Grand Rounds “Blurred Vision in a Young Male” Mohammad Ali Sadiq, MD – PGY2 Nov 09, 2018

Patient Presentation CC HPI “Decreased vision in right eye” 31 year old white male with no past medical history presented with: Decreased vision in OD for the past several months No other symptoms.

History Past Ocular Hx: Has been diagnosed with a retinal dystrophy in the past. Past Medical Hx: Non contributory Family Hx: Father had blindness Meds: None Allergies: None Social Hx: No smoking/alcohol/drugs ROS: Negative except as in the HPI

External Exam OD OS BCVA 20/150 20/30 Refraction +0.75 +0.60 x 50 Pupils 3→2mm, No rAPD IOP 15 mmHg EOM Full CVF

Anterior Segment Exam SLE OD OS External/Lids WNL Conj/Sclera White and quiet Cornea Clear Ant Chamber Deep and quiet Iris Lens

Posterior Segment Exam OD OS Nerve Pink and Sharp. C/D 0.3 Macula Disciform scar with some RPE hyperplasia Elevated region centrally with small membrane inferior to fovea and some yellowish deposits. Vessels Normal Caliber Vitreous Clear Periphery No Holes or Tears. Attached 360 Degrees.

Fundus Photographs - OU Bilateral symmetric oval regions in central fibrotic scar tissue, in addition areas of RPE hyperplasia were seen in OD and some yellowish deposits are seen in OS

OCT - OD Compatible with scar area on exam. Intraretinal fluid.

OCT - OS Sub RPE fluid corresponding with a large PED with some hyperreflective deposits inferiorly.

Assessment A 31 year old white male with a family history of legal blindness in father and bilateral symmetric macular lesions with secondary CNVM. The patient had been previously diagnosed with Best’s disease. EOG performed showed an arden ratio of 1.1 and a normal ERG. Differential Diagnosis: Macular Dystrophy Best’s disease Sorsby’s fundus dystrophy Other pattern dystrophies Adult-onset Vitelliform Dystrophy Idiopathic CNVM Central Serous Chorioretinopathy

Plan Diagnosis: Best’s disease with CNVM OU and disciform scar OD Plan: Treat with Anti-VEGF injections OU

Best’s Disease Named after Dr. Friedrich Best in 1905 Hereditary retinal dystrophy involving the RPE Characteristic bilateral yellow “egg-yolk” appearance of macula Presents in childhood/early adulthood and is associated with a good visual prognosis.

Etiology Autosomal dominant pattern with variable expression Causative gene BEST1 located on long arm of chromosome 11. 100 different mutations have been described. Transmembrane protein bestrophin 1, located on basal aspect of plasma membrane of RPE cells Ca sensitive chloride channel protein

Most common in individuals with European ancestry No gender predilection Onset is between 3-15 years , with an average of 6 years However the condition is not detected until later in life when vision goes down

Diagnosis Clinical appearance Family history Adjuvant testing

Stage I Previtelliform: Normal macula or subtle RPE changes are seen

Stage II Vitelliform: classic “egg-yolk” lesion. Normal vision or mild visual loss.

Stage III Pseudohypopyon: layering of lipofuscein

Stage IV Vitelleruptive: breakup of material gives “scrambled egg” appearance.

Stage V Atrophic: Central RPE and retinal atrophy. Vision may range from 20/30 – 20/200.

CNV: This complication occurs in about 20% of patients.

The Stages of Best’s Disease

IMAGING

Imaging - FP

Fluorescein Angiography Choroidal changes Thinning of choriocapillaris Dilation of choroidal vessels Thickening of walls of outer vascular layers

OCT Choroidal changes Thinning of choriocapillaris Dilation of choroidal vessels Thickening of walls of outer vascular layers

OCT

Fundus Autofluorescence Choroidal changes Hypoautofluorescence corresponding to sub retinal fluid Punctate hyperautofluorescence corresponding to elongated photoreceptor outer segments

OCT-A Delayed filling in early phase Large choroidal venous dilatation Focal choroidal hyperfluorescence Dansingani KK, Tan ACS, Gilani F, et al. Subretinal Hyperreflective Material Imaged With Optical Coherence Tomography Angiography. American journal of ophthalmology. 2016;169:235-248.

Diagnostic Testing Electro-oculogram (EOG): Universally abnormal, with an Arden ratio (light:dark) of 1.3 or less. Electro-retinogram (ERG): Completely normal.

Prognosis Visual prognosis is good for at least the first 6 decades of life Most patients retain reading vision in at least 1 eye 1. Spontaneous resolution in 3-4 months 2. PDT – using standard fluence -600 or reduced fluence -300 can be used. 3. Resolution in about 25% of cases is seen.

Management No medical/surgical management Anti-VEGF therapy for CNV

Purpose: To describe the presenting features and functional outcomes in a series of patients with choroidal neovascular membrane complicating BEST1-related retinopathy (Best disease and autosomal recessive bestrophinopathy) Methods: Retrospective review of consecutive cases at a tertiary care eye hospital. 

RESULTS: The median age at CNVM discovery was 15.5 years (range 6-72). CNVM were active early in the disease course before vitelliruption. Seven eyes were treated with intravitreal bevacizumab, 7 eyes were monitored On average, patients required a single treatment (median = 1, range 1-10). The median gain in visual acuity was greater in the treated versus the observed group-0.46 versus 0.17 decimalized units of Snellen acuity A significant reduction in central macular thickness was evident in both groups, 150 μm (treated) and 104 μm (observed) Active treatment was not associated with greater thinning than observation (P > 0.05 Mann-Whitney U test). CONCLUSION: There is a high rate of spontaneous recovery of BEST1-related choroidal neovascular membrane Active treatment, here with intravitreal bevacizumab, is associated with better functional outcomes than observation alone

Acknowledgements Niloofar Piri Sidharth Puri

References Dansingani KK, Tan ACS, Gilani F, et al. Subretinal Hyperreflective Material Imaged With Optical Coherence Tomography Angiography. American journal of ophthalmology. 2016;169:235-248. Retina and Vitreous. BCSC series. 2. http://eyewiki.aao.org/Best_Disease 4. The Retinal Atlas, Second Edition. Freund, K. Bailey, MD; Sarraf, David, MD; Mieler, William F., MD; Yannuzzi, Lawrence A., MD

Thank you