The Clinical Features And Gene Analysis Of Best Vitelliform Macular Dystrophy

Ⅰ.Collection of the clinial data of Best vitelliform macular dystrophy Objective.To collect clinical data of Best vitelliform macular dystrophy(BVMD) in Chinese patients.Methods.The clinical data of patients diagnosed as BVMD between Feburary 2004 and March 2007 by the fundus photography,EOG,fluorescein angiography(FFA) and optical coherence tomography(OCT) were analyzed retrospectively.Results.Eighteen patients from 6 unrelated families and 8 isolated patients were diagnosed as BVMD.These 26 patients came from 9 different areas in China.52 eyes of the 26 patients were affected staging 0 toⅣ.Conclusions.The data collection made a good prepration for further study of clinical manifestations and gene mutations of BVMD patients in China.Ⅱ.Clinical manifestations of Best vitelliform macular dystrophyPartⅠ.Clinical features of Best vitelliform macular dystrophyObjective.To investigate the clinical features of Best vitelliform macular dystrophy (BVMD) in Chinese patients.Methods.Twenty-six consecutive patients(52 eyes) were diagnosed as BVMD by the fundus photography,EOG,fluorescein angiography(FFA) and optical coherence tomography(OCT).Their clinical data were analyzed retrospectively.Results.All eyes were classified into stage 0,Ⅰ,Ⅱa,Ⅱb,ⅢandⅣaccording to Mohler classification.Each stage had different manifestations of fundus photography and FFA features.Of the 52 eyes of the 26 patients with BVMD,6 eyes had Stage0 lesions with normal macular both in fudus examination and FFA.BCVA ranged from 20/20 to 20/20.Two eyes had StageⅠlesions with subtle RPE changes fudoscopically and small window defect shown in FFA.BCVA ranged from20/20 to 20/20.Nineteen eyes had StageⅡwith classic vitelliform lesions or scrambled-egg appearance in fudus examination.Blocking defect may be found on FFA consistent with the vitelliform materials.BCVA ranged from 20/125 to 20/20.Three eyes had StageⅢcombined withⅣ.BCVA ranged from 20/50 to 20/40.FFA showed blocking defect below the fluid level and staining owing to the scar formation.Twenty-two eyes had StageⅣ.BCVA ranged from 20/400 to 20/25.FFA can detect classic fluorescent leakage from the CNV,transmission from the atrophy lesions or staining from the scar formation.Conclusions.BVMD has specific manifestations in FFA.Macular and visial acuity of the better eyes of the probands changed in all probands during the follow-up period.PartⅡ.In vivo microscopy of Best's vitelliform macular dystrophy: optical coherence tomography studyObjective.To study the optical coherence tomography(OCT) of Best vitelliform macular dystrophy(BVMD) in Chinese patients.Methods.Twenty-five patients with BVMD were examined with OCT between Feburuay 2004 and March 2007.The OCT data were studied retrospectively.Restult.In six of 50 eyes Staged 0,nomal anatomical stucture may be revealed by OCT.In nineteen of 50 eyes StagedⅡ,the broadening of the outer-retina-choroid-complex signal may be observed with the retinal elevation.In StageⅡa a conical mound would be seen corresponding to the scrambled vitelliform lesion. In"pseudohypopon" plus atrophy phase,the retinal sensory layer was not affected, there's a large volume of serous retinal detachment.In eyes with a fibrous macular or foveal atrophy seen in the fundus photograph,the thinning of the foveal retinal layer may be shown.In eyes with subfoveal neovascular lesions,.OCT scan revealed retinal elevation adjacent to a fusiform thickening of outer-retina-choroid-complex consistent with the subfoveal neovascular lesion with or without retinal edema.Conclusions.OCT is a noninvasive and useful tool that provides novel information in different stages of BVMD.The present study suggests the hypothesis that the yellowish material is located under the RPE and could explain the progressive visual changes in each stage.OCT can detect choroidal neovascularization,which is important for the evaluation of prognosis and the results of treatment.PartⅢ.Photodynamic Therapy With Verteporfin for Subfoveal Choroidal Neovascularization in Best vitelliform macular dystrophy Purpose.To describe the effects and efficiency of photodynamic therapy using verteporfin for the treatment of subfoveal choroidal neovascularization(CNV) in Best's vitelliform macular dystrophy(BVMD).Methods.Seven eyes of four continuous young BVMD patients complicated with subfoveal CNV were treated with verteporfin.The clinical data of best-corrected visual acuity(BCVA),fundus photograph,fudus fluorescein angiography(FFA) and optical coherence tomography(OCT) were prospectively followed pre-and every 1 to 3 months post the therapy.Re-treatment was decided on the basis of the detection of leakage on FFA.Results.CNV was detected in six eyes of four patients with BVMD initially and one more eye during the follow-up period.The mean follow-up was 29.8±10.6 months.PDT with Verteporfin was used 9 times in 7 eyes of 4 patients totally.The average therapeutic times in the first year were 1.After the treatments,the patients were examined and observed in the same way before the treatment during the follow-up period ranging from 22 to 44 months.After first PDT therapy,BCVA was improved or stabled in all eyes.Conclusions.Photodynamic therapy for subfoveal CNV associated with BVMD can stablize visual acuity.Ⅲ.Gene analysis in Chinese families with Best vitelliform macular dystrophyObjective.To describe the clinical phenotype in Chinese families with Best vitelliform macular dystrophy(BVMD) and to identify the mutation of the VMD2 gene in these families.Methods.Seven patients(14 eyes) from two different families were diagnosed as BVMD by the fundus photography,EOG,fluorescein angiography(FFA) and optical coherence tomography(OCT).Their clinical data were analyzed retrospectively. Molecular genetic analysis was performed on DNA extracted from peripheral leucocytes of all the patients and 2 unaffected members in each family.Exon 1 to 11 of the VMD2 gene were amplified by polymerase chain reaction for direct sequencing.Results.The pedigrees showed an autosomal dominant inheritance.Fourteen eyes from 7 patients were classified into Stage 0,Ⅱa,Ⅱb,ⅢandⅣwith different clinical manifestations.Direct sequencing of affected members revealed two amino acid-changing vatiants in the VMD2 gene(Asp301Glu and Thr307Ile) which have been reported previously in white patients and five polymorphic sequence changes.Conclusions.Asp301Glu and Thr307Ile mutations of the VMD2 gene are found in Chinese patients with BVMD.Molecular genetic approach may be useful for the proper diagnosis of BVMD.