Download Update on Diabetic Macular Edema - aocoo-hns

Scott M. Pfahler D.O.
Dayton Vitreo-Retinal Associates
AOCOO-HNS
Palm Springs, CA 2012
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Proliferative Diabetic Retinopathy
 Laser Treatments
 Medical Treatment
 Surgical Treatment
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Diabetic Macular Edema
 Laser Treatments
 Medical/Pharmacotherapy
 Surgical Management
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25.8 Million Americans
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8.3% of population
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79 Million pre-diabetics
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1.9 New cases in 2010
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Leading cause of new blindness among adults
20-74 years of age
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4.2 million have diabetic retinopathy
 28.5 % of diabetics
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Prevalence (DME) is 30% in adults with diabetes for
20 years or more
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At 20 years
 60% of Type 2 diabetics with retinopathy
 100 of Type 1 diabetics with retinopathy
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Mild NPDR
 3% have DME
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Moderate to Severe NPDR
 38% have DME
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Proliferative NPDR
 71% have DME
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DCCT
 Type 1 diabetics
 Intensive treatment group 34% chance of significant
progression vs. 76% in less intense
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UKPDS
 Type 2 diabetics
 Intensive group 25% fewer microvascular complications
 12% lower rate of blindness, renal failure, amputation and
death
 Tight blood pressure control better
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Relationship between lipid levels and diabetic
retinopathy
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Lowered progression of retinopathy with
intensive lipid control
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Fundoscopic examination
 60, 78, 90D lens
 Contact lens
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Color Photos
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Optical Coherence Tomography
 Time domain
 Spectral domain
 Map vs. line scan
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Fluorescein angiography
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Microaneursyms
Ischemia
Leakage
Neovascularization
Be aware of
 Corneal surface disease
 Lenticular opacities
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Look for microaneurysms, lipid, hemorrhage,
neovascularization
 Often associated with edema
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If view is poor, consider contact lens
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If IOP is elevated
 Gonioscopy to look for neovascularization of angle
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Can be used to monitor for changes
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Some centers use for screening in lieu of
clinical examination
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Wills Eye Network Example
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Importance in use alongside clinical exam,
OCT and FA??
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Intraretinal cysts
Intraretinal lipids
Subretinal fluid
Line Scan
Map/Volume
SD vs. TD ?
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Proliferative Diabetic Retinopathy
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Diabetic Macular Edema
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Treatment Options
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Neovascularization
 Bevacizumab (Avastin)
 Pan-retinal Photocoagulation (PRP)
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Pars Plana Vitrectomy
 Non-clearing vitreous hemorrhage
 Tractional Retinal Detachment (macula)
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“Traditional” Laser Photocoagulation
 Argon
 Nd:YAG 532nm
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“Pattern” Photocoagulation
 Pascal System (OptiMedica)
 Navilas System (OD-OS)
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Considerations
 Cost
 Time of treatment
 Effectiveness?
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Focal?
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Avastin?
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Avastin then PRP?
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PRP alone?
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Iridex Nd:Yag 532 nm
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Topical anesthesia*
 retrobulbar
 subconjunctival lidocaine
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Settings
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200-300 mW
0.1 sec duration
200 micron spot size
1200-1500 spots initially*
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Ensure regression of neovascularization
 Clinically
 Fluorescein angiography
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If treating with Pascal System may need to
adjust parameters or add additional
treatment
 Diabetic Macular Edema
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Chronic hyperglycemia
 Vascular dysfunction
▪ Vascular occlusion
▪ Chronic low grade inflammation
▪ Hypoxia
▪ Thickening of vascular endothelium
▪ Loss of pericytes
▪ Upregulation of growth factors
▪ VEGF
▪ Cytokines
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Starlings Law
 Movement of fluid depends upon hydrostatic
pressure vs. plasma osmotic pressure
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LaPlace’s Law
 Increased hydrostatic pressure causes vessel to
dilate and increased tortuosity
 Tight junctions disrupted and increased fluid loss
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Laser Therapies
 Focal laser photocoagulation (standard)
 Sub-threshold photocoagulation
 Peripheral Photocoagulation
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Intravitreal pharmacotherapy
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Triamcinolone acetonide
Dexamethasone
Flucinolone
Anti-VEGF
▪ Ranubizumab (Lucentis)
▪ Bevacizumab (Avastin)
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Vitrectomy
When do we treat??
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Established focal laser photocoagulation as standard
treatment for DME
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Laser photocoagulation reduced the rate of moderate
vision loss by 50% in eyes with CSME
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Treatment eyes rarely improved to 20/40 or better…
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3% of eyes had > 3 lines of improvement in vision at 36
months post treatment
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Eyes with diffuse DME responded less well
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Clinically Significant Macular Edema
(CSME)
 Retinal thickening within 500 microns of center
fovea
 Lipid exudation within 500 microns of center
fovea associated with retinal thickening
 Retinal thickening > 1 disc area within 1 disc
diameter of the center of fovea
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“Traditional” focal laser photocoagulation
 Gold standard
 Navigated treatment (Navilas)
 Pattern style (Pascal)
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Subthreshold diode micropulse treatment
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Peripheral photocoagulation
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Areas of Edema?
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Microaneuyrsms ?
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Lipids ?
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Hemorrhages ?
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Modified ETDRS
 Direct treatment to microaneurysms and grid to thickened areas only
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Mild Macular Grid Laser Technique
 Diffuse widespread area of grid treatment to macula in thick and non-
thick areas
 No treatment of microaneurysm
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Primary Outcome Measures
 OCT thickness
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Secondary Measure
 Visual Acuity
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12 months
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Modified ETDRS had slightly greater
reduction in OCT
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Modified ETDRS trended towards better
vision
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Topical anesthesia
Macular contact lens
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Iridex Nd:Yag
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532nm
50-100 mW
0.1 sec duration
Treatment parameters vary
Use a fixation light
Be careful with juxtafoveal treatment!
▪ Especially inferior
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Navilas® System (OD-OS)
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Combines Fundus Camera with laser system
 Fundus photography and fluorescein angiography
 FA and Color images annotated by physician for
treatment
 System treats targeted lesions
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810 nm Diode Laser
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Subthreshold treatment of macular region
 Minimization of “collateral” damage
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Smaller studies showing promise in DME
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Less chance of scotoma?
Better contrast sensitivity?
Cost of additional laser?
Lack of large randomized clinical trials…
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Peripheral ischemia promotes VEGF and other
cytokines which promotes DME
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Targeting peripheral ischemia with PRP will
decrease VEGF/Cytokines and result in
decreased DME
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Coat’s disease, FEVR, von-Hippel angioma,
radiation retinopathy
 Associated peripheral ischemia and macular edema
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Steven D. Schwartz M.D. and Paul Tornambe
M.D. have lead recent interest
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Pre-treatment with Bevacizumab followed by
targeted laser treatment to ischemic areas with
re-treatment of Bevacizumab on followup
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Ongoing, but early success with selected cases
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Clinical trials needed
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Triamcinolone Acetonide (Kenalog)
Dexamethasone
Bevacizumab (Avastin)
Ranibizumab (Lucentis)
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Typically not used as 1st line therapy
 1mg, 2mg, 4mg Typical Doses
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Duration usually 2-3 months
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Effect usually significant
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Side effects
 Cataract formation
 Ocular hypertension/glaucoma
 Risk of injection
Is Kenalog superior to focal
laser photocoagulation for
DME??
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DRCR.net Study
 840 eyes (693 pts)
 1 mg, 4mg, of IVK vs. Focal group
 Retreat for new/persistent edema at 4 month
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At 4 month—IVK better vision than focal
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At 1 year – no visual acuity difference
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16 months – focal group better than IVK
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Bevacizumab (Avastin)
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Ranibizumab (Lucentis)
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Both off-label for use in DME
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Lid Speculum
32 gauge needle
3.5 mm to 4.0 mm
Betadine
 Significant evidence
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Inferior/Inferior-temp
No talking
No pre or post antibiotics
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We have
 Laser
 Kenalog
 Avastin/Lucentis
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What should we do??
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854 eyes (691 patients)
VA 20/32 to 20/320
Central DME > 250 micron on OCT
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4 Treatment groups
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 Sham injection plus focal laser
 0.5 mg Ranibizumab plus focal laser
 0.5 mg Ranibizumab plus deferred laser
 4 mg Intravitreal kenalog plus laser
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Initial four monthly injections
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At 16 weeks (5th visit) could hold on
treatment if criteria met (20/20 or nml OCT)
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If criteria not met 2 additional injections
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For remaining 7 Visits, treatment continues if
success not met
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At week 60, if success, then followup in 8
weeks
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At week 68, if success, the followup in 16
weeks…
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First six months
 Median number of injections of ranibizumab
groups was six
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Second six months
 Two treatment in ranibizumab/prompt laser
 Three treatments in ranibizumab/deferred laser
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Second year
 Two treatment in ranibizumab/prompt laser
 Three treatments in ranibizumab/deferred laser
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At 16 weeks only 25% of ranibizumab group
eyes met success criteria
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90% “relapse” during first year
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In deferred laser group 28% underwent laser
treatment in first year, 14% in second year
 About 60% did not receive laser in this group
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In ranibizumab/prompt laser, about 70% had
additional laser in 1st year
 50% received laser in second year
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Best Corrected Visual Acuity at 12 months
 Significantly better in ranibizumab groups
 9 Letters each (p<0.001)
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Triamcinolone groups
 4 letter improvement (p<0.31)
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Sham plus laser treatment
 3 letter improvement
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Safety issues
 3 eyes endophthalmitis (0.8%)
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No evidence of tractional retinal detachment
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60% of triamcinolone eyes underwent cataract
surgery vs 14% of ranibizumab eyes at 2yrs
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28% of triamcinolone eyes require IOP lowering
meds vs. 4% of ranibizumab and 5% of laser
groups at 2yrs
 Ranibizumab with either
prompt or deferred laser
resulted in superior anatomical
and visual outcomes versus
laser alone at 2 years
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Focal ?
Avastin ?
Kenalog ?
Micropulse ?
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Phone call to PCP for management of BP
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Recommended follow-up 2-3 weeks
 Possible treatment if DME/CME persists
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Blood pressure medications adjusted
BP= 142/78
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Remember to keep in mind systemic risk
factors and modify as much as possible
Keep in touch with PCP (phone call/letter/fax)
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Call PCP if patient’s glucose, blood pressure
or lipids are significantly elevated
Try to communicate often with
PCP/Endocrine teams
Communicate with patient every visit
Make the patient an active player
Stop smoking!!

Patient specific
 Duration
 Amount and type of edema
 Location of edema
 Past ocular/medical history
▪ Cataract?
▪ Recent MI/CVA?
 Usually combination
 Avastin/Focal
 Especially useful if diffuse edema or subretinal
fluid
 Avastin 1st then possible return 1-2 weeks for focal
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Focal only—selected cases
 Localized CME
 MA with circinate ring
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Intravitreal Kenalog
 Covers more cytokines
 Longer duration
 IOP and cataract issues
▪ Less IOP issues with 2mg dose
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When all else fails…
 Vitrectomy with or without ILM peeling
Improved oxygenation
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Removal of harmful growth factors
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Removal of tractional forces
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Usually reserved for refractory cases
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Cylindrical polyimide tube with 190µg of
fluocinolone acetonide
Intravitreal injection delivery
Sustained release over 24-36 months
FAME (Fluocinolone Acetonide in DME)
 Signficant effect however, safety concerns
 FDA rejects New Drug Application (NDA) in
2011
 Use in Europe, Future here???
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PRP remains standard treatment for high risk PDR
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Anti-VEGF has changed our treatment paradigm for DME
 Significant body of evidence to support use in DME
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Consider initial use of Anti-VEGF for CSME
 May require ongoing monthly treatment
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However, DME is more than Anti-VEGF driven… so still
roles for focal laser, photocoagulation, kenalog
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More studies needed to investigate micropulse, peripheral
laser……
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Early Treatment Diabetic Retinopathy Study Research Group. Early Treatment
Diabetic Retinopathy Study Design and baseline characteristics. ETDRS Report 7.
Ophthalmology. 1991; 98: 741-756.
Early Treatment Diabetic Retinopathy Study Research Group. Treatment
techniques and clinical guidelines for photocoagulation of diabetic macular
edema. ETDRS Report 2 Ophthalmology. 1987; 94: 761-774.
Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation
for diabetic macular edema. ETDRS Report 1. Arch Ophthalmol. 1985; 103:17961806.
DRCR.net
AAO preferred practice patterns
Yannuzzi, L. The Retina Atlas, Elsevier, 2010
Wilson DJ, Finkelstein D, Quigley HA, et al. Macular grid photocoagulation: an
experimental study on the primate retina. Arch Ophthalmol. 1988;106:100-105.
Arnarsson A, Stefansson E. Laser treatment and the mechanism of edema
reduction in branch retinal vein occlusion. Invest Ophthalmol Vis Sci. 2000;41:877879.
Ogata N, Tombran-Tink J, Jo N, et al. Upregulation of pigment epitheliumderived factor after laser photocoagulation. Am J Ophthalmol. 2001;132:427-429.