DIABETIC RETINOPATHY

It refers to retinal changes seen in patients with
diabetes mellitus. With increase in the life expectancy
of diabetics, the incidence of diabetic retinopathy (DR)
has increased. In Western countries, it is the leading
cause of blindness.
Etiopathogenesis
Risk factors associated with occurence of DR are:
1. Duration of diabetes is the most important
determining factor. Roughly 50 percent of patients
develop DR after 10 years, 70 percent after 20
years and 90 percent after 30 years of onset of
the disease.
2. Sex. Incidence is more in females than males (4:3).
3. Poor metabolic control is less important than
duration, but is nevertheless relevant to the
development and progression of DR.
4. Heredity. It is transmitted as a recessive trait
without sex linkage. The effect of heredity is
more on the proliferative retinopathy.
5. Pregnancy may accelerate the changes of diabetic
retinopathy.
6. Hypertension, when associated, may also
accentuate the changes of diabetic retinopathy.
7. Other risk factors include smoking, obesity and
hyperlipidemia.
Classification
Diabetic retinopathy has been variously classified.
Presently followed classification is as follows:
I. Non-proliferative diabetic retinopathy (NPDR)
Mild NPDR
Moderate NPDR
Severe NPDR
Very severe NPDR
II. Proliferative diabetic retinopathy (PDR)
III. Diabetic maculopathy
IV. Advanced diabetic eye disease (ADED)
I. Non-proliferative diabetic retinopathy (NPDR)
Ophthalmoscopic features of NPDR include:
Microaneurysms in the macular area (the earliest
detectable lesion).
Retinal haemorrhages both deep (dot and blot
haemorrhages) and superficial haemorrhages
(flame-shaped). Hard exudates-yellowish-white waxy-looking
patches are arranged in clumps or in circinate
pattern. These are commonly seen in the macular
area.
Retinal oedema characterized by retinal
thickening.
Cotton-wool spots (if > 8, there is high risk of
developing PDR).
Venous abnormalities, beading, looping and
dilatation.
Intraretinal microvascular abnormalities
(IRMA).
Dark-blot haemorrhages representing haemorrhagic
retinal infarcts.
On the basis of severity of the above findings the
NPDR has been further classified as under:
1. Mild NPDR (Fig. 11.14A).
At least one microaneurysm or intraretinal
hemorrhage.
Hard/soft exudates may or may not be present.
2. Moderate NPDR (Fig. 11.14B)
Moderate microaneurysms/intraretinal hemorrhage.
Early mild IRMA.
Hard/soft exudates may or may not present.
3. Severe NPDR. Any one of the following (4-2-1
Rule) (Fig. 11.14C):
Four quadrants of severe microaneurysms/
intraretinal hemorrhages.
Two quadrants of venous beading.
One quadrant of IRMA changes.
4. Very severe NPDR. Any two of the following
(4-2-1 Rule) (Fig. 11.14D):
Four quadrants of severe microaneurysms/
intraretinal hemorrhages.
Two quadrants of venous beading.
One quadrant of IRMA changes.
II. Proliferative diabetic retinopathy (PDR)
Proliferative diabetic retinopathy (Figs. 11.14 E&F)
develops in more than 50 percent of cases after about
25 years of the onset of disease. Therefore, it is more
common in patients with juvenile onset diabetes. The
hallmark of PDR is the occurrence of
neovascularisation over the changes of very severe
non-proliferative diabetic retinopathy. It is
characterised by proliferation of new vessels from
the capillaries, in the form of neovascularisation at
the optic disc (NVD) and/or elsewhere (NVE) in the
fundus, usually along the course of the major temporal
retinal vessels. These new vessels may proliferate in
the plane of retina or spread into the vitreous as
vascular fronds. Later on condensation of connective
tissue around the new vessels results in formation of
fibrovascular epiretinal membrane. Vitreous
detachment and vitreous haemorrhage may occur in
this stage.
Types. On the basis of high risk characteristics
(HRCs) described by diabetic retinopathy study
(DRS) group, the PDR can be further classified as
below:
1. PDR without HRCs (Early PDR) (Fig. 11.14E), and
2. PDR with HRCs (Advanced PDR). High risk
characteristics (HRC) of PDR are as follows
(Fig. 11.14F):
NVD 1/4 to 1/3 of disc area with or without
vitreous haemorrhage (VH) or pre-retinal
haemorrhage (PRH)
NVD < 1/4 disc area with VH or PRH
NVE > 1/2 disc area with VH or PRH
III. Diabetic maculopathy
Changes in macular region need special mention, due
to their effect on vision. These changes may be associated with non-proliferative diabetic
retinopathy (NPDR) or proliferative diabetic
retinopathy (PDR). The diabetic macular edema occurs
due to increased permeability of the retinal capillaries.
It is termed as clinically significant macular edema
(CSME) if one of the following three criteria are
present on slit-lamp examination with 90D lens:
Thickening of the retina at or within 500 micron
of the centre of the fovea.
Hard exudate at or within 500 micron of the centre
of fovea associated with adjacent retinal
thickening.
Development of a zone of retinal thickening one
disc diameter or larger in size, at least a part of
which is within one disc diameter of the foveal
centre.
Clinico-angiographically diabetic maculopathy can be
classified into four types:
1. Focal exudative maculopathy (Fig. 11.14G). It is
characterised by microaneurysms, haemorrhages,
macular oedema and hard exudates which are usually
arranged in a circinate pattern. Fluorescein
angiography reveals focal leakage with adequate
macular perfusion.
2. Diffuse exudative maculopathy. It is characterised
by diffuse retinal oedema and thickening throughout
the posterior pole, with relatively few hard exudates.
Fluorescein angiography reveals diffuse leakage at
the posterior pole.
3. Ischaemic maculopathy. It occurs due to
microvascular blockage. Clinically it is characterised
by marked visual loss with microaneurysms,
haemorrhages, mild or no macular oedema and a few
hard exudates. Fluorescein angiography shows areas
of non-perfusion which in early cases are in the form
of enlargement of foveal avascular zone (FAZ), later
on areas of capillary dropouts are seen and in
advanced cases precapillary arterioles are blocked.
4. Mixed maculopathy. In it combined features of
ischaemic and exudative maculopathy are present.
IV. Advanced diabetic eye disease
It is the end result of uncontrolled proliferative
diabetic retinopathy. It is marked by complications
such as:
Persistent vitreous haemorrhage,
Tractional retinal detachment and
Neovascular glaucoma.
Investigations
Urine examination,
Blood sugar estimation.
Fundus fluorescein angiography should be carried
out to elucidate areas of neovascularisation,
leakage and capillary nonperfusion.
Management
I. Screening for diabetic retinopathy. To prevent
visual loss occurring from diabetic retinopathy a
periodic follow-up is very important for a timely
intervention. The recommendations for periodic
fundus examination are as follows:
Every year, till there is no diabetic retinopathy or
there is mild NPDR.
Every 6 months, in moderate NPDR.
Every 3 months, in severe NPDR.
Every 2 months, in PDR with no high risk
characteristic.
II. Medical treatment. Besides laser and surgery to
the eyes (as indicated and described below), the
medical treatment also plays an essential role. Medical
treatment for diabetic retinopathy can be discussed
as:
1. Control of systemic risk factors is known to
influence the occurrence, progression and effect
of laser treatment on DR. The systemic risk factors
which need attention are.
Strict metabolic control of blood sugar,
Lipid reduction,
Control of associated anaemia, and
Control of associated hypoproteinemia
2. Role of pharmacological modulation. Pharmacological
inhibition of certain biochemical
pathways involved in the pathogenesis of retinal
changes in diabetes is being evaluated These
include:
Protein kinase C (PKC) inhbitors,
Vascular endothelial growth factors (VEGF)
inhibitors,
Aldose reductase and ACE inhibitors, and
Antioxidants such as vitamin E
3. Role of intravitreal steroids in reducing diabetic
macular oedema is also being stressed recently
by following modes of administration:
Flucinolone acetonide intravitreal implant and
Intravitreal injection of triamcinolone
(2 to 4 mg)
III. Photocoagulation. It remains the mainstay in the
treatment of diabetic retinopathy and maculopathy.
Either argon or diode laser can be used. The protocol
of laser application is different for macula and rest of
the retina as follows (Fig. 11.15):
i. Macular photocoagulation. Macula is treated
by laser only if there is clinically significant
macular oedema (CSME). Laser treatment is
contraindicated in ischaemic diabetic maculopathy.
In patients with PDR associated with CSME,
macular photo-coagulation should be considered
first i.e., before PRP since the latter may worsen
macular oedema. Macular photocoagulation
includes two techniques:
Focal treatment (Fig. 11.15A) with argon laser
is carried out for all lesions (microaneurysms,
IRMA or short capillary segments) 500-3000
microns from the centre of the macula, believed
to be leaking and causing CSME. Spot size of
100-200 μm of 0.1 second duration is used.
Grid treatment. Grid pattern laser burns are
applied in the macular area for diffuse diabetic
macular oedema (Fig. 11.15B).
ii. Panretinal photocoagulation (PRP) or scatter
laser consists of 1200-1600 spots, each 500 μm in
size and 0.1 sec. duration. Laser burns are applied
2-3 disc areas from the centre of the macula
extending peripherally to the equator (Fig. 11.15C).
In PRP temporal quadrant of retina is first
coagulated. PRP produces destruction of
ischaemic retina which is responsible for the
production of vasoformative factors.
Indications for PRP are:
PDR with HRCs,
Neovascularization of iris (NVI),
Severe NPDR associated with:
– Poor compliance for follow up,
– Before cataract surgery/YAG capsulotomy,
– Renal failure,
– One-eyed patient, and
– Pregnancy
IV. Surgical treatment. It is required in advanced
cases of PDR. Pars plana vitrectomy is indicated for
dense persistent vitreous haemorrhage, tractional
retinal detachment, and epiretinal membranes.
Associated retinal detachment also needs surgical
repair.