Diabetic Retinopathy - Download Now PowerPoint

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					    Normal Retina

                 Fovea
Photoreceptors



      RPE


      Choroid            Macula
A range of visual defects with macular pathology

                                 Neovascular AMD
                                Neovascular AMD
                 Distortion           Blur            Scotoma




  Normal



                   DMEDME                DME with proliferative DR

                         Blur                 Blur + scotomas
      RISK FACTORS
Age
Smoking
Positive family history
Hypertension
Females
Raised cholesterol
Light iris color
            DIET
Vitamins – C 500 mg, E 400 IU
Micronutrients – Zinc 80mg with 2mg
cupric oxide
Beta carotene 15mg – Avoid in smokers
Fish
Nuts
Lifestyle modification
Avoid smoking
Reduce obesity
Use sunglass & Hats
Avoid alcohol
                 VEGF Inhibition in AMD
     FDA approved
       Pegaptanib
             –     Aptamer
             –     Specific for VEGF-A isoform 1651
             Ranibizumab
             –     Recombinant, humanized antibody fragment
             –     Blocks all VEGF-A isoforms
     Off label
         Bevacizumab
             –     Recombinant humanized monoclonal antibody
             –     Blocks all VEGF-A isoforms



1Gragoudas   ES, et al. N Engl J Med. 2004;351:2805.
              VEGF-A Is a Key Mediator of
      Environmental
         factors
                    Angiogenesis binding and
                    1          VEGF-A
        (hypoxia,2 pH)                                                 activation of VEGF
     Growth factors,                                                        receptor3
       hormones1
      (EGF, bFGF, PDGF,
      IGF-1, IL-1, IL-6,
          estrogen)                                                        Endothelial cell
                                                                             activation3




                                        Endothelial cell activation,             VASCULAR
      ANGIOGENESIS3                      proliferation, migration4               LEAKAGE3
VEGF-A = vascular endothelial growth factor A; EGF = epidermal growth factor; bFGF = basic fibroblast
growth factor; PDGF = platelet-derived growth factor; lGF = insulin-like growth factor; IL= interleukin.
1. Dvorak HF. J Clin Oncol. 2002;20:4368. 2. Aiello LP, et al. Arch Ophthalmol. 1995;113:1538.
3. Ferrara N, et al. Nat Med. 2003;9:669. 4. Griffioen AW and Molema G. Pharmacol Rev. 2000;52:237.
                 VEGF Inhibition in AMD
     FDA approved
       Pegaptanib
             –     Aptamer
             –     Specific for VEGF-A isoform 1651
             Ranibizumab
             –     Recombinant, humanized antibody fragment
             –     Blocks all VEGF-A isoforms
     Off label
         Bevacizumab
             –     Recombinant humanized monoclonal antibody
             –     Blocks all VEGF-A isoforms



1Gragoudas   ES, et al. N Engl J Med. 2004;351:2805.
    Different gold standard diagnostics with
            common ancillary tests
           Neovascular AMD                                                                  DME
   Early detection of neovascular                                DME is diagnosed stereoscopically
    AMD is possible with an                                        as retinal thickening in the macula
    Amsler grid1                                                   using fundus contact lens
   FA is essential to confirm                                     biomicroscopy3
    diagnosis of neovascular AMD,
    and to identify the location and
    composition of the CNV1

                                                              Ancillary tests:3
Ancillary tests:2
                                                                  FA – identification and evaluation
   ICGA – delineation of choroidal                                of fluid leakage from lesions
    vessel morphology
                                                                  OCT – measurement of retinal
   OCT – measurement of retinal                                   thickness
    thickness


                                                                                  1. Sickenberg M. Ophthalmologica 2001;215:247–253
                                                      2. The Royal College of Ophthalmologists. AMD: guidelines for management. 2009.
                      http://www.rcophth.ac.uk/docs/publications/AMD_GUIDELINES_FINAL_VERSION_Feb_09.pdf [accessed Sep 2009]
                                                                                       3. Bhagat N et al. Surv Ophthalmol 2009;54:1–32
   Standard of care: improvement with
neovascular AMD vs stabilization with DME
            Neovascular AMD                                                             DME

   Ocular treatment – Anti VEGFs                            Ocular treatment –
    IVI1                                                      laser photocoagulation2–4
    •   Maintenance of vision can be                          •     Rarely provides visual
        expected in 90–95% of patients                              improvement
    •   Improvement of vision by                              •     In the 1985 ETDRS, VA improved
        ≥3 lines can be expected in                                 in 16%, was unchanged in 77%
        30–40% of patients                                          and worsened in 7% of patients
                                                             Systemic treatment4
                                                              •     Glucose control
                                                              •     Blood-pressure control
                                                              •     Blood-lipid control
                                                              •     Multifactorial metabolic
                                                                    interventions



                                                               1. Schmidt-Erfurth UM et al. Acta Ophthalmol Scand 2007;85:486–494
                                                                                   2. Bhagat N et al. Surv Ophthalmol 2009;54:1–32
                               3. Early Treatment Diabetic Retinopathy Study research group. Arch Ophthalmol 1985;103:1796–1806
                                                                     4. Furlani BA et al. Expert Opin Emerg Drugs 2007;12:591–603
                 Diabetes and vision loss
      Diabetes mellitus (DM) is a prevalent disease. Most
      common complications are microvascular changes1
      Diabetic retinopathy (DR) is a common microvascular
      complication of diabetes2
      Diabetic macula edema (DME) is a common cause of
      blindness in people of working age2,3 and can develop
      in both Type 1 and 2 DM4
      About 8% of diabetic patients develop DME with
      visual impairment5
        1King et al. Diabetes Care 1998; 21: 1414-1431; 2Royal College of Ophthalmology. Diabetic Retinopathy Guidelines 2005.
http://www.rcophth.ac.uk/docs/publications/publishedguidelines/DiabeticRetinopathyGuidelines2005.pdf. Accessed February 2009;
3Watkins. BMJ 2003; 326: 924-926; 4Klein et al. Ophthalmology 1998; 105: 1801-1815; 5Calculated from: Ling et al. Eye 2002; 16:

          140-145; Broadbent et al. Eye 1999; 13: 160-165; Knudsen et al. Br J Ophthalmol 2006; 90: 1404-1409; Hove et al. Acta
                 Ophthalmol Scand 2004; 82: 443-448; Romero-Aroca et al. Arch Soc Esp Oftalmol 2007; 82: 209-218; Zietz et al.
                          Dtsch Med Wochenschr 2000; 125: 783-788; Kristinsson. Acta Ophthalmol Scand Suppl 1997; 223: 1-76
DME: the main cause of central
 vision loss in DR


DME was shown to affect approximately
10% of the diabetic population




                          Klein et al. Ophthalmology 1995; 102: 7-16
             VEGF165 in DR
Retinal VEGF165
levels are elevated in
experimental diabetes
Increased VEGF165
levels are found in the
vitreous of eyes with
proliferative DR
Patients with DR have
higher VEGF165
levels in the aqueous
        Qaum et al. IOVS 2001; 42: 2408-2413; Aiello et al. N Engl J Med 1994; 331: 1480-1487
      Factors affecting DME
Incidence of DME increases with
– elevated levels of HbA1C
– severity of DR
– duration of DM
– elevated diastolic blood pressure
– gender (more frequent in females)
– serum lipid levels



                           Klein et al. Ophthalmology 1998; 105: 1801-1815
                  DME: current treatment
      Systemic treatment
      –   glucose control
      –   blood-pressure control
      –   blood-lipid control
      –   multifactorial metabolic interventions
      Ocular treatment
      – laser photocoagulation (standard treatment for DR /
        DME)
      – vitrectomy
      – pharmacologic therapy
                                        AAO Guidelines. Diabetic Retinopathy. http://www.aao.org/ppp. Accessed February 2009
                                                        Royal College of Ophthalmology. Diabetic Retinopathy Guidelines 2005.
http://www.rcophth.ac.uk/docs/publications/publishedguidelines/DiabeticRetinopathyGuidelines2005.pdf. Accessed February 2009
DME: aims of therapy


  Reduction in vessel hyperpermeability
  and leakage in macular edema




 Treatment of neovascularizatio in PDR
Laser photocoagulation for DME
 Standard treatment – helps to slow fluid leakage
 and reduce the amount of fluid in the retina
 (macula edema)
 Aim of treatment is to stabilize / prevent further
 vision loss
 Limitations of treatment include
 – does not eliminate possibility of further vision loss
 – improvement in visual acuity is uncommon
 – complications including permanent damage to the retinal pigment
   epithelium and secondary choroidal neovascularization
                                                  National Eye Institute, National Institutes of Health. Diabetic Retinopathy.
                                         http://www.nei.nih.gov/health/diabetic/retinopathy.asp#4a Accessed February 2009
                                  AAO Guidelines. Diabetic Retinopathy. http://www.aao.org/ppp. Accessed February 2009
                                                   Royal College of Ophthalmology. Diabetic Retinopathy Guidelines 2005.
http://www.rcophth.ac.uk/docs/publications/publishedguidelines/DiabeticRetinopathyGuidelines2005.pdf. Accessed February
                                                                                                                         2009
                         DR and DME:
                   the unmet treatment needs
Despite the use of standard interventions for DR, vision
loss as a result of the disease still occurs in many
patients1
Good metabolic and blood-pressure control are often
difficult to achieve in clinical practice, and sight-
threatening DR still develops2
Laser treatment is destructive and cannot restore vision
loss that has already occurred; it therefore cannot be
regarded as an ideal treatment, and there is a need for
better-tolerated and less-destructive therapies3

                                  1Comer& Ciulla. Curr Opin Ophthalmol 2004; 15: 508-518
2The DIRECT Programme Study Group. J Renin Angiotensin Aldosterone Syst 2002; 3: 255-261
                                            3Fong. Surv Ophthalmol 2002; 47: S238-S245
  Intravitreal Ranibizumab
           Summary
Intravitreal ranibizumab with prompt or deferred
(≥24 weeks) focal/grid laser had superior VA and
OCT outcomes compared with focal/grid laser
treatment alone.

     ~50% of eyes had substantial improvement
     (≥10 letters) while ~30% gained ≥15 letters
     Substantial visual acuity loss (≥10 letters)
     was uncommon
     Results were similar whether focal/grid laser
     was given starting with the first injection or it
     was deferred >24 weeks

				
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