Diabetic retinopathy

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.

Most common cause of blindness of

working-age people.

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

Chronic hyperglycemia

AGEs DAG ROS

PKC

Retinal vascular damage

Increased microvascular permeability Microvascular occlusion

Ishcaemia / hypoxia

VEGF

Proliferative DR

Macular oedema

-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.

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.

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.

Ischaemia

Shunts / IRMA

Venous beading

Cotton-wool exudates

Increased VEGF

Neovascularization

Fibrovascular proliferation

Tractional retinal detachment

Vitreous haemorrhage Neovascular glaucoma

Blot hemorrhage

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

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.

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

R2 Pre-proliferative

venous beading / venous reduplication / multiple blot haemorrhages

intraretinal microvascular abnormality (IRMA)

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

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

(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)

R3a R3s

M Maculopathy

•MO No maculopathy, absence of any M1 features.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.

*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

M1a M1c

M1b

P Photocoagulation

P0 No evidence of previous photocoagulation (default)

P1 focal/grid to macula or peripheral scatter

U Ungradable

U An image set that cannot be graded (Digital Screening / Surveillance)

U Retinal status cannot be determined by slit lamp biomicroscopy

Rule 4,2,1

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

Classification based on slit lamp biomicroscopy or retinography

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.

DMO

•Absent

•Present

•Clinically significant mo

•Non clinically significant mo

•Thickening 1 disc area

with different

characteristics.

Classification based on FFA

Classification of diabetic retinopathy from fluorescein angiograms. ETDRS report number 11. Early Treatment Diabetic

Retinopathy Study Research Group. Ophthalmology. 1991;98(5):807-22.

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 based on FFA

Classification based on OCT

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

Retinal morphology Tractional components

E1 simple noncystoid macular oedema T0absence of epiretinal hyper-reflectivity

E2

E2a

cystoid macular oedemacystoid spaces with vertical diameter <400 μm

T1

presence of a continuous line of flat hyper-reflectivityand adherent to the retina without significant retinal distortion

E2b

CMOcystoid spaces with vertical diameter ≤600 μm

T2

presence of continuous line of hyper-reflectivity withmultiple points of adhesion to the retina and with significantretinal distortionE2c

CMOlarge confluent cavities with retinoschisisappearance;

E3 serous macular detachment T3antero-posterior traction with “gull wings” configuration

Classification based on OCT

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

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.

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)

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).

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

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.

*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.

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*.

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).

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

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

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

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.

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.

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

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

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

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

Follow up recommendations (AAO).

Focal Points: Update in the Management of Diabetic Retinopathy. AAO; 2011

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.

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


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.

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 OphthalmolClin. 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

The usual technique is to deliver the initial treatment posterior to the ora serrataoutside the vascular arcade with emphasis on ischaemic retina near NVE but avoiding direct NV application.


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

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

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

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.

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.


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


Ranibizumab (Lucentis®)

Anti-VEGF most widely used at the moment.



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



DRCR.net (Diabetic Retinopathy Clinical Research Network)

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

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



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.

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 intravitrealfluocinolone 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 Vitreomaculartraction

Consider vitrectomy with/without adjunctive intravitreal anti-VEGF or steroid treatment (Level C)

RCOPHT RECOMMENDATIONS

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).

http://guidance.nice.org.uk/TA274

http://guidance.nice.org.uk/TA301

DMO

No centre involving Centre involving

Treat according to

ETDRS guidelinesNo vision loss Vision loss due to

DMO

Observe and treat

according to ETDRS

guidelines

Ranibizumab

Diabetic retinopathy

Health & Medicine

Transcript of Diabetic retinopathy