A 31-year-old Vietnamese male presented with gradual decreased vision in both eyes since adolescence. Examination revealed pigment epithelial atrophy in the foveal area of both eyes. Fluorescein angiography showed window defects from absent choriocapillaries in the macula of both eyes. He was diagnosed with central areolar choroidal dystrophy, a rare autosomal dominant condition characterized by atrophy of the neuroepithelium, pigment epithelium, and part of the choroid resulting in gradual visual loss.

1. Doheny Eye Institute Grand Rounds Presenter Irina Bykhovskaya, MD Discussant SriniVas Sadda, MD 4/20/2007

2. Patient Presentation 31yo Vietnamese male with c/o gradual decrease in vision OU since adolescence He has been using magnifying glass in the past 3 years for reading FHx: mother and brother also with “visual problems” PMH: h/o malaria 2 years ago treated with oral medications SHx: recent immigrant from Vietnam

3. Patient Examination VA: 8ft/200 OD and 6ft/200 OS Pupils: RR, no RAPD Ta 18 OU LLL: wnl OU S/C: w/q OU K: clear OU I: brown, flat OU AC: d/q OU L: 2+ PSC OU

4. Fundus Photos Horizontal oval, slightly areolar zone of pigment epithelial atrophy in foveal area OU

5. Red Free Fundus Photos

6. Fluorescent Angiogram Window defects reveal absent choriocapillaries in the macula OU Hyperfluorescence at the lesion margins from dye leakage from intact choriocapillaries

7. Central Areolar Choroidal Dystrophy Rare Autosomal Dominant (rarely recessive, occasionally sporadic) Pathology: atrophy of neuroepithelium, pigment epithelium and part of the choroid

8. Symptoms and Ophthalmoscopic Feautures Gradual visual loss in one or both eyes Onset: between 30 and 40 yo Pigment stippling and mottling = pigment epithelial dystrophy  RPE atrophy affect the whole macula Patches of atrophy develop with frequent horseshoe shape around the fovea Fovea is affected leading to vision drop

9. Copyright restrictions may apply. Keilhauer, C. N. et al. Arch Ophthalmol 2006;124:1020-1027. Clinical Findings

10. FA Findings Early cases: - hyperfluorescence due to RPE atrophy Late stages: - choriocapillaries and diffuse background hyperfluorescence disappear - hyperfluorescence at lesion margins from dye leakage from intact choriocapillaries - more choroidal vessels seen on FA than from ophthalmologic exam

11. Visual Functions Visual Acuity – severely affected (CF) Visual Fields – normal in the periphery with central or paracentral scotoma Color Vision – moderately affected Dark Adaptation - normal Electroretinography – normal full-field, abnormal multifocal Electro-oculography – usually normal

12. Histology Well-demarkated avascular zone in posterior choroid Atrophy and fibrosis No outer layers of retina or RPE corresponding to underlying choroidal atrophy Usually no breaks in Bruch’s membrane

13. Pathogenesis Hypothesis Likely primary dystrophy of the choroidal vessels Vs Primary tapetochoroidal dystrophy or primary dystrophy of RPE with secondary choroidal involvement

14. Differential Diagnosis Pseudoinflammatory dystrophy – Sorsby Choroideremia Myopia gravior Macular coloboma Angioid streaks Gyrate atrophy Peripapillary and circinate choroidal dystrophy End stages of Stargardt’s disease Cone dystrophy Progressive bifocal chorioretinal atrophy Multifocal placoid pigment epitheliopathy

15. Mode of Inheritance Autosomal Dominant - mutation in the Peripherin/RDS gene on chromosome 6 - plays role in assembly, orientation, and structural stability of outer segment discs and accounts for an increased turnover of instable membranous segments Autosomal Recessive Sporadic

16. References K. Zhang, D.C. Garabaldi, R.E. Carr and J.S. Sunness , Hereditary choroidal disease. In: S.J. Ryan, Editor, Retina (3rd ed.), Mosby, St. Louis (2001), pp. 462–463. Hoyng CB, Deutman AF. The development of central areolar choroidal dystrophy. Graefes Arch Clin Exp Ophthalmol. 1996;234:87-93. Castori M, Valente EM, Maurizio C, Tormene AP, Brancati F, Caputo V, Dallapiccola B. A Novel Locus for Autosomal Dominant Cone and Cone–Rod Dystrophies Maps to the 6p Gene Cluster of Retinal Dystrophies. Invest Ophthalmol Vis Sci. 2005 Oct;46(10):3539-44. Keilhauer CN, Meigen T, Weber BH. Clinical findings in a multigeneration family with autosomal dominant central areolar choroidal dystrophy associated with an Arg195Leu mutation in the peripherin/RDS gene. Arch Ophthalmol. 2006 Jul;124(7):1020-7. Nagasaka K, Horiauchi M, Shimada Y, Yuzawa M. Multifocal electroretinograms in cases of central areolar choroidal dystrophy. Invest Ophthalmol Vis Sci. 2003 Apr;44(4):1673-9.