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Hereditary Choroidal Disease

Hereditary Choroidal Disease. Juan G. Santiago, MD Vitreo -Retinal Fellow Valley Retina Institute, P.A. Choroid. Vascular layer containing connective tissue, lying between the retina and the sclera 4 layers Bruch’s membrane Choriocapillaris

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Hereditary Choroidal Disease

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  1. Hereditary Choroidal Disease Juan G. Santiago, MD Vitreo-Retinal Fellow Valley Retina Institute, P.A.

  2. Choroid • Vascular layer containing connective tissue, lying between the retina and the sclera • 4 layers • Bruch’s membrane • Choriocapillaris • Major source of nutrition for RPE and outer retinal layers • Stroma • Suprachoroidal space

  3. Hereditary Choroidal Dystrophies • Choriocapillaris can be affected by the RPE, and gene mutations affecting functions of RPE can lead to atrophy of both RPE and choriocapillaris. • The considerable number of diseases and the broad and overlapping range of phenotypes associated with each disease make it likely that some of these choroidal dystrophies may be caused by mutations in the same gene.

  4. Hereditary Choroidal Dystrophies • Characteristics • Presenting symptoms of decreased central vision and a visual field defect. • Bilateral fundus abnormalities on ophthalmoscopy and FA. • ERG and EOG generally not affected until later stages of the disease.

  5. Hereditary Choroidal Dystrophies • Localized dystrophies • Central areolarchoroidal dystrophy • Sorsby fundus dystrophy • Peripapillarychoroidal dystrophy • Progressive bifocal chorioretinal atrophy • Bietti crystalline retinopathy • Generalized choroidal dystrophies • Choroideremia • Gyrate atrophy

  6. Central AreolarChoroidal Dystrophy • Initially described by Nettleship in 1884 • Slowly progressive bilateral disease with age of onset between the 2nd and 4th decades. • Visual prognosis is good. • 20/100 to 20/200 VA in the 7th-8th decade of life. • Mapped to chromosome 6p (RDS /peripherin), 17p25 (CACD) • Most cases appeared sporadically • However AD inheritance has been documented in the literature.

  7. Central AreolarChoroidal Dystrophy Early changes include nonspecific granular hyperpigmentation of the fovea.

  8. Central Areolar Choroidal Dystrophy • Well demarcated circumscribed area of atrophy of photoreceptors, RPE and choriocapillaris develops in the macula in the later stage. • Visible underlying larger choroidal vessels.

  9. Central AreolarChoroidal Dystrophy End stage CACD  Large area of atrophy of photoreceptors, RPE, and choriocapillaris.

  10. Sorsby Fundus Dystrophy • First described in a 1949 study of five British families by Sorsby • Presents by the 3rd or 4th decade of life with decreased central vision and nyctalopia. • AD trait mapped to chromosome 22q13 (Weber et al. 1994) • Large Canadian family of Irish origin • Mutations in TIMP-3 gene

  11. Sorsby Fundus Dystrophy • Abnormal accumulation of confluent, drusen-like material at the level of Bruch’s membrane • Thickening of Bruch’s membrane, that impairs the metabolic activity of the choriocapillaris and the RPE • CNV and GA may occur as a result of degeneration of the choriocapillaris, RPE, and outer photoreceptor cells.

  12. Sorsby Fundus Dystrophy

  13. Sorsby Fundus Dystrophy • Atrophy of photoreceptors, RPE, and choriocapillaris, as well as subretinal neovascularization and scarring

  14. Sorsby Fundus Dystrophy • Jacobson et al (1995) • Hypothesis that night blindness is caused by chronic photoreceptor vitamin A deprivation • A dosage of 50000 IU per day was shown to reverse night blindness in 2 SFD patients at the early stages • Further study is necessary due to potential toxicity of high dose vitamin A

  15. PeripapillaryChoroidal Dystrophy • Choroidal atrophy presents in the macula and outward from the optic nerve in all unpredictable directions. • Very rare and only 2 reports in the literature • Sveinsson (1939) • Franceschetti et al. (1974) • Isolated cases from the older literature probably represent other well recognized diseases in which PPA is a 2ry change • Serpiginouschoroiditis • Peripapillary pigment epithelial dystrophy • Helicoidperipapillarychorioretinal degeneration

  16. PeripapillaryChoroidal Dystrophy Peripapillary atrophy that radiates along the vascular arcade and spares the macula.

  17. Progressive Bifocal Chorioretinal Atrophy • Rare bilateral, progressive chorioretinal dystrophy characterized by • Nystagmus • Equatorial pigmentary degeneration • Disc pallor • Poor vision • Mapped to chromosome 6 • Overlaps with a gene for NCMD • Described initially in a single large Scottish family with AD inheritance

  18. Progressive Bifocal Chorioretinal Atrophy • Findings • At birth Temporal focus of atrophic retina and choroid, with sclera being visible (at birth) • Early in life  Nasal focus of atrophy • Areas of degeneration coalesce • A wide band of atrophic retina and choroid is noted but never crosses the midline • Two separate foci of chorioretinal atrophy with an intervening isthmus of normal retina extending above and below de disc

  19. Bietti Crystalline Retinopathy • Initially described by Bietti in 1937 as a corneoretinal degeneration • Hu(1983) • 35 patients in 25 families in China • Autosomal recesive inheritance • Onset at 29 years • Richards, et al (1991) • Autosomal dominant inheritance • Marked variability in the fundus changes

  20. Bietti Crystalline Retinopathy • ? Systemic abnormality of lipid metabolism • Corneal and conjunctival biopsies revealed cholesterol • Complex lipid inclusions in fibroblasts and epithelium • Lipid inclusions in lymphocytes

  21. Bietti Crystalline Retinopathy Clinical Features: • Numerous glistening crystal deposits in all layers of the retina associated with varying degrees of choriocapillaries and RPE loss • Superficial limbal corneal crystals

  22. Bietti Crystalline Retinopathy

  23. Bietti Crystalline Retinopathy • FA demonstrates loss of RPE and choriocapillaris with normal adjacent areas. • Slowly progressive disease in which the areas of atrophy and photoreceptor loss gradually become larger. While this occurs, the crystals disappear. • Progressive decline in ERG amplitude and progressive nyctalopia.

  24. Gyrate Atrophy • Autosomal recessive disorder characterized by chorioretinal degeneration. • Mapped to chromosome 10q26 • Metabolic abnormality • Deficiency of ornithine-delta-aminotransferase (OAT) • Elevated plasma ornithine levels (10-20x) • Low lysine levels • ?Pathogenesis -- Loss of RPE integrity with subsequent loss of photoreceptors and choriocapillaris.

  25. Gyrate Atrophy Presentation • 1st decade of life • Nyctalopia, high myopia, and astigmatism • 2nd decade • Posterior subcapsular cataracts • 4th – 5th decade • Progressive constriction of VF • Eventual loss of central VA

  26. Gyrate Atrophy Clinical Features • Circular, well circumscribed regions of chorioretinal atrophy with hyperpigmented margins in the midperiphery.

  27. Gyrate Atrophy • These regions enlarge and coalesce in a “scalloped” pattern, spread anteriorly and posteriorly and eventually encroach the macula, threatening central vision.

  28. Gyrate Atrophy

  29. Gyrate Atrophy • Other findings • Subclinical skeletal muscle changes on CT and MRI • Abnormalities on EEG; seizures • Premature atrophy and white matter lesions on brain MRI • FA • May observe leakage at the margins of healthy and affected tissue, with hyperfluorescence within the gyrate lesions. • Electrophysiologic tests • Impaired scotopic and photopic responses, which becomes extinguished as the disease progresses.

  30. Gyrate Atrophy • Treatment  reducing plasma ornithine levels • Vitamin B6 (pyridoxine) supplementation • Long term effects on visual prognosis are unknown • Diets restricted or arginine (precursor of ornithine) • Delay the progression of visual deficits

  31. Choroideremia • First described by Mauthner in 1871 • X-linked recessive disorder • Mapped to Xq13-q22 • Characterized by the progressive degeneration of the RPE, retina, and choroid. • Onset in the 1st or 2nd decade • Dark adaptation problems  Night blindness  Significant constriction of VF Severe impairment in central VA (5th to 7th decade)

  32. Choroideremia Fundus abnormalities • Early -- 1st decade • Pigment stippling and focal atrophy of the RPE

  33. Choroideremia • Late disease • Regions of choroidal atrophy with subsequent exposure of choroidal vessels, eventually leaving only scattered small areas of intact choroid in the macula and periphery. • Extensive choroidal atrophy.

  34. Choroideremia The FA reveals the loss of the RPE (the large choroidal vessels are well visible) and the loss of the choriocapillarisexept in the fovea.

  35. Choroideremia • Female carriers - Salt and pepper fundus • Scattered areas of reduced photoreceptor number • RPE atrophy • Pigment clumping • Areas of choriocapillaris loss

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