Grand RoundsGrand RoundsBest DiseaseBest Disease

Mark Sherman MDMark Sherman MD

University of LouisvilleUniversity of Louisville

Department of Ophthalmology and Visual Department of Ophthalmology and Visual SciencesSciences

04/04/201404/04/2014

SubjectiveSubjectiveCC:CC: Distorted vision x several months Distorted vision x several months

HPIHPI: 45 year old white male presented to general : 45 year old white male presented to general clinic with complaint of worsening distortion of clinic with complaint of worsening distortion of vision in both eyes for several months. Patient vision in both eyes for several months. Patient stated he had noticed a deterioration in his vision stated he had noticed a deterioration in his vision in his early 30s but the distortion was new over the in his early 30s but the distortion was new over the past several months. Patient denied any other past several months. Patient denied any other ocular complaints.ocular complaints.

POHPOH: None : None PMH:PMH: COPD COPD Meds:Meds: Inhalers, Prednisone Inhalers, PrednisoneFH:FH: Uncle: Best Dz, Grandfather: AMD Uncle: Best Dz, Grandfather: AMD

ExamExam ODOD OSOS

BCVABCVA: 20/25 : 20/25 20/25 20/25

Pupils:Pupils: 5 53 3 5 53 3

No APDNo APD

IOPIOP:: 14 14 14 14

EOM:EOM: Full OUFull OU

SLE:SLE: ODOD OSOS

L/LL/L WNLWNL WNLWNL ConjunctivaConjunctiva WNLWNL WNLWNL KK WNLWNL WNLWNL ACAC WNL WNL WNLWNL I/LI/L WNL WNL WNLWNL

Anterior SegmentAnterior Segment

DFEDFE

Bilateral round, yellow lesions involving the fovea

OCTOCT

Bilateral subretinal lesions with preservation of the retinal architecture

OD

OS

Assessment/Differential Assessment/Differential DiagnosisDiagnosis

Assessment:Assessment: 45 year old white male 45 year old white male with bilateral “yolk-like” subretinal with bilateral “yolk-like” subretinal lesionslesions

DDx:DDx: 1) Adult Vitelliform 1) Adult Vitelliform DystrophyDystrophy

2) Best Disease2) Best Disease

Adult Vitelliform Pattern Adult Vitelliform Pattern DystrophyDystrophy

Caused by mutations in the Caused by mutations in the RDS/peripherin geneRDS/peripherin gene

Characterized by: Characterized by: Yellow subfoveal lesions that are bilateralYellow subfoveal lesions that are bilateral Round or oval shapeRound or oval shape Typically one-third disc diameter in sizeTypically one-third disc diameter in size Often contain a central pigmented spotOften contain a central pigmented spot

Adult Vitelliform Pattern Adult Vitelliform Pattern DystrophyDystrophy

Usually appears in the fourth to sixth Usually appears in the fourth to sixth decade of lifedecade of life

Presenting symptoms include: mild Presenting symptoms include: mild blurring of vision and metamorphospiablurring of vision and metamorphospia

Over time the lesions fade and leave an Over time the lesions fade and leave an area of RPE atrophyarea of RPE atrophy

Visual prognosis is guarded and is directly Visual prognosis is guarded and is directly related to the size of the lesion and its related to the size of the lesion and its location within the maculalocation within the macula

Best DiseaseBest Disease

Autosomal dominant maculopathyAutosomal dominant maculopathy

Caused by mutations in the Best1 (VMD2) Caused by mutations in the Best1 (VMD2) gene on chromosome 11 which codes for gene on chromosome 11 which codes for the protein bestrophinthe protein bestrophin Bestrophin: functions as a transmembrane Bestrophin: functions as a transmembrane

chloride channel in the basolateral plasma chloride channel in the basolateral plasma membrane on the RPEmembrane on the RPE

The dysfunctional ion transport leads to The dysfunctional ion transport leads to accumulation of lipofuscinaccumulation of lipofuscin

Best DiseaseBest Disease Affected individuals present with a yellow, Affected individuals present with a yellow,

yolk-like (vitelliform) macular lesion in yolk-like (vitelliform) macular lesion in childhood or early adulthoodchildhood or early adulthood

The lesion eventually breaks down, The lesion eventually breaks down, leaving a mottled geographic atrophic leaving a mottled geographic atrophic appearanceappearance

Best DiseaseBest Disease

Diagnosis:Diagnosis: Primarily a clinical diagnosisPrimarily a clinical diagnosis EOG: Always abnormal EOG: Always abnormal ERG: Typically normalERG: Typically normal

Prognosis:Prognosis: Visual prognosis is usually good with most Visual prognosis is usually good with most

patients maintaining 20/30 acuitypatients maintaining 20/30 acuity Choroidal neovascularization does occur in Choroidal neovascularization does occur in

approximately 20% of cases approximately 20% of cases

Best Disease vs Adult Best Disease vs Adult Vitelliform DystrophyVitelliform Dystrophy

Lesion size:Lesion size: Usually larger in Best disease, Usually larger in Best disease, typically 1/3 disc diameters in adult typically 1/3 disc diameters in adult vitelliform dystrophyvitelliform dystrophy

Age of presentation:Age of presentation: Childhood to early Childhood to early adulthood in Best disease and typically adulthood in Best disease and typically between the fourth and sixth decade in adult between the fourth and sixth decade in adult vitelliform dystrophyvitelliform dystrophy

Electro-oculogram (EOG):Electro-oculogram (EOG): Abnormal in best Abnormal in best disease and normal in adult vitelliform disease and normal in adult vitelliform dystrophydystrophy

Intravitreal bevacizumab for Intravitreal bevacizumab for choroidal neovascularization choroidal neovascularization

associated with Best’s Diseaseassociated with Best’s Disease Case report of a 27 year old woman who Case report of a 27 year old woman who

presented with 20/200 vision in her right presented with 20/200 vision in her right eye; was found to have intraretinal eye; was found to have intraretinal hemorrhage in the macula with a hemorrhage in the macula with a neurosensory detachmentneurosensory detachment

The left eye showed a vitelliform lesion in The left eye showed a vitelliform lesion in the maculathe macula

Best disease was confirmed with EOGBest disease was confirmed with EOG Patient was given a single dose of Patient was given a single dose of

intravitreal Avastinintravitreal Avastin Four weeks after treatment the vision had Four weeks after treatment the vision had

improved to 20/25 and remained stable for improved to 20/25 and remained stable for 12 months of follow up12 months of follow up

ReferencesReferences BCSC: Retina and Vitreous. BCSC: Retina and Vitreous. Vitelliform Vitelliform

Degenerations.Degenerations. Pgs: 236-237 Pgs: 236-237 Boon CJ, Levering BJ, Leroy BP, Hoyng CB, et al. The Boon CJ, Levering BJ, Leroy BP, Hoyng CB, et al. The

spectrum of ocular phenotypes caused by mutations spectrum of ocular phenotypes caused by mutations in BEST1 gene. in BEST1 gene. Prog Retin Eye Res.Prog Retin Eye Res. 2009;28(3):187- 2009;28(3):187-205205

Fishman GA, Baca W, Alexander KR, et al. Visual Fishman GA, Baca W, Alexander KR, et al. Visual acuity in patients with Best vitelliform macular acuity in patients with Best vitelliform macular dystrophy. dystrophy. OphthalmologyI. 1993;100(11):1665-1670OphthalmologyI. 1993;100(11):1665-1670

Petrukhin K, Koisti MJ, et al. Identification of the Petrukhin K, Koisti MJ, et al. Identification of the gene responsible for Best macular dystrophy. gene responsible for Best macular dystrophy. Nat Nat Genet.Genet. 1998;19(3)241-247. 1998;19(3)241-247.

Velazquez-Villoria D, Macia C, et al. Intravitreal Velazquez-Villoria D, Macia C, et al. Intravitreal bevacizumab for choroidal neovascularization bevacizumab for choroidal neovascularization associated with Best’s Disease. associated with Best’s Disease. Arch Soc Esp OphtArch Soc Esp Opht. . 2014.2014.