Benvenuto! Retina Grand Rounds

Carlo Pelino, OD [email protected]

Joe Pizzimenti, OD [email protected] Willkommen!

Salute Our Financial Disclosure ! Honoraria " Alcon " Notal Vision Sponsors! " Reichert ! Scientific Advisory Boards " Zeavision " Carl Zeiss Meditec ! Proprietary Interests " None ! CEO/Founder " Optometryboardcertified.com

Course Goals ! To apply principles of: The eye is the only part of the " Functional anatomy " Examination body where neurological and " Imaging and other diagnostic workup vascular tissues can be viewed " Management/Co-mgt ! Clinical cases directly. ! Evidence based treatment ! Interactive

1 Case History

• A 32 year-old black female presented with gradual, bilateral reduced vision, photophobia, and poor color vision.

• Ocular History was positive for previous episodes of pars Hereditary Dystrophic Dx planitis and anterior uveitis OU.

• Health history was positive for mitral valve prolapse of 10 years duration and occasional migraines.

• The patient was taking no medications at the time of the visit.

• Her moderate myopia was corrected with soft daily wear disposable contact lenses.

Case Report

• Best-corrected acuities were 20/25 OD, 20/30 OS. • Amsler revealed a central ring-shaped defect OD and inferotemporal distortion OS. • The patient was unable to identify shapes and numbers on Ishihara color testing. • Dilated fundoscopy showed a bilateral, irregular, atrophic, “bull’s eye” maculopathy. • Automated threshold perimetry revealed paracentral defects OD and OS.

Imaging CD with OCT

! SD-OCT revealed disruption of the photoreceptor inner-segment/outer-segment junction, external limiting membrane.

2 OD OS OD 10/2005 OD 4/2006: Note increased flattening and more “blue”

Mf-ERG revealed a “ring-depression” surrounding a small central peak in each eye.

Cone Dystrophy

! Probably part of the retinitis pigmentosa spectrum in which cones are affected more than rods At right, another " Cone-Rod Dystrophy patient with full ! Inheritance presentation of cone " A/R - earlier onset A/D - generally later; commonest, first 2 decades dystrophy (20/40 VA) X/L - Rare; tapetal sheen, Mizuo-Nakamura FX

Cone Dystrophy Imaging CD with FAF

! Presentation ! Fundus (FAF) " Childhood (4-8) or young adulthood (teens-30) autofluorescence may demonstrate increased ! Symptoms autofluorescence ring " Photophobia and central spots in ! Signs the foveola. " Bull’s eye macula common " Diffuse macular pigment changes

3 Cone Dystrophy Cone Dystrophy

! Signs ! No treatment " Acquired nystagmus ! Some animal studies have shown that antioxidant vitamins can slow further vision loss. " Defective color vision ! Some mice with cone dystrophy have been ! ERG - abnormal photopic response effectively treated with gene therapy, but it is EOG – subnormal unknown if the approach will work in humans. ! Low Vision Rehabiliattion ! Variable VA ! Genetic counseling

Outcome and Conclusions

! Patient is currently being followed with periodic mfERG, central threshold perimetry, contrast sensitivity, OCT, color vision, and dilated QUESTIONS AND fundoscopy. COMMENTS? ! She continues to enjoy successful contact lens wear. ! This case underscores the importance of electrodiagnostic testing when photoreceptor disease is suspected. ! MfERG is of significant value in the detection of CD in patients that develop symptoms later in life.

Coup/contrecoup Injury

Blunt Trauma

Compression, Decompression, Overshoot, Oscillation

4 L floor fracture w/blood in maxillary sinus. Medial wall of L orbit also fractured.

Traumatic Choroidal Rupture

5 Surgical Video-IOFB Sx

Courtesy: Steven Sinclair, MD

Neoplastic Disease QUESTIONS AND COMMENTS?

6 To Find Small Ocular Melanoma To Find Small Ocular Melanoma

T= thickness No risk factors (<4%) F= subretinal fluid 1 risk factor (36%) S= symptoms 3 risk factors (50%) O= orange pigment 5 risk factors (70%) M= margin touches disc

DOCUMENTED GROWTH - MEANS EVERYTHING

Using Helpful Hints = Ultrasound hollow, halo

NEVOMA

FAF in Choroidal Melanoma Echography

Acoustic hollowness on B-scan of small melanoma.

Echography of large melanoma Choroidal Metastasis

7 Choroidal Metastasis

Capillary Hemangioblastoma

Cavernous Hemangioma Astocytic Hamartoma

Retinoblastoma Choroidal Osteoma

8 Retinoblastoma Leukemia

Infection QUESTIONS AND and COMMENTS? Inflammation

Cytomegalovirus Retinitis (CMV) Cytomegalovirus Retinitis

HIV encephalopathy, Toxoplasmosis

9 Acute Retinal Necrosis Toxoplasmosis

Initial Presentation

Toxoplasmosis Toxoplasmosis Day 13 Day 3 Day 6

Ocular Histoplasmosis Syndrome (OHS) Toxoplasmosis

• From exposure to fungus Histoplasma capsulatum via respiratory tract • Endemic to Ohio/Mississippi River Valley where more than 60% test positive

10 Case Hx: A 16 year old Caucasian male presented with a chief complaint of blurred vision and floaters in both eyes for a one month duration.

Floaters began immediately following a viral prodrome with mild headache.

He then noticed progressive blur OS > OD.

Visual field defects were also noted in both eyes.

No other ocular complaints.

Medical history: negative Medications: none

Allergies: None to environment/medications

Inflammatory “White Dot Syndrome” - APMPPE

• Occurs in healthy men or women between 20 – 50 years old • Acute bilateral vision loss • Prodromal viral illness in about 30 % of patients

Symptoms:

• Central or paracentral scotomas/hotopsia/floaters • Reduced visual acuity

Signs:

• Mild vitreous cells are usually present • Yellow/white placoid lesions located in the posterior pole/midperiphery • Located at the level of the retinal pigment epithelium/choriocapillaris • Lesions start to fade within 2 weeks • Lesions are replaced with atrophy and hyperpigmentation

11 White Dot Syndromes

• Multifocal Choroiditis/Panuveitis (MCP) The White Dot Syndromes are • Acute retinal pigment epitheliitis (ARPE) characterized by bilateral choroidal • APMPPE (Acute posterior multifocal pigment placoid epitheliopathy) infiltrates and retinal vasculitis. • Vitiliginous choroiditis (Birdshot) • MEWDS (Multiple Evanescent White Dot Syndrome)

• DUSN (Diffuse Unilateral Subacute Neuroretinitis)

• Punctate Inner Choroidopathy (PIC)

• Sarcoid Choroidopathy

• Intraocular lymphoma (Retinal/Vitreal or Uveal )

Birdshot Retinochoroidopathy

White Dot Syndromes

Non-infectious Choroidopathies

RPED, ERM in Birdshot Cellular debris in vitreous

12 APMPPE Birdshot in another patient: FA Pathology: • Immune response from a virus ? • Infarction of the choroid secondary to a vasculitis • Described with Mumps, Strep infections, TB, Hep B vaccine, Lyme, Sarcoidosis, Thyroiditis Treatment: • No systemic or ocular treatment needed • VA 20/40 or better within 8 weeks in 80% of untreated patients • Systemic steroids if central nervous system or foveal involvement Systemic Evaluation: • Venous stage hyperfluorescence • No systemic evaluation needed unless CNS involvement • Extensive late intraretinal and disc leakage • Headaches or neuro signs – get MRI • Associations with adenovirus type 5, cerebral vasculitis – must undergo a systemic and neurologic evaluation

Importance of Dilated Post Birdshot Retinochoroidopathy Seg Exam in All Uveitis Cases • Vitreous Exam ! Treatment: " Immunosuppressive therapy reduces the risk of • Technique vision loss from CME. (Cyclosporine) • Anterior vitreous • Posterior vitreous " Chronic low dose oral corticosteroids (10mg or less), does not seem to prevent the occurrence of CME. • Inflammatory cells and protein " Immunosuppressive therapy may reduce the risk of progressive diffuse retinal dysfunction. • Comes from the choroid, retina and ciliary body

JE Thorne, DA Jabs, et al. AJO 2005;140:45-51. • “Vitritis”??

Immune Privilege

• The eye enjoys a special relationship We do encounter situations in with the immune system. – Ability to quench unwanted immune-mediated clinical practice when the eye’s inflammation. immune privilege is overcome. – This ability is known as immune privilege. Uveitis is an example. – Immune privilege enables ocular tissues to remain clear.

13 The Optic Nerve in Posterior Uveitis

• Disc hyperemia

• Papillitis

• Disc edema may occur with toxoplasmosis, viral retinitis, lymphoma, or sarcoidosis. Sarcoid

Sarcoid OCT

• Cystoid Macular Edema in a Sarcoid patient with chronic uveitis.

Common Etiologies of Posterior Uveitis Toxocariasis • Toxoplasmosis (photo below) • HSV, HZV • Granulomatous disease (e.g. tuberculosis, sarcoidosis, Lyme disease, syphilis) • Histoplasmosis • Birdshot or Serpiginous • Inflammatory choroidopathies

14 Common Etiologies of Multifocal Choroiditis and Panuveitis Panuveitis • Bilateral, chronic uveitis – Punched-out chorioretinal lesions • Infections, such as similar to POHS. – Infantile toxocariasis • CNV is the most worrisome – Post-op bacterial endophthalmitis potential complication. – Toxoplasmosis • Conservative monitoring • Granulomatous Dx. and timely steroid • Multifocal treatment essential to care. Choroiditis and • Immunosuppressive drug Panuveitis (right) therapy appears to limit the – MCP in a 27 y/o Asian Female number of recurrences.

Beyond Anterior Uveitis

Slide 58 Iluvien 8 Emerging Treatments for Posterior Uveitis • Iluvien (formerly known as • Dexamethasone Drug Delivery System Medidure) – OZURDEX (intravitreal implant) – Tube 3.5mm x 0.37mm containing 0.7mg (Allergan) fluocinolone – Implanted into vitreous w/ 25g – Intraocular, biodegradable implant for the (~0.5mm) inserter treatment of persistent ME • Sutureless – Clinical trial validated Ozurdex – Designed to provide sustained effect for ME in CRVO up to 24 months – FAME (fluocinolone acetonide in DME) results favorable

15 32 y/o BF Second Opinion Diagnostic Criteria for VKH http://www.nova.edu/optometry/41 1 No history of penetrating ocular trauma or surgery 1/Summer/FacSced.html 2 No evidence of other ocular or systemic disease 3 Bilateral ocular disease Early manifestation Late manifestation 4 Neurologic and auditory findings 5 Dermatologic findings

QUESTIONS AND COMMENTS? Most types of anterior uveitis are sterile inflammatory reactions. Many of the posterior uveitic syndromes are caused by infections.

Case History

! 61 yo BF Neovascular Disease ! CC: Referred for evaluation of “retinal cysts” ! POHx: Unremarkable ! PMHx: + HTN/Hypercholesterolemia ! Medication: Atenolol, Maxzide

16 DFE: OD Ocular Examination

! Best-corrected VA: 20/20 OD, 20/20 OS

! Pupils: Equal & round –APD

! EOM/CVF: Unremarkable

! SLE: Unremarkable

DFE: OS

New lesion

OCT-Evaluation

PIGMENT EPITHELIUM DETACHMENT

17 Another case…60 y/o BF OD 60 y/o BF OD

60 y/o BF OS Final Diagnosis

! Polypoidal Choriodal Vasculopathy (PCV)

! Multiple recurrent serosanguineous detachments of the RPE, sensory retina

serosanguineous Polypoidal Choroidal Vasculopathy ! First described in 1982

“Posterior Uveal Bleed Syndrome” -or- “Multiple, Recurrent Retinal Pigment Epithelial Detachments in Black Women”

Fluid (serum) / hemorrhagic ! Idiopathic Polypoidal Choroidal Vasculopathy (IPCV) (blood) disorder

18 PCV Demographics

! Higher incidence in dark pigmented people " African American, Hispanic, and Asian " Predilection for African American women

Clinical Features Pathogenesis of PCV

! Inner choroid ! Aneurysmal structures at the ! Network of branching vessels with terminal termination of a network of aneurysmal red spheroidal dilitations (polyps) dilated choroidal veins " Dilated, thin-walled vessels of choriocapillaris ! Recurrent hemorrhage and leakage ! Recurrent hemorrhagic/exudative ! Variant of inner choroidal neovascularization detachment of the RPE (CNV)

Combined

Ahuja, R. M et al. Br J Ophthalmol 2000;84:479-484

19 Montage fundus photograph of OS reveals peripapillary red-orange nodular lesions contiguous with elevated, sinuous, tubular lesions extending through the macular region Key Findings

! Usually bilateral ! Lack of drusen ! Chronic, recurrent RPED and neurosensory detachment ! Exacerbations/remissions ! Rosa, R. H. et al. Arch Ophthalmol 2002;120:502-508. Serosanguineous (serum and/or blood)

Key Findings

! Chronic, remitting-relapsing course ! Peripapillary region most often affected ! Good visual prognosis, unless… " PCV in the fovea ! Average age of diagnosis is 60

AMD vs PCV AMD vs PCV

! Features that distinguish Wet AMD from PCV: " race " macular location " elderly patients " presence of drusen " rapid rate of progression " disciform scarring SUSPICIOUS POLYPOIDAL " poorer visual prognosis AMD -SUBRETINAAL HEMORRHAGE

20 Polypoidal lesion OD ICGA is diagnostic for PCV

IGCA reveals saccular dilations ICG- early phase of choroidal vasculature Late staining of the vascular network and filling of the PED

SCHNEIDER, U. et al. Br J Ophthalmol 1998;82:98-99

Treatment

! Conservative management " Observation

! Spontaneous regression ! Longstanding non-progressive exudation ! Control underlying systemic condition

Br J Ophthalmol 2008;92:661-666 doi:10.1136/bjo.2007.135103

PCV and Systemic Disease Treatment

! Concomitant systemic microvascular disease ! Argon Laser Photocoagulation ! Photodynamic Therapy Diabetes Hypertension " ICGA-guided PDT ! Thermal Laser Therapy Dyslipidemia ! Anti-VEGF therapy Idiopathic " Intravitreal injections of bevacizumab ! Principle: reduce abnormal vasculature of PCV

Matsuoka et al and Tong et al

21 Polypoidal Choroidal Vasculopathy

! Conclusions ! It is important to differentiate from CNV in AMD ! Remember patient demographic More Neovascular Disease ! ICG is diagnostic, reveals saccular dilations of the choroidal vasculature Proliferative Diabetic Retinopathy

Severe Non-Proliferative Diabetic Retinopathy Proliferative Diabetic Retinopathy

Factors that modify Why do some patients microvasculopathy in progress while others don’t? diabetes.

22 #1. Hb A1C under 7% (6.5% better)

#2. Hypertensive patients with diabetes need a BP of 125/80 or better Sleep Apnea #3. Cholesterol needs to be under control + #4. Sleep Apnea needs to be ruled out/addressed DR #5. Anemia needs to be ruled out = hemaglobin needs to be above 11 =

#6. Proteinuria (albuminuria) – Starlings Law Blindness ( hydrostatic vs. osmotic pressure)

SAS and DR

! DME " Higher prevalence of DME " Recurrence " Unresponsive to Anti-VEGF ! PDR " Higher prevalence of PDR " Worsening of PDR ! Improvement of DME, PDR w/CPAP

Impaired blood flow in SAS CPAP: “Up your nose with a rubber hose!”

23 #7. BMI (body mass index) less than 30 .... better if 32 yo WM less than 25

#8. Stop smoking

#9. Vasculitis (rule out gum disease, leg ulcers, gastritis, urinary tract infections) ! 5 ft 8 in tall, 265 lbs #10. Vitamin D deficiency ! “sees red” OD (African Americans that live in the north have ! Type 2 DM x 3 yrs decreased levels of Vitamin D) ! Recent Dx. Obstructive Sleep Apnea

Cigarette Smoking, Ocular & Vascular Disease

! Increased arteriolar stiffness (arteriolar sclerosis) DM + Smoking = ! Increased Vascular Endothelial Growth Factor Blindness (VEGF) ! Development, worsening of DR ! Development, worsening of AMD

Post pole heme is typically DR, HR Retinal Heme is much like real estate.

24 Hypoperfusion Retinopathy Carotid Occlusive Dx: Bruit

Dot and Blot hemes in mid-peripheral retina

Where peripheral heme predominates ….

Proliferative Sickle Cell Retinopahty

25 QUESTIONS AND COMMENTS?

Proliferative Sickle Cell Retinopahty

Pigmented Retinal Lesions

Outcome:

• Congenital Hypertrophy of Retinal Pigment Epithelium (CHRPE)

• Photos taken

• Patient referred back to Optometrist

• Monitor 1 year

26 The Real Deal on CHRPE CHRPE

! Dark black, only slightly raised ! No malignant potential ! When present in multiple locations, investigate for Gardner’s Syndrome " This is familial polyposis coli, which can lead to colorectal carcinoma. " Autosomal dominant condition " Probe family history, patient GI symptoms " Consider gastroenterology consult if symptomatic or + family history

The Vitreoretinal Interface

Vitreomacular Adhesion

Epiretinal Membrane Macular Hole VMTS AMD DME

retinalphysician.com

Anomalous PVD: VMTS

Complete PVD

27 Vitreoretinal Interface

The Vitreous The Vitreous

DFE- OD 80 y/o WM Loss of foveal detail

! CC: “I’m experiencing gradual-onset anisekonia”. OD 15% > OS ! Patient was referred from BV clinic after ruling out anisemetropia. ! VA moderately reduced: 20/30 OD/OS ! Amler: metamorphopsia OD>OS ! Grade 1 lens opac OD/OS ! Good overall health

28 DFE - OS Is there other testing you would like to perform?

OCT - OD ERM Slab Analysis

OCT - OS Epiretinal Membrane

! Subjective " Mild/mod central vision loss " Diplopia, photopsia, macropsia " Aniseikonia ! Objective " Posterior Vitreous Detachment (PVD) " Irregular light reflex (sheen) " Wrinkled Internal Limiting Membrane (ILM)

29 Epiretinal Membrane Epiretinal Membrane

! Objective (cont’d) " Tortuous perifoveal vessels " Ectopic fovea " Bilateral 30% of time

! Assessment " Diagnostic testing " OCT reveals jagged ILM or partial non-adherence " FA shows perifoveal BV leakage

Epiretinal Membrane SD-OCT

Thickness Thickness Map Map Overlay

ILM Layer Fundus Image

ERM with MP Epiretinal membrane with macular pucker

30 Etiology of ERM Ddx. of Causes of ERM

! Age-related after focal ! Trauma/Surgery patches of PVD ! Macular Hole ! Retinal glial cells ! Retinal Vascular Occlusive Dx. dissociate from their normal position. ! Diabetic Retinopathy " become metaplastic ! Sickle Cell Hemoglobinopathy ! Glial cells proliferate on ! Intraocular Tumor retinal surface, transform ! Retinitis Pigmentosa into fibroblasts ! Retinal Breaks/RD

Watzke-Allen Test

! Subjective ! Purpose: identify full- thickness v. lamellar ! Fundus lens at SL ! Vertical beam ! Central break indicates full-thickness ! Maddox rod, direct scope Macular Hole

Macular Hole Macular Hole Sx. ILM Peel

31 Thank you!

QUESTIONS AND Carlo COMMENTS? Joe

[email protected] [email protected]

32