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ABCs of retinal disease Idaho Optometric Physicians 2016 Leo Semes, OD, FAAO

Disclosures Stockholder: HPO Honoraria, Consultant or Advisory Board:

Alcon, Allergan, B&L, Arctic Dx, Sucampo, Zeiss.

ABCs – three major threats to vision where 1o care intervention may be helpful

•!A = AMD

•!B = BRVO

•!C = CSME, CSR

ABCs

•!A = AMD

•!B = BRVO

•!C = CSME, CSR

01/16/2007 20/40 20/40

What interventions were available at the time to possibly alter the natural history of this AMD?

Current regimen: Centrum Silver + 5 mg Lutein) Continue vitamin supplements RTC X 1 year

01/09/2008 20/60 20/30 Positive Amsler (wavy lines temporal and inferior OD) Continue vitamin supplements RTC X 1 year

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04/14/2009: I woke up in the middle of the night and I couldn t see the middle number on the digital clock with my right eye. 20/60 20/40

Note significant RPE disruption

Management & Follow-up •!Retinal consult for CNVM •!Avastin injection same day •!05/09 2009 !!VA 20/60, 20/50 stable macula !! Follow X 3 months

Fast forward to 3/21/13

20/80 OD, OS S/P numerous IVAvastin injections

3/21/13 3/21/13

Could the conversion to WAMD have been averted?

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Seen most recently April 1, 2014

20/200 20/200 Note spontaneous release of VMA

Ferris FL, et al. Ophthalmology. 2013 Apr;120(4):844-51

Ferris FL, et al. Ophthalmology. 2013 Apr;120(4):844-51 Ferris FL, et al. Ophthalmology. 2013 Apr;120(4):844-51

Ferris FL, et al. Ophthalmology. 2013 Apr;120(4):844-51 Ferris FL, et al. Ophthalmology. 2013 Apr;120(4):844-51

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Smoking

Lack of Physical Activity

Excessive Weight

18% Additional Risk Reduction by Adding L/Z and Eliminating Beta-carotene

Age-Related Eye Disease Study 2 Research Group. JAMA. 2013;309(19):2005-2015.

0%

10%

20%

30%

40%

0 1 2 3 4 5

Prob

abili

ty o

f Pr

ogre

ssio

n

Years

AREDS with beta-carotene AREDS without beta-carotene with L/Z

HR=0.82 P=.02

*AREDS formulations contains 80 mg Zinc **But one randomization arm used only 25 mg

The influence of genetic profile on supplement outcome

Zinc alone or antioxidants alone can be HARMFUL depending on your genetic profile [compared to A + Z]

Awh CC, Lane AM, Hawken S, Zanke B, Kim IK. CFH and ARMS2 genetic polymorphisms predict response to antioxidants and zinc in patients with age-related macular degeneration. Ophthalmology. 2013 Nov;120(11):2317-23. Epub 2013 Aug 21.

Zn++ harmful

2014 Guidance

•!New Risk Calculations

•!AREDS 2 formulation for those at greatest risk

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AMD progression in a low-risk patient •! 7X W/F •! 20/25 OS •!Baseline

30

AMD progression in a low-risk patient •! 7X W/F •! 20/200 OS •! S/P Avastin

31

Call for Early Diagnosis

David Brown, MD, FACS Retina Consultants of Houston

“Many AMD patients are arriving at our practice with unnecessary vision loss. Ideally these patients would see their primary eye physician and be diagnosed earlier.”

Curcio CA, Johnson M. Structure, function, and pathology of Bruch’s membrane. In: Ryan SJ, et al, eds."Retina, Vol 1, Part 2: Basic Science and Translation to Therapy."5th ed. London: Elsevier; 2013:466–481.

Cholesterol accumulation leads to panmacular

deposits (BlinD and BlamD)

Peaks in these deposits eventually become clinically

visible drusen

These extracellular cholesterol deposits affect

photoreceptor health, causing inflammation

and predisposing to CNV

In addition, they impair normal transport,

including that of vitamin A, across Bruch’s membrane

AMD Pathogenesis

RPE

Bruch’s Membrane

Photoreceptors

Sclera

Drusen

Curcio CA, Johnson M. Structure, function, and pathology of Bruch’s membrane. In: Ryan SJ, et al, eds."Retina, Vol 1, Part 2: Basic Science and Translation to Therapy."5th ed. London: Elsevier; 2013:466–481.

RPE

Bruch’s Membrane

In effect, AMD causes a localized

deficiency of vitamin A, and

dark adaptation is the best test to measure this

change

AMD Diagnostic Landscape

Genetic Tests

Amsler Grid Foresee PHP

Fundus Camera SD-OCT

Macular Pigment Optical Density (MPOD)

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Dark Adaptation

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Dark Adaptation

Dark adaptation is the process of adjusting from day vision to night vision

Easy-to-measure aspect of night vision

Dark Adaptation

Jackson GR, et al. Vision Res. 1999;39(23):3975-3982. Leibrock CS, et al. Eye (Lond). 1998;12(pt 3b):511-520.

AMD Causes Major Impairment of Dark Adaptation Rapid Test: #6.5 minutes Extended Test: #20 minutes

AMD

Normal

First dark adaptometer for rapid, routine clinical use

Simple, objective tool to measure dark adaptation as earliest functional correlate of macular dystrophies

Two clinical protocols •! #6.5-minute rapid test (for quick

assessment) •! #20-minute extended test (for

benchmarking)

How AdaptDx® Works

Simple, noninvasive test performed in-office by ophthalmic technician

While continuously focusing on fixation light, patient is exposed to a mild bleaching flash and asked to indicate when a progressively dimmer stimulus light appears (randomly timed)

stimulus light fixation light

trial lens holder

forehead rest

chin rest

“ALSTAR Study”

Prospective Study of Subclinical AMD

Sample consisted of 325 adults without clinically detectable AMD. At baseline, 24% of the subjects exhibited impaired dark adaptation. AMD status

determined at 3-year follow-up visit.

Owsley, C, McGwin G, Clark M, et al. Delayed rod-mediated dark adaptation is a functional biomarker for incident early age-related macular degeneration. Ophthalmology. 2016; 123:344-51. .

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ALSTAR Study Results

Owsley, C, McGwin G, Clark M, et al. Delayed rod-mediated dark adaptation is a functional biomarker for incident early age-related macular degeneration. Ophthalmology. 2016; 123:344-51. .

•! Impaired dark adaptation identifies subclinical AMD at least three years before it can be seen with other methods. •!Subjects with impaired dark adaptation were two times as likely to

develop clinically evident AMD and eight times as likely to advance beyond the earliest stage of AMD.

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ABCs •!A = AMD

•!B = BRVO

•!C = CSME , CSR

45 F

•!VA = 20/20 •!Normal history •!Baseline photo 2000

•! Predisposing conditions to retinal vein obstruction?

52 W F

!!Sudden onset of reduced VA (X 7 $ yrs)

!!20/80 w/central disturbance

!!What are you going to do?

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*Most prevalent coagulation and anti-coagulation disorders in BRVO

Rehak J, Rehak M. Branch retinal vein occlusion: pathogenesis, visual prognosis, and treatment modalities. Curr Eye Res. 2008;33:111-31.

52 W F 9/ 4/ 2008 Involvement confined to the inner retina

52 W F 9/ 9/ 2008 Cystoid macular edema; Started on Xibrom (bromfenac) qid)

52 W F 9/ 22/ 2008 VA 20/200; distinct macular involvement; Now what?

52 W F 1/ 14/ 2009 Continued on Xibrom qid Some resolution

52 W F 1/ 19/ 2009 Continued on Xibrom qid

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52 W F 2/ 17/ 2009 Continued on Xibrom qid

52 W F 2/ 16/ 2009 Recommend anti-VEGF intravitreal injection

2/ 24/2009 And an Avastin injection VA = 20/25!!! Restoration of normal anatomy

*Treatments for ME following RVO

SCORE 5 •! CRVO – standard care =

observation •! Neither 1 mg nor 4 mg IVTA

offered better outcome

SCORE SRG Arch Ophthalmol 2009; 127; 1101.

SCORE 6 •! BRVO – standard care =

grid photocoagulation •! Both 1 mg and 4 mg IVTA

showed 15-letter gains in ! 25% of eyes @ 12 mo.

•! Fewer IOP elevations and cataract in the lower dose

*But wait! There’s still more!!! CRUISE •! CRVO intervention for CME

trial 0.3 or 0.5 mg intravitreal ranimizubab (Lucentis)

•! 46.2 and 47.7 % of eyes gained >/= 15 letters @ 6 mo. (1.1 in the sham group)

Retina Congress September 2009 NYC

BRAVO •! BRVO intervention for CME

(same dosing as CRUISE)

•! 55.2 and 61.1% of eyes demonstrated >/= 15 letters @ 6 mo. (1.9 in the sham group)

FDA-approved June 27, 2010

59

For the treatment of CME secondary to BRVO/CRVO

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BRVO consequences

•! Identify macular edema

•! Prompt treatment with anti-VEGF agent

ABCs •!A = AMD

•!B = BRVO

•!C = CSME , CSR

born: 7 April 1957 (S.T.)

•!First seen 19 April 2012 •!DIABETIC (insulin) / HTN X 20 yrs

(2 meds) •!BS: 140-200; A1C is unknown

19 April 2012 VA 20/25 OD = OS

Note cotton wool spots Esp.

Note: macula is definable

Left eye has CWS as well Right eye

Normal macular contour No thickening centrally

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Left eye Normal macular contour No fluid or thickening

OD Note mild retinal thickening outside the macula but absence of fluid

OS Note mild retinal thickening (consistent w/CWS) surrounding macula but absence of fluid at the macula

High-definition images

Mild retinal thickening without fluid accumulation

Each macula shows mild thickening

Note RNFL profile comparing OD and OS to normal Overly thick RNFL = CWS areas

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Subsequent Visits •! VA (1 June 2012) No OCT or photos !! 20/20- 20/40

•! VA (21 June 2012) No OCT or photos !! 20/25 20/25

Recommend retina specialist consult; Treatment recommended; Pt. refuses treatment

17 July 2012 VA = 20/20 20/25 [diffuse DME] ST RNFL defect

2 October 2012 CSME 20/50 (reduced from 20/25 in April 2012)

RNFL defect (not glaucoma) And “muddy macula”

RNFL defect following CWS in hypertension

Zhang L, Xu L, Zhang JS, Zhang YQ, Yang H, Jonas J Cotton-wool spot and optical coherence tomography of a retinal nerve fiber layer defect. Arch Ophthalmol. 2012 Jul 1;130(7):913.

Note distinctive RNFL thinning on OCT

Before After

Left eye appears less involved 20/30 Except nasally . . .

Note NV and Pre-retinal heme Nasal to ONH

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Note fluid IT to macula = CSME Macular thickening

Similar pattern but not as severe fluid accumulation OS Macular thickening corresponds to CWS & fluid

Note thickening of RNFL on OCT corresponding to CWS and thinning corresponding to RNFL defect [OD]

High definition images show CWS and macular fluid / thickening consistent with CSME (OD, 20/50).

High definition images show CWS and macular fluid / thickening consistent with CSME (OD, 20/50).

High definition images show CWS and macular fluid / thickening consistent with CSME (OS 20/30).

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CSME

•! The leading cause of vision loss due to diabetic retinopathy; often asymmetrical

•! These patients deserve consultation to consider surgical intervention

ABCs •!A = AMD

•!B = BRVO

•!C = CSME , CSR

46 Asian Male

•! “blurry vision” 11/20/2012 !! X 3 mo OS; began only last night OD

•!Began new BP med last week •!Has never had eye exam •!Central blur in OS has improved somewhat •!+ floaters X 1 yr •! - flashes, discharge, pain

46 Asian Male

•! Previous ocular history is negative for refractive correction, injury, glaucoma, cataract, strabismus, amblyopia, etc. •! Family medical / ocular histories negative •!No known allergies •!Began lisinopril qD X 1 wk. [ACE inhibitor] •!BP 150/100

46 Asian Male

•!VA 20/40- 20/400 (PHNI) •! -RAPD •! IOP: 14/14 •!No EOM restrictions •!Confrontation FTFC OD, OS •! -1.50 / -2.25 -0.50 X 070 VA NI •!Anterior segment unremarkable OD, OS

11/20/12

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Note •! vitreous traction

•! inverted foveal contour

•! mild inner thickening

•! significant SRF

•! RPE intact

Note serous sub-retinal fluid and cystic macula

Note RPE intact and serous sub-retinal fluid

Note serous sub-retinal fluid RPE appears intact

Note disc margin elevation And CWS

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And RNFL defect (OS)

46 A M with CSR, HR

•! Initiated Nevanac bid (11/20/12) •!RTC X 1 wk •!Correspond with PCP

•!@ 1- wk F/U (11/27/12) •!BP = 138/92 •!VA 20/25 , 20/40 !!! !! (-1.00 / -0.75 – 0.50 X 070)

•!Continue Nevanac bid

46 A M with CSR, HR

•! Initiated Nevanac bid (11/20/12)

•!@ 2- wk F/U (12/4/12) •!BP = 140/92 •!VA 20/20- , 20/20- !!! !! (refraction unchanged)

•!Continue Nevanac bid •!RTC X 1 Wk

12/11/12

D/C Nevanac

12/11/12

D/C Nevanac

12/11/12

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12/11/12 12/11/12 Restoration of macular thickness

& Contour VA 20/20- - OD, OS