Ppt diabetic retinopathy

2.  Diabetic retinopathy is the number one cause
of new blindness in most industrialized
countries.
 The vast majority of diabetic individuals who
lose vision do so, not because of an inability
to treat their disease, but rather due to a
delay in seeking medical attention.
 In addition, in many developing countries,
the incidence of diabetes is increasing
dramatically.

3.  Duration of disease
 Poor glycemic control
 Pregnancy
 Hypertension
 Nephropathy
 males>females
 hyperlipidemia
 Anaemia
 Smoking

4.  Reduced corneal sensitivity
 Dry eye
 Corneal abrasions
 NVI
 POAG
 Snow flake cataract
 Diabetic retinopathy
 Diabetic papillopathy
 Diabetic macular oedema
 Optic neuropathy
 Cranial neuropathy-3,4,6 cranial nerves

5.  The best predictor of diabetic retinopathy is the duration
of the disease.
 The first 5years of type 1 diabetes has a very low risk of
retinopathy.
 However, 27% of those who have had diabetes for 5–
10years and 71–90% of those who have had diabetes for
longer than 10years have diabetic retinopathy.
 After 20–30years, the incidence rises to 95%, and about
30–50% of these patients have proliferative diabetic
retinopathy (PDR).

6.  Yanko et al. found that the prevalence of
retinopathy 11–13years after the onset of
type 2 diabetes was 23%; after 16 or more
years, it was 60%; and 11 or more years after
the onset, 3% of the patients had PDR.
 Klein et al. reported that 10years after the
diagnosis of type 2 diabetes, 67% of patients
had retinopathy and 10% had PDR.

7.  The duration of diabetes after the onset of
puberty appears to be most important.
 The risk of retinopathy is roughly the same
for two 25-year-old patients, of whom one
developed diabetes at the age of 6 and the
other at the age of 12years.
 The risk of retinopathy in children diagnosed
prior to the age of 2years have a negligible
risk of retinopathy for the first 10years.

8.  The Diabetes Control and Complications Trial
(DCCT) showed emphatically that patients
with type 1 diabetes who closely monitored
their blood glucose (four measurements per
day = tight control) do far better than
patients treated with conventional therapy
(one measurement per day).

9.  The tight control group had a 76% reduction in the rate of
development of any retinopathy (primary prevention
cohort) and a 54% reduction in progression of established
retinopathy (secondary intervention cohort) as compared
with the conventional treatment group.
 For advanced retinopathy, even the most rigorous control
of blood glucose may not prevent progression. The DCCT
was halted early after 6.5years when the benefit of tight
control was deemed unlikely to be reversed with time

10.  Most of the participants were followed in the
Epidemiology of Diabetes Interventions and
Complications (EDIC) study.
 The EDIC study showed a continued benefit for
the former tight control group compared to the
former conventional treatment group, despite a
normalization of glucose control. This benefit
persisted even after 7years of follow-up.
 The value of intensive treatment has been
demonstrated for type 2 diabetes, as well. The
United Kingdom Prospective Diabetes Study
(UKPDS) revealed a 21% reduction in the 1-year
rate of progression of retinopathy

11.  Renal disease, as evidenced by proteinuria,
elevated blood urea nitrogen levels, and
elevated blood creatinine levels, is an
excellent predictor of the presence of
retinopathy.
 Even patients with microalbuminuria are at
high risk of developing retinopathy.
 The UKPDS demonstrated that tighter blood
pressure control reduced the progression of
diabetic retinopathy significantly.

12.  In women who begin a pregnancy without
retinopathy, the risk of developing
nonproliferative diabetic retinopathy (NPDR) is
about 10%.
 Those with NPDR at the onset of pregnancy and
those who have or who develop systemic
hypertension tend to show progression, with
increased hemorrhages, cotton-wool spots, and
macular edema.
 There is usually some regression after delivery.
 About 4% of pregnant women with NPDR
progress to PDR.

13.  Those with untreated PDR at the onset of
pregnancy frequently do poorly unless they
are treated with panretinal photocoagulation
(PRP).
 Previously treated PDR usually does not
worsen during pregnancy. Women who begin
pregnancy with poorly controlled diabetes
who are suddenly brought under strict
control frequently have severe deterioration
of their retinopathy and do not always
recover after delivery.

14.  Aldose Reductase
 Aldose reductase converts sugars into their
alcohols
 glucose is converted to sorbitol and galactose
is converted to galactitol.
 Because sorbitol and galactitol cannot easily
diffuse out of cells, their intracellular
concentration increases. Osmotic forces then
cause water to diffuse into the cell, resulting
in electrolyte imbalance

15.  Vasoproliferative Factors
 vasoproliferative factors released by the retina itself,
retinal vessels, and the retinal pigment epithelium,
which are thought to induce neovascularization.
 Vascular endothelial growth factor (VEGF), which
inhibits the growth of the retinal endothelial cells in
vitro, has been implicated in diabetic retinopathy.
Evidence suggests that VEGF has a direct role in the
proliferative retinal vascular abnormalities that are
found in diabetes

16.  The resultant damage to lens epithelial cells,
which have a high concentration of aldose
reductase, is responsible for the cataract seen
in children and in experimental animals with
galactosemia and in animals with experimental
diabetes mellitus.
 Because aldose reductase is also found in high
concentration in retinal pericytes and Schwann
cells, some investigators suggest that diabetic
retinopathy and neuropathy may be caused by
aldose reductase-mediated damage.

17. HYPOXIA
Promotes
angiogenesis
Stimulates
endothelial
proliferation
Increases
vascular
permeability
Breakdown
of blood
retinal
barrier

18.  VEGFR-2 is expressed on vascular endothelial cells and is
the receptor that is mostly responsible for angiogenesis.
 Activation of VEGFR-2 in PDR increases endothelial cell
permeability,stimulates cellular migration ,survival and
proliferation and leads to neovascularisation.
 The central role of VEGF in the pathogenesis is supported
by the successful clinical use of anti-VEGF agents for the
treatment of diabetic macular oedema.

19.  Studies have demonstrated that VEGF
expression correlates with the development
and regression of neovascularization.
 The concentration of VEGF in aqueous and
vitreous directly correlates with the severity
of retinopathy.
 Angiogenesis is a complex process; many
other growth factors and cytokines have
been implicated in the development of
diabetic retinopathy.

20.  VEGF mediated activation of Proten Kinase C has been
shown to alter the tight junctions in retinal endothelial
cells,promoting vascular permeability by phosphorylation
of occludin.
 This becomes internalised into endosomes,resulting in
breakdown of blood retinal barrier.
 Thus there is breakdown of the neurovasular unit which is
dependent on the blood-retinal barrier and breakdown of
this barrier results in abnormal retinal function.

21.  Platelets and Blood Viscosity
 Diabetes is associated with abnormalities of
platelet function.
 It has been postulated that platelet
abnormalities or alterations in blood viscosity
in diabetics may contribute to diabetic
retinopathy by causing focal capillary
occlusion and focal areas of ischemia in the
retina which, in turn, contribute to the
development of diabetic retinopathy.

22.  Hemodynamic changes and RAAS System:
 Hypertension –thought to contribute to progression of DR
through:
 1) Mechanical stress
 2)RAAS
 ACE-I and II and angiotensin receptor levels are reported
to increase in the retiina during PDR.
 ACE inhibition has been shown to hamper
neovascularisation in experimental models.

23.  The DR Candesatran trials and RAS study both reported a
reduction in the incidence of retinopathy in type1 diabetes
at baseline,as well as a reduction in the progression of
retinopathy,when ACE inhibitors were utilised.

24.  INFLAMMATION
 In diabetics,there is a subclinical increase in the overall
inflammatory state that leads to development and
progression of diabetic complications.
 In the retinal vasculature,this results in increased
leukostasis and VEGF mediated vascular permeability.
 The extent of this disruption leads to variable capillary
nonperfusion influencing DR progression.

25.  There is a significant increase in the expression
of proinflammatory chemokines,cytokines and
surface adhesion molecules .
 Most notable aspect is the synergy between
endothelial dysfunction and increased surface
adhesion molecules in causing leukocytosis.

26. Adhesion of
leukocytes to
vascular walls
Increased expression
of cytokines and
growth factors
Increased vascular
permeability

27.  REACTIVE OXYGEN SPECIES
 Diabetes is associated with increased production of ROS
through multiple mechanisms including activation of polyol
pathway,formation of AGEs,and increased inflammation.
 The resulting oxidative stress causes damage to cellular
stuctures and may also induce epigenetic changes.
 Oxidaive stress has been considered to be a unifying
mechanism linking the various biochemical pathways
important in development of DR.

28.  EPIGENETICS
 Is the study of changes in gene expression that occur
without changes in DNA sequence.
 Epigenetic control is mediated through the recruitment of
enzymatic complexes that alter the chromatin structure by
covalently modifying the histones.
 Instructing tight glycemic control in previously poorly
controlled diabetic patients does not immediately slow the
progression of DR.
 This is because of metabolic memory-i.e epigenetic
changes lead to persistent gene expression
alterations,even after the institution of good glycemic
control.

29.  No DR – Review in 12 months
 Very mild NPDR-Microaneurysms only-R/W in
12 months

30.  Microaneurysms are the first ophthalmoscopically detectable
change in diabetic retinopathy, seen as small red dots in the middle
retinal layers.
 When the wall of a capillary or microaneurysm is weakened
enough, it may rupture, giving rise to an intraretinal hemorrhage. If
the hemorrhage is deep (i.e., in the inner nuclear layer or outer
plexiform layer), it usually is round or oval (“dot or blot”).

31. FA shows scattered hyperfluorescent spots
in the posterior fundus

32.  Fluorescein angiography helps to distinguish
patent microaneurysms because they leak
dye.
 If the hemorrhage is superficial, in the nerve
fiber layer, it takes a flame or splinter shape
indistinguishable from a hemorrhage seen in
hypertensive retinopathy.
 Diabetics who have normal blood pressure
may have multiple splinter hemorrhages.

33.  Any or all of: microaneurysms, retinal
haemorrhages, exudates, cotton wool spots,
up to the level of moderate NPDR.
 No intraretinal microvascular anomalies
(IRMA) or significant beading.
 Review range 6–12 months, depending on
severity of signs, stability, systemic factors,
and patient’s personal circumstances .

35.  Severe retinal haemorrhages (more than
ETDRS standard photograph 2A: about 20
medium–large per quadrant) in 1–3 quadrants
or mild IRMA •
 Significant venous beading can be present in
no more than 1 quadrant •
 Cotton wool spots commonly present

37.  Venous anomalies seen in ischaemia consist
of generalized dilatation and tortuosity,
looping, beading (focal narrowing and
dilatation) and sausage-like segmentation.
 The extent of the retinal area exhibiting
venous changes correlates well with the
likelihood of developing proliferative
disease.

40.  Review in approximately 6 months
 Proliferative diabetic retinopathy (PDR) in up
to 26%, high-risk PDR in up to 8% within a
year

41. 1 or more of
 Severe haemorrhages in all 4 quadrants
 • Significant venous beading in 2 or more
quadrants
 • Moderate IRMA in 1 or more quadrants

42.  Intraretinal microvascular abnormalities (IRMA) are arteriolar–
venular shunts that run from retinal arterioles to venules, thus
bypassing the capillary bed and are therefore often seen
adjacent to areas of marked capillary hypoperfusion .
 Signs: Fine, irregular, red intraretinal lines that run from
arterioles to venules, without crossing major blood vessels.
 FA shows focal hyperfluorescence associated with adjacent areas
of capillary closure (‘dropout’) but without leakage.

43. Intraretinal microvascular
abnormalities. (A) Histology shows
arteriolar-venular shunt and a few
microaneurysms within a poorly
perfused capillary bed – flat
preparation of Indian ink-injected
retina; phase contrast microscopy;

45.  Review in 4 months
 PDR in up to 50%
 high-risk PDR in up to 15% within a year

46.  Two or more of the criteria for severe NPDR
 Review in 2–3 months High-risk PDR in up to
45% within a year

47.  The ETDRS found that IRMA, multiple retinal
hemorrhages, venous beading and loops,
widespread capillary nonperfusion, and
widespread leakage on fluorescein angiography
were all significant risk factors for the
development of proliferative retinopathy.
 Interestingly, cotton-wool spots were not.

48. MILD TO MODERATE PDR
 New vessels on the disc (NVD) or new vessels
elsewhere (NVE), but extent insufficient to
meet the high-risk criteria
 Treatment considered according to severity
of signs, stability, systemic factors, and
patient’s personal circumstances such as
reliability of attendance for review.
 If not treated, review in up to 2 months

50.  New vessels on the disc (NVD) greater than
ETDRS standard photograph 10A (about 1/3
disc area)
 • Any NVD with vitreous haemorrhage
 • NVE greater than 1/2 disc area with
vitreous haemorrhage
 TREATMENT ADVISED-
 Should be performed immediately when
possible, and certainly same day if
symptomatic presentation with good retinal
view

53.  Although the macular edema, exudates, and capillary
occlusions seen in NPDR often cause legal blindness,
affected patients usually maintain at least ambulatory
vision.
 PDR, on the other hand, may result in severe vitreous
hemorrhage or retinal detachment, with hand-movements
vision or worse.
 Approximately 50% of patients with very severe NPDR
progress to proliferative retinopathy within 1year

54.  Proliferative vessels usually arise from retinal veins and
often begin as a collection of multiple fine vessels.
 When they arise on or within one disc diameter of the
optic nerve they are referred to as NVD
(neovascularization of the disc).

55. FA shows leaking disc vessels, with
extensive peripheral capillary dropout and
a small focus of leaking vessels elsewhere

56.  When they arise further than one disc diameter away, they
are called NVE (neovascularization elsewhere).
 Unlike normal retinal vessels, NVD and NVE leak
fluorescein into the vitreous.

58.  The new vessels usually progress through a stage of further
proliferation, with associated connective tissue formation.
 As PDR progresses, the fibrous component becomes more
prominent, with the fibrotic tissue being either vascular or
avascular.
 The fibrovascular variety usually is found in association
with vessels that extend into the vitreous cavity or with
abnormal new vessels on the surface of the retina or disc.
 The avascular variety usually results from organization or
thickening of the posterior hyaloid face.
 Vitreous traction is transmitted to the retina along these
proliferations and may lead to traction retinal
detachment.

59.  NVE nearly always grows toward and into zones of retinal
ischemia until posterior vitreous detachment occurs. Then, the
vessels are lifted into the vitreous cavity.
 The end stage is characterized by regression of the vascular
systems.
 No further damage may take place, but there may be contraction
of the connective tissue components, development of subhyaloid
bands, thickening of the posterior vitreous face, and the
appearance of retinoschisis, retinal detachment, or formation of
retinal breaks.

60.  Posterior vitreous detachment in diabetics is characterized
by a slow, overall shrinkage of the entire formed vitreous
rather than by the formation of cavities caused by vitreous
destruction.
 Davis et al. have stressed the role of the contracting
vitreous in the production of vitreous hemorrhage, retinal
breaks, and retinal detachment. Neovascular vessels do
not “grow” forward into the vitreous cavity; they are
pulled into it by the contracting vitreous to which they
adhere.

61.  Confirmation of the importance of the vitreous in the
development and progression of proliferative retinopathy
comes from the long-term follow-up of eyes that have
undergone successful vitrectomy.
 The existent neovascularization shrinks, leaks less
fluorescein, and new areas of neovascularization rarely
arise.

62.  A large superficial hemorrhage may separate the internal
limiting membrane from the rest of the retina. Such
hemorrhages usually are round or oval but also may be
boat shaped.
 The blood may remain confined between the internal
limiting membrane and the rest of the retina for weeks or
months before breaking into the vitreous. Sub-internal
limiting membrane hemorrhages were formerly thought to
occur between the internal limiting membrane and the
cortical vitreous and were called subhyaloid or preretinal
hemorrhages.

65.  It is now felt that true subhyaloid hemorrhages probably
are quite rare. Tight sub-internal limiting membrane
hemorrhages are dangerous, because they may progress
rapidly to traction retinal detachment.

66.  As the vitreous contracts, it may pull on the optic disc,
causing traction striae involving the macular area, or
actually drag the macula itself, both of which contribute
to decreased visual acuity.

67.  Two types of diabetic retinal detachments occur, those
that are caused by traction alone (nonrhegmatogenous)
and those caused by retinal break formation
(rhegmatogenous).
 Characteristics of nonrhegmatogenous (traction)
detachment in PDR include the following:
 The detached retina usually is confined to the posterior
fundus and infrequently extends more than two thirds of
the distance to the equator.
 The detached retina has a taut and shiny surface.
 The detached retina is concave toward the pupil.
 No shifting of subretinal fluid occurs

69.  Traction on the retina also may cause focal areas of
retinoschisis, which may be difficult to distinguish from
full-thickness retinal detachment; in retinoschisis the
elevated layer is thinner and more translucent.

70.  When a detachment is rhegmatogenous, the borders of the
elevated retina usually extend to the ora serrata. The
retinal surface is dull and grayish and undulates because of
retinal mobility due to shifting of subretinal fluid.
 Retinal breaks are usually in the posterior pole near areas
of fibrovascular change.
 The breaks are oval in shape and appear to be partly the
result of tangential traction from the proliferative tissue,
as well as being due to vitreous traction

71.  Hemorrhage-Pre-retinal(retrohyaloid),
intragel or both
 Tractional retinal detachment
 Rubeosis Iridis(iris neovascularisation)-
seen in eyes with PDR;If severe may lead to
neovascular glaucoma.
NVI is particularly common in eyes with
severe retinal ischaemia or persistent retinal
detachment following unsuccessful pars
plana vitrectomy

73.  Mild NPDR -Microaneurysms only
 Moderate NPDR-more than just micro
aneurysms
 Severe NPDR-at least one of these 3:
 More than 20 intraretinal hemorrhages in
each of four retinal quadrants
 Venous beading-in 2 or more quadrants
 Prominent IRMAs in one or more quadrants

74.  PDR-Neovasularisation or vitreous
hemorrhage.

76.  Mild to moderate NPDR-Every 6-12 months
 Severe NPDR/PDR-Every 2-4 months
 CSME-every 2-4 months

77.  Hyperglycemia,through several compplex
physiological mechsnisms,is thought to be
the principal cause of the microvasular
damage seen in diabetic retinopathy.
 ADA and EASD suggest that reasonable goals
for
 HbA1C -<7%
 BP-140/80 mmHg

78.  Comprehensive care for the diabetic patient
should include ,at minimum,an annual
dilated eye examination.
 For women with pre-existing diabetes who
become pregnant,the ADA currently suggests
an HbA1C goal of <6%,if it can be achieved
without excessive hypoglycemia.

79.  GLYCATED HEMOGLOBIN:
 ADA recommends measuring HbA1C at least 2 times per
year in patients meeting treatment goals and four times
per year in those whose therapy has recently been
changed/not meeting treatment goals.

80.  DCCT
 MULTICENTER,RCT
 TYPE 1 DIABETES
 Patients-followed for 6.5 years with regular clinical
assessment.
 Conventional therapy:1-2 daily injections of insulin,daily
self monitoring of blood glucose levels and education
about diet and exercise.
 Intensive therapy:administation of insulin 3 or more times
per day with self-monitoring and adjustment of doses.

81.  In primary prevention cohort,intense therapy reduced the
mean risk of developing retinopathy by 76%,when
compared with conventional therapy.
 In the secondary-intervention cohort(mild and moderate
retinopathy)-intensive therapy slowed the progression of
retinopathy by 54% and reduced the development of severe
non proliferative and or proliferative retinopathy by 47%.
 Thus concludes that intensive therapy for patients with
type 1 DM reduces the risk of developing and delays the
onset and progression of diabetic retinopathy when
compared to conventional therapy.

82.  UKPDS-3,867 Newly diagnosed patients with
type 2 diabetes.
 Randomly assigned to intensive or
conventional treatments.
 Over 10 years,HbA1C level was 7% in
intensive treatment group compared with
7.9% in the conventional treatment group.
 The risk for developing microvascular
complications was reduced 25% in the
intensive therapy group compared to the
conventional group.

83.  Diabetes in early pregnancy study was
designed to evaluate the progression of DR
during pregnancy.
 155 Patients from periconceptional period to
1 month postpartum.
 Progression of retinopathy was observed in
10.3% of patients with no retinopathy at
baseline and in 54.8% of patients with
moderate to severe NPDR at baseline.

84.  Elevated HbA1C levels at baseline were
associated with a higher risk of progression
of retinopathy.
 ADA suggests an HbA1C goal of <6% for
women with pre-existing diabetes who
become pregnant.

85.  Patient education is critical, including regarding the need
to comply with review and treatment schedules in order to
optimize visual outcomes.
 •Other risk factors, particularly systemic hypertension
(especially type 2 diabetes) and hyperlipidaemia should be
controlled.
 • Fenofibrate 200 mg daily has been shown to reduce the
progression of diabetic retinopathy in type 2 diabetics and
prescription should be considered
 • Smoking should be discontinued, though this has not
been definitively shown to affect retinopathy.
 • Other modifiable factors such as anaemia and renal
failure should be addressed as necessary.

86.  Scatter laser treatment i.e panretinal photocoagulation
continues to be the mainstay of PDR treatment, with
intravitreal anti-VEGF injection and other modalities
remaining adjunctive.
 The Diabetic Retinopathy Study (DRS) established the
characteristics of high-risk proliferative disease and
demonstrated the benefit of panretinal photocoagulation
(PRP)
 For instance, severe NVD without haemorrhage carries a
26% risk of visual loss at 2 years that is reduced to 9% with
PRP
.

87.  It was found that PRP decreases the production of
vasoproliferative factors by eliminating some of the
hypoxic retina or by stimulating the release of
antiangiogenic factors from the retinal pigment
epithelium.
 An alternative hypothesis suggests that by thinning the
retina, PRP increases oxygenation of the remaining retina
by allowing increased diffusion of oxygen from the
choroid.
 Another hypothesis is that PRP leads to an increase in
vasoinhibitors by directly stimulating the retinal pigment
epithelium to produce inhibitors of vasoproliferation

88.  Informed consent
 Co-existent DMO
 Lens- A contact lens is used to provide a stable magnified
fundus view. A panfundoscopic lens is now generally
preferred to a three-mirror lens, as it is more difficult to
inadvertently photocoagulate the posterior pole through
the former.
 Some practitioners prefer to use a higher-
magnification/smaller area contact lens (e.g. Mainster®,
Area Centralis®) for the more posterior component of
treatment.
 It is essential to constantly bear in mind that an inverted
and laterally reversed image is seen.

89.  Topical anaesthesia is adequate in most
patients, although sub-Tenon or peribulbar
anaesthesia can be administered if necessary

90.  Spot size. A retinal burn diameter of 400 μm is usually
desired for PRP
.
 The diameter selected at the user interface to achieve this
depends on the contact lens used and the operator must
be aware of the correction factor for the particular lens
chosen.
 As an approximation, with panfundoscopic-type lenses the
actual retinal spot diameter is twice that selected on the
laser user interface; 200 μm is typically selected for PRP
,
equating to a 400 μm actual retinal diameter once relative
magnification is factored in.

91.  DURATION depends on the type of laser: 0.05–0.1 s was
conventionally used with the argon laser.
 But newer lasers allow much shorter pulses to be used and
0.01–0.05 s (10–50 ms) is the currently recommended
range.
 Multispot strategies available on some machines utilize a
combination of short pulse duration (e.g. 20 ms), very
short intervals and pre-programmed delivery arrays to
facilitate the application of a large number of pulses in a
short period.

93.  Power should be sufficient to produce only a
light intensity burn.
 Spacing. Burns should be separated by 1–1.5
burn widths.

94.  Extent of treated area. The initial treatment session
should consist of 1500 burns in most cases, though more
may be applied if there is a risk of imminent sight loss
from vitreous haemorrhage.
 The more extensive the treatment at a single session, the
greater the likelihood of complications. Reported figures
vary, but 2500–3500 burns are likely to be required for
regression of mild PDR, 4000 for moderate PDR and 7000
for severe PDR.
 The number of burns offers only approximate guidance, as
the effective extent of treatment is dependent on
numerous variables.

95.  Pattern of treatment: Treatment is generally restricted to
the area outside the temporal macular vascular arcades; it
is good practice to delineate a ‘barrier’ of laser burns
temporal to the macula early in the procedure to help to
reduce the risk of accidental macular damage.
 Many practitioners leave two disc diameters untreated at
the nasal side of the disc, to preserve paracentral field.
 In very severe PDR it is advisable to treat the inferior
fundus first, since any vitreous haemorrhage will gravitate
inferiorly and obscure this area, precluding further
treatment.
 Areas of vitreoretinal traction should be avoided.

96.  Review is dependent on PDR severity and the
requirement for successive treatment
applications; initial treatment should be
fractionated over 2–3 sessions.
 Once an adequate number of burns have been
applied review can be set for 4–6 weeks.

97.  Indicators of regression include blunting of vessel tips,
shrinking and disappearance of NV, often leaving ‘ghost’
vessels or fibrosis, regression of IRMA, decreased venous
changes, absorption of retinal haemorrhages, disc pallor.
 Contraction of regressing vessels or associated induction of
vitreous separation can precipitate vitreous haemorrhage.
 Significant fibrous proliferation can lead to tractional
retinal detachment . Patients should remain under
observation, as recurrence can occur with a requirement
for additional PRP.

98. Severe proliferative disease 3 months later the new vessels
have regressed-there is residual
fibrosis at the disc

99.  Some retinal specialists feel that there is no upper limit to
the total number of burns and that treatment should be
continued until regression occurs.
 The only prospective, controlled study found that eyes
that received supplementary PRP treatment had no
improved outcome over those that received standard PRP
only.
 About two thirds of eyes with High Risk Charateristics that
receive PRP have regression of their HRC by 3months after
treatment.

100.  The ETDRS found that PRP significantly retards the
development of HRC in eyes with very severe NPDR and
macular edema.
 After 7 years of follow-up, 25% of eyes that received PRP
developed HRC as compared with 75% of eyes in which PRP
was deferred until HRC developed.
 Nevertheless, the ETDRS concluded that treatment of
severe NPDR and PDR short of HRC was not indicated for
three reasons.
 First, after 7years of follow-up 25% of eyes assigned to
deferral of PRP had not developed HRC.
 Second, when patients are closely monitored and PRP is
given as soon as HRC develops, severe visual loss can be
prevented.

101.  After 7years of follow-up, 4.0% of eyes that did not receive
PRP until HRC developed had a visual acuity of 5/200 or
less, as compared with 2.5% of eyes assigned to immediate
PRP
. The difference was neither clinically nor statistically
significant.
 Third, PRP has significant complications. It often causes
decreased visual acuity by increasing macular edema or by
causing macular pucker.
 Fortunately, the edema frequently regresses spontaneously
over 6months, but the visual field usually is moderately,
but permanently, decreased. Color vision and dark
adaptation, which often are already impaired, also are
worsened by PRP
.

102.  In summary, the Diabetic Retinopathy Study
and the ETDRS conclusively proved that
timely laser photocoagulation of diabetic
retinopathy can reduce severe visual loss by
95%.
 Such treatment makes sense, not only from
the humanitarian point of view, but also from
a cost-effectiveness view

103.  Intravitreal anti-VEGF injection has an adjunctive role in
the treatment of PDR.
 Indication can include attempted resolution of persistent
vitreous haemorrhage (with prior B-scan ultrasonography
to exclude retinal detachment) with the aim of avoiding
vitrectomy, the initial treatment of rubeosis iridis whilst a
response to PRP is realized, and possibly the rapid control
of very severe PDR to minimize the risk of haemorrhage.

104.  Wide-field fluorescein angiography allows
accurate delineation of peripheral capillary
non-perfusion .
 Selective treatment of these areas with
scatter laser has been reported as effectively
leading to regression of NV whilst minimizing
potential complications.

106.  Vitrectomy plays a vital role in the management of severe
complications of diabetic retinopathy.
 The major indications are nonclearing vitreous
hemorrhage, macular-involving or macular-threatening
traction retinal detachment, and combined traction-
rhegmatogenous retinal detachment.
 Less common indications are macular edema with a
thickened and taut posterior hyaloid, epiretinal
membrane, severe preretinal macular hemorrhage, and
neovascular glaucoma with cloudy media

107.  To evaluate whether early vitrectomy (in the absence of
vitreous hemorrhage) might improve the visual prognosis
by eliminating the possibility of later traction macular
detachment, the Diabetic Retinopathy Vitrectomy Study
(DRVS) randomized 370 eyes with florid neovascularization
and visual acuity of 20/400 or better to either early
vitrectomy or to observation.

108.  After 4years of follow-up, approximately 50% of both
groups had 20/60 or better, and approximately 20% of each
group had light perception or worse.
 Thus, the results indicate that such patients probably do
not benefit from early vitrectomy. They should be
observed closely so that vitrectomy, when indicated, can
be undertaken promptly

109.  Many clinicians feel that in most cases vitrectomy
should be deferred for about 6months or longer if the
retina is attached, to give a chance for spontaneous
clearing to occur.
 Some patients will not need the surgery but, more
importantly, 25% of the patients in the DRVS who
received an immediate vitrectomy had a final visual
acuity of no light perception.

110.  Exceptions to this general rule are patients who have
bilateral visual loss because of vitreous hemorrhage, with
chronically recurring hemorrhage, and known traction
retinal detachment close to the macula.
 If surgery is deferred, ultrasonography and ERG should be
performed at regular intervals to make sure that traction
retinal detachment is not developing behind the
hemorrhage.
 The results of vitrectomy for nonclearing vitreous
hemorrhage using this plan are excellent
 In patients who have recurrent vitreous hemorrhage after
vitrectomy, a simple outpatient air-liquid exchange may
restore vision without the need for a repeat vitrectomy

111.  A possible cause of failure following an otherwise
successful vitrectomy is NVI resulting in neovascular
glaucoma.
 The risk is higher if there is preoperative NVI (33% versus
17%), if there is persistent retinal detachment after
surgery, if the lens is removed during surgery, and if there
is florid NVD and retina.
 In eyes without these factors, the incidence of
neovascular glaucoma is only about 2%.

112.  Another vision-threatening complication is
neovascularization that originates from the anterior retina
and extends along the anterior hyaloid to the posterior
lens surface (anterior hyaloidal fibrovascular
proliferation).
 This is more common in young, phakic diabetics who have
extensive capillary nonperfusion.

113.  Thank you…