as impaired glucose tolerance (an inability of the body to handle glucose) and type 2 diabetes. Source: American Diabetes Association, 2006, www.diabetes.org. Fact 11 …
Summary of Diabetic Retinopathy Studies
The Diabetes Control and Complications Trial DCCT NEJM 1993:329:977-86
Introduction: The DCCT was a multi center, randomized clinical trial
designed to compare intensive with conventional diabetes
therapy with regard to their effects on the development and
progression of diabetic retinopathy
Methods: ?1441 patients, 29 centers, all IDDM
?Two cohorts: 1Primary intervention ? no DR, 2 Secondary
Intervention ? mild to moderate DR used ETDRS criteria
Treatment and Follow up: ?Conventional tx consisted of 1 to 2
injections of insulin Intensive tx consisted
of three or more injections or insulin pump
Outcome: ?25 steps graded, three step change sustained for 6
months
?Severe NPDR
?PDR
Results: ?Primary intervention: Until 36 mths no difference
36 mths at least 50 reduction
Mean 6 yrs 76 reduction of DR
?Secondary intervention: 36 mths 54 reduction
?47 reduction in severe DR
Conclusion: ?Intensive tx of glucose in IDDM delays onset and slows
progression of DR
Diabetic Retinopathy Study DRS Arch Ophthalmol 97:654-55, 1979
Ophthalmology 88:583-600, 1981
Report 1 of DRS two years follow up
Introduction: The DRS is a randomized controlled clinical trial
sponsored by the NEI to evaluate photocoagulation treatment
for PDR Begun in 1971 1700 patients at 15 centers
Expedited results based on two year follow up
Eligibility: ?VA ?20/100 in each eye
?PDR in at least one eye or severe NPDR in both
?Severe DR defined as 3 of 4:extensive hem/Ma, CWS, IRMA,
VB
?Both eyes suitable for photocoagulation
Follow up treatment: ?three month interval
?One eye of each patient randomly selected for
treatment and the other observed
?Randomized further to either xenon or argon laser
?PRP and focal laser to NV
on retinal surface
?Standard photo 10a for NVD termed mild
Study Design: ?One eye of each patient assigned randomly to PRP /-
focal tx /- macular tx The other eye assigned to follow
up with no treatment
Outcome: ?SVL defined as 5/200 at two consecutive visits 4 months
apart
Results:
SVL TX No Tx Reduction
41 94 54
Recovery VA 5/200 TX No TX
122 286
Cumulative SVL2yrs Tx No TX Reduction
64 163 61
Small loss of VA 2 to 4 lines
Argon laser tx then no tx but same after 2 years
Xenon laser tx 178 no tx 81
VF scores
Same in all groups except xenon
Cumulative event rate SVL
No new NV Tx no Tx
27 24
NVE Tx no Tx
45 96
NVD Tx no TX Reduction
84 245 66
Report 3 further defined as did this article the high risk PDR by
studying these cumulative
risks
Conclusions: ?PRP focal tx has benefit in reducing event over a two
year period Some evidence that small VA loss VF loss
occurred in xenon group
?High risk PDR was clearly defined So NVE with VH all
NVD were associated with high occurrence of SVL in
untreated compared to treated groups Follow report 3
Report 3 of DRS
Identified four retinopathy factors that increase the 2 year
risk of developing SVL 5/200 at 2 visits, 4 mths apart The
risk grows as the number of risk factors grows
Risk Factors and Associated Risk
| | | |
|Risk |Risk factor |Risk of SVL |
| | | |
|1 |Preretinal hemorrhage |Risk of SVL is approx 3|
| | |to 6 for any factor |
| | |alone |
| | |Risk of SVL is 6 for |
| | |two factors |
| | |Risk soars to 25 to 35|
| |
|for 3 risk factors |
| | | |
|2 |NV | |
| | | |
|3 |NVD within 1 dd | |
| | | |
|4 |NVD: 1/4 to 1/3 DA | |
| |10a NVE: DA | |
Report 8 of DRS
Introduction: The DRS is a randomized controlled clinical trial
sponsored by the NEI to evaluate photocoagulation treatment
for PDR
Eligibility: ?VA ?20/100 in each eye
?PDR in at least one eye or severe NPDR in both
?Both eyes suitable for photocoagulation
Follow up treatment: ?four month interval
?Eyes randomized between argon and xenon arc
photocoagulation
DRS Photocoagulation Techniques
| | | |
|Scatter |Argon |Xenon |
| | | |
|No Of burns |800-1600
500? |400-800 3 |
| | | |
|Size |500-1000 1000? |200-400 45 |
| | | |
|Exposure |01 sec |not specified |
| | | |
|Focal |NVE, NVD, CSME |same |
Study Design: ?One eye of each patient assigned randomly to PRP /-
focal tx /- macular tx The other eye assigned to follow
up with no treatment
Outcome: ?SVL defined as 5/200 at two consecutive visits 4 months
apart
Results:
Risk of SVL at 24 Months
| | | | |
|Classification |Treatment |Controls |Reduction in event |
| | | | |
|High risk PDR |11 |26 |50 |
| | | | |
|Without high risk PDR |3 |7 |50 |
|
| | | |
|Severe NPDR After 36 |3 |7 |50 |
|mths | | | |
Key points; ?Xenon effect was greater than Argon However, greater
harmful effects
?Similar results at 5 years follow up In other words
still 50 reduction in event TX 17 vs control 34
?Harmful effects of laser: constriction of VF, vVA
?Complete regression of NV in 30, partial regression in
25 12 months post PRP In another study by Blackenship it
has been shown that complete regression of NVD 3 weeks post
tx correlates with good visual outcome
?Perisistent NVD 1 year out: Treated 382
Untreated 633
Conclusions: ?Treat if high risk PDR present DRS did not answer
what best choice is if non high risk PDR or severe NPDR
present answered in ETDRS
Early Treatment Diabetic Retinopathy Study ETDRS
Report 1: Photocoagulation for
Diabetic Macular Edema
Introduction: The ETDRS is a NEI supported multi center,
randomized clinical trial designed to answer the following
three major questions:
1 When in the course of DR is it most effective to
initiate PRP?
2 Is photocoagulation effective in the TX of macular
edema?
3 Is ASA TX effective in altering the course of DR?
Report 1 only deals with question 2 29 centers involved
Patients/Methods: April 1980 to August 1985 3,928 patients were
enrolled Patients had early PDR, mild to severe NPDR
and/or macular edema in each eye
Eligibility: For this study only patient with mild to mod NPDR
and macular edema were studied
VA ?20/200 no other ocular disease
Study Design: For this part of the study the following eyes were
considered They underwent two randomizations
I Patients with CSME mild to mod NPDR? Immediate
Photo vs Deferral until HR/PDR
2 Immediate Photo?Panretinal f/u focal vs Immediate
Focal
Immediate focal vs deferral was compared
Treatment: Used FA Macular edema: retinal thickening 1 DD or HE
CSME
Focal: Ma and focal leakage sites?50 to 100? argon
blue green or green only, 01sec to obtain
whitening with no Bruchs rupture
TX 500? to 2DD initially If VA 20/40 CSME
persists than up to 300? treated unless
perifoveal capillary dropout
Diffuse: Diffuse leakage or non perfusion within 2 DD of
center txd with grid
Light to mod intensity burns ?200? in size
Use 50 to 200? One burn between
In papillomacular bundle but not closer than
500? from center
Treatable Lesions
Discrete points of retinal hyperfluorescence or leakage most
Ma
Areas of diffuse leakage
Ma
IRMA
Diffuse leaking cap bed
Retinal avascular zone
Outcome: Doubling of visual angle ie 20/20 to 20/40 called
moderate visual loss corresponds to 15 letters
FM 100 hue test Goldman perimetry
Without regard to ASA as it didnt really make a
difference
Follow up: 6 weeks than every 4 months
Results: VA
Risk of MVLsame for eyes VA20/100
| | | | |
|Time |Treatment |Control |Reduction |
| | | | |
|1 year |5 |8 |50 |
| | | | |
|2 years |7 |16 |50 |
| | | | |
|3 years |12 |24 |50 |
Key points: ?Visual prognosis worse in eyes with low VA at baseline
But if Va was 20/40 then improvement of 6 letters on avg
Not much improvement with good initial improvement
?Beneficial effect demonstrated in eyes with CSME and not
in NON-CSME eyes Non CSME eyes developed CSME at the
same
rate with or without treatment
?Pretreatment 75 had RT At one year 35 in tx group had
RT whereas 63 in deferral group did
?Small statistically insignificant differences observed in
tx vs no tx with VF No difference with FM-100 observed
Conclusions: 1 Most people use argon green laser to avoid
xanthophyll uptake with blue wavelength
2 Diffuse leakage carries worse prognosis
3 Focal and grid treatment is indicated for CSME Need
CLE to detect RT do as soon as CSME Even good
acuity benefits
Report 2 of the ETDRS
Purpose: To define CSME define treatable lesions
CSME: 1 RT ?500 m from center
2 HE ?500 m from center with assoc RT
3 1 DA of RT within 1 DD from center
Treatable lesions:
Directed at all lesions 2DD from center defined as treatable
if associated with RT
1 Discrete points of retinal hyper fluorescence or leakage most
Ma that were 500m from center
2 Focal leaks 300 to 500 m from center
3 Areas of diffuse leakage
Ma
IRMA
4 Diffuse leaking cap bed
5 Retinal avascular zone outside 500? only other then FAZ
Treatment techniques:
Focal: 1 Ma and focal leakage sites?50 to 100? argon blue green or
green only, 01sec to obtain whitening with no Bruchs
rupture Avoid flame hem D/B heme 125 If within 500
m 50 and 005 sec
2 TX 500? to 2DD initially If VA 20/40 CSME persists
than up to 300? treated unless perifoveal capillary
dropout
Diffuse: 1 Diffuse leakage or non perfusion within 2 DD of center
txd with grid
2 Light to mod intensity burns 50 to 200? in size Use 50
to 200? One burn between
3 In papillomacular bundle but not closer than 500? from
center
Follow up treatment:
4 months after initial treatment and 4 month intervals thereafter if CSME
then additional treatment
Clinical guidelines:
1 ETDRS did not address the timing of macular laser But since tx only
preserves vision then seems stupid to wait for
worsening PRP and
cataract surgery worsen the edema
2 Treatment for RT in center requires judgement as to timing
HE with RT 500 less urgent
RT 1DA within 1 DD less urgent still
ETDRS taken from Jakobiec
Eligibility: 1 VA ?20/40
2 Mild NPDR to non high risk PDR /-mac edema
3 Both eyes suitable for photocoagulation
Major Design Features: 1 One eye of each pt assigned randomly to early
PRP and the other to deferral careful f/u and
PRP if high risk PRP develops
2 Pts assigned to ASA vs placebo
Conclusions: 1 Both early and deferral were followed by low rates
of SVL
After 5 years SVL deferral 2-10
After 5 years SVL early 2-6
2 PRP is not indicated for mild to moderate NPDR but
should be considered as retinopathy approaches the
high risk stage and usually should not be delayed
when high risk stage is present
The Diabetic Retinopathy Vitrectomy Study Research Group
Report 5
Arch Ophthalmol 1990: 108:958-964
Introduction: DRVS is a multi center clinical trial sponsored by the NEI
includes a randomized trial of early Vitrectomy for eye with severe
vitreous hemorrhage due to DR
Eligibility: ?VA ? 5/200 at two visits for 1 month
?VH for no more than 6 months 1-6 months
?Macula on by U/S
?Type 1 DM if Dx 20 years and on insulin Type II if age 40 years
or not on insulin
Major Study Design: ?One eye eligible
?Eligible eyes randomized to either immediate tx or
deferral Deferral group underwent Vitrectomy if VH
still present, VA 5/200 after 12 months or if center of
macula came off
Results: ?Early Vitrectomy group had better chance of VA 20/50 or better
at F/U to 4 years if the following: Type I DM, Type I DM less than
20 years Type I DM 20 years still had benefit but not as
great
?In most severe PDR 10/20 at 4 years in 50 of early vit group
vs 12 in conventional management
?No sustained effect in Mixed or Type II DM
?Early Vitrectomy group
had greater chance of NLP
Conclusions: ?Early Vitrectomy indicated in VH of Type I DM patients
NB Also an arm of this study which looked at extensive, active, NV, or
fibrovascular proliferations
Major design same as previous except waiting time was only 6 months
Chance of VA 10/20 increased by early Vitrectomy at least in eyes with
sever vessels
Group NR Very severe PDR with useful vision
Eligibility Criteria: 1 VA?20/200
2 Center macula on
3 Extensive, active, neovascular, or fibrovascular
proliferations
Major study design: Same as above except conventional tx included
Vitrectomy after 6 months
Conclusions: Chance of VA?10/20 increased by early Vitrectomy, at least
for eyes with very severe new vessels
Source:thumbresources.org
