1) Clinical trials have shown that intraocular injections of anti-VEGF drugs are more effective than laser monotherapy for treating diabetic macular edema (DME), but nearly half of patients still require supplemental laser treatment after several months. 2) While anti-VEGF drugs provide excellent initial results for DME, their effects wear off and leakage/edema can return without permanent effects on the retina and blood vessels like laser therapy provides. 3) Subthreshold laser therapy, which causes no scarring or permanent retinal damage, has shown potential for reducing DME with better visual acuity outcomes compared to conventional laser therapy.

1. RETINA SURGERY FEATURE STORY
JULY/AUGUST 2015 RETINA TODAY 1
Laser Use and the
Future of Retina
Practice
T
he number of available options for treating
diseases of the posterior segment continues to
grow, and the technologies behind these options
are ever changing and improving. It is only natu-
ral, then, to question whether any of the old options and
technologies will eventually fall by the wayside. As far as
the use of lasers goes, it is here to stay—at least for the
foreseeable future. The role of lasers in the treatment of
diabetic macular edema (DME) alone is proof enough.
A COMPARISON OF TREATMENT METHODS
DME is one of the major causes of significant visual
acuity loss in working-age adults and is the most com-
mon cause of visual acuity loss from diabetic reti-
nopathy. For years, the standard therapy was focal laser
photocoagulation, but the tide has changed, and many
surgeons now begin treatment with intravitreal injection
of a pharmacologic agent.
Recent studies have shown that monotherapy with
intraocular injections of anti-VEGF agents has the poten-
tial to stop the deterioration of vision in patients with
DME and even reverse it.1,2
This approach, however,
requires multiple and frequent treatments. Furthermore,
after the effect of the medication wears off, the leakage
recurs and macular edema returns.
Laser therapy, by contrast, may yield a more per-
manent effect on the retina and retinal blood vessels.
Nevertheless, studies have shown that the ability of
laser as monotherapy to maintain or improve visual
acuity is limited, possibly because of the develop-
ment of retinal scars, which decrease the potential for
improved visual acuity.3-5
Subthreshold laser therapy has the potential to reduce
DME with better visual acuity results compared with
conventional laser, as it does not cause collateral damage
in the retina.6 Indeed, subthreshold laser uses low energy
and causes no scars or permanent damage to the retina.
As a result, visual acuity may not only stop declining, but
also improve.
Recent findings support the combination of pharmacologic and laser therapies
for retinal diseases.
BY ANAT LOEWENSTEIN, MD
At a Glance
• Although pharmacologic therapy provides
excellent results in the treatment of diabetic
macular edema, roughly half of patients will
require supplemental laser.
• Because it does not cause collateral damage
in the retina, subthreshold laser therapy may
produce better visual acuity results than
conventional laser.
• Laser therapy remains the primary therapy for
patients with remote macular edema.
”Subthreshold laser therapy has the
potential to reduce DME with better
visual acuity results compared with
conventional laser... .”

2. RETINA SURGERY FEATURE STORY
2 RETINA TODAY JULY/AUGUST 2015
CLINICAL FINDINGS
Clinical trials such as RISE, RIDE, RESTORE, READ 2,
and several Diabetic Retinopathy Clinical Research
Network (DRCR.net) studies have shown that mono-
therapy with laser has some benefits but with less effi-
cacy than monotherapy with anti-VEGF drugs.7-14
In the DRCR.net Protocol I study, the use of
anti-VEGF therapy plus deferred laser resulted in visual
acuity similar to that achieved with anti-VEGF therapy
plus immediate laser.10-13 As a result, the consensus
among retina specialists is that most patients with
center-involving macular edema (the typical patients
who were included in these trials) do not require laser
up front. In patients with more remote macular edema,
the use of laser therapy limited to the edematous areas
is still common as primary therapy. Steroids are also a
potential treatment for patients who do not respond
to anti-VEGF therapy after multiple injections or who
had a recent severe cardiovascular ischemic event.
Keep in mind that, in patients in whom anti-VEGF
therapy did not completely reverse the disease, add-
ing laser may still be beneficial. In fact, results from
the recently published Protocol T study support
this claim.14
In Protocol T, 660 patients with center-
involving DME were randomly assigned to monthly
intraocular injections of one of three anti-VEGF drugs:
1.25-mg bevacizumab (Avastin, Genentech), 0.3-mg
ranibizumab (Lucentis, Genentech), or 2.0-mg afliber-
cept (Eylea, Regeneron). After 24 weeks, researchers
withheld injections if the edema was not yet resolved
and if visual acuity neither improved nor worsened
after two consecutive injections. In such cases, the pro-
tocol instructed the treating physician to administer
laser treatment and to resume the injections later if the
visual acuity or the retinal thickness worsened.
At the 1-year follow-up visit, data in all three arms
indicated visual acuity improvements. There were no
differences among treatments in patients starting the
trial with visual acuities between 20/32 and 20/40.14
Interestingly, this study found that in all three groups,
a substantial number of patients (56% for bevaci-
zumab, 46% for ranibizumab, and 37% for aflibercept)
needed laser rescue after 24 weeks.14
In these patients,
the beneficial effects of the anti-VEGF drugs reached a
plateau, and vision-threatening edema remained, neces-
sitating additional therapy in the form of laser rescue
(Figures 1 and 2).
CONCLUSION
Pharmacologic therapy provides excellent results in
the treatment of DME. However, nearly half of patients
Figure 1. A 44-year-old man with nonproliferative diabetic
retinopathy in both eyes. The patient received laser
treatments in June 2013 and August 2014. Top, left to right:
fundus photograph, red-free photograph, and fluorescein
angiography of the right eye in June 2014. Bottom: B-scans and
spectral-domain optical coherence tomography maps (insets)
of the right eye at treatment and follow-up visits.
Figure 2. Corresponding images and scans of the left eye of
the same patient as in Figure 1.
”Clinical trials ... have shown
that monotherapy with laser has
some benefits but with less efficacy
than monotherapy with
anti-VEGF drugs.”

3. RETINA SURGERY FEATURE STORY
JULY/AUGUST 2015 RETINA TODAY 3
need supplemental laser after several months of
monthly intraocular injections.
In collaboration with my colleagues Michaella
Goldstein, MD, and Dafna Goldenberg, MD, I have had
an excellent experience using a subthreshold laser pro-
totype to treat patients with extrafoveal DME. Because
of the location of the edema, the visual acuity loss
that resulted was not significant, so we did not expect
significant changes in visual acuity. Surprisingly, these
patients showed significant reductions in edema and
retinal thickness.6 Regarding safety, this treatment did
not leave scars or permanent retinal damage. Taking
these findings into consideration along with the clinical
trial results discussed above, it seems clear that laser
still has a place in the treatment of DME.
According to the current consensus, a patient with
DME who does not respond to pharmacologic therapy
should be considered for laser therapy. The main crite-
rion for using laser is whether after several months of
such pharmacologic treatment the edema is still pres-
ent. If so, laser therapy should be considered. n
Anat Loewenstein, MD, is a professor and
the director of the department of ophthalmol-
ogy at Tel Aviv Sourasky Medical Center and
vice dean of the Sackler Faculty of Medicine at
the Tel Aviv University. She is a consultant to
Lumenis. Dr. Loewenstein may be reached at
anatl@tlvmc.gov.il.
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