BY ABDHISH R. BHAVSAR, MD
this issue we will explore the controversial subject of which treatment to use as
the first-line therapy for diabetic macular edema (DME). Although laser treatment
has traditionally been the standard treatment for DME, there may be circumstances
in which either pharmacotherapy with intravitreal triamcinolone (IVTA), bevacizumab
(Avastin, Genentech), pegaptanib sodium (Macugen, (OSI) Eyetech, Pfizer), or vitrectomy
surgery may be beneficial. While we are not recommending any particular treatment
for your patients, the column will be a nice exercise in exploring pro and con aspects
of treatment decisions that we face daily.
TOPICS WILL BE EXPLORED IN THIS ISSUE:
1. Laser as first-line treatment for DME
2. Pharmacotherapy (IVTA/Avastin) as first-line treatment for
3. Vitrectomy surgery as first-line treatment for DME
Laser as First-Line Treatment for DME
Einar Stefánsson MD, PhD:
is a metabolic imbalance, and/or hypoxia, in DME and this leads to production of
permeability factors (VEGF, etc.) and increased hydrostatic pressure in microvasculature
(Starling's law). We have means to permanently correct the metabolic imbalance through
laser destruction of photoreceptors. Antigrowth factor drugs are a temporary method
to block growth factors, while they do not influence the underlying metabolic imbalance.
Steroids are also a temporary block of the permeability increase, and the underlying
metabolic defect persists and takes over again when the drug clears.
B. Landers, III, MD: Because
the United States is not a single, homogenous population, many patients will continue
to present initially with advanced macular edema; extensive laser treatment initially
in these patients may produce extensive scarring. New modalities (intravitreal kenalog
and intravitreal anti-VEGF drugs) appear to significantly ameliorate the diabetic
CSME initially. Once that is accomplished, it now may well be the most appropriate
time to apply relatively light laser treatment, to achieve its beneficial effects
with minimal attendant damage to the retina and RPE.
(IVTA/AVASTIN) as First-Line Treatment for DME
Michael W. Stewart, MD:
Intravitreal pharmacotherapy avoids the permanent scarring of the retina and RPE
that would be caused by laser photocoagulation.
2. The medications offer a reasonable chance of improving
and not just maintaining visual acuity.
3. By binding VEGF or decreasing its production, pharmacotherapy
may decrease or prevent diabetes-related neovascularization of the disc, retina,
4. As reported in individual case discussions, VEGF-binding may
improve capillary perfusion and, thereby, possibly reverse ischemia-driven macular
5. Intravitreal injections do not require expensive equipment
6. The costs for individual injections are quite low (triamcinolone
and bevacizumab but not pegaptanib).
G. Syrquin, MD:
remember treating patients for macular edema secondary to CRVO using focal laser
while a fellow at the Jules Stein Eye Institute. This treatment was thought to be
of value prior to the release of the CRVO study. Without a well-constructed prospective
randomized clinical trial, I may have been performing an unnecessary procedure on
my patients, but we now know better. Similarly, by treating our patients with DME
using pharmacologic agents without a randomized clinical trial to support our treatment,
we may again be introducing our personal bias. Our gold standard should be evidence-based
Vitrectomy Surgery as
First-Line Treatment for DME
J. Browning, MD: It
is reasonable to consider an intervention that includes vitrectomy as a primary
intervention for severe cases of DME. The definition of severe will mean different
things to different people. In my mind, this means that best-corrected visual acuity
is 20/60 or worse and central subfield macular thickness is over 450 μm. Vitrectomy
by itself as an intervention is difficult to defend, but as the foundation for a
combination primary intervention that might also include internal limiting membrane
(ILM) stripping, focal laser, panretinal laser (should midperipheral ischemia exist
by fluorescein angiography), and intravitreal pharmacologic therapy, the idea has
merit, for the following reasons:
1. Vitrectomy raises preretinal oxygen concentration, which may
downregulate VEGF in hypoxic retina.
2. Vitrectomy decompartmentalizes potential pockets of increased
preretinal growth factors and relieves diffusion barriers to the outmigration of
these factors from the retina.
3. Vitrectomy releases traction, which may decrease intraretinal
4. Vitrectomy changes the state of the eye, like photocoagulation,
and unlike a pharmacologic injection. Case series suggest that the effects of vitrectomy
to thin the edematous macula do not wane, at least time courses up to a year.
5. The effect size of vitrectomy is larger than that of focal
laser as a fraction of baseline thickening in case series, and is a more appropriate
match for markedly edematous maculas.
S. Boyer, MD:
prospective randomized clinical trials, vitrectomy surgery for DME should only be
considered for patients who have a taut posterior hyaloid and have not responded
to less-invasive treatments. The ETDRS study was a well-done multicentered clinical
trial that has given us guidelines to treating patients with DME. The DRCR.net is
exploring, in well-controlled prospective clinical trials, the role of vitrectomy,
anti-VEGF drugs, and steroids to treat patients who have DME; many who have failed
laser treatment. Despite the advances in vitrectomy surgery, there are still significant
risks involved with vitrectomy surgery for taut hyaloid in patients with diabetes.
These prospective trials will determine the role of surgery in the future.
R. Bhavsar, MD, is an attending retina surgeon at the Phillips Eye Institute, director
of clinical research at the Retina Center, P.A., in Minneapolis, Minn, and adjunct
assistant professor at the University of Minnesota. He also serves as state chair
of the Minnesota Diabetes Eye Exam Initiative. E-mail him about Face Off
Retinal Physician, Issue: May 2006