1

Retina UpdateCurrent treatment and evolving therapies

Polly A. Quiram MD, PhD

Vitreoretinal Surgery, PA

May 20thh, 2017

Regions Course

No financial disclosures

General overview

Age Related Macular Degeneration (ARMD)

Diabetic eye diseases (PDR and DME)

Surgical diseases

Overview of AMD Impact

Classification – Dry and Wet

Pathophysiology

Treatment for Wet

What drug?

What interval?

Is treatment effective? Making the decision to treat

Treatment for Dry

Novel therapies you will hear about

Age-related Macular Degeneration (AMD)

#1 cause of blindness in those >65 years old

This group expected to grow most rapidly in the next 30 years

Large % of Medicare $ spent fighting this disease

AMD Classification

Two main types of AMD

Dry = ~ 90% of those affected

Vision loss due to atrophy

~10% of those with severe vision loss

Wet = ~ 10% of those affected

Vision loss from bleeding and leakage from

abnormal blood vessels

~90% of those with severe vision loss

Dry AMD with DrusenDry AMD w ith Atrophy

WetAMD w ith heme, fibrosis

Vision not affected

AMD Risk Factors

Non-modifiable

Genetic

Gender – female

Age

Modifiable Diet – low anti-oxidant intake

Cigarette smoking – 4x

Physical activity/obesity

Lutein (10mg)/Zeaxanthin (2mg)

No beta-carotene

No additive improvement with omega 3

AREDS II Results

2

Wet AMD: Why does this happen?

Development of CNV CNV is more than a vascular disease- complicated

process

CNV is a complex process that also involves nonvascular components

RPE cells

Macrophages and other inflammatory cells

Myofibroblasts

Involves components of wound healing response

Inflammation

Angiogenesis

Fibrosis

Abnormalities in complement cascade also involved –CHF and ARMS2 genetic markers

Drusen accumulate between Bruch´s membrane and RPE: Complement deposition with loss of complement

regulation

Oxidative and inflammatory processes

Blood-retina barrier break down

Oxidative Stress may contribute to CNV

O xidativ e Stress

Bainbridge JW et al. Clin Sci. 2003;104:561-575.Schlingemann RO. Graefes Arch Clin Exp Ophthalmol. 2004;242:91-101.Ferris FL III et al. Arch Ophthalmol. 1984;102:1640-1642.Ambati J et al. Surv Ophthalmol. 2003;48:257-293.

CNV Progression

Inflammatory Mediators

and Proangiogenic C y tokines

Inappropriate V essel Grow th

Exudation and Hemorrhage

Discoid Scar Formation

O xidativ e Stress

VEGF

Fovista

Lampa

AMD Treatment Options

There is currently no true cure for macular degeneration

Wet AMD: Anti-VEGF Agents

VEGF: vascular

endothelial growth factor

Controls growth of

abnormal blood vessels in

wet AMD

Inhibiting VEGF prevents

and targets newly formed

blood vessels

Treatment for Wet

What drug? Avastin

Lucentis

Eylea

What interval? Monthly – fixed interval

PRN

Extend and treat

What if it doesn’t work Switch therapies

What drug?

VIEW

IVAN

HARBOR

ANCHOR

7 up

PRONTO

CATT

LUCAS

Ranibizumab (Lucentis™) Bevacizumab (Avastin®)

Lucentis

(ranibizumab)(48 kDa)

Affinity

maturation (140x)

rhu Fab

V1

Insertion of murine

anti-VEGF-A sequences into a

human FAb

framework

Anti-VEGF-A

Murine Mab(~150 kDa)

Presta, LG, 1997. Cancer Res.57:4593; Chen Y. 1999 J.Mol. Biol.293:865

Avastin

(bevacizumab)(149 kDa)

Insertion of murine

anti-VEGF-A sequences into a

full-length human

IgG framework

Humanization

Humanization

3

Note: Vertical bars are ± one standard error of the mean.

Sham (n=238) Ranibizumab (Lucentis)

0.5 mg (n=240)

P<0.01

ET

DR

S l

ett

ers

2 4 6 8 10 12 14 16 18 20 22 24

-15

-10

-5

0

5

10

−14.9

+6.6*

15

Month

Mean Change in VA over Time

21.4 letter

benefit *

Comparison of AMD Treatments Trials (CATT)

Lucentis-Avastin Trial

Supported by Cooperative Agreements from the National Eye Institute, National Institutes of Health, DHHS

Patients treated with Lucentis and

Avastin have identical visual outcomes

Change in Visual Acuity- GEE Model

Equivalent, prn 4-5 fewer injections, more eyes completely dry with Lucentis, no SS diff SAEs

All Groups –Averaged over Weeks 12 ,24, 36, 52

8.5

8.0

Week

Le

tte

rs

6.8

5.9

0

5

10

15

0 4 8 12 16 20 24 28 32 36 40 44 48 52

Lucentis Monthly

Avastin Monthly

Lucen tis PRN

Avastin PRN

7.2 (0.7)

7.3 (0.8)

6.4 (0.6)

6.1 (0.7)

+8.5+8.0

+6.8

+5.9

Fusion protein of key domains from

human VEGF receptors 1 and 2 w ith

human IgGFc

Blocks all VEGF-A isoforms and

placental grow th factor (PlGF)

High affinity - binds VEGF-A and

PlGF more tightly than native

receptors

Binds VEGF betw een its arms

w ithout risk of complex formation

Intravitreal aflibercept is specially

purified and formulated to be iso-

osmotic for intravitreal injection

Eylea - Aflibercept

1

3

2

4

5

6

7

1

3

2

4

5

6

7

Fc

VEGF Trap

Kd < 1 pM

VEGFR-1

Kd 10-30 pM

VEGFR-2

Kd 100-300 pM

Mean Change in Visual Acuity

LOCF; Full analysis set; *P = 0.0054 vs. Rq4 †P = NS vs. Rq4

VIEW 2 (n=1202)

9.4 Rq4

7.6† 2q4

9.7† 0.5q4

8.9† 2q8

VIEW 1 (n=1210)

8.1 Rq4

10.9* 2q4

6.9† 0.5q4

7.9† 2q8

Integrated (n=2412)

8.7 Rq4

9.3 2q4

8.3 0.5q4

8.4 2q8

Minor intergroup differences

are not reproduced between

studies

0

2

4

6

8

10

12

0 4 8 12 16 20 24 28 32 36 40 44 48 52

Rq4 2q4 0.5q4 2q8

ETDR

S le

tters

0

2

4

6

8

10

12

0 4 8 12 16 20 24 28 32 36 40 44 48 52

Rq4 2q4 0.5q4 2q8

Wet AMD: Lucentis efficacy

Anti VEGF efficacy (Lucentis/Avastin/Eylea): 25-40% visual improvement

>90% visual stabilization

Best treatment to date

Different mechanism of action

If all are the same, why not just use Avastin?

Avastin vs Lucentis vs Eylea

Cost Insurance coverage

Access to safely compounded Avastin Changing regulations - FDA

Efficacy in certain ARMD subtypes Tachyphylaxis

diminished therapeutic response to a drug following repeated administration over time

Retina. Jun 2009; 29(6): 723–731.

Durability?

What interval?

Monthly

PRN

Extend and Treat

Reduce risk of endophthalmitis

Prevent additional damage due active CNVM

Reduce vision loss secondary to possible VEGF related atrophy

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“If I want to avoid recurrences, why not just inject monthly”

The PrONTO StudyVisual Acuity Results at Month 12 (N=40)

Month 12Mean +9.3 letters p< 0.001

Day 14Mean + 6 lettersp< 0.001

Nu

mb

er

of

Le

tte

rs G

ain

ed

Months Since Initial Injection

0 1 2 3 4 5 6 7 8 9 10 11 12

Mean

Median

Fung et al. AJO 2007;143(4):566-583

Marina/Anchor – 12 injections, PRN – mean of 6 injections

Change in Visual Acuity- GEE Model

Equivalent, prn 4-5 fewer injections, more eyes completely dry with Lucentis, no SS diff SAEs

All Groups –Averaged over Weeks 12 ,24, 36, 52

8.5

8.0

Week

Le

tte

rs

6.8

5.9

0

5

10

15

0 4 8 12 16 20 24 28 32 36 40 44 48 52

Lucentis Monthly

Avastin Monthly

Lucen tis PRN

Avastin PRN

7.2 (0.7)

7.3 (0.8)

6.4 (0.6)

6.1 (0.7)

+8.5+8.0

+6.8

+5.9

LUCAS

Treat and extend protocol validated with Level 1 evidence Monthly until dry, extend by 2 weeks until 3 months

Lucas- extend and treat, +8 letters

Anchor – monthly, lucentis +10 letters

Ivan- monthly,PRN, lucentis, avastin +7-8

CATT - Monthly, PRN, lucentis, avastin +6

January 2015 Volume 122, Issue 1, Pages 146–152

LUCAS

January 2015 Volume 122, Issue 1, Pages 146–152

Evidence

CATT, IVAN, 7 UP – progression of dry component of ARMD with long term treatment

CATT and IVAN Pts that underwent monthly injections – more

atrophy than prn group

1/3 pts increase in atrophy

Majority of pts with gradual, sustained visual loss

34

Percent with Geographic AtrophySame Regimen for 2 Years

35

Geographic Atrophy

36-107 000 104

Baseline

Week 104

Atrophy following anti-VEGF

?disease process

?Macular atrophy associated with CNVM

?Anti VEGF Increased atrophy with monthly vs prn

dosingRisk for GA in CATT trial Ophthalmology, 2014

5

Management of ARMD

One dosing strategy or drug is not appropriate for every patient

“Customizable therapy”

Based on experience of treating thousands of patients

What drug/overtreat/undertreat/stop?

Cases

Case 1 – 67 year old recently retired male presents with loss of vision OD

20/100 20/25

Dr. X is doing these injections. Can I get my injections with him?

Patient returns 1 year later

Loss of vision OS

Patient returns with end stage scar OD

Patient returns w ith end stage scar OD

Patient now with high risk PED OS 20/25

Recommendation

Patient with high risk ARMD OS

Disciform scar OD

Requires close monitoring

RTC 2 months or sooner if changes

Returns 1 year later

Presents with loss of vision OS

s/p 3 avastin injections with Dr.X – sent for emergency referral, 20/100

6

Now Disciform scar OD, poor vision with active lesion OS – Avastin in not working!

Switch to Eylea

20/20

Pt getting monthly Eylea, increase in SRF w hen extends to q5w eeks

I saw Dr. X for glasses. He did the same scan in the office and says I don’t need these injections anymore.

Wet ARMD has periods of quiescence/activity

Some patient require hypervigilant monitoring/aggressive treatment

Case 2

82 year old woman with bilateral active CNVM s/p avastin X 25

20/25 OU

Worsening despite monthly injections-tachyphylaxis

Switch to Eylea

Doing well on Eylea

Insurance changes terms – pt now has 20% copay and doesn’t qualify for assistance program

Wants to switch back to Avastin

Vision declined to 20/30

follow ing 3 monthly

injections of avastin

3 monthly injections of

avastin

VA declined to 20/40 Stable for two months on Avastin, but

then significantly worsens OD – 20/25 -----20/30

OS – 20/25------20/40

Now has secondary insurance that covers Eylea

Not every drug w orks for every patient, tailor management

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Case 3

79 year old author/medical malpractice lawyer treated with avastin q4-6 weeks

20/25 OD, 20/200 OS

Significant worsening despite monthly treatment with Avastin

Switch to Eylea

Stable with q4-6 week Eylea

Relatively quiescent disease

If develops more active disease - decrease interval

Periods of inactivity/activity

Patients can have very poor outcomes w ithout close monitoring

Treatment of Wet ARMD summary

It is complicated!

One dosing strategy or drug is not appropriate for every patient

“Customizable therapy”

What is on the horizon?

Bainbridge JW et al. Clin Sci. 2003;104:561-575.Schlingemann RO. Graefes Arch Clin Exp Ophthalmol. 2004;242:91-101.Ferris FL III et al. Arch Ophthalmol. 1984;102:1640-1642.Ambati J et al. Surv Ophthalmol. 2003;48:257-293.

CNV Progression

Inflammatory Mediators

and Proangiogenic C y tokines

Inappropriate V essel Grow th

Exudation and Hemorrhage

Discoid Scar Formation

O xidativ e Stress

VEGF

Fovista

Lampa

Penfold PL et al. Clin Exp Immunol. 2000;121:458-465.

Kaiser PK. Curr Med Res Opin. 2005;21:705–713.

Clinical Trials in the Pipeline- Drugs you will be hearing about…..

“Extended release” medications for wet ARMD

ICONIC – anti-TF

Ophthotech – “Fovista” – Anti -PDGF

Dry ARMD – trials ongoing

Acucela- emixustat – modulate visual cycle, decrease A2E (toxic fluorophores) accumulation

Lampalizumab – anti-factor D, Mahalo decrease 20%

MDRTC- Macular Degeneration Research and Treatment Center

Fovista + anti-VEGF Monotherapy with Anti-VEGF may not be adequate

Chronic treatment results in maturation of CNVM –pericytes

Combination treatments alters NV

Anti - PDGF-B/PDGFR-β – strip pericytes

Anti-VEGF – regression of neovascularization

Now pericyte-deficient vessels are more permeable and susceptible to anti-VEGF therapy

Decrease scarring and atrophy

8

DRY ARMD Trials

No animal models

Preserve the RPE, photoreceptors and choroid by modulating the immune system

Genetic associations - ARMS2, CFH: modulate the complement system

Lampalizumab- antifactor D

Molecule

Fab of a humanized monoclonal antibody Targets complement factor D of the

alternative pathway

Target

Complement factor D is a rate-limiting enzyme in the alternative pathway and present in relatively low abundance

Scientific Rationale

Genetic polymorphisms in alternative complement pathway proteins are associated with the risk of AMD

Complement hyperactivity has been implicated in AMD

C3a

C3b

C5b

C5a

C5

C3b

C3b

C3b

Bb

Bb

Classical pathway

MBL pathway

C3b

C4b

C2a

C4b

C2a

C3

Alternative pathway

fB

fD

fB

fD

fH

fH

AFDInflammation

MAC*

Inflammation

Amplification

*Membrane Attack Complex

Lampalizumab (anti-factor D): Selective inhibitor of the alternative complement pathway

C1q

AFD

Wet AMD: It’s complicated!

Wet ARMD is chronic

disease with periods of

quiescence and activity

Detect it early

Complex management

strategies to avoid

overtreat/undertreat

Summary

There is no “cure”

Evolving treatments for ARMD promising

Diabetic Eye Disease

Impact

Classification

Pathogenesis

Treatment

New potential

treatments

Diabetic eye disease Overview

Prevalence of DM – the epidemic

8.3% of population - 25.8 million people

65 years and older - 26.9% have diabetes

2020 – 20% of population

2 million people/year with new diagnosis

30% of those with DM have retinopathy

*American Diabetes Association , 2010

2 main causes of visual loss

Proliferative

Macular Edema

Diabetes is a disease of small blood vessels!!!!!!

Rapid Progression of PDR

9/08 6/09

<9 months later

9

Slower vision loss with CSDME Diabetic Macular Edema (DME)

Main cause of mild to moderate vision loss inDiabetic Retinopathy (DR) Will develop in 14% of diabetics over 10 years

Incidence of DME increases with increasing DR severity 3% in mild nonproliferative

38% in moderate /severe nonproliferative

71% in proliferative

50% of DME patients will lose 2 lines of visualacuity within 2 years

Ferris and Patz. Surv Ophthalmol. 1984; Hikichi et al. Ophthalmology. 1997;Klein et al. Ophthalmology. 1995.

Focal Macular Edema

A single or localized cluster of leakage sites

Hard exudates common

Photographs courtesy of Baruch Kuppermann, MD. 2004.

Diffuse Macular Edema Generalized breakdown

of blood-retinal barrier with leakage from blood vessels throughout the posterior pole of the eye

Hard exudates less common Why does this happen?

Pericytes

Diabetes is a disease of small blood vessels

Thickening of BM in vessels

Loss of pericytes

Increased permeability of vessels

Vessel closure

Pathophysiology of DME

Blood-retinal barrier breakdown with increased vascular permeability in retinal vessels Loss of pericytes surrounding capillaries, leading to

capillary wall weakness

Development of microaneurysms

Endothelial basement membrane thickening leading tofocal closure of some capillaries; increased blood flow in other vessels

Prostaglandins, interleukin (IL-1), vascular endothelialgrowth factor (VEGF), and other inflammatory mediators are involved in key steps of this process

Pelzek and Lim. Ophthalmol Clin North Am. 2002.

Vessel damage/leakage and closure

Ischemia

Drives production of VEGF

Makes VEGF

Stimulates more abnormal

vessel formation

10

Treatment options

Control blood sugars!!

Laser

Pharmacologic agents

Vitrectomy

All of the Above!!!!

LaserFocal/Grid Laser

ETDRS

Laser reduced risk of 2 line loss by 50% - 3 years after initial treatment

One line gain in 16%

Standard of care

Slows progression

Damage to retina

Does not improve VA

Lower VEGF levels

56 year old woman with 15 year history of DM

Hb A1C 8.0

OD OS

20/40 20/25

Laser performed20/40 20/25

Diffuse CSDME

What can we do to treat DME(other than laser)????

11

Intravitreal Steroids

Triamcinolone acetonide

Depot steroid

Effect for 3-6 months

Side effects Glaucoma

Cataract

Endophthalmitis

Psuedoendophthalmitis

Intravitreal anti-VEGF agents

Bevacizumab (Avastin) and Ranibizumab (Lucentis)

Lucentis and DME READ2

Lucentis injections result in significantly better visual outcomes than focal/grid laser in diabetic macular edema (DME) at 6 months

ETDRS has shown that focal/grid laser reduces the risk for moderate visual loss in eyes with DME

22% improved 3 or more lines- laser 0%

46% improved 2 or more lines- 5%

Long term results with IVK show laser is better long term

Anti-VEGF

Rapid onset to reduce macular edema

Temporary fix

May improve response of laser alone

Reduces vascular permeability

Avastin alone (monthly injections) 6 months - 55% of patients with

normalization of OCT

No glaucoma, cataract formation

DRCR Protocol T

Compares Avastin, Lucentis, Eylea for foveal involving diabetic macular edema

If VA better than 20/50 – all comparable

If VA worse than 20/50 – Eylea superior

DRCR Protocol I

Lucentis vs laser

Patients with Lucentis and deferred laser had better visual outcomes (2 lines) compared to those receiving early laser at 5 years

Combination therapy?

DME – result of damaged, leaking blood vessels

Laser – seals blood vessels and permanently treats areas of damaged retina producing VEGF

Avastin/Lucentis/Steroids- decreases vascular permeability – transcient?

Summary – Goal of Treatment for DME

Optimize medical care

Pharmacologic therapy (Steroids and Anti-VEGF agents)

Laser – if needed for long term control

Vitrectomy Surgery

12

Surgical Treatment

Surgical Approaches to Common Vitreoretinal

Diseases

Surgical Diseases of the Retina The vitreous is the enemy of the eye surgeon!

PVD formation (aging of the vitreous) causes:

Surgical Diseases of the Retina

Retinal detachment

Epiretinal membranes (ERM)

Macular Holes

Vitreomacular traction (VMT)

Vitreous Opacities (floaters)

Pediatric retinal diseases

RETINAL DETACHMENT

•Requires repair•Office procedure

•Laser

•Pneumatic Retinopexy

•Procedure in operating room

•Scleral buckle•Vitrectomy

Retinal detachment Pneumatic Retinopexy

Uncomplicated retinal detachments

Retinal break located superior 8 clock hours

Able to maintain specific head posture

Retinal break

Detached retina

Gas bubble

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Pneumatic Retinopexy

Highest single operation success – 70%

Phakic

One quadrant detachment

One break

Located upper 8 clock hours

Retinal detachment Scleral Buckle

•Identify and treat the retinal breaks•Support the breaks with the buckle•Drain the fluid from underneath the retina (+/-)

Scleral Buckle

•Support the breaks with the buckle

Scleral Buckle

Pars Plana Vitrectomy•Enter the eye with small instruments

•Vitreous cutter, light, infusion

•Remove the vitreous gel•Reattach the retina•Laser•Tamponade – air, gas, siliconeoil

Cataract formation

Giant retinal tear

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The Dilemma: SB or PPV or Both

???

SBP < PPV/SBP > PPV???

Retrospective Comparison Studies

Single Operation Success Rate

SB PPV SB/PPV

Oshima et al., 2000 91% 91%

Miki et al., 2001 92% 92%

Roider et al., 2001 98% 93%

Afrashi et al., 2004 80% 90% *

Wickham et al., 2004 89% 73%

Mansouri et al., 2010

(phakic subgroup)

86.2% 77.8% 83.8%

Mansouri et al., 2010

(pseudophakic subgroup)

80.0% 86.5% 80.3%

* statistically significant

Surgical Principles: Bottom Line

Simple phakic RD – office/pnemo

Non-complex, phakic RD - SB

Non-complex, pseudo RD – SB, vit/SB, vit

Complex RD - vit/SB

Timing of RD Surgery – is it an emergency?

Macula-on

Macula-off

D’Amico DJ. N Engl J Med. 2008 Nov 27;359(22):2346-54.

Duration of Macular Detachment

Ross et al.

Macula-off detachments ≤7 days, repaired with SB

No difference in final VA of subgroups (1-2d, 3-4 d, 5-7 d)

Ophthalmology. 1998 Nov;105(11):2149-53.

ERM

•Caused from ce llular changes in the vitreous – aging, trauma•Fibroproliferative tissue that forms on the re tinal surface•Can cause distortion of the macula and visual loss

•Treatment – observation or surgical intervention – visually significant

ERM – Surgical intervention

•Progressive visual loss•Recommend vitrectomy with membrane peeling (stripping)•Mechanical removal – no laser

•Surgical success- prevent further visual loss, 85% improve

Macular Hole

•Caused from vitreous traction on the macula•Central loss of photoreceptors•Results in distortion of the macula and central visual loss

•Treatment – surgical intervention

Macular Hole- surgical repair

•Remove the vitreous gel•Peel the ILM•Fluid-air exchange•Gas Tamponade•Face down positioning

15

Macular Hole

•Requires Face Down positioning 1-7 days to position the bubble

Macular Hole – surgical success•95% success rate with one surgery•Surgical success depends on size of hole, positioning, chronicity•Visual potential – small hole , good preoperative vision

20/30 20/400

Vitreomacular Traction•Can be mildly asymptomatic-PPV if VS•Can spontaneous resolve (50%)•Can cause progressive visual loss or macular hole

•Surgical repair similar to ERM/MH repair•Option of treatment with Ocriplasmin “chemical vitrectomy”

Enzymatic Manipulation of the Vitreous: “Chemical

Vitrectomy” Recombinant Ocriplasmin - Jetrea

Non surgical induction of a PVD to relieve vitreous traction and treat retinal diseases

Jetrea

Recombinant 29,000 Kd protein Plasmin catalytic domain cleaves the VR interface

Cleaves type IV collagen and fibronectin

Not toxic by ERG

Plasmin Ocriplasmin

88Kd 29Kd

Baseline

Day 7

+10 letters

Month 6

+21 letters

A

B

C

Vitreous Opacities•Floaters!!•Symptomatic or asymptomatic•PPV if VS

Case 1

33 year old attorney presents with debilitating floaters

“can’t read”

20/20 OU

-7D OU

No PVD

Mother blind from glaucoma

Referred for possible vitrectomy

16

Floater log Potential outcomes

Infection

Glaucoma

Cataract Anisometropia

PPV or observation?

Floaterectomy

RD - 10.9 % of cases

CME - 5.5 % of cases

ERM - 3.6 % of cases

85% satisfied – cured from floaters

15% unsatisfied –

5.6% - complications resulted in permanent visual loss

Pediatric Retinal Diseases

Pediatric retinal diseases are diseases of retinal

development

Vasculogenesis

Normal development

Vasculogenesis

Retinal

differentiation

Angiogenesis

Retinal

Development

VASCULOGENESIS

Fzd4

LRP

NORMAL

CAMK2 PKC

-CATENIN

NDP

VEGF

Normal VasculogenesisCell-cell signal transduction pathw ay

Wnt-receptor:-catenin signaling

17

Abnormal VasculogenesisAssociated with disruption of the the

Wnt-receptor:-catenin pathway

ROP Norrie’s PFV FEVR Coats’ etc

Vasculogenesis

Retinal

differentiation

Angiogenesis

Retinal

Development

Environmental

Genetic

Pediatric Retina

Increased use of Retcam and FA

Treatment of previously untreatable diseases

Coat’s disease

FEVR

18

Pediatric Vitreoretinal Surgery

Pediatric Retinal surgery is not a smaller scale version of adult surgery No margin for error Pathology is different

Posterior hyaloid is tightly adherent to the retina and removing it can cause damage

Pediatric retinal problems are related to development

Summary

Increased prevalence of ARMD, diabetic eye disease

Evolving and innovative treatments on the horizon

Surgical interventions are effective

Thank you!!