Doyne Honeycomb Degeneration of the Retina

Doyne Honeycomb Macular Dystrophy

Clinical Characteristics

Ocular Features

Beginning usually in midlife, the retina has radially localized white, large drusen in the posterior pole.  These may begin as small drusen that later enlarge and become confluent creating a honeycomb pattern.  The disease begins as an accumulation of material between the Bruch membrane and the RPE.  Eventually drusen occupy the entire thickness of the Bruch membrane and are continuous with or internal to the RPE basement membrane.  Vision early is normal and a slow loss of vision occurs sometime after the drusen appear in most individuals.  In some patients geographic atrophy, pigmentary changes, and a subfoveal neovascular net develops with macular scarring, vitreous hemorrhage, and severe reduction of vision.

Systemic Features

No systemic disease is associated.

Genetics

Doyne honeycomb macular disease, or dominant drusen, is the result of mutations in the EFEMP1 gene at 2p16 in the majority of cases.  The mutant protein product (a member of the fibulin famiy) is folded abnormally and secreted inefficiently.  It is also resistant to degradation which may lead to receptor damage by limiting access to nutrients from the choriocapillaris.  Some genetic heterogeneity may exist since a few cases seem to be linked to a locus at 6q14.  It is an autosomal dominant disorder.  Some have considered Malattia Leventinese and Doyne honeycomb retinal dystrophy as separate entities but mutations in the same gene seem to be responsible for both conditions suggesting they are clinical variations of the same disorder.

Treatment Options

The subfoveal net responds to photodynamic therapy.

References

Fu L, Garland D, Yang Z, Shukla D, Rajendran A, Pearson E, Stone EM, Zhang K, Pierce EA. The R345W mutation in EFEMP1 is pathogenic and causes AMD-like deposits in mice. Hum Mol Genet. 2007 Oct 15;16(20):2411-22.

PubMed ID: 
17666404

Marmorstein L. Association of EFEMP1 with malattia leventinese and age-related macular degeneration: a mini-review. Ophthalmic Genet. 2004 Sep;25(3):219-26. Review.

PubMed ID: 
15512998

Dantas MA, Slakter JS, Negrao S, Fonseca RA, Kaga T, Yannuzzi LA. Photodynamic therapy with verteporfin in mallatia leventinese. Ophthalmology. 2002 Feb;109(2):296-301.

PubMed ID: 
11825812

Stone EM, Lotery AJ, Munier FL, Héon E, Piguet B, Guymer RH, Vandenburgh K, Cousin P, Nishimura D, Swiderski RE, Silvestri G, Mackey DA, Hageman GS, Bird AC, Sheffield VC, Schorderet DF. A single EFEMP1 mutation associated with both Malattia Leventinese and Doyne honeycomb retinal dystrophy. Nat Genet. 1999 Jun;22(2):199-202.

PubMed ID: 
10369267