Diabetic Retinopathy: Pathophysiology, Diagnosis, Management and Treatment

1
Diabetic RetinopathyPathophysiology,
Diagnosis, Management and Treatment

• C. A. Ferreira, M.D.
• August 4, 2004
• Diseases of the Eye Conference
• Region VII Rehabilitation Continuing Education
  Program

2
Diabetes

• Defined as a group of metabolic disorders
  characterized by hyperglycemia resulting from
  defects in insulin secretion, insulin action, or
  both
• Diabetes can be associated with serious
  complications and premature death
• Heart disease, Stroke, Hypertension
• Retinopathy
• Nephropathy
• Neuropathy
• Amputations
• Periodontal disease
• Complications of pregnancy
• Diabetic ketoacidosis and Hyperosmolar coma
• Susceptibility to infections

3
Diabetes

• 1.3 million new cases of diabetes is diagnosed
  per year in people 20 yrs
• Diabetes was the 6th leading cause of death
  listed on US death certificates in 2000 (213,062
  deaths)
• Risk for death among people with diabetes is 2
  times that of people without diabetes
• American Diabetes Association National Diabetes
  Fact Sheet, 1999-2001 National Health Interview
  Survey

4
Diabetes

• Prevalence of total diabetes in the US, of all
  ages was 18.2 million, (6.3 of the population)
  in 2002
• Prevalence among people lt 20 yrs was 206,000,
  0.25 of all people in this age group
• Approximately 1 in every 400-500 children and
  adolescents has Type 1 DM
• Type 2 DM is becoming more common among Native
  American/American Indian, African American, and
  Hispanic and Latino children and adolescents
• Prevalence of total diabetes in the US, among
  people 20 yrs was 18 million, 8.7 of all
  people in this age group
• Among people 60 yrs, 8.6 million, 18.3 of all
  people of this age group
• American Diabetes Association National Diabetes
  Fact Sheet, 1999-2001 National Health Interview
  Survey

5
Diabetes

• Prevalence of total diabetes by ethnicity among
  people 20 yrs in the US in 2002
• Non-hispanic whites 12.5 million, 8.4 of this
  group
• Non-hispanic blacks 2.7 million, 11.4 of this
  group
• 1.6 times more likely to develop diabetes than
  non-Hispanic whites of similar ages
• Hispanic/Latino Americans 2 million, 8.2 of
  this group
• 1.5 times more likely to develop diabetes than
  non-Hispanic whites of similar ages
• American Indians and Alaska Natives 107,775,
  14.5. of this group
• 2.2 times more likely to develop diabetes than
  non-Hispanic whites of similar ages
• American Diabetes Association National Diabetes
  Fact Sheet, 1999-2001 National Health Interview
  Survey

6
Diagnosis of Diabetes Mellitus

• The American Diabetes Association Diabetes Expert
  Committee recommends a diagnosis of diabetes when
  one of three criteria is met in non-pregnant
  adults
• Random plasma glucose of 200 mg/dL, plus
  classic signs and symptoms of diabetes, i.e.
  polydipsia, polyuria, unexplained weight loss
• Fasting plasma glucose of 126 mg/dL on at least
  2 occasions
• Fasting plasma glucose of lt 126 mg/dL, but a 75g
  2 hr oral glucose tolerance test plasma glucose
  of 200 mg/dL

7
Diabetes Classification

• Terms insulin-dependent diabetes and
  non-insulin-dependent diabetes and their
  acronyms (IDDM, NIDDM) were eliminated since
  based on pharmacologic rather than etiologic
  considerations
• Diabetes subdivided into major groups
• Type 1 diabetes
• Type 2 diabetes
• Other specific types
• Gestational diabetes mellitus (GDM)

8
Type 1 Diabetes

• Formerly IDDM or juvenile-onset diabetes
• Deficiency of endogenous insulin secretion
  secondary to destruction of the insulin producing
  islet beta cells of the pancreas
• 2 Types
• Immune mediated Type 1 diabetes
• 90 occur by an autoimmune process
  (immune-mediated destruction)
• Characterized by autoantibodies
• Patients prone to other autoimmune disorders i.e.
  Graves disease, Hashimotos thyroiditis, Addison,
  vitiligo, pernicious anemia

9
Type 1 Diabetes (cont.)

• 2 Types (cont.)
• Idiopathic Type 1 diabetes
• 10 of cases
• No autoantibodies present
• No evidence of pancreatic beta cell autoimmunity
• Symptoms of polyuria, polydipsia, rapid weight
  loss, ketonuria
• Prone to ketoacidosis
• Treatment includes Healthy (eucaloric) diet and
  insulin

10
Type 2 Diabetes

• Formerly NIDDM
• Results from insulin resistance, mainly caused by
  visceral obesity, with a defect in compensatory
  insulin secretion
• Accounts for 90 of Americans with diabetes
• Strong genetic predisposition
• Most are older than 40 yrs and obese (80-90)
  when diagnosed
• Frequently undiagnosed for years because
  hyperglycemia develops slowly and symptoms are
  not severe enough to warrant attention

11
Type 2 Diabetes (cont.)

• Increased risk for microvascular and
  macrovascular complications
• Hypertension, dyslipidemia, atherosclerosis
• Symptoms of polyuria, polydipsia
• Ketonuria and weight loss uncommon at diagnosis
• Candidal vaginitis may be initial manifestation
  in women
• Treatment includes
• Non obese Healthy (eucaloric) diet or diet plus
  oral agent or insulin
• Obese Weight reduction or hypocaloric diet,
  plus oral agent or insulin

12
Other Specific Types of Diabetes

• Genetic defects of beta cell function
• Maturity onset diabetes of the young (MODY),
  Mitochondrial DNA mutations
• Genetic defects in insulin action
• Diseases of the exocrine pancreas
• Pancreatitis, Trauma/pancreatopathy, Neoplasia,
  Cystic fibrosis, Hemochromatosis
• Endocrinopathies
• Acromegaly, Cushings, Glucagonoma,
  Pheochromocytoma, Hyperthyroidism,
  Somatostatinoma, Aldosteronoma

13
Other Specific Types of Diabetes (cont.)

• Drug or chemical-induced
• Vacor, Pentamidine, Nicotinic Acid,
  Glucocorticoids, Thyroid hormone, Diazoxide,
  ß-Adrenergic agonists, Thiazides, Dilantin,
  a-Interferon
• Infections
• Congenital rubella, Cytomegalovirus
• Uncommon forms of immune-mediated
• Other genetic syndromes associated with diabetes
• Down, Klinefelter, Turner, Wolfram, Friedreich
  ataxia, Huntington chorea, Laurence-Moon-Biedl,
  Mytonic dystrophy, Porphyria, Prader-Willi

14
Gestational Diabetes Mellitus (GDM)

• Any degree of glucose intolerance with onset or
  first recognition during pregnancy
• Complicates 4 of all pregnancies in the United
  States
• More common among African American,
  Hispanic/Latino Americans, American Indians
• More common among obese women and women with a
  family history of diabetes
• In 30-50, Type 2 diabetes will develop within 10
  yrs of initial diagnosis

15
Manifestations of Diabetes Mellitus

• Acute manifestations Polydipsia, polyuria,
  polyphagia, weight loss, diabetic ketoacidosis
  (Type 1), hyperosmolar coma (Type 2)
• Insulin deficiency or resistance results
• Decreased glucose uptake (hyperglycemia,
  glycosuria, osmotic diuresis, electrolyte
  depletion)
• Increased protein catabolism (increased plasma
  amino acids, nitrogen loss in urine)
• Increased lipolysis (increased plasma FFAs,
  ketogenesis, ketonuria, ketonemia)
• Leads to dehydration, acidosis
• Results in coma, death

16
Manifestations of Diabetes Mellitus (cont.)

• Chronic manifestations Nonenzymatic
  glycosylation
• Small vessel disease (diffuse thickening of
  basement membranes)
• Retinopathy
• Nephropathy (nodular sclerosis, proteinuria,
  chronic renal failure, arteriosclerosis leading
  to HTN)
• Large vessel disease
• Large vessel atherosclerosis
• Coronary artery disease
• Peripheral vascular occlusive disease and
  gangrene
• Cerebrovascular disease
• Neuropathy (motor, sensory, autonomic
  degeneration)
• Cataracts, Glaucoma

17
Diabetic Retinopathy Epidemiology

• Frequent cause of blindness in the United States
• Leading cause of blindness in patients 20-64 yrs
• Prevalence of all types of retinopathy increases
  with duration of diabetes and patient age
• Rare to find DR in children lt 10 yrs, regardless
  of duration
• Risk of developing DR increases after puberty

18
Epidemiology

• Wisconsin Epidemiologic Study of Diabetic
  Retinopathy
• Between 1979-1980
• 1210 patients with Type 1
• 1780 patients with Type 2 predominantly white
  population
• After 20 yrs of diabetes, 99 of Type 1 and 60
  of Type 2 diabetics had some degree for DR
• 3.6 of Type 1 and 1.6 of Type 2 diabetics were
  legally blind
• 86 of Type 1 blindness attributable to DR
• 1/3 of Type 2 blindness attributable to DR

19
Diabetic Retinopathy (DR)

• Advanced Diabetic Retinopathy is associated with
  cardiovascular disease risk factors, i.e.
• Family history of CVD
• Increased age
• Hypertension
• Tobacco use
• Physical inactivity
• Stress
• Dyslipidemia
• Patients with Proliferative Diabetic Retinopathy
  (PDR) are at increased risk of heart attack,
  stroke, diabetic nephropathy, amputation, death

20
Pathogenesis of Diabetic Retinopathy

• Exact cause of diabetic microvascular disease is
  unknown
• Prolonged exposure to hyperglycemia results in
  biochemical and physiologic changes that
  ultimately cause vascular endothelial damage
• Hyperglycemia and hypertension from diabetes can
  affect
• Retina (retinopathy)
• Retinal vasculature (increased incidence of other
  retinal vaso-occlusive phenomenon, i.e. CRVO)
• Vitreous (vitreous hemorrhage, fibrosis)
• Lens (accelerated cataract formation)
• Optic Nerve (chronic and acute vaso-occlusive
  disease can lead to rubeosis and glaucoma
• Cranial Nerves (cranial mononeuropathies)

21

• Retina
• Innermost lining of the eye
• Consists of the sensory retina composed of
  light-sensitive neural elements connecting to
  other neural cells, and the retinal pigment
  epithelium
• Vitreous
• Transparent, colorless mass of soft, gelatinous
  material filling the eye behind the lens
• Lens
• Transparent, biconvex structure suspended in the
  eye between the aqueous and the vitreous
• Functions to bring rays of light to focus on the
  retina and in accommodation
• Optic Nerve
• Nerve that carries visual impulses from the
  retina to the brain

22
Pathogenesis (cont.)

• Normal retinal circulation is unique
• Retinal capillaries are non-fenestrated and
  capillary endothelial cells have tight junctions
  normal retinal capillaries do not leak fluid,
  blood
• No lymphatic system in the retina
• In the presence of retinal pathology, leaking
  fluid can accumulate and cause edema or swelling
• Retina responds to ischemia by stimulating growth
  factors to produce new vessels (called
  neovascularization)

23
Pathogenesis (cont.)

• Specific retinal vascular changes include
• Loss of pericytes (cells that control vessel
  flow)
• Basement membrane thickening, which compromises
  the capillary lumen (affecting the blood supply
  to the eye)
• Decompensation of the endothelial barrier
  function of retinal vessels

24
Pathogenesis (cont.)

• Thus, 2 key changes occur
• Vessel permeability
• Damaged endothelial wall becomes more porous
• Vessel leaks fluid, lipids, erythrocytes
• Accumulation of the fluid results in edema
  (macular edema if located within the central
  region of the retina)
• Vessel closure
• Supply of oxygen and nutrients are decreased
• New fragile growth occurs (secondary to ischemia)

25
Pathogenesis (cont.)

• Diabetic Retinopathy is a progressive disease
  that destroys retinal capillaries by depositing
  abnormal material along the walls of blood
  vessels in the retina
• Causes vessel permeability and closure retinal
  blood vessels
• Resulting vessel leakage of fluid, lipid, and
  blood and in ischemia (decreased oxygen and
  nutrients to retina) and growth in new abnormal
  retinal blood vessels

26
Classification of Diabetic Retinopathy

• Classified into 2 stages
• Nonproliferative Diabetic Retinopathy (NPDR)
• Early stage
• Also known as Background DR (BDR)
• Further categorized based upon extent of DR
• Minimal, Mild, Moderate, Severe, Very severe
• Proliferative Diabetic Retinopathy (PDR)
• More advance stage
• Further described as Early, High-risk, Advanced
• Macular edema
• May be present at any level of DR

27
NPDR

• Typically asymptomatic, but may have decreased or
  fluctuating vision with fluctuation in blood
  sugars
• NPDR can affect visual function through 2
  mechanisms, both which affect the macula
• Variable degrees of intraretinal capillary
  closure resulting in macular ischemia
• Increased retinal vascular permeability resulting
  in macular edema

28
NPDR

• Characterized by
• Microaneurysms
• Dot-blot hemorrhages
• Flame-shaped hemorrhages
• Retinal edema
• Hard exudates
• Venous dilation beading
• Intraretinal microvascular abnormalities (IRMA)
• Nerve fiber layer infarcts (cotton wool spots)
• Arteriolar abnormalities
• Areas of capillary nonperfusion

29
NPDR

• NPDR is diagnosed by dilated fundoscopic
  examination with use of the slit lamp, lenses,
  and binocular indirect ophthalmoscope

30
Minimal NPDR

• At least 1 Microaneurysms (m)
• Microaneurysms only
• Remainder of fundus normal

31
Mild NPDR

• Microaneurysms (m) and Dot hemorrhages (h)
• May also demonstrate macular edema and lipid
  exudate (e)

32
Moderate NPDR

• Cotton wool spots (w), Retinal hemorrhages (h)
  (Dot-blot, Flame), and Microaneurysms (m)
• Hemorrhages, Microaneurysms in at least 1
  quadrant, and cotton wool spots or venous beading
  in 1 quadrant only
• Less than Severe

33
Progression from NPDR to PDR

• Severe NPDR was defined by the Early Treatment of
  Diabetic Retinopathy Study (ETDRS)
• ETDRS devised the 421 rule to predict the
  progression of NPDR to PDR
• 421 rule is characterized by any one of the
  following
• Diffuse intraretinal hemorrhages and
  microaneurysms in 4 quadrants
• Venous beading in 2 quadrants
• Intraretinal microvascular abnormalities (IRMA)
  in 1 quadrant

34
Severe NPDR

• Hemorrhages (h) or Microaneurysms (m) in all 4
  quadrants
• Venous beading (b) in 2 or more quadrants
• IRMA (i) in 1 or more quadrants

35
Progression from NPDR to PDR

• ETDRS found that Severe NPDR had a 15 chance of
  progression to High-risk PDR within 1 yr
• ETDRS also defined Very severe NPDR as the
  presence of any two of the 421 features
• Very severe NPDR had a 45 chance of progression
  to High-risk PDR within 1 yr
• ETDRS indicated that Pre-proliferative diabetic
  retinopathy includes nerve fiber layer infarcts
  (cotton wool spots or soft exudates)

36
Progressive NPDR

• Retinal capillary nonperfusion is a feature
  commonly associated with progressive NPDR
• Fluorescein angiography can show the extent of
  diabetic ischemia and capillary nonperfusion

37
PDR

• More likely to become symptomatic than early NPDR
• May have decreased vision, sudden vision loss,
  floaters, cobwebs, flashes, dull eye ache
• PDR can also affect visual function by affecting
  the macula with resulting macular ischemia and/or
  edema

38
PDR

• Severe, advanced stage of DR in which new
  abnormal blood vessels proliferate on the retinal
  surface
• Neovascularization of the disc (NVD)
• Neovascularization elsewhere (NVE)

39
PDR

• PDR is diagnosed primarily by dilated fundoscopic
  examination, with use of the slit lamp, lenses,
  binocular indirect ophthalmoscope and sometimes
  by fluorescein angiography (FA)
• FA shows leakage at the disc, indicating abnormal
  new blood vessel growth of the disc (NVD)

40
PDR

• Characterized by
• Peripheral new vessels (v), neovascularization
  elsewhere (NVE)
• Disc new vessels, neovascularization of disc
  (NVD) lt 1/3 disc area (Not shown)
• Vitreous or preretinal hemorrhage with NVE lt ½
  disc area (Not shown)
• Retinal hemorrhage (h)

41
PDR
42
PDR

• PDR is present in varying stages
• Initial appearance of new vessels with minimal
  fibrosis
• Increase in size and extent of new vessels with
  increased fibrous component
• Regression of new vessels with residual
  fibrovascular proliferation along vitreous

43
High-risk PDR

• Diabetic Retinopathy Study (DRS) defined
  High-risk PDR as any one of the following
• Mild neovascularization of the disc (NVD) with
  vitreous hemorrhage
• Moderate to severe NVD with or without vitreous
  hemorrhage (showing gt ¼ to 1/3 disc area of NVD)
• Moderate (½ disc area) NVE with vitreous
  hemorrhage
• DRS defined High-risk PDR so as to recommend
  prompt treatment to these patients with the
  highest risk of severe vision loss (treatment
  with panretinal photocoagulation)

44
High-risk PDR

• Large frond of NVD (v)
• Pre-retinal hemorrhage (h)
• Cotton wool spots
• Intraretinal hemorrhage
• Venous beeding

45
Advanced PDR

• Complications may be exacerbated by tractions of
  the vitreous on elevated fibrovascular
  proliferative tissue
• Partial posterior vitreous detachments frequently
  develop in eyes with fibrovascular proliferation
• Resulting in traction on the new vessels and
  vitreous causing preretinal hemorrhage
  (hemorrhage above the retina and/or within the
  vitreous)
• Vitreous hemorrhage may not resolve, especially
  if there is an excessive fibrovascular component

46
Advanced PDR (cont.)

• Additional tractional complications include
  tractional retinal detachment, progressive
  fibrovascular proliferation
• Chronic retinal detachment or chronic retinal
  ischemia in eyes with PDR can increase the risk
  for development of iris neovascularization (NVI,
  rubeosis) and neovascular glaucoma (NVG)

47
Advanced PDR

• Fibrovascular proliferative (f) from old NVE and
  old NVD
• Preretinal and intraretinal hemorrhages

48
Advanced PDR

• Vitreous hemorrhage from NVE or NVD

49
Advanced PDR

• Tractional retinal detachment resulting from
  contraction of the fibrovascular proliferative
  tissue on the retina

50
NPDR and PDR
51
Diabetic Macular Edema (DME)

• Retinal edema threatening or involving the macula
  is an important visual consequence of abnormal
  retinal vascular permeability in DR
• Diagnosis is made by slit-lamp biomicroscopy of
  the retina using a contact lens
• Important observations include
• Location of retinal thickening relative to the
  fovea
• Presence and location of exudates
• Presence of cystoid macular edema
• Fluorescein angiography is useful in
  demonstrating the breakdown of the blood-retinal
  barrier by delineating retinal capillary leakage
  and capillary nonperfusion

52
Diabetic Macular Edema (DME)

• DME may manifest as focal or diffuse thickening
  with or without exudates
• 2 general categories of DME described
• Focal macular edema
• Characterized by areas of focal fluorescein
  leakage from specific capillary lesions
• May be associated with white to yellow lipid
  deposits, called hard exudates
• Diffuse macular edema
• Characterized by widespread retinal capillary
  abnormalities with diffuse leakage from extensive
  breakdown of blood-retinal barrier
• Often associated with cystoid macular edema

53
DME and CSME

• Early Treatment Diabetic Retinopathy Study
  (ETDRS) also defined clinically significant
  macular edema (CSME) as any one of the following
• Retinal edema located at or within 500 µm of the
  center of the macula
• Hard exudates at or within 500 µm of the center
  if associated with thickening of adjacent retina
• Zone of thickening larger than 1 disc area if
  located within 1 disc diameter of the center of
  the macula
• ETDRS demonstrated that eyes with CSME benefited
  from treatment with focal Argon laser

54
CSME

• CSME diagnosed primarily at the slit lamp (to
  assess retinal thickening)
• Hard exudates located within the center of the
  macula likely

55
Effect of Systemic Conditions on Diabetic
Retinopathy

• Elevated serum lipids are associated with
  presence and severity of retinal hard exudates in
  NPDR and DME
• Hypertension is usually associated with a higher
  risk of progression of DME and DR
• Asymmetric carotid artery occlusive disease
  worsens ocular ischemia and DR on the affected
  side
• Severe carotid artery occlusive disease may
  result in advanced PDR
• Advanced diabetic nephropathy and anemia may also
  have adverse influences on DR

56
Effect of Systemic Conditions on Diabetic
Retinopathy (cont.)

• Pregnancy is associated with worsening of DR
• Pregnant women require more frequent retinal
  evaluation
• All patients will have some regression of DR
  after delivery
• Although teratogenic effects of fluorescein have
  not been identified, FA is avoided in pregnant
  and breastfeeding women unless absolutely
  necessary
• Fluorescein crosses the placenta and will be
  transmitted to breast milk
• Photocoagulation treatment is generally recommend
  if High-risk PDR develops during pregnancy

57
Management of Diabetes

• Requires ongoing medical care with a general
  practitioner or endocrinologist, and
  ophthalmologist or optometrist
• Annual evaluation of proteinuria, microalbinuria
• Eye exam (as indicated by eye doctor)
• Routine HbA1C
• Prevention of acute-illness and complications
• Patient and family education
• Wear necklace or bracelet
• Daily self-exam of feet
• Self blood glucose and blood pressure monitoring
• Increase physical activity
• Encourage patients to take an active role in
  their health care (empowerment)

58
Management of Diabetes

• Follow healthy diet that has been evaluated by
  physician and/or nutritionist/dietician
• Eucaloric if nonobese
• Hypocaloric if obese
• Control of plasma glucose via diet and/or oral
  hypoglycemics and/or insulin
• Control of blood pressure and plasma lipid
• Tobacco cessation
• ACE inhibition
• Protective effect on kidneys
• Baby ASA if not otherwise contraindicated

59
Diabetic Control and Diabetic Retinopathy

• Diabetes Control and Complications Trial (DCCT)
• Evaluated effect of intensive blood glucose
  control on subsequent progression of DR in Type 1
  diabetics without DR and with Mild-Moderate NPDR
• Study Groups Intensive control of blood sugar
  (multiple daily insulin injections or insulin
  pump) vs. Conventional management
• Results Intensive control reduced the risk of
  developing DR by 76 and slowed progression of DR
  by 54
• In patients with Mild-Moderate NPDR, DR worsened
  with intensive control during the first year
• Intensive control also reduced risk of clinical
  neuropathy by 60 and albuminuria by 54

60
Diabetic Control and Diabetic Retinopathy

• United Kingdom Prospective Diabetes Study (UKPDS)
  
• From 1977 to 1991
• Evaluated effect of intensive blood glucose and
  blood pressure control on subsequent progression
  of DR in Type 2 diabetics
• Study Groups
• Intensive control of blood sugar (oral agent or
  insulin) vs. Conventional management (diet)
• Tight control of blood pressure (ACE inhibitor
  and/or Beta-blocker) or less tight control
• Results Intensive control of blood glucose and
  blood pressure slowed progression of DR and
  reduced risk of other microvascular (and
  macrovascular with tight BP control)
  complications

61
Management of Diabetic Retinopathy

• Diabetic Screening
• Type 1 diabetics Dilated funduscopic exam (DFE)
  5 yrs after diagnosis
• Newly diagnosed patients with Type 1 diabetes
  rarely have retinopathy during the first 5 yrs
• Type 2 diabetics DFE at the time of diagnosis
• DR typically seen within 10 yrs of onset
• Type 2 diabetics typically diagnosed yrs after
  initial onset
• Significant portion of newly diagnosed Type 2
  diabetics have established DR at the time of
  diagnosis

62
Management of Diabetic Retinopathy

• Diabetic Follow-up
• Pregnant women DFE is recommended in the 1st
  trimester and thereafter at the discretion of the
  ophthalmologist
• Pregnant women are at high risk of progression of
  DR during pregnancy
• Depending upon the severity of DR and the threat
  to visual function from progression, suggested
  follow-up for patients with NPDR, PDR, and DME
  may differ

63
Follow-Up Based Upon Retinopathy Findings
64
Treatment of Diabetic Retinopathy

• Based on findings of the Diabetic Retinopathy
  Study (DRS), Early Treatment Diabetic
  Retinopathy Study (ETDRS), and other studies,
  laser photocoagulation is generally recommended
  for eyes with
• Clinically significant macular edema (CSME)
• ETDRS found focal Argon laser photocoagulation
  decreased risk of moderate visual loss and
  reduced retinal thickening
• High-risk Proliferative DR (PDR)
• DRS found Argon or Xenon laser panretinal
  photocoagulation (scatter PRP) reduced risk of
  severe vision loss compared to no treatment
• Treated eyes with High-risk PDR achieved the
  greatest benefit

65
Treatment of Diabetic Retinopathy

• ETDRS reported that provided follow-up can be
  maintained, scatter PRP was not recommended for
  patients with Mild or Moderate NPDR
• Scatter PRP can be considered when NPDR becomes
  Severe or Preproliferative NPDR and should not be
  delayed when reaches High-risk PDR
• Scatter treatment for eyes with Severe NPDR or
  Early PDR is effective in reducing severe vision
  loss in Type 2 diabetics

66
Focal Photocoagulation for CSME

• Fluorescein angiography and Fundus photos are
  obtained prior to initiation of laser therapy
• Ophthalmologist views the FA to guide treatment
  of CSME
• For focal leakage, direct laser therapy using
  green-only Argon laser is applied to all leaking
  microaneurysms between 500 and 3000 µm from the
  center of the macula
• For diffuse leakage or zones of capillary
  nonperfusion adjacent to the macula, a
  light-intensity grid pattern using green-only
  Argon laser is applied to all areas of diffuse
  leakage more than 500 µm from the center of the
  macula and 500 µm from the temporal margin of
  the optic disc
• Multiple sessions spread out over many months are
  frequently necessary for resolution of DME

67
Focal Photocoagulation for CSME

• Side Effects and Complications of Focal Laser
• Paracentral scotomata
• Transient increased edema/decreased vision
• Choroidal neovascularization (new abnormal blood
  vessel growth beneath the retina)
• Subretinal fibrosis
• Photocoagulation scar expansion
• Inadvertent foveolar burns

68
Panretinal Photocoagulation for High-risk PDR

• Scatter PRP almost always recommended for
  High-risk PDR
• Should be avoided in areas of prominent
  fibrovascular membranes, vitreoretinal traction,
  and tractional retinal detachment

69
Panretinal Photocoagulation for High-risk PDR

• Goal is to cause regression of existing
  neovascular tissue and to prevent progressive NV
  in the future
• Amount of therapy necessary to achieve these
  endpoints is determined by clinical response to
  treatment
• Full PRP includes 1200 or more 500 µm burns
• Treatment may be devided into 2 or more sessions

70
High-risk PDR Pre- and Post-PRP
71
PRP for High-risk PDR

• Side Effects and Complications of Scatter PRP
• Decrease in night vision, color vision, and/or
  peripheral vision as well as a loss of 1 or 2
  lines in visual acuity in some
• Glare
• Temporary loss of accommodation
• Photopsia (flashes)
• Worsening of macular edema, if present prior to
  treatment

72
Cataract Surgery in Diabetics

• Various studies suggest that DR may progress
  following cataract surgery
• Patients who undergo cataract surgery with CSME,
  Severe NPDR, or PDR should be considered for
  photocoagulation prior to cataract removal
• If density of cataract precludes adequate
  evaluation of the retina or precludes treatment,
  prompt post-operative retinal evaluation and
  treatment can be considered

73
Neovascularization of the Iris (NVI)

• Neovascularization in PDR may manifest as NVD,
  NVE, or NVI (neovascularization of the iris,
  rubeosis)
• NVI involving the anterior chamber angle (NVA)
  may lead to increased intraocular pressure,
  neovascular glaucoma (NVG) and resulting optic
  nerve damage
• Patients with extensive neovascularization of the
  iris or involving the anterior chamber angle
  require panretinal photocoagulation whether or
  not High-risk PDR is present
• To cause regression of existing neovascular
  tissue and to prevent progressive
  neovascularization in the future

74
Surgical Treatment of PDR

• Surgical Vitrectomy (removal of the vitreous gel)
  is indicated in the following diabetic patients
• Dense, nonclearing vitreous hemorrhage
• Tractional retinal detachment involving the
  macula
• Combined tractional and rhegmatogenous retinal
  detachment
• Presence of dense, nonclearing vitreous
  hemorrhage requires echography (use of
  B-scan/Ultrasound) to evaluate the presence or
  absence of retinal detachment
• If retinal detachment present, early vitrectomy
  suggested
• Patients with bilateral severe vitreous
  hemorrhage should undergo vitrectomy in one eye

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Prevention of Diabetic Retinopathy

• Prevention of diabetic retinopathy requires
  prevention of diabetes
• Patients at higher risk (i.e. family history,
  ethnicity) of developing diabetes can adjust
  modifiable risk factors
• Healthy diet
• Exercise
• Blood pressure control
• Tobacco cession
• Weight reduction (if obese)

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Prevention of Diabetic Retinopathy

• Tight blood sugar and blood pressure control
• Tight control slows the progression of diabetic
  retinopathy
• Annual dilated fundoscopic examinations (DFE) by
  an ophthalmologist and/or optometrist
• To evaluate for retinopathy, cataracts, and
  glaucoma
• More frequent follow-up with an ophthalmologist
  depending upon extent of retinopathy
• Pregnant women with DR or GDM should have a DFE
  during the first 3 months
• More frequently depending upon diagnosis of
  retinopathy
• Tobacco cessation