Scott M. Pfahler D.O. Dayton Vitreo-Retinal Associates AOCOO-HNS Palm Springs, CA 2012
Proliferative Diabetic Retinopathy Laser Treatments Medical Treatment Surgical Treatment Diabetic Macular Edema Laser Treatments Medical/Pharmacotherapy Surgical Management
25.8 Million Americans 8.3% of population 79 Million pre-diabetics 1.9 New cases in 2010
Leading cause of new blindness among adults 20-74 years of age 4.2 million have diabetic retinopathy 28.5 % of diabetics
Prevalence (DME) is 30% in adults with diabetes for 20 years or more At 20 years 60% of Type 2 diabetics with retinopathy 100 of Type 1 diabetics with retinopathy Mild NPDR 3% have DME Moderate to Severe NPDR 38% have DME Proliferative NPDR 71% have DME
DCCT Type 1 diabetics Intensive treatment group 34% chance of significant progression vs. 76% in less intense 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
Relationship between lipid levels and diabetic retinopathy Lowered progression of retinopathy with intensive lipid control
Fundoscopic examination 60, 78, 90D lens Contact lens Color Photos Optical Coherence Tomography Time domain Spectral domain Map vs. line scan Fluorescein angiography Microaneursyms Ischemia Leakage Neovascularization
Be aware of Corneal surface disease Lenticular opacities Look for microaneurysms, lipid, hemorrhage, neovascularization Often associated with edema If view is poor, consider contact lens If IOP is elevated Gonioscopy to look for neovascularization of angle
Can be used to monitor for changes Some centers use for screening in lieu of clinical examination Wills Eye Network Example Importance in use alongside clinical exam, OCT and FA??
Intraretinal cysts Intraretinal lipids Subretinal fluid Line Scan Map/Volume SD vs. TD?
Proliferative Diabetic Retinopathy Diabetic Macular Edema
Treatment Options Neovascularization Bevacizumab (Avastin) Pan-retinal Photocoagulation (PRP) Pars Plana Vitrectomy Non-clearing vitreous hemorrhage Tractional Retinal Detachment (macula)
Traditional Laser Photocoagulation Argon Nd:YAG 532nm Pattern Photocoagulation Pascal System (OptiMedica) Navilas System (OD-OS) Considerations Cost Time of treatment Effectiveness?
Focal? Avastin? Avastin then PRP? PRP alone?
Iridex Nd:Yag 532 nm Topical anesthesia* retrobulbar subconjunctival lidocaine Settings 200-300 mw 0.1 sec duration 200 micron spot size 1200-1500 spots initially*
Ensure regression of neovascularization Clinically Fluorescein angiography If treating with Pascal System may need to adjust parameters or add additional treatment
Diabetic Macular Edema
Chronic hyperglycemia Vascular dysfunction Vascular occlusion Chronic low grade inflammation Hypoxia Thickening of vascular endothelium Loss of pericytes Upregulation of growth factors VEGF Cytokines
Starlings Law Movement of fluid depends upon hydrostatic pressure vs. plasma osmotic pressure LaPlace s Law Increased hydrostatic pressure causes vessel to dilate and increased tortuosity Tight junctions disrupted and increased fluid loss
Laser Therapies Focal laser photocoagulation (standard) Sub-threshold photocoagulation Peripheral Photocoagulation Intravitreal pharmacotherapy Triamcinolone acetonide Dexamethasone Flucinolone Anti-VEGF Ranubizumab (Lucentis) Bevacizumab (Avastin) Vitrectomy
When do we treat??
Established focal laser photocoagulation as standard treatment for DME Laser photocoagulation reduced the rate of moderate vision loss by 50% in eyes with CSME Treatment eyes rarely improved to 20/40 or better 3% of eyes had > 3 lines of improvement in vision at 36 months post treatment Eyes with diffuse DME responded less well
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
Traditional focal laser photocoagulation Gold standard Navigated treatment (Navilas) Pattern style (Pascal) Subthreshold diode micropulse treatment Peripheral photocoagulation
Areas of Edema? Microaneuyrsms? Lipids? Hemorrhages?
Modified ETDRS Direct treatment to microaneurysms and grid to thickened areas only Mild Macular Grid Laser Technique Diffuse widespread area of grid treatment to macula in thick and nonthick areas No treatment of microaneurysm Primary Outcome Measures OCT thickness Secondary Measure Visual Acuity
12 months Modified ETDRS had slightly greater reduction in OCT Modified ETDRS trended towards better vision
Topical anesthesia Macular contact lens Iridex Nd:Yag 532nm 50-100 mw 0.1 sec duration Treatment parameters vary Use a fixation light Be careful with juxtafoveal treatment! Especially inferior
Navilas System (OD-OS) Combines Fundus Camera with laser system Fundus photography and fluorescein angiography FA and Color images annotated by physician for treatment System treats targeted lesions
810 nm Diode Laser Subthreshold treatment of macular region Minimization of collateral damage Smaller studies showing promise in DME Less chance of scotoma? Better contrast sensitivity? Cost of additional laser? Lack of large randomized clinical trials
Peripheral ischemia promotes VEGF and other cytokines which promotes DME Targeting peripheral ischemia with PRP will decrease VEGF/Cytokines and result in decreased DME Coat s disease, FEVR, von-hippel angioma, radiation retinopathy Associated peripheral ischemia and macular edema
Steven D. Schwartz M.D. and Paul Tornambe M.D. have lead recent interest Pre-treatment with Bevacizumab followed by targeted laser treatment to ischemic areas with re-treatment of Bevacizumab on followup Ongoing, but early success with selected cases Clinical trials needed
Triamcinolone Acetonide (Kenalog) Dexamethasone Bevacizumab (Avastin) Ranibizumab (Lucentis)
Typically not used as 1 st line therapy 1mg, 2mg, 4mg Typical Doses Duration usually 2-3 months Effect usually significant Side effects Cataract formation Ocular hypertension/glaucoma Risk of injection
Is Kenalog superior to focal laser photocoagulation for DME??
DRCR.net Study 840 eyes (693 pts) 1 mg, 4mg, of IVK vs. Focal group Retreat for new/persistent edema at 4 month At 4 month IVK better vision than focal At 1 year no visual acuity difference 16 months focal group better than IVK
Bevacizumab (Avastin) Ranibizumab (Lucentis) Both off-label for use in DME
Lid Speculum 32 gauge needle 3.5 mm to 4.0 mm Betadine Significant evidence Inferior/Inferior-temp No talking No pre or post antibiotics
We have Laser Kenalog Avastin/Lucentis What should we do??
854 eyes (691 patients) VA 20/32 to 20/320 Central DME > 250 micron on OCT 4 Treatment groups 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
Initial four monthly injections At 16 weeks (5 th visit) could hold on treatment if criteria met (20/20 or nml OCT) If criteria not met 2 additional injections For remaining 7 Visits, treatment continues if success not met
At week 60, if success, then followup in 8 weeks At week 68, if success, the followup in 16 weeks
First six months Median number of injections of ranibizumab groups was six Second six months Two treatment in ranibizumab/prompt laser Three treatments in ranibizumab/deferred laser Second year Two treatment in ranibizumab/prompt laser Three treatments in ranibizumab/deferred laser
At 16 weeks only 25% of ranibizumab group eyes met success criteria 90% relapse during first year In deferred laser group 28% underwent laser treatment in first year, 14% in second year About 60% did not receive laser in this group In ranibizumab/prompt laser, about 70% had additional laser in 1 st year 50% received laser in second year
Best Corrected Visual Acuity at 12 months Significantly better in ranibizumab groups 9 Letters each (p<0.001) Triamcinolone groups 4 letter improvement (p<0.31) Sham plus laser treatment 3 letter improvement
Safety issues 3 eyes endophthalmitis (0.8%) No evidence of tractional retinal detachment 60% of triamcinolone eyes underwent cataract surgery vs 14% of ranibizumab eyes at 2yrs 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
Focal? Avastin? Kenalog? Micropulse?
Phone call to PCP for management of BP Recommended follow-up 2-3 weeks Possible treatment if DME/CME persists
Blood pressure medications adjusted BP= 142/78
Remember to keep in mind systemic risk factors and modify as much as possible Keep in touch with PCP (phone call/letter/fax)
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 1 st then possible return 1-2 weeks for focal Focal only selected cases Localized CME MA with circinate ring
Intravitreal Kenalog Covers more cytokines Longer duration IOP and cataract issues Less IOP issues with 2mg dose When all else fails Vitrectomy with or without ILM peeling
Improved oxygenation Removal of harmful growth factors Removal of tractional forces Usually reserved for refractory cases
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???
PRP remains standard treatment for high risk PDR Anti-VEGF has changed our treatment paradigm for DME Significant body of evidence to support use in DME Consider initial use of Anti-VEGF for CSME May require ongoing monthly treatment However, DME is more than Anti-VEGF driven so still roles for focal laser, photocoagulation, kenalog More studies needed to investigate micropulse, peripheral laser
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; 103:1796-1806. 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;41:877-879. Ogata N, Tombran-Tink J, Jo N, et al. Upregulation of pigment epitheliumderived factor after laser photocoagulation. Am J Ophthalmol. 2001;132:427-429.