may mimic albinism, however albinism has normal cone function and colour vision), lack of foveal reflex
  • Hyperopia

• Tests

  • ERG: unrecordable cone responses (normal rod responses)

    • Differentiates from Leber's congenital amaurosis which shows an extinguished ERG

  • OCT: may be normal or show foveal hypoplasia

Blue cone monochromatism

• X-linked
• Preservation of blue cone function and partial achromatopsia
• Nystagmus
• Progressive myopia (cp achromatopsia)
• VA typically better than 6/60
• Normal fundus initially with then progressive macular atrophic changes
• Protan and deutan defects on colour testing
• Reduced cone response on ERG

Congenital stationary night blindness

• Disorders causing infantile nyctalopia

• Non-progressive

• Normal fundus appearance

  • Types 1 (complete) and 2 (incomplete)

• Abnormal fundus appearance (aka Oguchi disease)

  • Golden yellow colour to fundus in light-adapted state (normalises after prolonged dark adaptation -Mizuo phenomenon)

• ERG: absent bipolar function (reduced b-wave)

Macular dystrophies

Best vitelliform macular dystrophy

• Early-onset/juvenile macular dystrophy
• Second most common macular dystrophy after Stargardt’s
• BEST1 gene: autosomal dominant
• Late in course, vision deteriorates due to CNV, scarring of GA
• Features
  • Pre-vitelliform stage: Reduced EOG (Arden index <1.5) in asymptomatic child
  • Vitelliform stage: Well-defined ‘yolk-like’ lesion at the macula (vision may be unaffected at this stage)
  • Vitelliruptive: lesion breaks up and vision drops
  • Pseudohypopyon: lesion regression (often in puberty)
  • Atrophic stage: pigment disappearance leaving atrophic RPE

Adult Foveolar Vitelliform Dystrophy

• Essentially an adult-onset Bests
• Autosomal dominant mutations in PRPH2 or BEST2 genes
• Onset is between 30-50 years old
• Features
  • Mild visual loss
  • Yellow foveal deposits at the RPE level
  • Does not affect peripheral vision or cause nyctalopia

Sorsby macular dystrophy

• Autosomal dominant mutation of TIMP3
• Bilateral yellow-grey drusen-like lesions at the macula at Bruch’s
• Progress to subfoveal disciform CNV which may extend peripherally (unlike ARMD)
• Managed with anti-VEGF

Choroidal dystrophies

Gyrate atrophy

• Autosomal recessive: OAT gene mutation (chromosome 10)

• Elevated plasma ornithine: toxic to the retina and choroid

• Features

  • Gyrate retinal lesions: paving-stone areas of atrophy coalescing with scalloped borders between normal and abnormal RPE
  • Generalised hyperpigmentation of the residual RPE distinguishes from choroideremia
  • Posterior subcapsular cataracts
  • High myopia with astigmatism
  • Hyperornithinaemia
  • Normal visual acuity until approximately age 10
  • Nyctalopia

• Management: dietary restriction of arginine and vitamin B6 supplementation (pyridoxine) +/- proline supplementation

Choroideremia

• May appear similar to gyrate atrophy
• X-linked recessive therefore causes visual loss in males. CHM gene (gene deletion also associated with deafness and learning disability)
• Female carriers show fine RPE atrophy
• Features
  • Nyctalopia
  • Field loss
  • Variable loss of VA from middle age
  • Patchy RPE and choroidal atrophy sparing the retinal vessels and optic disc
  • Posterior subcapsular cataract
  • Early vitreous degeneration
  • Reduced ERG (rods first then cones)

Miscellaneous

Cancer associated retinopathy

• Paraneoplastic syndrome

• Associated with an auto-antibody to a 23kD retinal photoreceptor protein: recoverin

• Melanoma associated retinopathy has been found to be associated with auto-antibodies to TRPM1 cation channels on bipolar cells

  • Presents acutely/subacutely with

    • Reduced vision
    • Nyctalopia
    • Photopsias
    • Vitelliform lesions may be seen but anterior/posterior segments may be unremarkable
    • Mild vitritis

  • VF: central, cecocentral, paracentral scotomas

  • OCT: attenuation of the parafoveal ellipsoid zone (IS/OS junction), indicative of degeneration of photoreceptors

  • ERG: attenuation of the b-wave (compared to a-wave) “electronegative response”

    • (this indicates loss of the bipolar cell response -b wave- with preservation of the photoreceptor response -a wave)

• NB: MAR affects rod function while CAR affects both rods and cones (cones moreso)

Incontinentia pigmenti

• X-linked dominant genodermatosis (neurocutaneous disorder)

• Lethal in males

• Cutaneous stages

  • Vesicular (1-2 weeks)
  • Verrucous (2-6 weeks)
  • Hyperpigmented (3-6 months)
  • Hypopigmented (2-3rd decade)

• Skin findings: bullae on extremities, hyperpigmented macules on trunk, alopecia, eyelash hypogenesis

• Brain abnormalities: microcephaly, seizures, LD

• Ocular findings (20-35%): ROP-like signs including incomplete peripheral retinal vascularisation leading to neovascular membranes, vitreous hemorrhage and tractional RD

  • Strabismus
  • Cataracts
  • Optic atrophy
  • Microphthalmos

• Dental: partial anodontia, delayed dentition, impactions

• Skeletal: scoliosis, spina bifida, congenital hip dislocation

Susac syndrome

• Microangiopathy of brain retina and cochlea, triad of:

  • Encephalopathy: migraine-like headaches, ataxia, vertigo, sensory disturbance
  • BRAO
  • Sensorineural hearing loss: typically permanent
  • *these may not present concurrently*

• Presumed autoimmune epitheliopathy causing microinfarcts

• F>M, presenting between 20 and 40 years old

• Tests:

  • MRI: supratentorial white matter lesions eg. ‘snowball lesion’ in corpus callosum
  • FFA: ‘Gass plaques’ ie yellowish-white retinal wall plaques
  • Audiogram
  • OCT

• Management: early, aggressive immunosuppression

  • High dose glucocorticoids
  • Cyclophosphamide
  • Rituximab
  • IVIG/plasmapheresis

Bietti’s crystalline dystrophy

• Autosomal recessive mutation of CYP4V2

• Chorioretinal dystrophy: multiple small intraretinal crystalline deposits

  • Also found in cornea and lymphocytes
  • Crystals composed of cholesterol and lipid

• More common in East Asia

• RPE and choroidal atrophy: moth-eaten appearance of FFA

• Night blindness

• Progressive field loss

• Abnormal ERG and EOG

Angioid streaks

• Breaks in Bruch’s membrane which is also thickened

• Systemic associations ("PEPSI" mneumonic)

  • Pseudoexanthoma elasticum
  • Ehlers-Danlos
  • Paget’s disease
  • Sickle cell
  • Idiopathic
  • Beta thalassaemia

• Features

  • Irregular red-brown lines radiating from optic nerve to periphery
  • CNV
  • Peripapillary atrophy
  • Optic nerve head drusen
  • Optic atrophy
  • FFA: hyperfluorescence early with late staining

• Complications

  • Choroidal rupture after minor trauma: avoid contact sports
  • CNV

• Management

  • Avoid contact sports
  • anti-VEGF for subfoveal CNV

White without pressure

• Typically affects asians and afro-caribbeans
• Presents as white sheen of retina skin to during normal scleral indentation
• Absent choroidal markings
• May mimic shallow retinal detachments

Summarised medical retinopathies

Name	Genetics	Findings	Tests
Stargardt’s	AR ABCA4	Pisciform yellow-white flecks, bull’s eye atrophy, ‘beaten-bronze’ atrophy	FFA: dark choroid ERG: macular dysfunction
Congenital stationary night blindness	AD, AR, XL Normal fundi vs abnormal (Oguchi’s) Complete vs incomplete	Golden yellow sheen to fundus in Oguchis	ERG: reduced/undetectable rod ERG, negative bright flash response
Best’s	AD BEST1	Retain good vision Yolk-like lesion at posterior pole (eventually breaks down to mottled geographic atrophy)	EOG: reduced Arden ratio ERG: normal
Gyrate atrophy	AR OAT gene	RPE/choroidal atrophy, scalloped appearance, enlarging	Reduced ERG (rod>cone) Elevated plasma ornithine
Choroideremia	XL CHM gene	Fine RPE atrophy, granular pigment in mid-periphery, sparing vessels/disc	Reduced ERG (rod>cone)
Lebers congenital amaurosis	>25 genes A subtype of RP RPE65 GUCY2D	Congenital blindness, pendular, roving nystagmus, hypermetropia. Normal fundus Eye poking (oculo-digital sign) Keratoconus	Extinguished ERG
Achromatopsia	AR Lack of cone function	Pendular nystagmus Hypermetropia Roving eye movements Photophobia	Absent cone ERG Normal rod ERG
X-linked retinoschisis	X-linked RS1	Foveal schisis, spoke-wheel, hyperopia