This document discusses diabetic retinopathy, including its classification, risk factors, and evidence from studies on the importance of glycemic control. It covers different classification systems based on features, fluorescein angiography, and OCT. National screening programs are outlined that use digital retinal photography to detect retinopathy and sight-threatening diabetic retinopathy. Guidelines recommend annual eye exams for those with diabetes to monitor for retinopathy and referrals for proliferative retinopathy or other complications.

2.  Heterogeneous disorder of carbohydrate metabolism with multiple
etiologic factors that ultimately lead to hyperglycemia.
› Type 1 (IDDM)
 Autoimmune disease (loss of pancreatic islet cells)
 Begins < 30 yo (childhood)
› Type 2 (NIDDM)
 Deficiency in the regulation of insulin secretion and or in its action at
the cellular level in the liver and peripheral tissues.
 Late onset (obese patients)
› Secondary types
Hyperglycemia
Aldose reductase-mediated cell damage, vasoproliferative factors produced by hypoxic
retina, growth hormone and platelet, erythrocyte and blood viscosity abnormalities.

3.  Most common cause of blindness of
working-age people.

5.  Retinal neurodegeneration is an early event (prior
to microvascular damage)
› High levels of glutamate
› Overexpression of RAS components (renin / angiotensin)
Progressive apoptosis of retinal ganglionar cells, outer nuclear layer,
photorreceptors, neuroglia of microvasculature

6. Chronic hyperglycemia
AGEs DAG ROS
PKC
Retinal vascular damage
Proliferative DR
VEGF
Ishcaemia / hypoxia
Macular oedema
Increased microvascular permeability Microvascular occlusion
-Alteration of endothelial tight juntions.
-Loss of pericytes.
-Weaking of the capillary walls.
-Increased secretion of VEGF (vascular
endothelial growth factor).
-Breakdown of the inner blood-retinal
barrier.
-Thickening of basement
membrane.
-Damage and proliferation of
endothelial cells.
-Deformation and increased
rouleaux formation of red blood
cells.
-Increased platelet stickiness –
abnormal fibrinolysis.

7. Microaneurisms
First clinical sign of DR.
Individual microaneurysms may
leak resulting in:
dot haemorrhage,
oedema and
exudate.
Spontaneous thrombosis may
lead to resorption of
haemorrhage oedema and
exudate. The thrombosed
microaneurysm usually
disappears from clinical view,
but occasionally remains visible
as a white dot.

8. Increased microvascular permeability
Macular oedema
Hard exudates
Haemorrhages
Dot haemorrhages cannot
always be differentiated
from microaneurysms as
they are similar in
appearance but with
varying size. Hence it is
traditional not to attempt
differentiate them on
clinical examination.
Instead the term dot
haemorrhage/
microaneurysm (H/Ma) is
used.

9. Ischaemia
Shunts / IRMA
Venous beading
Blot hemorrhage
Cotton-wool exudates
Increased VEGF
Neovascularization
Vitreous haemorrhage Fibrovascular proliferation
Neovascular glaucoma
Tractional retinal detachment
deep retinal infarct
swollen ends
of interrupted
axons where
build-up of
axoplasmic
flow occurs at
the edge of
the infarct
foci of venous
endothelial cell
proliferation
that have failed
to develop into
new vessels

10. Two different approaches to classification have emerged:
(a)those designed to cover the full range of retinopathy and aimed at
the ophthalmologist that are based on the original Airlie House /
EDTRS classification and
(b)those which are proposed for use in population screening.

11. R1 Background
microaneurysm(s) / retinal haemorrhage(s) / venous loop
any exudates in the presence of other features of DR
any number of cotton wool spots (CWS) in the presence of
other features of DR

12. R2 Pre-proliferative
venous beading / venous reduplication / multiple blot haemorrhages
intraretinal microvascular abnormality (IRMA)

13. R3 Proliferative
R3a (Active Proliferative Retinopathy)
New vessels on disc (NVD)
New vessels elsewhere (NVE)
New pre-retinal or vitreous haemorrhage
New pre-retinal fibrosis
New tractional retinal detachment
Reactivation in a previous stable R3s eye

14. (If discharged from the Hospital
Eye Service a photograph
should be taken at or shortly
after discharge from the
Hospital Eye service (HES) that
records these features)
R3 Proliferative
R3s (Stable post treatment)
Stable pre-retinal fibrosis + peripheral retinal scatter laser
Stable fibrous proliferation (disc or elsewhere) + peripheral retinal scatter laser
Stable R2 features (from feature based grading) + peripheral retinal scatter laser
R1 features (from feature based grading) + peripheral retinal scatter laser
R3a R3s

15. M Maculopathy
•MO No maculopathy, absence of any M1 features.
*A group of exudates is an
area of exudates that is
greater than or equal to half
the disc area and this area
(of greater than or equal
half the disc area) is all
within the macular area
Any microaneurysm or haemorrhage within 1DD of the centre of the fovea if
associated with a best VA of < 6/12 where the cause of the reduced vision is known and
is not diabetic macular oedema.
•M1
-M1a: Exudates within 1 disc diameter (DD) of the centre of the fovea
-M1b: Group of exudates within the macula*.
-M1c: Any microaneurysm or haemorrhage within 1DD of the centre of the fovea
only if associated with a best VA of < 6/12 (if no stereo)
-Retinal thickening within 1DD of the centre of the fovea (if stereo available).
-CSMO (only if grading in slit lamp biomicroscopy surveillance)
-Retinal thickening at or within 500 microns of the centre of the macula.
-Hard exudates at or within 500 microns of the centre of the macula, if
associated with thickening of the adjacent retina (not residual hard exudates
remaining after disappearance of retinal thickening)hard exudates remaining.
-A zone or zones of retinal thickening one disc area or larger, any part of which
is within one disc diameter of the centre of the macula.

16. M1a M1c
M1b

17. P Photocoagulation
P0 No evidence of previous photocoagulation (default)
P1 focal/grid to macula or peripheral scatter

18. U Ungradable
U An image set that cannot be graded (Digital Screening / Surveillance)
U Retinal status cannot be determined by slit lamp biomicroscopy

19. Rule 4,2,1

20. High-risk PDR was defined as any one of the following:
1. NVD ≥ 1/3 disc area
2. Any NVD with vitreous hemorrhage
3. NVE ≥ ½ disc area with vitreous hemorrhage
High-risk PDR was also defined as three or more of the
following high-risk characteristics (HRC’s):
1. Presence of vitreous hemorrhage or pre-retinal
hemorrhage
2. Presence of any active neovascularization
3. Location of neovascularization on or within one
disc diameter of the optic disc
4. NVD > 1/3 disc area or NVE > ½ disc area

22. Classification based on slit lamp biomicroscopy or retinography
DMO
•Absent
•Present
•Clinically significant mo
•Non clinically significant mo
•Thickening 1 disc area
with different
characteristics.
Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early
Treatment Diabetic Retinopathy Study research group. Arch Ophthalmol. 1985;103(12):1796-806.

23. Classification based on FFA
Depending on the location of leakage or loss of blood supply due to
capillary loss. DMO can be classified as:
•Focal maculopathy: localized leakage (from 1 or more microAn)
• Diffuse/indeterminate maculopathy: generalised thickening of the
central macula caused by widespread leakage from dilated
capillaries.
•Ischaemic maculopathy: enlargement and alteration of the FAZ.
•Mixed maculopathy: combined pathology, particularly of diffuse
oedema and ischaemia
Classification of diabetic retinopathy from fluorescein angiograms. ETDRS report number 11. Early Treatment Diabetic
Retinopathy Study Research Group. Ophthalmology. 1991;98(5):807-22.

24. Classification based on FFA

25. Classification based on OCT
Retinal morphology Tractional components
E1 simple noncystoid macular oedema T0
absence of epiretinal hyper-reflectivity
E2
E2a
cystoid macular oedema
cystoid spaces with
vertical diameter
<400 μm
T1
presence of a continuous line of flat
hyper-reflectivity
and adherent to the retina without
significant retinal distortion
E2b
CMO
cystoid spaces with
vertical diameter
≤600 μm
T2
presence of continuous line of
hyper-reflectivity with
multiple points of adhesion to the
retina and with significant
CMO
large confluent cavities
with retinoschisis
appearance;
E2c retinal distortion
E3 serous macular detachment T3
antero-posterior traction with “gull
wings” configuration
Panozzo G, Parolini B, Gusson E, Mercanti A, Pinackatt S, Bertoldo G, et al. Diabetic macular edema: an OCT-based
classification. Semin Ophthalmol. 2004;19(1-2):13-20

26. Classification based on OCT

36.  Evidence: visual loss could be avoided
› Control of glycaemic levels and risk factors
› Improving screening programs
Epidemiology of Diabetes Interventions and Complications (EDIC): design, implementation, and preliminary results of a
long-term follow-up of the Diabetes Control and Complications Trial cohort. Diabetes Care. 1999;22: 99-111

37. RISK FACTORS
Non-modifiable:
Genetic factors, gender and duration of diabetes
Modifiable:
Glycaemia, blood pressure, lipid levels, anemia, tobacco and
obstructive apnea.
Additional factors:
Carotid arterial disease, pregnancy and renal impairment.

38. Different studies that have provided good evidence on the
importance of glycaemic control on the development of
retinopathy and its progression
Good glycaemic control early in the course of diabetes has an important
impact on long-term outcome of retinopathy. (Level A)

39. The Diabetes Control and Complications Trial (DCCT)1:
After a mean duration of follow-up of 6.5 years DCCT intensive therapy
achieved a reduction in mean HbA1c from 76 mmol/mol (9.1%) to 56
mmol/mol (7.3%) with significant reduction in progression of
retinopathy (3-step increase on the ETDRS scale) by 76% in the primary
prevention group and by 54% in the secondary intervention cohort
(Level 1).
2
1. Diabetes control and complications trial. The relationship of glycemic exposure (HbA1c) to the risk of development
and progression of retinopathy in the diabetes control and complications trial. Diabetes 1995 Aug;44(8):968-83.
2. Aiello LLP, DCCT/EDIC Research Group. Diabetic Retinopathy and Other Ocular Findings in the Diabetes Control and
Complications Trial/ Epidemiology of Diabetes. Interventions and Complications Study. Diabetes Care. 2014;37:17-23.

40. The duration of diabetes,
systolic blood pressure,
diabetic neuropathy,
anemia, and peripheric
atherosclerosis are positively
associated with DR in
Chinese T2DM patients,
while C-peptide is
negatively associated with
DR. Monitoring and
evaluation of these related
factors will likely contribute
to the prevention and
treatment of DR*.
*He BB, Wei L, Gu YJ, Han JF, Li M, Liu YX, et al. Factors associated with diabetic retinopathy in chinese patients with type
2 diabetes mellitus. Int J Endocrinol. 2012;2012:157-940.

41. HBP
Intensify therapy aiming for systolic ≤130mmHg in those with established
retinopathy and/or nephropathy (Level A).
Encourage regular monitoring of blood pressure in a health care setting
and at home if possible.
Recognise that lower pressures may be beneficial overall but evidence is
lacking for retinopathy. (Level B)
Recognise that specific therapies blocking the renin-angiotensin system
(RAS) may have additional benefits, particularly for mild retinopathy, but
should be discontinued during pregnancy. (Level B)
Establish a personalised mean systolic blood pressure target in all patients
who do not have retinopathy, usually < 140mmHg (Level A).

42. DYSLIPIDEMIA
FIELD study1:
Treatment with fenofibrate in individuals with type 2 diabetes mellitus
reduces the need for laser treatment for diabetic retinopathy,
ACCORD Eye study2:
Showed a 40% reduction in the odds of having progression of
retinopathy over four years in patients allocated to fenofibrate (160 mg
formulation/day) in combination with a statin, compared to simvastatin
alone.
1.Keech AC, Mitchell P, Summanen PA, O’Day J, Davis TM, Moffitt MS, et al. Effect of fenofibrate on the need for laser
treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet. 2007;370:1687-97
2.ACCORD Study Group; ACCORD Eye Study Group, Chew EY, Ambrosius WT, Davis MD, Danis RP, Gangaputra S, Greven
CM, et al. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med. 2010;363:233-44

43. The ophthalmologists can take the opportunity to ensure appropriate
care and medical targets are being pursued.
Medical questions for patients with diabetic retinopathy
1. Who helps you to look after your diabetes?
General practitioner , Specialist diabetes nurse in community/GP surgery in hospital or diabetes centre
Diabetes specialist
2. When is your next appointment?
3. What is your long-range diabetes test result?
glycated haemoglobin (HbA1c) or fructosamine when was the
last test done?
3. What is your usual blood pressure? How often it is checked?
measured at home , measured in surgery or clinic
4. Do you know what your blood cholesterol level is?
5. What is your current treatment?
Diabetes , Blood pressure , Cholesterol
6. Does your current treatment include any of the following?
pioglitazone (Actos) aspirin , ramipril or sartan family of drugs warfarin , fenofibrat

44. National screening programmes for diabetic retinopathy based on digital
retinal photography were developed and implemented in England1 ,
Scotland2 , Wales3 and Northern Ireland4 between 2002 and 2007:
- to detect any retinopathy
- to detect the presence of sight threatening diabetic retinopathy(STDR)
- to allow precise quality assurance at all steps
- to minimise false positive referral to the hospital eye service

45. DM type 1
Assess yearly, or more frequently if indicated, by visual acuity and digital
photography after mydriasis with tropicamide.
Childrenand adolescents with type I DM should undergo dilated fundus
photography annually from age of 12.
If sudden loss of vision, rubeosis iridis, pre-retinal or vitreous haemorrhage,
or retinal detachment are detected, refer for emergency review.
If new vessel formation, refer for rapid review.
If pre-proliferative retinopathy, significant maculopathy, or unexplained
change in visual acuity, refer for review.

46. DM type 2
Arrange or perform eye screening at or around the time of diagnosis.
Repeat structured eye surveillance annually, unless findings require other
action.
Perform visual acuity testing as a routine part of eye surveillance
programmes.
Emergency review by ophthalmologist for:
sudden loss of vision, rubeosis iridis, pre-retinal or vitreous haemorrhage,
retinal detachment.
Rapid review by ophthalmologist for new vessel formation.
Refer to ophthalmologist if:
there are features of maculopathy, ithere are features of pre-proliferative
retinopathy any unexplained drop in visual acuity.

47. DM and pregnancy
Pregnant women with pre-existing diabetes should be offered retinal
assessment by digital imaging following their first antenatal clinic
appointment and again at 28 weeks if the first assessment is normal. If
any diabetic retinopathy is present, additional retinal assessment should
be performed at 16–20 weeks.
Women who have pre-proliferative diabetic retinopathy diagnosed
during pregnancy should have ophthalmological follow-up for at least 6
months following the birth of the baby.
Tropicamide alone should be used if mydriasis is required during
pregnancy

48. DM and pregnancy
Moderate NPDR:
Funduscopy every 4-6 weeks.
If progression detected every
2 weeks
If high risk characteristics
develop photocoagulation
should be carried out
promptly and monitored by
funduscopy.
In those with severe sight
threatening retinopathy, laser
photocoagulation should be
performed before pregnancy
or promptly when high risk
characteristics develop

49. Background diabetic retinopathy (R1)
Can be managed in the community screening programme at
appropriate intervals
Pre-proliferative diabetic retinopathy (R2)
Careful monitoring due to increased risk of progression to proliferative
retinopathy. Follow up every 4-6 montsh
Closer follow-ups should be scheduled under the care of
ophthalmologists where interval between visits should be based on
severity of retinal signs, systemic control and patient factors (Level A).
If there is concern about patient compliance and where retinopathy is
progressive, retinal laser photocoagulation may be considered
(Level B):
in older patients with type 2 diabetes24 (Level 1)
where retinal view is difficult
prior to cataract surgery: inflammation possibly associated with progression25
in only eye where first eye lost to PDR
where regular clinic attendance is likely to be poor
difficult to examine patient for other reasons

50. Follow up recommendations (AAO).
Fundus Follow up
Normal Annually or biannually
depending on the risk
factors
Mild NPDR Every 9 months
Moderate NPDR Every 6 months
Severe NPDR Every 4 months
CSMO Every 2-4 months
Non-CSMO Every 6 months
PDR Every 2-3 months
Focal Points: Update in the Management of Diabetic Retinopathy. AAO; 2011

51. When to do a FFA:
•The presence of CSME is the principal justification for FA in DR patients. It may not be
needed to guide treatment if DME is occurring from a well-defined ring of hard
exudates or from focal maculopathy. Nevertheless, FA should be performed
whenever diffuse macular oedema is present, in order best to identify sources of
perimacular leakage and nonperfusion,guiding focal and grid laser treatment
•FA may be warranted in selected cases of severe NPDR to assess severity of retinal
ischaemia, to detect subtle NVE or in assessing patients with PDR before PRP. It may
also be warranted in certain cases to determine adequate regression of DR after laser
treatment.
•Use FA to assess signs of likely macular ischaemia.
•When there is visual loss without known reason.
•Fluorescein angiography (FA) is not appropriate to screen for DR.

52. Proliferative diabetic retinopathy (R3)
Gold Standard: panretinal photocoagulation.
Aim: prevent blindness.
ineffective in some patients (advanced PDR)
2º effects
Wherever possible PRP should be delivered the same day or should be
arranged within 2 weeks of diagnosis of high risk proliferative diabetic
retinopathy
Argon laser PASCAL (PAttern SCAn Laser)
Produces two major peaks of
energy in the 488nm and 514nm
wavelengths.
This green laser energy is absorbed
both by haemoglobin and by
pigment epithelium.
A burn if gently applied causes a
blanching of the outer neural
retina; a more intense laser burn
will produce marked whitening of
the entire retinal thickness, a
pigment ring surrounding the laser
spot develops later.
Frequency doubled YAG laser with
a wavelength of 532 nm
Power settings for Pascal are in
general twice that of argon for
comparable treatments. However,
pulse duration is one fifth that of
conventiaonl argon laser
treatment

53. Proliferative diabetic retinopathy (R3)
The ETDRS recommended an initial treatment consisted of 1,200 to 1,600 burns of moderate
intensity, 500-μm size, one-half to one-spot diameter spacing at 0.1-second duration, divided over
at least two sessions1.(Argon laser)
The use of 1500, 20ms PRP burns in a single session was shown to be a safe regimen in the MAPASS
trial. However, for long-term PDR regression, 72% of eyes required top-up PRP treatment2.
PASCAL: 200 μm size spot at 20 ms duration.
The usual
technique is to
deliver the initial
treatment
posterior to the
ora serrata
outside the
vascular arcade
with emphasis on
ischaemic retina
near NVE but
avoiding direct
NV application.
1.Early Treatment of Diabetic Retinopathy Study Group. Early Photocoagulation Study Group. Techniques for scatter and local
photocoagulation treatment of diabetic retinopathy: the Early Treatment of Diabetic Retinopathy Study report no. 3 Int Ophthalmol
Clin. 1987;27:254-264.
2.Al-Hussainy S, Dodson PM, Gibson JM. Pain response and follow-up of patients undergoing panretinal laser photocoagulation with
reduced exposure times. Eye (Lond) 2008; 22(1): 96–99

54. Proliferative diabetic retinopathy (R3)
Side effects of laser:
•Pain
•The cause of the pain is unclear but may be due to direct thermal damage to
branches of the posterior ciliary nerves. Pain may be prevented with the use of
simple analgesia but on occasion may require periocular anaesthesia, or less
frequently general anaesthesia
•Vitreous haemorrhage
•Rare, but laser therapy can cause marked regression of vessels which separate
from the posterior hyaloid face and produce vitreous and subhyaloid
haemorrhage.
•Reduction in visual field is around 40-50% after full PRP.
•Secondary choroidal neovascularization
•If laser application is applied very close to the macula and is of a high energy
•Inadvertent foveal burn
•Transient macular oedema
•It is advisable to treat the maculopathy either at the same time or prior to
peripheral scatter retinal photocoagulation

55. Advanced Proliferative diabetic retinopathy (R3a)
Vitreous haemorrhage
If laser photocoagulation is not possible, anti-VEGF intravitreal injection and
early vitrectomy for vitreous haemorrhage that persists for more than one month
should be considered (<3m for DMT2 and <6months DM1).
Tractional retinal detachment
Vitrectomy + dissect fibrovascular membranes and thickened hyaloid face
structures or taut ILM.
Iris / angle neovascularization
Prompt treatment with PRP. There have been recent favourable case
reports of the benefits of intravitreal antiVEGF injection in preventing blindness from
progression to neovascular glaucoma (NVG)
NVG with useful vision: co-management with glaucoma specialist.
NVG blind eye, should be kept pain free (cycloablation….)
Early Vitrectomy for severe proliferative diabetic retinopathy in eyes with useful vision. Resultds of a randomised trial.
Diabetic Retinopathy Vitrectomy Research Group. Ophthalmology 1988;95:1307-1320

56. Control of systemic risk factors
Photocoagulation treatment
The modified ETDRS focal/grid was performed as follows:
Focal laser: All leaking microaneurysms 500 to 3000μm from fovea
treated directly with 50μm spot size, duration 0.05-0.1s.
Direct whitenening of the micronaneurysm was not required, but a
greyish reaction beneath the microaneurysm was needed. Grid treatment
was performed to areas of retinal thickening.
Grid laser was performed from 500 to 3000μm superiorly and inferiorly
and to 3500μm temporally. The spots were 2 burn widths apart and no
burns were performed within 500μm of the disc.
Time between treatments: 3-4 months

57. Intravitreal steroid treatment
Preservative free intravitreal triamcinolone (IVT)1,2,3 (Not in UK)
DRCR-net group: IVT monotherapy is inferior to laser treatment at 3-year
follow-up. IVT combined with laser is also inferior to ranibizumab with
immediate or deferred laser, except in patients who are pseudophakic.
A 700μg dexamethasone intravitreal drug delivery system (Ozurdex ®
Allergan) off-label.4
Recent studies. Anatomic improvement > functional benefit.
Non-biodegradable intravitreal insert of Fluocinolone acetonide (Iluvien ®)5
reduced frequency of treatment required. Indicated in chronic DMO
unresponsive to laser / anti-VEGF.
Side effects. Glaucoma (4,8%), Cataract (90%).
1.Diabetic Retinopathy Clinical Research Network. A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema.
Ophthalmology. 2008;115(9):1447-9, 1449.e1-10.
2.Diabetic Retinopathy Clinical Research Network, Beck RW, Edwards AR, Aiello LP, Bressler NM, Ferris F, Glassman AR, et al. Three-year follow-up of a randomized trial comparing
focal/grid photocoagulation and intravitreal triamcinolone for diabetic macular edema. Arch Ophthalmol. 2009;127(3):245-51.
3. Diabetic Retinopathy Clinical Research Network, Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB, Edwards AR, et al. Randomized trial evaluating ranibizumab plus prompt or
deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010;117(6):1064-77.e35.
4.Karydis A, Shao EH, Gemenetzi MK, Taylor SR. Intravitreal bevacizumab vs dexamethasone implant in retinal vein occlusion: a crossover study. ARVO 2014; 3911 – C0213.
5. Campochiaro PA, Brown DM, Pearson A, Chen S, Boyer D, Ruiz-Moreno J, et al; FAME Study Group. Sustained delivery fluocinolone acetonide vitreous inserts provide benefit for at
least 3 years in patients with diabetic macular edema. Ophthalmology. 2012;119(10):2125-32.

58. Intravitreal VEGF inhibitors
Pegaptanib (Macugen®)1
was the first anti VEGF treatment (specific to the 165 isoform of VEGF to
show a favourable effect on DMO.
Bevacizumab (Avastin®) not licensed for intraocular use.2
intravitreal anti-VEGF treatment (with or without laser) achieves
superior visual outcomes compared to laser treatment alone.
There has not yet been any reported data directly comparing the
efficacy of ranibizumab vs bevacizumab in diabetic macular oedema
but studies are on-going.
1.Cunningham ET, Adamis AP, Altaweel M et al. A phase II randomized double-masked trial of pegaptanib, an anti-vascular
endothelial growth factor aptamer, for diabetic macular edema. Ophthalmology 2005; 112(10):1747-1757
2. Solaiman KA, Diab MM, Abo-Elenin M. Intravitreal bevacizumab and/or macular photocoagulation as a primary
treatment for diffuse diabetic macular edema. Retina 2010 Nov-Dec;30(10):1638-45.

59. Intravitreal VEGF inhibitors
Aflibercept (VEGF-Trap-Eye) Eylea®
Eylea treatment is initiated with one injection per month for five
consecutive doses, followed by one injection every two months. There
is no requirement for monitoring between injections.
After the first 12 months of treatment with Eylea, the treatment
interval may be extended based on visual and anatomic outcomes.
Do DV, Nguyen QD, Boyer D, Schmidt-Erfurth U, Brown DM, Vitti R, Berliner AJ, Gao B, Zeitz O, Ruckert R, Schmelter T,
Sandbrink R, Heier JS; DAVINCI Study Group*. One-Year Outcomes of the DA VINCI Study of VEGF Trap-Eye in Eyes with
Diabetic Macular Edema. Ophthalmology 2012; 119: 1658-1665

60. Intravitreal VEGF inhibitors
 Ranibizumab (Lucentis®)
 Anti-VEGF most widely used at the moment.

61. Intravitreal VEGF inhibitors
 Ranibizumab (Lucentis®)
 RESTORE study
The RESTORE study: ranibizumab
monotherapy or combined with
laser versus laser monotherapy
for diabetic macular
edema.Mitchell P, Bandello F,
Schmidt-Erfurth U, Lang
GE,Massin P, Schlingemann RO,
Sutter F, Simader C, Burian
G,Gerstner O, Weichselberger
A; RESTORE study group.
Ophthalmology. 2011
Apr;118(4):615-25

62. Intravitreal VEGF inhibitors
 Ranibizumab (Lucentis®)
 DRCR.net (Diabetic Retinopathy Clinical Research Network)
Prompt laser
gives no
additional
benefit and may
show worse
results in the long
term.
Initial
monotherapy
supplemented
by delayed laser
may be better
approach in
longer term
DRCR Network. Elman MJ, Aiello LP, Beck RW et al. Randomized Trial Evaluating Ranibizumab Plus Promptor Deferred
Laser or Triamcinolone Plus Prompt Laser for Diabetic Macular Edema. Ophthalmology; 117(6): 1064-1077.e1035-1064-
1077.e1035

63. Intravitreal VEGF inhibitors
 Ranibizumab (Lucentis®)
 RETAIN study.
 Efficacy and Safety of Ranibizumab in Two "Treat and Extend" Treatment Algorithms Versus
Ranibizumab As Needed in Patients With Macular Edema and Visual Impairment Secondary to
Diabetes Mellitus (RETAIN)
http://clinicaltrials.gov/show/NCT01171976
Lucentis treat and
extend showing similar
benefits to prn lucentis
with fewer review
appointments.

64. CSMO Centre
involving
Visual acuity Lens OCT Treatment options
Yes No Either Photocoagulation (level A)
Yes Yes Normal, or minimally
reduced by macular
oedema (eg greater
than 78 letters).
Either Photocoagulation or observe if the source of
leakage is very close to fovea and there are no
other treatable lesions suitable or safe to laser
(Level C)
Yes Yes VA in region of 78-24
letters (but eyes with
better vision may under
certain circumstances
warrant treatment if
oedema progressing
and symptomatic)
Phakic ≥250μm
central
subfield
thickness
Intravitreal anti-VEGF treatment (*see
comment below) with or without laser (Level
A). For eyes unresponsive to other treatments,
intravitreal fluocinolone implant may be
considered, but bearing in mind the potential
side-effects (Level A)
Yes Yes VA in region of 78-24
letters
Pseudophakic ≥250μm
central
subfield
thickness
Intravitreal anti-VEGF treatment *, OR
Intravitreal triamcinolone (preservative –free)
with or without adjunctive laser may also be
considered . (Level A) OR intravitreal
fluocinolone implant may be considered if
available, and eye unresponsive to other
treatments (level A)
Yes Yes <24 letters Pseudophakic ≥250μm
central
subfield
thickness
Observation may be appropriate, especially if
longstanding and no response to previous
laser, or if considerable macular ischaemia .
Otherwise may consider anti-VEGF treatment
or intravitreal steroid after careful consultation
and consent. (Level B)
Yes Yes Either Vitreomacular
traction
Consider vitrectomy with/without adjunctive
intravitreal anti-VEGF or steroid treatment
(Level C)
RCOPHT RECOMMENDATIONS

65. NICE guidance
Ranibizumab is recommended as an option for treating visual impairment due to
diabetic macular oedema only if:
the eye has a central retinal thickness of 400 micrometres or more at the
start of treatment and
the manufacturer provides ranibizumab with the discount agreed in the patient
access scheme revised in the context of this appraisal.
People currently receiving ranibizumab for treating visual impairment due to
diabetic macular oedema whose disease does not meet the criteria above
should be able to continue treatment until they and their clinician consider it
appropriate to stop.
Fluocinolone acetonide intravitreal implant is recommended as an option for
treating chronic diabetic macular oedema that is insufficiently responsive to
available therapies only if:
the implant is to be used in an eye with an intraocular (pseudophakic) lens and
the manufacturer provides fluocinolone acetonide intravitreal implant with the
discount agreed in the patient access scheme.
Ranibizumab for treating diabetic macular oedema (rapid review of technology
appraisal guidance 237) (NICE technology appraisal guidance 274).
Fluocinolone acetonide intravitreal implant for treating chronic diabetic macular
oedema after an inadequate response to prior therapy (rapid review of
technology appraisal guidance 271) (NICE technology appraisal guidance 301).

66. DMO
No centre involving Centre involving
Treat according to
ETDRS guidelines
No vision loss Vision loss due to
DMO
Observe and treat
according to ETDRS
guidelines
Ranibizumab