SEEING WHITE DOTS Jessica Schiffbauer OD, FAAO June 12th, 2021 North Carolina Optometric Society Spring Congress Financial Disclosures

■ Eyevance Pharmaceuticals Agenda

■ Common presentations of white dot syndromes ■ Review of diagnostic testing ■ Treatment and management Case #1

■ 43 y/o Hispanic Female ■ CC: hazy vision and difficulty seeing computer screen OU ■ Medical History: Irritable Bowel Syndrome, Pancreatitis, Hysterectomy ■ Ocular History: s/p PPV OU in 2016 ■ Medications: Levothyroxine, Vitamin D Exam Findings

■ VAcc: 20/40 OU ■ Vitreous: 2+ cell OU ■ IOP: 21/19 ■ : mild blurring of disc margins OU ■ Anterior Chamber: 2+ cell OU ■ : multiple deep yellow lesions ■ : trace cortical w/ pigment OU OU Plan

■ Posterior OU ■ Order Labs: ACE, CBC/Diff, ESR, CMP, HLA-B27, FTA-ABS, HLA-A29, QuantiFERON Gold, RPR, Toxoplasmosis IgG, Urinalysis ■ Order Chest X-Ray ■ Treatment: Difluprednate q2h OU Standardization of Uveitis Nomenclature (SUN) Working Group

■ Anatomical classification of uveitis ■ Types of anterior uveitis ■ Grading of anterior chamber flare and cells ■ Criteria for onset, duration, and course of uveitis ■ Grading of Vitreous Haze ■ Terminology to Grade Activity of Uveitis Classification of Uveitis (SUN)

Type Primary Site of Inflammation Manifest Conditions Include Anterior Uveitis Anterior chamber ( and Iritis ) Iridocyclitis Anterior Cyclitis Intermediate Uveitis Vitreous Pars Planitis Posterior Cyclitis Hyalitis Posterior Uveitis Retina or Focal or Diffuse Choroiditis Retinochoroiditis Neuroretinitis

Panuveitis Anterior chamber, vitreous, retina or choroid White Dot Syndromes

■ Inflammatory chorioretinopathies with unknown etiology ■ Typically seen in young, healthy adults ■ Multiple yellow-white lesions affecting multiple layers of the retina, retinal pigment epithelium, choriocapillaris, and choroid ■ Some may be affiliated with viral prodrome ■ Possible link to autoimmune etiology White Dot Syndromes

■ Acute Retinal Pigment ■ Multifocal Choroiditis Epitheliopathy ■ Birdshot Chorioretinopathy ■ Multiple Evanescent White Dot ■ Serpiginous Choroidopathy Syndrome (MEWDS) ■ Multifocal Choroiditis and ■ Acute Posterior Multifocal Placoid Panuveitis (MCP) Pigment Epitheliopathy (APMPPE) ■ Acute Macular Neuroretinopathy ■ Acute Zonal Occult (AZOOR) ■ Punctate Inner Choroidopathy (PIC) Two Week Follow-Up

■ (+) HLA-A29 ■ VAcc: OD: 20/50+2 and OS: 20/40 ■ IOP: 23/25 ■ Anterior Chamber: 1+ cells OU ■ OCTM: increase in size of intraretinal cysts OU ■ Treatment: Difluprednate QID, start Combigan BID and Prednisone 20mg 3 pills PO x 2 weeks then taper ■ Follow up with rheumatologist- started on Cellcept Birdshot Chorioretinopathy

■ Chronic, bilateral posterior uveitis ■ 40-60 year old Caucasian females ■ (+)HLA-A29 ■ Autoimmune response due to retinal S antigens ■ Multiple yellow-white choroidal lesions clustered around optic nerve & posterior pole that radiate towards periphery ■ 1-2% of all types of uveitis Ocular Symptoms and Findings

■ ■ Uniform vitritis, typically bilateral ■ Photopsia ■ Yellow lesions at level of the deep retina that radiate out from the ■ Decreased vision optic nerve – Visual complaint >> visual acuity loss ■ Attenuation of retinal vasculature ■ Poor color vision ■ Optic nerve pallor ■ Poor night vision ■ Cystoid ■ Paracentral Diagnosis of Birdshot Chorioretinopathy

■ Bilateral, >3 peripapillary birdshot lesions,

■ Early stages= retinal vasculitis ■ Middle stage= birdshot lesions ■ Late stages= cystoid macular edema, vascular attenuation, RPE changes, optic nerve atrophy, and subretinal neovascularization Diagnostic Testing

■ Fundus Autofluorescence: – Abnormal areas of hypopigmentation ■ Fluorescein Angiography: – Highlights cystoid macular edema, optic nerve head leakage, and retinal vasculitis – “Quenching”- vessels empty dye faster than normal individuals ■ Electroretinogram – Moderate-to-severe depression of rod and cone function ■ Visual Field – Overall depression – Paracentral Treatmentà Ozurdex

■ 0.7mg Dexamethasone intravitreal injection ■ Approved for macular edema caused by vein occlusion and diabetic macular edema caused by and non-infectious posterior uveitis ■ Can last up to 6 months ■ Complications: , increased IOP, conjunctival hemorrhage 2 months s/p Ozurdex OU

■ VAcc: OD: 20/30-2 and OS: 20/20-2 ■ AC and vitreous: quiet OU ■ Hypopigmented lesions surrounding optic nerve head & extending into posterior pole OU 3 months s/p Ozurdex OU

■ VAcc: OD: 20/30 and OS: 20/25+2 ■ IOP: 26/30 ■ Anterior Chamber: 1+ cells ■ Posterior Segment: multiple hypopigmented lesions OU; improvement in intraretinal fluid OU Evaluation

■ IOP: mid 20s to low 30s ■ Medications: Dorzolamide TID OU, Combigan TID OU, Netarsudil qhs OU, and Methazolamide 25mg PO QD ■ Gonioscopy OU: scleral spur 360 with 2+ pigment, no PAS ■ OCTG: no thinning 360 OU ■ HVF 24-2: OD: non specific changes, OS: early superior arcuate Addressing IOP and Cataracts

■ s/p phaco w/ OMNI Surgical System OU ■ In between surgeries, Ozurdex OD (~3 months later) ■ IOP still elevated in OD following surgery ■ Ozurdex OS (~6 months later) ■ 5-6 months following surgery: – IOP: 18/17 with target of 21 or below OU – Drops: Netarsudil qhs OD, Latanoprostene Bound qhs OD, Dorzolamide BID OU, Combigan BID OU Addressing Glaucoma

■ Ozurdex administered 3 months later OU ■ s/p Ahmed Valve OD in January ■ Ozurdex OU administered ~2 months following glaucoma surgery ■ IOP prior to surgery: 30 and following sx: 16 Last Visit

■ VAcc: OD: 20/40+1 and OS: 20/30-1 ■ IOP: 13/12 (on Combigan BID OU and Dorzolamide BID OU) ■ Posterior Segment: multiple choroidal lesions, (+) CME OS ■ Plan: Ozurdex OS

■ *Patient also taking Humira 1x/week for 2 months Treatment and Management

■ Steroids: topical, oral, intravitreal ■ Coordinate care with rheumatologist ■ Immunomodulatory Therapy: Cyclosporine A, Methotrexate, Humira, Mycophenolate ■ Glaucoma Medications ■ – MIGS Study Results

■ 88.9% of patients treated with Infliximab achieved control of inflammation at the 1 year follow-up and throughout 7 years of study ■ Low dose methotrexate more effective in improving visual acuity than ■ Intravitreal sustained-release device successfully controlled inflammation and led to better visual acuity Clinical Pearls

■ HLA-A29 ■ Risk of cataracts and glaucoma ■ Rheumatology referral Case #2

■ 36 y/o Caucasian female ■ CC: gray shadow in peripheral vision OS ■ Medical History: Celiac Disease, Anemia, Anxiety, Antiphospholipid Antibody Syndrome ■ Ocular History: unremarkable ■ Medications: Buspirone, Citalopram, Rivaroxaban, Levocetirizine Dihydrochloride Exam Findings

■ VAcc: OD: 20/20, OS: 20/25 ■ Vitreous: clear OU ■ CFF: OS: constricted ST quadrant ■ Optic Nerve: 0.1H/V OU ■ IOP: 12/14 ■ Retina: OD: multiple white lesions nasal, RPE changes inferior nasal, ■ Anterior Chamber: unremarkable chorioretinal scar, OS: multiple OU white lesions nasal, chorioretinal scar Multiple Evanescent White Dot Syndrome (MEWDS)

■ 20-50 year old healthy women ■ Typically unilateral ■ Moderate ■ Viral prodrome Ocular Symptoms and Findings

■ Decreased vision ■ Vision ranges from 20/20-20/400 ■ Shimmering photopsias ■ ? APD ■ Dyschromatopsia ■ Mild vitreous cell ■ Scotoma ■ Multiple, discrete white dots in RPE or outer level ■ Hyperemic disc Diagnostic Testing

■ Fluorescein Angiography: – Punctuate hyperfluorescent lesions in wreathlike pattern – Hyperemia of in late stages ■ OCT: – Disruption of outer layers ■ Visual Field: – Enlarged blind spot – Temporal or paracentral scotomas ■ Electroretinogram: – Reduction of a-wave amplitude Treatment and Management

■ Restored vision in 7-10 weeks ■ Resolves spontaneously without treatment ■ Recurrent cases can be treated with cyclosporine ■ Possibility of choroidal neovascular membrane ■ Visual field loss may persist Clinical Pearls

■ Healthy individuals ■ Defect on confrontation fields ■ Self-limiting condition Case #3

■ 30 y/o Caucasian female ■ CC: constant black spot in central vision OS ■ Medical History: Cesarian Section, Removal of Gall Bladder ■ Ocular History: Myopia ■ Medications: none Exam Findings

■ VAcc: 20/20 OU ■ Vitreous: clear OU ■ No APD ■ Optic Nerve: 0.4H/V OU ■ Anterior Chamber: unremarkable ■ Macula: OD: flat and clear, OS: area OU of RPE changes nasal, (+) foveal light reflex ■ Periphery: WNL OU Acute Macular Neuroretinopathy

■ Typically unilateral ■ Paracentral scotomas in teens-30s year old Caucasian females ■ Possibly due to microvascular abnormality in deep capillary plexus of the retina ■ Risk factors- viral prodrome, oral contraceptives, hypotension, intravenous contrast, caffeine, intravenous ephedrine, pre-eclampsia, prothrombin, sinus infection Ocular Symptoms and Findings

■ Symptoms>>findings ■ One or multiple reddish-brown petaloid perifoveal lesions ■ Decreased vision ■ Tip of lesion directed towards fovea ■ Scotoma ■ Floaters ■ Photopsia ■ Metamorphopsia Types of Acute Macular Neuroretinopathy Typical Acute Macular Paracentral Acute Middle Neuroretinopathy/Acute Outer Macular Retinopathy

■ Inner retinal involvement ■ Outer retinal involvement ■ Hyperreflectivity superficial to outer ■ Hyperreflectivity deep to outer plexiform layer plexiform layer ■ Inner nuclear layer involved- ■ Outer nuclear layer involved- possible thinning possible thinning Diagnostic Testing

■ OCT: – Hyperreflective plaque between outer plexiform and outer nuclear layer – Disruption of ellipsoid zone – Thinning of outer nuclear layer in late stage ■ Visual Field: – scotoma ■ Amsler Grid: – scotoma Treatment and Management

■ Observe ■ Good visual prognosis ■ No complete resolution of scotoma Clinical Pearls

■ Symptoms >> findings ■ Full resolution of scotoma has never been reported Case #4

■ 34 y/o Caucasian female ■ CC: decreased vision with occasional floaters OU ■ Medical History: Depression, Asthma, Allergies ■ Ocular History: Myopia ■ Medications: Lorazepam, Sertraline HCl Exam Findings

■ VAcc: OD: 20/25-2, OS: 20/30+1 ■ Vitreous: clear OU ■ No APD ■ Optic Nerve: 0.5H/V OU ■ Anterior Chamber: unremarkable ■ Macula: OD: flat and clear, OS: OU multiple chorioretinal scars ■ Periphery: OD: WNL, OS: few pinpoint chorioretinal scars Punctuate Inner Choroidopathy

■ Inflammatory condition of the choroid ■ May be due to thrombosis of of choriocapillary layer by an unidentified organism, variant of multifocal choroiditis, form of limited myopic degeneration, or relation with Epistein-Barr Virus ■ 18-40 year old myopic females Ocular Symptoms and Findings

■ Decreased vision (20/50 to ■ Typically bilateral chorioretinal 20/400) lesions in the inner choroid and RPEà atrophic scars ■ Photopsia ■ No vitritis ■ Central or paracentral scotoma ■ Disc edema with serous retinal ■ Metamorphopsia detachments ■ Possible choroidal neovascular membrane Diagnostic Testing

■ Fluorescein Angiography- early hyperfluorescence, variable late leakage/staining of lesions with cystoid macular edema and choroidal neovascular membranes ■ Visual Field- enlargement of blind spot, central or paracentral scotomas ■ OCT- RPE atrophy or elevation ■ Fundus Autofluorescence- hyperfluorescent halo around active lesion 3 Month Follow-Up Visit

■ CC: gray spot with waviness OS ■ VAcc: OD: 20/20, OS: 20/30-2 ■ Anterior Chamber: unremarkable OU ■ Macula: OD: WNL, OS: RPE changes with new hyperreflective spot temporal to fovea w/ hemorrhage Treatment and Management

■ Observe if inactive lesion ■ Reoccurrences common within first three months ■ Systemic, intraocular, or periocular corticosteroids ■ Immunomodulatory therapy ■ Photodynamic therapy – Higher rates of CNV recurrence ■ Anti-VEGF injection ■ Submacular Surgery – Recurrences common Studies Evaluating Anti-VEGF Injection for PIC

■ All small studies ■ 4 cases treated with 3 monthly anti-VEGF injections had improved VA and no leakage at three and six months ■ 9/10 cases treated with ~1.9 anti-VEGF injections had maintained or improved vision ■ Two studies showed improvement/decrease in macular thickness with anti-VEGF injections Clinical Pearls

■ 90% are myopic females ■ Need follow-up due to risk of CNVM ■ Common reoccurrences Case #5

■ 13 y/o African American male ■ CC: decreased vision OD ■ Medical History: unremarkable ■ Ocular History: Myopia OU ■ Medications: none Exam Findings

■ VAcc: OD: 20/400, OS: 20/20 ■ Vitreous: clear OU ■ No APD ■ Optic Nerve: OD: 0.2H/V, OS: 0.4H/V ■ Anterior Chamber: unremarkable OU ■ Macula: OD: scar inferior to fovea, OS: WNL ■ Periphery: OD: multiple areas of chorioretinal scarring, OS: WNL Plan

■ Order labs: ACE, Bartonella Antibodies, CRP, ESR, FTA-ABS, QuantiFERON Gold, RPR, Toxoplasmosis IgG & IgM, TORCH titers ■ Order Chest X-Ray ■ Start Ketorolac QID OD due to leakage ■ Oral Prednisone Multifocal Choroiditis

■ Inflammatory condition with multiple lesions in the retina and choroid ■ Possibly due to past infection that stimulated an immune response ■ Commonly affects RPE and choriocapillaris ■ Associated with interleukin-10 and tumor necrosis factors Ocular Symptoms and Findings

■ Blurry vision ■ Mild anterior chamber inflammation ■ Floaters ■ Vitritis ■ Photopsia ■ Yellow to gray lesions in the RPE and choroid ■ Metamorphopsia ■ Cystoid macular edema ■ Subretinal fluid ■ Optic disc edema ■ Punched out retinal lesions ■ Choroidal neovascularization and atrophy Diagnostic Testing

■ Fluorescein Angiography- early and late hyperfluorescence, staining ■ OCT- RPE elevation, subretinal fluid, choroidal thickness ■ Fundus Autofluorescence- diffuse hyper-autofluorescent lesions and/or hypoautofluorescent atrophic lesions Treatment and Management

■ Order labs and Chest X-Ray ■ Oral, periocular, or intravitreal corticosteroids ■ Anti-VEGF injections ■ Good vs. poor visual prognosis Clinical Pearls

■ Asymptomatic? ■ Vitritis present ■ No known systemic or ocular disease Take Home Points

■ Rule out inflammatory/infectious causes ■ Education about visual prognosis ■ Work alongside retina specialist ■ Watch out for the zebras! THANK YOU! [email protected]