1. Update On The Ocular Complications of Diabetes
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Update On The Ocular Complications of Diabetes
W. Craig Lannin, D.O.
Ophthalmologist with retinal subspecialty practice
Former member of Monty Python
Sorry, not really, I was deliberately wasting your time.
The BBC apologizes for that faulty introduction.

3. Disclosure
Presentation will include discussion of off-label uses of medication, i.e. bevacizumab [Avastin].
Off-label use extremely common in ophthalmology, particularly in retinal practices. Sometimes standard of care!
No financial conflict of interest

4. How does diabetes affect the eye?
Refractive fluctuation
Influence on cataract formation
Diabetic corneal disease [keratopathy]
Increased risk of glaucoma
Cranial nerve ischemic mononeuropathies
Optic neuropathy
Diabetic retinopathy

5. Diabetic Refractive Shifts
Diabetic refractive shifts often accompany episodes of uncontrolled hyperglycemia, or abrupt lowering of serum glucose by initiation or change of medication.
This a frequent early manifestation of diabetes, and may lead to suspicion and diagnosis.
When this happens, it may not be the best time for a patient to update their glasses.

6. Diabetic Refractive Shifts
Mechanism(s) not completely understood.
Shift may be myopic or hyperopic [influence of patient age?, diabetes type?, duration of diabetes?]
Not usually felt to lead to any long-lasting ocular effect, but some authors suggest that if there are repetitive episodes of significant refractive shift, this may contribute to earlier cataract formation.

7. Diabetes and other Ocular Disease
Greater incidence of primary open-angle glaucoma among diabetics
Earlier development of age-related cataracts
Diplopia/EOM paresis associated with diabetic ischemic mononeuropathy
Diabetic AION [diabetic papillopathy variant of anterior ischemic optic neuropathy]
Diabetic autonomic neuropathy [tonic pupil]
Diabetic keratopathy [peripheral neuropathy]

8. Diabetic Ischemic Third Nerve Palsy
Ophthalmoplegia with pupillary sparing.
Location usually subarachnoid or nerve fascicle.
Can be quite painful.
Characteristically resolves within 4-16 weeks without Tx.
Resolution is almost always complete, and aberrant regeneration is extremely rare.

9. Diabetic Ischemic Third Nerve Palsy
Further investigation warranted if:
No pupillary sparing
Ophthalmoplegia is incomplete, even with pupillary sparing
Other associated neurologic signs or symptoms
Headache as opposed to ocular/orbital pain
No resolution after 3 months
Aberrant regeneration develops

10. Diabetic Ischemic Sixth Nerve Palsy
Loss of abduction with/without esotropia [deviation toward nose] in primary position.
Probably the most common cranial nerve palsy in diabetics.
Recovery is usually complete in ischemic cases of CN-VI palsy, within 2-4 months.
Must differentiate CN-VI cause of abduction loss from myopathic [e.g. thyroid] & neuromuscular [e.g. myasthenia]

11. Diabetic Ischemic Sixth Nerve Palsy
Further investigation warranted if:
Other associated neurologic signs or symptoms [e.g. gaze palsy, trigeminal sensory neuropathy, facial paresis, hearing loss, or Horner’s syndrome]
If there is any associated redness, swelling, or proptosis, consider cavernous sinus disease [diabetics also susceptible to mucormycosis].
No recovery after 4 months.
Onset of symptoms was gradual rather than sudden.

12. Diabetic Ischemic Fourth Nerve Palsy
Much less common than third or sixth nerve palsy. More difficult to recognize when it does occur.
Vertical diplopia greatest in downgaze to the opposite side.
Ischemic cases usually recover completely.
Most patients with CN-IV palsy demonstrate torticollis.
Again, if not isolated unlikely to be ischemic.

13. Diabetic Papillopathy
Unilateral or bilateral optic disc edema in diabetic patients, the majority of whom [80%] will have DR.
Originally described in young patients with Type I DM, but is now known to occur in older people with Type II DM. Frequently associated with DME.
Probably represents a mild form of NAION.
Visual loss is usually mild-moderate, unless the macula is also edematous.
VF testing usually shows only BS enlargement.

14. Diabetic Papillopathy
The optic disc may demonstrate typical hyperemic edema, but about 50% of cases will demonstrate marked dilation and telangiectasia of the disc microvasculature, enough in some cases to be mistaken for NVD.
Bilateral cases require neuroimaging and LP to rule out intracranial lesions and/or increased ICP.
Untreated, the disc edema usually resolves over a period of 2-10 months, with minimal residual optic atrophy in ~20% of cases. No proven effective Tx.
Long-term visual prognosis usually dictated by course of the diabetic retinopathy.

15. Case #6: DM Example of diabetic papillopathy:
68 yo man with Type II DM. He described some decrease in vision OS dating back 6 months, but noticed more significant loss over past 2-3 weeks.
History also remarkable for hypertension.
BS control “not very good”.
No constitutional Sx. ESR=2 CRP=1.1
He recalled two brief episodes of visual obscuration with a duration of several minutes, and was also aware of a desaturation of red objects when viewed with his left eye.

16. Case #6: DM Exam findings [8/17/10]: BVA: OD=20/25 OS=20/50
VF: Mild blind spot enlargement OS; minimal contraction.
Pupils: Trace RAPD OS.
Fundus: Disc OD flat with C/D <0.1 Significant disc edema OS, with prominent dilation/telangiectasia of disc microvasculature. No clinical DR OU.
MRI: Old lacunar infarct in left centrum ovale. No intracranial or orbital mass.
Developed mild, segmental optic atrophy OS, but VA remained 20/40 -2 at his most recent exam 2/13/12.

18. Diabetic Keratopathy
Results from decreased corneal sensitivity, and is considered another manifestation of diabetic peripheral neuropathy.
Delayed corneal wound healing, so must be selective re candidacy for contact lens wear.
Predisposed to recurrent corneal erosion and neurotrophic corneal ulcer.
Regular use of ocular lubricants is helpful.

19. Diabetic Retinopathy
By far the most significant ocular manifestation of diabetes, both in terms of morbidity and its cost to our society.
Lost productivity in the prime years of life, as opposed to a disease primarily affecting the elderly.
Great progress has been made in the last 10 years, both in our understanding of the disease and in our ability to treat it.

20. Epidemiology of Diabetic Retinopathy
Incidence/Prevalence
Influence of Type I/II Status
Diabetic Retinopathy and Blindness: Statistics
Economic Impact of Diabetic Retinopathy
Risk Factors

21. Four-year Incidence of DR in Young-onset DM (WESDR)

22. Four-year Incidence of DR in Older-onset DM (using insulin)

23. Four-year Incidence of DR in Older-onset DM (No insulin)

24. Prevalence of any DR and of PDR in Young-onset Diabetics, by Diabetes Duration

25. Prevalence of DR/PDR in Older-onset Diabetics, +/- Insulin, by Diabetes Duration

26. Influence of Type I/II Status
Type I DM
Longer time to onset
Progression more rapid
Higher frequency of PDR
Higher rate of legal blindness
Type II DM
Shorter time to onset
Progression less rapid
Lower frequency of PDR
CSME biggest problem
Lower rate of legal blindness

27. Diabetic Retinopathy Statistics
~ 25% of diabetics and 40% of diabetics over 40 have some form of DR [50% mild, 30% moderate, 20% severe].
Prevalence of DR in Type I is 70%.
Up to 95% of Type I will develop DR at some point in their lifetime.
Of all adults in the U.S. over 40, prevalence of DR is 3.4% [vision-threatening 0.75%].
Vision-threatening DR occurs in 8.2% of diabetics.

28. Diabetic Retinopathy and Blindness
Diabetes is the leading cause of new cases of legal blindness among working-age Americans
Blindness is 25 times more common in persons with diabetes than in the general population
More than 10,000 new cases of diabetic blindness each year in the United States

29. Economic Impact of Diabetes
Cost to society: : ~$132 billion : ~$156 billion : ~$192 billion (Direct medical costs + work loss, disability, and early mortality)
Per Capita Cost: $13,243

30. Economic Impact of Diabetic Retinopathy
Computer model predicted that over their lifetime 72% of Type I patients will eventually develop PDR requiring PRP, and that 42% will develop CSME requiring Tx.
If Tx recommendations of clinical trials are followed, the model predicts a cost of $966 per person-year of vision saved from PDR and $1120 per person-year of central acuity saved from macular edema.

31. Economic Impact of Diabetic Retinopathy
These numbers are significantly less than the cost of a year of Social Security disability payments for those disabled by vision loss (est. annual savings M)
Therefore, Tx yields a substantial savings compared to the direct cost to society of the case of the untreated Type I patient.
The indirect costs, in lost productivity and human suffering, are even greater.

32. Risk Factors/Modulating Influences
Sex
Race
Genetic factors
Age
Duration of diabetes
Puberty
Pregnancy
Hyperglycemia
Obesity
Hypertension
Hyperlipidemia
Proteinuria and Diabetic Nephropathy
Anemia
Cigarette smoking?

33. Sex Race
In the WESDR, higher frequency of PDR in young-onset males compared to females
No significant differences in the prevalence, incidence, or rate of progression to PDR between sexes in older-onset DM
Variable results have been found, but there has been some trend to higher rates of DR in blacks and Hispanics in the USA.
Some American Indian tribes appear to be at increased risk of PDR development.

34. Genetic Factors Age
Inconsistent data, but specific HLA-DR antigens have been shown to influence the risk of DR progression
Glycosylation, elevated Protein Kinase C, aldose reductase activity, & VEGF.
Prevalence & severity of DR increase with increasing age in young-onset persons.
Less DR in those <13 years of age, no matter the duration of DM.
No consistent effect of age on DR prevalence in older-onset DM.

35. Duration of Diabetes
For young-onset persons, both the frequency and severity of retinopathy increase with increasing duration of DM.
In the early years after diagnosis of DM, retinopathy is more frequent in the older-onset compared with the young-onset group.
This trend reverses as time goes on, especially for the frequency of PDR.

36. Puberty Pregnancy
After controlling for other factors, young-onset persons who are postmenarchal are 3.2 times as likely to have DR as those who are premenarchal.
IGF-1, sex hormones, growth hormone, BP, and worse BS control?
Pregnancy is a significant predictor of progression of DR, after controlling for glycosylated Hgb, BP, and other variables.
10-26% risk of NPDR.
4-22% risk of progression to PDR, if have NPDR at outset.

37. Anemia
Anemia is a strong exacerbating influence on diabetic retinopathy.
Effect is greater in men than women. Diabetic men with anemia are twice as likely to develop diabetic retinopathy than those without anemia.
In those with existing DR, anemia significantly increases the risk of progression to both CSDME and PDR.

38. Renal Status Blood Pressure
Data suggest that in those with IDDM, gross proteinuria is a risk indicator for PDR.
Rheological, lipid, and platelet abnormalities associated with nephropathy may be involved in the pathogenesis of DR.
Data only show BP to be a significant marker for DR incidence and progression in young-onset DM.
When those with nephropathy are excluded, BP is not a very strong risk factor.
Worse DR when both nephropathy and Htn.

39. Serum Lipids Smoking
Elevated serum cholesterol is a significant predictor of visual loss in DR.
Patients with elevated total cholesterol and LDL are much more likely to have severe macular HE, which correlates strongly with visual loss.
A specific association of cigarette smoking with incidence or progression of DR has not been established.
Diabetic patients should be advised not to smoke because of the increased risk of MI, PVD, COPD, and cancer.

40. Metabolic Syndrome Significant Obesity Hyperlipidemia Hypertension
Some Type of Glucose Intolerance
Prevalence: 44% of those age 50+ in US
Affected men have 3.7X risk of CAD & 24.5X risk of Diabetes

41. Hyperglycemia
DCCT results demonstrated that intensive insulin Tx was associated with a 76% reduction in the rate of development of any DR, and an 80% reduction in progression of established DR (in IDDM).
However, the increased risk of macrovascular adverse events have led to revision of HgbA1c goal, particularly in older patients and others at high risk.
May be initial worsening of NPDR.
Benefits of rigorous control of BS do not extend to eyes with advanced DR.

42. Hyperglycemia
In the WESDR, the glycosylated Hgb level at baseline was found to be a significant predictor of the 4- and 10-year incidence of DR, progression, progression to PDR, and incidence of macular edema.
Decrease in glycosylated Hgb is associated with significant decrease in progression of DR and the incidence of PDR.
Prior to onset of severe DR, no “point of no return” was demonstrated.

43. Clinical Aspects of Diabetic Retinopathy
Classification of Diabetic Retinopathy
Screening Issues
Ancillary Diagnostic Studies
Treatment Modalities
Complications

44. Classification of Diabetic Retinopathy
Nonproliferative diabetic retinopathy (NPDR)
[Impact on vision primarily based on increased permeability]
Proliferative diabetic retinopathy (PDR)
[Impact on vision primarily based on ischemia]

45. NPDR Microaneurysms Intraretinal (“dot & blot”) hemorrhages
Cotton-wool patches (focal ischemia)
Hard exudates (lipid)
Macular edema
IRMA
Retinal capillary nonperfusion
Venous beading

50. Severe & Very Severe NPDR
ETDRS found that significant IRMA, numerous retinal hemorrhages, venous beading and loops, widespread capillary nonperfusion, and widespread leakage on fluorescein angiography are all significant risk factors for the development of PDR.
Approximately 50% of patients with very severe NPDR progress to PDR with HRC within 1 year.

51. Severe NPDR with IRMA

52. Severe NPDR with venous beading

53. Very Severe NPDR

54. Very Severe NPDR

55. Proliferative Diabetic Retinopathy (PDR)
Neovascularization
a) Disc (NVD); NV on or within 1 DD of the optic disc
b) Elsewhere (NVE); NV further than 1 DD from the optic disc.
c) Iris (NVI or INV); NV on the iris surface, also referred to as rubeosis.
d) Angle (ANV); NV within the filtration angle, visible only with gonioscopy.

60. Screening Issues Timing of Initial Ocular Examination
Influence of Type I/II Status
Importance of Dilated Pupil, Stereopsis, and Experience for Accurate Diagnosis and Classification
Appropriate Follow-up Intervals

61. Eye Examination Schedule

62. DR Examination Protocol*
07/16/96
DR Examination Protocol
Diabetics should be examined by ophthalmologists, who have been demonstrated to be more effective than non-ophthalmologists in detecting the presence and severity of diabetic retinopathy.
In one study, non-ophthalmologists missed all cases of macular edema and most cases of PDR.
Dilated pupil and stereoscopic viewing are necessary components of optimal evaluation *

63. DR Examination Protocol
Detailed examination is indicated in the presence of any of the following:
a) Unexplained visual loss or central vision symptoms;
b) Suspected macular edema, based on the presence of retinal thickening, intraretinal hemorrhage, or lipid/HE;
c) Suspected neovascularization, on the basis of exam findings or Sx of floaters.

64. DR Examination Protocol
“Ophthalmologists with specialized knowledge and experience in the management of diabetic retinopathy are best able to detect and treat serious disease. Patients with significant retinopathy should be referred to such a specialist.”*
* Diabetic Retinopathy Preferred Practice Pattern monograph, American Academy of Ophthalmology

65. Public Education
Unfortunately, many diabetic patients are not managed appropriately:
a) In one study, 46% of eyes with DRS HRC had not received laser PRP.
b) In another study, 11% of Type I and 7% of Type II patients with DRS HRC had not been seen by an ophthalmologist within 2 years.
Role of the PCP in referral is crucial.

66. Ancillary Diagnostic Studies
Traditional modalities:
Color stereo fundus photography
Fluorescein angiography
Ultrasonography/electrodiagnostic studies
Current predominant modality:
Optical coherence tomography [OCT]

67. Optical Coherence Tomography (OCT)
Greatest value in DR is in assessment of treatment effect on diabetic macular edema.
Fluorescein angiography is useful for evaluating the extent of macular ischemia, but has been largely supplanted by OCT in following DME progression and response to anti-VEGF therapy, focal laser or other Tx modality.

68. Cellular Architecture of the Retina

69. Retinal Path Slide Prep

70. Retinal Landmarks in OCT Image

71. Landmarks in Normal OCT

72. Normal OCT with Data

73. OCT in Diabetic Macular Edema

74. OCT in Diabetic Macular Edema

75. OCT in Diabetic Macular Edema

76. Fluorescein Angiography

82. DR Treatment Modalities
Medical therapies
Laser photocoagulation
a) Focal/grid laser for CSDME
b) Panretinal (PRP) laser for PDR with high risk characteristics (HRC)
Anti-VEGF Tx, intravitreal steroids
Pars plana vitrectomy
Combination treatments

83. Clinical Trials Diabetic Retinopathy Study (DRS) - PDR
Early Treatment Diabetic Retinopathy Study (ETDRS) - CSDME
Diabetic Retinopathy Vitrectomy Study (DRVS)
Diabetes Control and Complications Trial (DCCT)
RISE/RIDE/VIVID/VISTA
DRCR.net Protocol T (Recent, important trial)
MEAD/FAME

84. New Era of Biologic Treatments
Age-related Macular Degeneration
Diabetic Retinopathy
Other Retinal Vascular Diseases
Retinitis Pigmentosa & related disorders

85. Why is the Retina so Susceptible to Oxidative Damage?
Natural high O2 tension
Tremendous exposure to light
Higher proportion of polyunsaturated fatty acids in photoreceptor outer segments
Numerous chromophores (lipofuscin, melanin, rhodopsin) in retina & RPE
RPE phagocytosis creates ROIs [reactive oxygen intermediates]

86. Vascular Endothelial Growth Factor (VEGF)
Secreted by RPE
Secreted in response to ischemia
Induced by signaling molecules
Induces Multiple Effects:
Vascular permeability
Endothelial cell permeability
Endothelial cell survival
Inflammatory cell chemotaxis
Homodimeric glycoprotein
- 165 AA

87. Properties of VEGF Stimulates angiogenesis
Potent inducer of vascular permeability
Proinflammatory
Ferrara et al. Endocr Rev
Ishida et al. J Exp Med

88. Milestones in VEGF Research
Michaelson, Ashton, and Wise contribute to “Factor X”’ hypothesis
1971 Folkman publishes tumor angiogenesis factor hypothesis
1983 Dvorak demonstrates tumor secretion of vascular permeability factor
1989 Ferrara clones VEGF and identifies it as an angiogenesis factor (identity with VPF)
1997 First clinical trials of anti-angiogenic therapy in cancer
1999 Aptamer blocking VEGF165 first tested in humans
(Macugen for AMD, Eyetech/Pfizer)
2003 First Anti-VEGF therapy shown to be efficacious in AMD
2004 First FDA approved Anti-VEGF therapy for colorectal cancer

89. The VEGF Family VEGF Family Members Receptors Functions
“VEGF” (VEGF-A)
VEGFR VEGFR-2 Neuropilin-1
Angiogenesis
Vascular maintenance
VEGF-B
VEGFR-1
Not established
VEGF-C
VEGFR VEGFR-3
Lymphangiogenesis
VEGF-D
VEGFR VEGFR-3
VEGF-E (viral factor)
VEGFR-2
PlGF
VEGFR Neuropilin-1
Inflammation

90. VEGF in the Diseased Eye
VEGF is implicated in:
Choroidal neovascularization
Diabetic retinopathy
Retinal vein occlusion
Retinopathy of prematurity
Corneal neovascularization
Iris neovascularization

91. VEGF in Diabetic Retinopathy
Retinal VEGF levels elevated in experimental diabetes
VEGF165 injected in primates induces vascular leakage
Increased VEGF levels found in vitreous of eyes with proliferative DR
DR patients have higher VEGF levels in the aqueous
Quam et al. IOVS. 2001; Tolentino et al. Ophthalmology. 1996; Funatsu et al. AJO. 2002;
Adamis et al. AJO. 1994; Aiello et al. NEJM

92. Intravitreal Injection Delivery

93. The Intravitreal Medication Dilemma
Invasive with risk
Patient acceptance
Often requires prolonged treatment
Cost of drug?
Disruption of practice patterns
The development of slow-release delivery systems is anticipated.

94. Anti-VEGF Options Bevacizumab Ranibizumab
Recombinant humanized monoclonal AB
“Avastin”
Genentech/Roche
Off-label use in ophthalmology
Use validated in CATT trial
Recombinant humanized Fab fragment
“Lucentis”
Genentech/Roche
rhuFab
antibody

95. Off-Label Bevacizumab (Avastin) Ophthalmic Compounding
Licensed pharmacy, follows USP 797 standards
Prepared in laminar hood, with microbiologic assay
Glass or PVC syringe to avoid protein adherence
Refrigerated for 14 days, or frozen for 45 days (USP 797)
Average cost $50-$60/syringe
AVASTIN
LUCENTIS
$5.50
per mg
$3,300

96. Aflibercept
Recombinant fusion protein, consisting of VEGF receptor components fused to FC fragment of human IgG. Known as VEGF Trap-eye.
Stronger VEGF binding affinity
“Eylea”
Regeneron Pharmaceuticals
Most recent anti-VEGF agent approved for use in diabetic macula edema.

97. Eylea Structure

98. VEGF Trap

100. DRCR.net Protocol T
First trial to compare the efficacy of the three commercially available anti-VEGF drugs for the Tx of DME: Avastin, Lucentis and Eylea.
Several conclusions at one year report:
All three groups showed improvement at 1 month, and substantial improvement at one year.
In each group, less than 2% had substantial vision loss.
Response to Eylea was statistically greater relative to Lucentis or Avastin, but this was only clinically relevant in patients with initial VA 20/50 or worse.

101. DRCR.net Protocol T
The worse the DME [as measured by OCT thickness] and VA at outset, the greater the relative advantage of Eylea.
This is felt to reflect the more prolonged VEGF binding with Eylea.
In patients with good VA and milder edema at the outset, it is reasonable to consider Avastin as first line Tx, given its ~ $67 cost per dose vs. $1961 for Eylea.

102. DRCR.net Protocol T
No differences were identified among the three groups in death rates, serious adverse events, hospitalization, or prespecified systemic adverse events.
The recommendation of Avastin to a patient presupposes the availability of a compounding pharmacy that meets safety and reliability standards. This has been tightened after several localized problems in other areas of the country.

103. Eylea in DME: Patient Case
OCT prior to Eylea Induction
OCT after Eylea Induction

106. Role of Anti-VEGF Tx in DR
As supplement to focal laser in DME? [Initial strategy]
As primary treatment for diffuse macular edema, which is more resistant to laser Tx? [Clear advantage]
As supplement or preparatory Tx prior to panretinal photocoagulation (PRP) for proliferative diabetic retinopathy (PDR)? [Emerging algorithm]
As supplement to PRP for iris/angle neovascularization?
As primary Tx for all cases of DME? [Current standard of practice]

107. Anti-VEGF Tx in DR
Anti-VEGF Tx has been found to have a significant and lasting effect in reducing the overall level of severity of diabetic retinopathy in many patients!
In the future, use of microparticles/nanoparticles for drug delivery may permit control of several retinal diseases with relatively few injections.
Combination Tx with drugs that target other contributors to retinal disease, e.g. PDGF.

108. Does Laser Still Have a Place in the Tx of Diabetic Retinopathy?
Yes. At this time, PRP remains the definitive Tx of PDR.
Yes. Selected cases of localized DME are good candidates for focal laser:
Circinate rings, with the leaking microaneurysms not proximal to the fovea, but HE threatening the fovea.
Avoid laser Tx anywhere close to the foveal avascular zone [FAZ].
When combined with anti-VEGF Tx, fewer burns and lower energy are necessary.

109. Steroid Tx of Diabetic Macular Edema
Limited use in my practice:
Lower therapeutic index.
Higher incidence of sustained elevation of intraocular pressure [IOP], often requiring prolonged Tx to avoid glaucomatous damage.
Potential for accelerated cataract formation.
Useful in selected cases of DME resistant to resolution with anti-VEGF Tx alone, often in combination with different anti-VEGF drug.

110. Influence of Cataract Surgery on Diabetic Retinopathy
Cataract surgery often has an adverse effect on the course of diabetic retinopathy.
Up to 50-75% of patients with active NPDR but no preoperative CSME will develop postoperative CSME (especially age > 63)
If macular edema is present preoperatively, it almost always worsens (especially > 63)
Similar adverse influence on the incidence and progression of PDR.

111. Influence of Cataract Surgery on Diabetic Retinopathy
If a patient has both clinically significant cataracts and significant diabetic retinopathy, the diabetic retinopathy should be treated first if at all possible.
All diabetic patients who have undergone cataract surgery demand very close scrutiny over the first 6 months following surgery.
The most dreaded complication following cataract surgery is NVI leading to NVG.

112. Complications of Diabetic Retinopathy
Ischemic maculopathy
Macular subretinal fibrosis
Macular pucker
Cystoid macular edema
Macular tractional retinal detachment
Combined tractional and rhegmatogenous retinal detachment
Vitreous hemorrhage
Severe fibrovascular proliferation
Neovascular glaucoma
Cataract
Phthisis bulbi

113. Ischemic Maculopathy

114. Diabetic Vitreous Hemorrhage

115. Diabetic Fibrovascular Proliferation

116. Diabetic Macular Traction Detachment

120. Summary Scope of the problem
Accomplishments to date and challenges for the future
Importance of public education efforts
Value of a multidisciplinary team approach
Economic benefits of eradicating all preventable diabetic blindness