Dominant Cystoid Macular Dystrophy Research Articles

Dominant cystoid macular dystrophy associated with mutations in the RP1L1 gene.

Dominant cystoid macular dystrophy associated with mutations in the RP1L1 gene.

Dominant Cystoid Macular Dystrophy

To describe the clinical characteristics and long-term follow-up in patients with autosomal dominant cystoid macular dystrophy (DCMD). Retrospective case series. Ninety-seven patients with DCMD. Extensive ophthalmic examination, including visual acuity (VA), fundus photography, fluorescein angiography (FA), fundus autofluorescence (FAF) imaging, optical coherence tomography (OCT), color vision testing, dark adaptation testing, full-field electroretinography (ERG), and electro-oculography (EOG). Blood samples were obtained for DNA extraction and subsequent haplotype analysis. Age at onset, VA, fundus appearance, and characteristics on FA, FAF, OCT, ERG, and EOG. Cystoid fluid collections (CFCs) were the first retinal abnormalities detectable in DCMD, developing during childhood. At long-term follow-up, the CFCs decreased in size and number, and eventually disappeared with concurrent development of progressive chorioretinal atrophy and hyperpigmented deposits in the posterior pole. Dominant cystoid macular dystrophy could be classified into 3 stages, based on characteristics on ophthalmoscopy, FAF, FA, and OCT, as well as on results of electrophysiologic analysis. The staging system correlated with age and VA. In stage 1 DCMD (20 patients; 22%), patients generally were younger than 20 years and had CFCs with fine folding of the internal limiting membrane and mild pigment changes. In stage 2 DCMD (48 patients; 52%), the CFCs tended to decrease in size, and moderate macular chorioretinal atrophy developed. Patients with stage 3 DCMD (24 patients; 26%) generally were older than 50 years and showed profound chorioretinal atrophy, as well as coarse hyperpigmented deposits in the posterior pole. Most patients were (highly) hyperopic (72 patients; 92%). All DCMD patients shared the disease haplotype at the DCMD locus at 7p15.3. Dominant cystoid macular dystrophy is a progressive retinal dystrophy, characterized primarily by early-onset cystoid fluid collections in the neuroretina, which distinguishes this disorder from other retinal dystrophies. The phenotypic range of DCMD can be classified into 3 stages. The genetic locus for this retinal dystrophy has been mapped to 7p15.3, but the involved gene is currently unknown.

Octreotide Acetate in Dominant Cystoid Macular Dystrophy

Dominant cystoid macular degeneration (DCMD) is an autosomal dominant trait of cystoid macular edema with poor visual prognosis. Until now, no efficient treatments for DCMD have been reported. The authors evaluated a somatostatin-analogue (octreotide acetate) as treatment for DCMD. The authors treated four patients with early DCMD by intramuscular longacting octreotide acetate, 20 mg every 4 weeks for 1 year. In addition to general ophthalmologic examination the authors performed fluorescein angiography (FA) before and after treatment. Seven out of eight eyes showed improvement on FA and stabilization of visual acuity. Somatostatin-analogues may reduce cystoid edema in DCMD and may thus prevent disease-related visual loss.

Optical Coherence Tomography Findings in Autosomal Dominant Macular Dystrophy

The authors report a case of autosomal dominant cystoid macular dystrophy in which optical coherence tomography outlined the pathology and assisted in determining the etiology of the patient's macular edema.

MRNA expression of the murine glycoprotein (transmembrane) nmb ( Gpnmb) gene is linked to the developing retinal pigment epithelium and iris

The murine homologue of the human glycoprotein (transmembrane) NMB ( GPNMB) gene was identified by subtractive cloning from in vitro cultured murine primary osteoblast cells and subsequent RACE-PCR. GPNMB is a highly glycosylated type I transmembrane protein that shares significant sequence homology to several melanosomal proteins. Increasing expression of Gpnmb mRNA was observed during differentiation of murine primary osteoblast cell cultures. To address the potential functions of GPNMB we analysed its mRNA-expression during murine embryonic development. In early development Gpnmb mRNA is detected at high levels in the outer layer of the retina. Later in development expression gets restricted to the retinal pigment epithelium and iris. At the cytoplasmic domain of GPNMB, a conserved di-leucin-based endosomal/melanosomal-sorting signal (ExxPLL) was located, present as well in several known melanosomal proteins. To analyse the subcellular localization we used EGFP-tagged GPNMB transfected in COS7 and HEK293 cells. In both non-pigmented cell lines, the EGFP–GPNMB fusion protein was localized to vesicular, endosomal like structures. Sequence homology to known melanosomal proteins, mRNA expression and subcellular localization are suggestive for GPNMB as an intracellular, endosomal/melanosomal compartment specific protein important for melanin biosynthesis and the development of the retinal pigment epithelium and iris. As the gene coding for human GPNMB was localized to chromosome 7p15, a locus involved in the human inherited disease cystoid macular edema, also known as dominant cystoid macular dystrophy (OMIM 153880) we highly suggest that GPNMB is a candidate gene for this human inherited disease.

Bilateral cystoid macular edema in a 21-year-old woman

Dominant cystoid macular dystrophy (DCMD) is characterized by a prolonged course of bilateral macular cystoid change associated with leakage on fluorescein angiography, progressive loss of central vision, peripheral retinal pigmentary disturbances and subnormal electro-oculogram. The pigmentary changes and the electro-oculographic findings suggest dysfunction of the retinal pigment epithelium. We report the case of a woman affected by this dystrophy with its characteristic features.

The EOG in Best's disease and dominant cystoid macular dystrophy (DCMD).

The electro-oculogram (EOG) was studied in 156 normal patients, 103 patients with Best's disease, and 52 patients with dominant cystoid macular dystrophy (DCMD). Statistical analysis was performed by comparing the distribution of Lp/Dt ratios of the groups. Strength of association between Lp/Dt ratio and age was studied with correlation and regression analysis. In normal patients and in those with Best's disease, there was no significant correlation between age and Lp/Dt ratio. Obviously, the gene defect in Best's disease causes an altered light-sensitive slow oscillation that remains stable throughout life. In DCMD patients, there was a significant negative correlation between age and Lp/Dt ratio for the total sample and for the female subgroup. Likely, the gene defect in DCMD interferes with capillary permeability, that becomes susceptible to changes of the female hormones.

Localization of the gene for dominant cystoid macular dystrophy on chromosome 7p.

In a family with autosomal dominant cystoid macular dystrophy (DCMD) linkage was detected with the dinucleotide marker D7S435 on the short arm of chromosome 7. With markers flanking D7S435, the DCMD locus could be assigned to the interval D7S493-D7S526 at 7p15-p21, which spans approximately 20 cM. Three-point linkage yielded a maximal lod score of 9.46 and location score of 43.5 and suggested that DCMD is 5,5 cM proximal to D7S493. Recently, a retinitis pigmentosa (RP7) locus has been mapped in roughly the same area of chromosome 7. Genetic data of both studies described below, allow a region of overlap between the location of the DCMD and the RP7 gene between D7S435 and D7S526. Both genes being one and the same will further substantiate the close relationship between macular degeneration and retinitis pigmentosa.

Acetazolamide in dominant cystoid macular dystrophy. A pilot study.

Eight patients (four men, four women), with low visual acuity caused by autosomal dominant cystoid macular dystrophy, were treated daily with oral 250 mg dose acetazolamide. Treatment ranged from two to 17 months. None of these eight patients had improvement of visual acuity of more than 0.1. Treatment with 250 mg acetazolamide appears not to be an effective therapy for cystoid macular oedema in dominant cystoid macular dystrophy. The electroretinography b-wave/a-wave ratio was normal. The primary lesion in dominant cystoid macular dystrophy remains obscure.

Dominant cystoid macular dystrophy (DCMD)

The data of 56 patients with dominant cystoid macular dystrophy are discussed. The dystrophy has an early onset of cystoid macular oedema resulting in macular atrophy and sometimes pericentral retinitis pigmentosa. Peripheral pigmentary changes and fluorescein leakage from peripheral vessels are not uncommon. There is hyperopia, shortened axial length and normal corneal curvature. In most cases the EOG Lp/Dt ratio is subnormal, the ERG normal. While the type of colour vision deficiency depends on the mode of fixation, the diminished red-sensitivity reflects receptoral disorientation. DCMD is a diffuse tapetoretinal dystrophy.

Retinal functions in dominant cystoid macular dystrophy (DCMD).

Dominant cystoid macular dystrophy (DCMD) occurred in 28 members of 5 unrelated families. The disease is characterized by cystoid macular oedema and leakage from retinal capillaries in the posterior pole. Colour vision examination reveals a type I red-green defect with concomitant blue-yellow defectiveness; the latter may be caused by the leaking capillaries. The ERG is normal. The EOG is subnormal. Darkadaptation curves are often slightly disturbed. There are frequently also aspecific pigmentary alterations in the peripheral fundus.