Panretinal Photocoagulation for

Diabetic Retinopathy in the RIDE

and RISE Trials
INTRODUCTION
used widely

1960
Since

for the treatment of various retinal pathologic

Retinal
photocoagulation
EFFECTIVE IN
REDUCING THE
RISK

severe vision loss compared with untreated

Panretinal Photocoagulation (PRP)
eyes in patients PDR and NPDR
BUT, Panretinal Photocoagulation (PRP) PRP is not without risk of complications Including :

Decreased
Diabetic Macular Decreased Color And Loss Of Visual Contrast
Edema (DME) Night Vision Acuity Sensitivity Pain
INTRODUCTION
The introduction of the antievascular endothelial growth factor (VEGF)

THE WAY TO
TREAT

Agents ranibizumab, bevacizumab and aflibercept Diabetic Macular Edema (DME)

In post hoc analyses intravitreal anti-VEGF agents have also been shown to impact
severity of diabetic retinopathy (DR), showing disease-modifying capabilities not
achievable with PRP

Bevacizumab is not Aflibercept was recently

Ranibizumab was approved for ophthalmic
approved based on use, but its pharmacologic
approved for treatment
pivotal phase 3 RIDE profile usefulness has of DR and DME based
and RISE trials resulted in its wide use as on the results of the
an off-label intravitreal PANORAMA trial
treatment for DR and DME
INTRODUCTION
PRP has another key advantage supporting its use to treat PDR.

This is the perception that it may be a 1-time procedure,

On this basis, PRP may be more suitable for those patients considered less likely to return
for followup visits for various reasons, in whom strict adherence to follow-up visits may be
questionable, or with a specific contraindication to the use of intravitreal anti-VEGF agents

To investigate whether PRP is a “1 and done,” or 1-time, procedure in patients with DR

and DME, we performed a post hoc analysis of the sham injection controlled RIDE
and RISE trials.
 PURPOSE
To evaluate panretinal photocoagulation
(PRP) treatment and re-treatment patterns
in patients with diabetic retinopathy (DR)
and diabetic macular edema (DME)
 METHODS
Analysis Population and End
Studi Design and Conduct
Points
1. All patients randomized In RIDE and RISE (n
Data for this post hoc analysis were ¼ 759)
derived from the phase 3 RIDE and RISE 2. From both studies, stratified into the 3
identifier, trials treatment groups
3. Analyzed according to baseline PRP status

End Points Statistical Analysis

Diabetic Retinopathy Severity Scale (DRSS), any
occurrence of newly diagnosed iris or retinal
neovascularization, new events of vitreous Using the Cochran-MantelHaenszel
hemorrhage, treatment with PRP or vitrectomy chi-square test and Kaplan-Meier methods
for DR-related reasons, or new cases of PDR
 RESULT
Patients and Treatment

Patient demographic and

clinical characteristics were
generally well balanced across
the 2 studies and 3 treatment
groups
 RESULT
Patients and Treatment

182 of 759 patients enrolled

in RIDE and RISE (24.0%)
entered the study having
undergone prior PRP
treatment, and the prevalence
of prior PRP was distributed
evenly across the 3 treatment
groups
 RESULT
577 patients without prior PRP
On-Study Panretinal Photocoagulation
Treatment
treatment at baseline,

19 of 200 patients (9.5%) in

the sham group underwent 1
or more PRP treatments
through month 24

2 of 189 patients (1.1%;

P ¼ 0.0002 vs. sham) in
ranibizumab 0.3 mg group

3 of 188 patients (1.6%; P ¼

0.0008 vs. sham) in
ranibizumab 0.5 mg group
 RESULT
In patients with prior PRP at
On-Study Panretinal Photocoagulation
Treatment
baseline,

11 of 57 sham-treated
patients (19.3%) underwent 1
or more PRP treatments
through month 24

No patients in the
Ranibizumab 0.3 mg group
(0/61; P ¼ 0.0003 vs. Sham)

No patients in the
Focusing on sham-treated patients only, the proportion of patients who Ranibizumab 0.5 mg group
underwent 1 or more PRP treatments was almost twice as high in
patients with prior PRP at baseline
(0/64; P ¼ 0.0002 vs. sham)
 RESULT 19 patients in the sham group
On-Study Panretinal Photocoagulation without prior PRP treatment, 11 of
Treatment 19 [57.9%] underwent more than 1
PRP treatment, with 7, 2, and 2
patients undergoing 2, 3, and 4 PRP
treatments

2 patients in the ranibizumab 0.3 mg

group who underwent on-study PRP
treatment, both underwent only 1
PRP treatment

3 patients in the ranibizumab 0.5 mg

group who underwent on-study PRP
treatment during the study, 2
underwent 2 PRP treatments and 1
underwent 5 PRP treatments.
 RESULT
On-Study Panretinal Photocoagulation
Treatment

11 patients
in the sham group with prior
PRP treatment at baseline who
underwent further on-study
PRP treatment, 8, 2, and 1
patient underwent
1, 2, and 3 additional PRP
treatments, respectively
 RESULT
In patients without prior PRP
Time to New Proliferative Events
treatment at baseline,
ranibizumab treatment
delayed the time to a new
proliferative event compared
sharm

DR progression was reduced

significantly by ranibizumab
treatment, with separation
between groups occurring as
early as month 3(P < 0.0001)
 RESULT
Time to New Proliferative Events
Ranibizumab also delayed the
time to a new proliferative
event in patients with prior
PRP treatment at baseline

Cumulative probability of DR
progression was approximately
4 times greater in sham-
treated patients
compared with ranibizumab-
treated patients
 RESULT
Clinical Experiences of Patients without Prior Panretinal
Photocoagulation Who Underwent On-Study Panretinal
Photocoagulation Treatment Among the 19 patients, 11
patients (57.9%) underwent
more than 1 PRP treatment
through month 24,

1. Vitreous hemorrhage : 12
patients (63.2%)
2. Retinal neovascularization : 9
patients (47.4%)
3. vitrectomies : 6 patients (31.6%)
4. iris neovascularization event : 2
patients (10.5%)
 RESULT
Clinical Experiences of Patients without Prior Panretinal
Photocoagulation Who Underwent On-Study Panretinal
Photocoagulation Treatment

1. Vitreous hemorrhage : 0 patients

2. Retinal neovascularization : 1 patients
3. vitrectomies : 0 patients
4. iris neovascularization event : 0 patients
 RESULT
Clinical Experiences of Patients without Prior Panretinal
Photocoagulation Who Underwent On-Study Panretinal
Photocoagulation Treatment

1. Vitreous hemorrhage : 1 patients

2. Retinal neovascularization : 1 patients
3. vitrectomies : 1 patients
4. iris neovascularization event : 1 patients
 RESULT
Clinical Experiences of Patients without Prior Panretinal
Photocoagulation Who Underwent On-Study Panretinal
Photocoagulation Treatment

A sham-treated patient without prior PRP treatment who underwent on-study PRP
experienced a 1-step DR severity improvement, from moderate PDR (DRSS level 65)
to mild PDR (DRSS level 60) on the ETDRS DRSS.
 RESULT
Clinical Experiences of Patients without Prior Panretinal Photocoagulation Who
Underwent On-Study Panretinal Photocoagulation Treatment

A patient without prior PRP who received

Ranibizumab 0.3 mg and no on-study PRP experienced a 3-step Improvement, from severe
NPDR (DRSS level 53) to mild NPDR (DRSS level 35) on the ETDRS DRSS.

The photographs from the ranibizumab treated patient show clear DR

severity improvement or regression over time
Discussion
1. The need for on-study PRP over 24 months was
significantly lower (P < 0.001) among patients who
received monthly intravitreal injections of ranibizumab
0.3 mg or 0.5 mg compared with sham, regardless of prior
PRP status.

2. The benefit afforded by ranibizumab of sparing patients

PRP was also evident when viewed in the context of
clinical outcomes

3. Patients in the ranibizumab groups had a comparatively

less complex clinical experience than those exposed to
PRP
Discussion
4. Ranibizumab treatment may have the potential to spare
patients with DR and DME the need for PRP and its
associated risks.

5. Similar to RIDE and RISE, PRP was not an isolated, 1-time

procedure in DRCR.net Protocol S, as 45% of eyes
randomized to undergo prompt PRP went on to undergo
additional on-study PRP through year 2

6. In CLARITY, 65% of patients randomized to receive

prompt PRP required supplemental PRP treatments from
weeks 12 through 52
Discussion
7. More recently, the PROTEUS study showed that the
combined treatment (ranibizumab plus PRP) was superior
to PRP alone in terms of best-corrected visual acuity
improvement and regression of neovascularization

8. The need for repeat PRP by month 12 was greater in the

PRP monotherapy group than in the combined treatment
group

9. Only approximately 30% of RIDE and RISE patients

showed PDR at Baseline
Discussion
11. Data from the DRCR.net Protocol S and CLARITY also
support our finding from RIDE and RISE that anti-VEGF
treatment reduces the need for on-study PRP treatment

12. Similar to RIDE and RISE, rates of on-study PRP treatment

were low with ranibizumab treatment in DRCR.net
Protocol S

13. The improvements in DR seen in the RIDE and RISE trials

and the DRCR.net studies were consistent
Discussion
14. .Ranibizumab treatment significantly reduced the risk of
experiencing a new proliferative event through 2 years
compared with sham treatment

15. VEGF is considered a primary factor driving

neovascularization in PDR.

16. By blocking the action of VEGF-A, ranibizumab induces

regression of DR disease severity while preserving the
retinal tissue and preventing vision loss resulting from
DME in patients with PDR without DME at baseline.
Discussion
17. Our findings challenge the perception that PRP is a 1-time
procedure and support DRCR.net’s Protocol S, CLARITY,
PROTEUS

18. other trials demonstrating that anti-VEGF treatment

results in better vision, anatomic, and DR severity
outcomes compared with PRP.

19. The growing body of evidence suggesting that anti-VEGF

therapies are most effective when initiated earlier in the
course of the disease
Discussion
21. DRCR.net’s Protocol S, and the PROTEUS study show that
when used in combination with PRP, ranibizumab
treatment significantly reduces the need for additional
PRP.

22. Another strength of the analyses reported is that they

support the findings of DRCR.net’s Protocol S and
CLARITY and additional streghts are high proportion

23. Ranibizumab treatment can reduce the overall need for

PRP and be a good treatment option in patients with
NPDR and PDR in the setting of DME.
Journal Appraisal
Author Profile
Thank You