SECTION 6: DIABETIC RETINOPATHY
BASIC
Microvascular abnormality
Normal blood sugar = 6.8
Beta cell destruction
Important to do fundus exam
TYPES
1
1.
2.
3.
4.
5.
6.
7.
Typically insulin dependent (IDDM) dietary regulation important
Absence of insulin to control glucose
Multi-genetic predisposition
Typically younger
Weight loss
Fruity breath (ketoacidosis smells alcohol)
Hx of cardiovascular disease (heart lipid)
1. Typically non-insulin dependent diabetes (Ranges from predominantly insulin
resistance to predominantly insulin secretory defect)
2. Resistance to insulin action
3. Insulin secretion is reduced
4. Typically obese
5. Genetic predisposition
DIAGNOSIS
1. Fasting Blood Sugar
- Norm = 3.3 to 5.9 mmol/l
- Suspect if > 6.7 (has to be repeat test)
- Likely if > 7.8
- Patient should not eat 8 hours prior test
2. Random blood sugar
- Should not be > 10
- Plasma shouldnt be > 11.1
3. Oral Glucose Tolerance Test
- If FBS is abnormal, OGTT requested
4. HbA1c value
- Glycated (glycosulated) haemoglobin
- Represents average of glucose levels in blood for previous six weeks
- More accurate than FBS (only represents glucose levels for that moment
- Measure of haemoglobin in RBCs can be elevated 3x in diabetes
- If > 11% of normal risk factor for re-proliferative DR
- Increased haemoglobin levels = decreased ability to transport oxygen
5. Other tests Urine analysis
- Look for glucose and ketones from breakdown of fat and muscle (Type 1)
- Ketones in blood = acidosis (low blood pH)
- Urine test alone doesnt diagnose diabetes
6. Symptoms of diabetes
1
Polyuria
Increased urination due to increased filtered level of glucose
in kidney
2
Polydipsia
Increased thirst due to dehydration because of polyuria
3
Polyphagia
Increased eating due to intracellular starvation
Body cant metabolize glucose
Transient blurred vision if its > 12
4
Mononeuropat
Loss of sensory motor or autonomic modalities attributable to
hy
involvement of single and peripheral nerve
Tingly feeling in extremities
Peripheral nerve involvement > pain, weakness and
numbness in limb or trunk
Cranial nerve involvement
- II, III usually, IV rare, VI
- Pupils spared 75-80%
- Better if its a dilated pupil than fixed NIII palsy (down and
out) > usually subdural hematoma
5
Weight loss
6
Fatigue
7
Delayed
wound
healing
7. Non-retinal ocular conditions (common)
When px has diplopia, DDx: Diplopia/ ghosting/ blurred images
1.
2.
3.
4.
5.
6.
7.
Xanthelasma and arcus
Cranial nerve palsies
Rubeosis iridis dilation sluggish (check px before dilating)
Chalazion
Anterior BM dystrophy of cornea/erosions
Tritan
Lenicular involvement:
a. Cortical vacuoles
b. Earlier onset (30-40)
c. Bilateral
d. Related to poor control of blood glucose
EPIDEMIOLOGY
Risk of DR with diagnosis of diabetes before 30y:
- 97% have retinopathy after 15y
- 40% have worsening retinopathy
- Incidence of PDR increases with duration of disease
Risk of DR with diagnosis of diabetes after 30y:
- 78% have retinopathy after 15y
- Incidence of PDR increases with duration of risk
Type 2 have 20% occurrence of DR with time diagnosis
- After 4y, 4% develop PDR with time diagnosis
Blacks > whites
Hispanics > white
Other ethnic groups > whites
Type 2 higher in native Americans
Type 2 with obesity and family Hx
HX AND EXAMINATION WORKUP
1. Type?
2. Duration?
3. Type of control (tablets/injection)
4. Self monitoring of blood glucose?
5. Other medication?
6. Family Hx?
7. Fluctuation of vision?
8. Anterior segment, especially cornea and iris
9. Dilated fundus exam
PATHOGENESIS
1. Capillary wall changes
- Loss of pericytes > loss of structural integrity > leakage, Mas, haemorrhages
- Out pouches can lead to macro aneurysms
- Increased BM thickness
2. Blood flow hemodynamics
- Increased platelet adherence
- Imbalanced coagulation fibrinolytic mechanism
- RBCs more dumb bell shaped
- Creates sludging of flow
3. Ischemia
- Due to wall changes, BM thickening, and intravascular factors (causing sludging
of blood)
- Results in retina ischemia, cotton wool spots, interruption of micro circulation
CLASSIFICATION OF DIABETIC RETINOPATHY
Non-proliferative diabetic retinopathy
1. Mild state NPDR
- At least one microaneurysm
- Occasional dot/blot haemorrhages (< standard photography 2A)
- Hard exudates away from macula
a. Hard waxy deposits of protein lipids within retina
b. Usually deposits at outer plexiform layer
c. Can have circular pattern where middle of circle = origin
2. Moderate NPDR
- Non-proliferative stage
Retinal DO indicate more leakage and non-perfusion (early hypoxia)
- Clinical signs:
Haemorrha
Greater than standard photo 2A in 4 retinal fields
ge &/ MA
CWS
Caused by non-perfusion fibre layer infarcts/soft exudates
Fluffy white patch in retina
Fluorescein angiogram reveals dark areas indicating nonperfusion and hypoxia
Venous
Venules appear sausage-linked in severe cases
beading or
Venous calibre abnormalities may be result of sludging of
tortuosity
blood in vessels + weaknesses in blood vessel walls
Calibre alterations in veins
Veins become narrow AKA cattle trucking
Intra-retinal
Standard photograph 8A
microvascul
Low integrity of venous walls
ar
Vascular abnormalities within sensory layer of retina
abnormaliti
Associated with areas of ischemia of retina
es
IRMA = shunt around ischaemic sensory retina or
abnormalities from existing retinal vessel
Blood vessels that shouldnt be there looks like neo
except theres no fine capillaries
3. Severe NPDR
- CWS, venous beading and IRMA in at least 2 fields (4-7) with at least 1 field
greater than standard photo 2A
- OR IRMA in fields 4-7 that exceeds standard photograph 8A
- Large haemorrhages in fields
- 10-40% of patients progress to proliferation in 1y
- Vascular loop
4. Very severe NPDDR
- No macular oedema
- 2/more conditions for severe non-proliferative DR
- No neo yet
Proliferative diabetic retinopathy
A. Clinical presentations
NVD
Neo classified 1DD from ONH
Presents in 2/3 of px with neo in fundus
Feathery appearance of blood vessels at ONH
NVE
Neo past 1DD from ONH
Presents in 1/3 of patients from neovasc in fundus
NVI
Rubeosis iridis
Neo at iris and angle
Leaky vessels cause Pas
Can lead to glaucoma
First appears at pupillary margin or in filtration angle and
later spreads across iris surface
Gonioscopy necessary to rule out neovasc
Fibro-vasc
Attach usually from ONH to different areas of retina
prolif
Made of naked new vessels, CT and ghost vessels
Can lead to RD from concentration of CT
Superficial
May separate internal limiting membrane from rest of retina
haem
May remain confined between internal limiting membrane
and rest of retina for weeks/months before breaking into
vitreous
Appears as blurry red blood
Choridal NV
Neovascular tufts may be source of haemorrhage
Will have keel or boat appearance to haemorrhage
B. Classification
Early PDR
High risk PDR
Rate of visual
loss
Blindness
No macular oedema
NVD or NVE doesnt meet high risk characteristics of ETDRS
1. Delineated three lesions Puts individual at more distinct risk
of severe visual loss
2. High risk characteristics (immediate referral to specialist for
laser Tx):
- NVD (1/4 1/3 of disc area) OR
- NVE (if fresh vitreous pre-retinal haem is present) OR
- NVD less than of disc area covered if fresh vitreous or
pre-retinal haem is present
3. Requires consult with retinal specialist within 48hrs
Acuity 5/200 or worse on 2/more consecutive 4 month followup visits
Reduced by 61% when treated with pan retinal
photocoagulation
1. Neo tufts
- From hypoxic retina > release vasoformative substance >
NV of ONH, retina and iris
2. Blindness due to
- Vitreous haem
- Neo-vascular glaucoma
- Fibrovascular traction causing RD
MACULAR OEDEMA May occur at any stage of DR
Definition
Clinically significant DR
Thickening of macula due to fluid accumulation from serous
leakage in form of exudates
In severe cases, enough fluid accumulates in outer plexiform
layer and inner nuclear layers that systoid spaces can be seen
clinically
Clinical
1. Best diagnosed with aid of stereopsis from 60/78/90D lens and
presentatio
Goldman contact lens (also Hruby)
ns
2. Elevated (thickened) neurosensory retina best viewed by optic
section of slitlamp beam
3. Blurring of underlying choroidal vascular pattern and RPE >
grainy texture
4. Normal foveolar light reflex is blunted or absent
5. Amsler may show distortion = metamorphopsia
ETDRS
Early treatment diabetic retinopathy study
definition of
MO
1. Thickening of retina at or within 1/3 DDD (500m) of macula
OR
2. Hard exudates at/within 1/3 DD (500m) of macula OR
3. A zone/zones of retinal thickening 1 disc area/larger, any
portion of which is within 1DD of centre of macula
NOTE
Macular oedema occurs in all phases of DR
Photocoagulation treatment most beneficial if VA is 20/60 or
better before Tx
Tx
Steroidal injection (anti-inflam)
OPTICAL COHERENCE TOMOGRAPHY
- Light reflectance is measured using low coherence interferometry
- Light is directed into eye, reflects off retina and interferes with light travelling a
known distance along moving reference arm
- OCT images used to qualitatively assess retinal features and pathologies OR to
objectively make quantitative measurements
- Retinal thickness measurements clinically important > may be used to diagnose
diseases and determine appropriate Tx
FLUORESCEIN ANGIOGRAM ANALYSIS
- NPDR
Dot/blot
Indicated by dark areas on FA due to view of fluorescein
haem
blocked by blood
HypoFl
MA
Areas of hyperFl approximately same time of vessel filling
phase
Helps in DDx of dot and blot
Appears as lighted dots in pattern (like Christmas lights)
Surrounding areas my hyperFl indicating serous leakage
Hard
HypoFl
exudates
Indicates dark areas due to view of Fl blocked by exudates
Possible surrounding areas of hyperFl indicating serous
leakage
MO and leak
HyperFl in late phase
May have flower petal appearance of hyperFl
CWS/NFLIs
Dark areas indicating capillary non-perfusion (no circulation)
IRMA
HyperFl hat appears to leak in late phase
Capillary
May not be seen by ophthalmoscopy
non Dark areas on FA
perfusion
-
PDR NVD and NVE
Areas of hyperFl with indistinct borders indicating leakage of serous fluid in
late phase
FA indicates that NV appears to be detailed lighted net in early phase
TREATMENT/MANAGEMENT OF DR
1. Always aim for strict control
- Patients under tight glucose control:
a. DR reduced
b. Diabetic nephropathy reduced
c. Diabetic neuropathy reduced
2. Mild NPDR
- If no MO follow up 6-12 months
- If clinically significant MO refer for FA and take baseline colour fundus photos
3. Moderate NPDR
- If no MO FU 3-6 months
- If CSME refer for FA
- Consider retinal consult if IRMA or 3 more signs present
4. Severe/very severe NPDR
- Refer for FA for possibility of scatter laser photocoagulation consult within 2-4
weeks
- Colour fundus photos
5. Proliferative
- FU and Tx needed by retinal specialist
- Tx performed by using laser photocoagulation and/or surgery
- Consult within 2 weeks if early PDR; 48 hrs if high risk PDR
LASER PHOTOCOAGULATION
1. For MO
- Focal treatment of MA or other sources of focal leakage thought to be
contributing to MO
- Grid treatment = mild 50-200m burns placed 1DD apart in areas of MO
thought to be related to diffuse leakage or capillary loss
2. For capillary non-perfusion over large areas of retina, possible NVD, NVI
- Scatter treatment of 500m burns of moderate intensity scattered across large
areas of retina
- Retinal ablation, pan retinal photocoagulation, pattern leaking
- Less likelihood for retina to need O2 therefore decreased NV
- Decreased VA in peripheral, but central VA saved px must not drive at night
3. NVE local treatment
4. Mechanism of efficacy of pan photocoagulation
Theories
Mechanism not exactly known but several theories exist
Diseased retinal vessels can deliver limited O2 to retina >
elimination of enough retina to allow retina circulation to supply
remaining retina better
Maximum drainage in outer retinal layers
Elimination by PRP facilitates diffusion of O2 from choriocapillaris
to photoreceptors in adjacent retina
Post laser Induces/exacerbates:
Tx
1. Tritan colour defects,
2. decreased vision,
3. decreased rods and cones,
4. decreased peripheral vision
DDV
VF loss
Poor dark adaptation
Tx failure
Rarely, secondary subretinal NV
5. Pharmacological approach
- Anti-VEG substances
- Intra vitreal injections
