dme diagnosis and management

16 Pages·2015·3.11 MB·English

Supplement to May/June 2015
NEW PARADIGMS IN
DME DIAGNOSIS AND
MANAGEMENT
A roundtable discussion among retina experts that includes
treatment options and management strategies for diabetic retinopathy
and diabetic macular edema in their respective countries.
Supported via advertising by
Allergan and Carl Zeiss Meditec
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Find and register for an upcoming meeting near you
at www.DMe2020.com
Diabetic macular edema (DME) is the leading cause of visual impairment in the
diabetic population.
By 2020, more than 42 million people will be living with diabetes in the US.
Given these alarming statistics, understanding the complex mechanisms of
DME and the clinical implications is critical.
PrOGrAM eDUCATiOnAl ObJeCTives
Gain understanding of diabetes mellitus and the effects of
systemic disease
Gain insights into the effects of diabetes on retinal and vascular
components of the eye
Learn about the emerging understanding of the multifactorial
pathophysiology of DME and potential clinical implications
Educational program developed in collaboration with:
Quan Dong nguyen, MD, Msc David s. boyer, MD
Program Chair, Retina-Vitreous Associates Medical Group
University of Nebraska Medical Center
Diana v. Do, MD
nicola Abate, MD University of Nebraska Medical Center
The University of Texas Medical Branch
Pravin Dugel, MD
Jay Ambati, MD Retinal Consultants of Arizona
University of Kentucky
seenu Hariprasad, MD
University of Chicago Medicine
Untitled-1 1 5/1/15 3:35 PM
NEW PARADIGMS IN DME DIAGNOSIS AND MANAGEMENT
NEW PARADIGMS IN
DME DIAGNOSIS
AND MANAGEMENT
As rates of diabetes are projected to rise in coming years, so will the increasing number
of patients with ocular complications from diabetes. Retina Today convened a panel of
world-renowned experts to discuss the treatment options and management strategies of
diabetic retinopathy and diabetic macular edema in their respective countries.
PANELISTS:
Rishi P. Singh, MD, Moderator
Dr. Rishi is Staff Physician at Cole Eye Institute and Medical Director of the Clinical Systems Office at The
Cleveland Clinic. He is also Assistant Professor of Ophthalmology at Case Western University in Cleveland,
Ohio. He serves as a consultant for Alcon, Bayer, Genentech, Regeneron, Shire, and Thrombogenics. Dr. Singh
may be reached at [email protected].
Paolo Lanzetta, MD, is an Associate Professor in the Department of Ophthalmology at the University of
Udine, Italy. He reports having a financial relationship with Alcon, Alimera, Allergan, Bausch + Lomb, Bayer,
Genentech, Lutronic, Novartis, Roche, and Teva. Dr. Lanzetta may be reached at [email protected].
Anat Loewenstein, MD, is Director of the Department of Ophthalmology at Tel-Aviv Medical Center, and a
Professor and Vice Dean of the Sackler School of Medicine at Tel-Aviv University, Israel. She reports having a
financial relationship with Allergan, Alcon, Bayer, Lumenis, NotalVision, and Novartis. Dr. Loewenstein may be
reached at [email protected].
Edoardo Midena, MD, PhD, is Professor and Chairman of the Department of Ophthalmology at University
of Padova in Italy. He reports no financial interests. Dr. Midena may be reached at [email protected].
Gisèle Soubrane, MD, PhD, is Professor and Chair In Ophthalmology at the Eye University Clinic of Créteil
in France. She reports having a financial relationship with Allergan, Bayer, Biocodex, and Théa. Dr. Soubrane
may be reached at [email protected].
MAY/JUNE 2015 SUPPLEMENT TO RETINA TODAY 3
NEW PARADIGMS IN DME DIAGNOSIS AND MANAGEMENT
A Roundtable Discussion on
New Paradigms in DME
Diagnosis and Management
According to the
International Diabetes
Federation, there are cur-
rently 387 million people
living with diabetes (a preva-
lence rate of 8.3%), and this
figure is expected to top 590
million by 2035.1 Europe has
the highest prevalence of
type 1 diabetes in children.1
The prevalence of diabetes is
slightly lower than the world-
wide figures, at 7.9%.
The World Health
Organization now counts dia-
betes among the top 10 causes of death worldwide, respon- Source: International Diabetes Federation. Reprinted with permission.
sible for 1.7 million deaths in 2012 (up from 1.0 million in continue to see increasing numbers of patients with ocu-
2000).2 The numbers are just as dire when it comes to the lar complications from diabetes. Retina Today convened
ophthalmic complications of diabetes—there are about a panel of world-renowned experts to discuss the treat-
93 million people with diabetic retinopathy (DR), 17 mil- ment options and management strategies of DR and
lion with proliferative DR, 21 million with diabetic macular DME in their respective countries. Here is what they had
edema (DME), and 28 million with vision-threatening DR.3 to say.
It is clear that retina specialists around the world will −Rishi P. Singh, MD
Dr. Singh: To begin, let us discuss diabetic patients Prof. Loewenstein: In Israel, we have a combination
in your region. How do diabetic patients get to you as a of telemedicine and direct retinal examinations. There is
specialist in your region? a great system of primary care physicians who are all fel-
lowship trained, and they know they need to screen the
Prof. Midena: At our clinic in Italy, we see patients patients. These patients are usually fairly well controlled
after a telemedicine screening. Most of that occurs in the systemically, know their A1c level and they are informed
diabetes clinics, so patients are not attending our clinics about treatments. But we also have a growing popula-
for naïve evaluation. They are already pre-screened for DR, tion of immigrants, mainly from Russia and Ethiopia,
which, of course, means they need immediate treatment. who present with extremely poor vision and advanced
disease. So, we address the combination.
Prof. Soubrane: At my hospital in France, we have a
special unit called diabetic ophthalmology. The endo- Prof. Lanzetta: In Udine, patients are either referred
crinology department refers all patients (diabetic or sus- by general ophthalmologists or by a diabetologist in the
pected diabetics) to that unit where they will be seen on medical department. Similar to what Prof. Loewenstein
a regular basis, depending on their initial presenting state discussed with her first patient group, we are rela-
of retinopathy. tively lucky because we usually see very well-controlled
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NEW PARADIGMS IN DME DIAGNOSIS AND MANAGEMENT
patients. Additionally, we have started a
pilot project to screen for DR with the aim
of increasing awareness of this condition
among diabetic patients and decreasing the
rate of severe cases.
Dr. Singh: It sounds as though a subset of
patients are aware of their diabetes diagnosis
and what is needed to manage it. But how
much awareness is there of their diabetic eye
disease in these patient populations?
Prof. Soubrane: In France, there are patient
associations for a number of diseases, which
educate them on diabetes or diabetic
complications, including diabetic eye dis- Figure 1. Example of very mild edema for laser or for observation.
ease. But a more challenging issue is that
not all the diabetic patients belong to these associations. on your patients? Do you perform optical coherence
Some of the younger patients with type 1 diabetes and tomography (OCT) on all your patients when they
some newly diagnosed adult patients are not as aware, present for diabetic eye evaluations? What other diag-
depending on the information provided by their general nostic tests and tools do you typically use during the
practitioner or diabetologist. initial evaluation?
Prof. Loewenstein: In Israel, most patients are very Prof. Loewenstein: We know that DME occurs very
much aware of their diabetic eye disease. The physicians rarely, unless the patient has at least moderate non-
make it their business to know that patients need to proliferative diabetic retinopathy (NPDR). If I do not see
get their systemic disease and their diabetic eye disease signs of DR when I see a patient, or if it is really very mild
under control. Physicians are incentivized to refer diabetic retinopathy (less than 5 microaneurysms), I would not
patients to an ophthalmologist, because it is a parameter do an OCT if I do not see a thickened retina on clini-
considered in the quality-of-care evaluation. So, patients are cal exam (Figure 1). But if I see any signs, even if I am
very aware they need to have their eyes examined regularly. not convinced there is retinal thickening, I would do an
OCT because it is more sensitive than my eye. So, if the
Prof. Midena: The amount of awareness depends on patient presents with more than mild NPDR, I do an
the patient, and I think this will change over time. Right OCT. I do not use fluorescein angiography (FA) unless I
now, health care professionals in a diabetic clinic are fol- think that the patient needs treatment.
lowing about 50% of the diabetic population, so they are
being educated about eye disease. But in our healthcare Prof. Soubrane: In adult patients, we typically perform
system, the general practitioner will have a major role in FA and get an OCT initially in order to have a baseline
the future diagnosis and treatment of diabetes. I expect document. After 5 to 10 years of active systemic disease,
the number of patients who are aware of diabetic eye or if abnormalities are observed on a biomicroscopy
disease will be reduced in the upcoming years if general exam in young and adult patients, we will always take
practitioners are not aware of the importance of patient another OCT. If we are considering treatment, we take
education. another FA then as well.
Prof. Lanzetta: In my region, the majority of the Dr. Singh: So, duration of diabetes is more important
diabetic population is unaware of very specific details than classification of the patient’s DR state.
of ocular complications like DR. However, they are well
aware that if they can better manage their diabetes over- Prof. Soubrane: I think that it is a good cut-off. Not in
all, they may reduce their complications in general. every case, but as a general rule of thumb.
Dr. Singh: We have a lot of diagnostic tools in our Prof. Loewenstein: Do you do an OCT even if the
armamentarium. Do you routinely run angiography patient has nothing?
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NEW PARADIGMS IN DME DIAGNOSIS AND MANAGEMENT
Prof. Soubrane: If nothing shows up on biomicros- tional information, but I do not know if it would influ-
copy, I do not do an OCT. There has to be some progres- ence me in my treatment decisions.
sion of disease first.
Prof. Lanzetta: The idea of checking the far periphery
Prof. Midena: Most of our patients are referred to us in DR in search of retinal ischemia or new vessels has
after already being diagnosed with retinopathy, so we been widely accepted in Europe for years now, even in
check everyone with OCT. FA is limited to patients with times when widefield angiography was not available. This
DME; we perform FA at baseline to determine treatment has been taught for years by well-known experts such as
plans for those with DME and to see what—if any— Prof. Brancato and Prof. Coscas. We have been carefully
involvement there is in the periphery. But if there is no checking the periphery for years. As a consequence, I
sign of DR, we will not use FA. do not think of widefield angiography as a “must-have”
instrument, but I do like the idea that with one image
Prof. Lanzetta: FA is not part of our routine diagnos- you can see the whole retina, including the periphery.
tic workup, unless the patient has proliferative disease
or we need it to confirm DME progression. For us, our Prof. Soubrane: To recognize retinal ischemia clini-
standard evaluation and monitoring regimen includes a cally, you need proper training, but not all ophthalmolo-
visual acuity exam and an OCT (even if the patient does gists are so specialized.
not have major signs of DR). I believe OCT should be
part of our standard work-up screening program. Dr. Singh: Generally speaking, what are your treat-
ment algorithms for a patient with DME?
Dr. Singh: What about ultra-widefield FA? Where do
you see its role in your patients right now? Prof. Midena: That is a very complicated story. There
are probably too many algorithms for the treatment of
Prof. Midena: The use of widefield FA is an advantage DME. I have a personal view, but this is very personal
because it is easier for a clinician to perform. Even in the and limited: I think about DME as a retinal disorder with
past, we were checking the periphery of the retina. We different retinal (local) phenotypes. And fundus biomi-
never limited FA to the posterior pole, even as far back croscopy is not the right way to differentiate them. So
as 20 years ago. But the advantage of widefield FA is that we need at least spectral domain OCT, analyzed in detail,
just one shot will encompass the entire retina, including not limited to central retinal thickness. There are differ-
the periphery. ent growing hypotheses now: VEGF is prevalent, but it
is not the only driver of DME. The studies are showing
Prof. Soubrane: Examining the periphery with ultra- a higher rate of nonresponders compared with patients
widefield imaging is an interesting concept—it is easy, who have age-related macular degeneration. We are now
and it provides us with more documentation. But if checking patients to differentiate if there is more inflam-
ultra widefield imaging is not available, at the mini- mation or more VEGF.
mum, clinicians should be performing biomicroscopy.
More and more patients are being followed for their Dr. Singh: Everyone here agrees that VEGF is not
macular edema on OCT, but only taking into account the only mediator of this disease state. So, how do you
the posterior pole and neglecting the periphery until approach the patient?
there are symptoms. It is more and more of a trend
that we presently do not pay enough attention to the Prof. Midena: I use the OCT to determine if there
peripheral ischemia. is more inflammation, and if so, I do not treat with an
anti-VEGF.
Prof. Loewenstein: Because I examine the patients
carefully, and I always look at the periphery, I know wide- Dr. Singh: What are the situations where you do not
field photography gives beautiful images. But remember treat with an anti-VEGF?
that also, even in the EDTRS, we just did the panretinal
photocoagulation (PRP) up to the equator, so we did Prof. Midena: We do not think VEGF is the most
not reach the far periphery, and it still worked. I think prevalent mechanism of DME in an individual patient. If
as of right now, we do not have enough evidence-based we believe patients have more retinal inflammation, our
data to determine if widefield imaging is really crucial in first line of therapy is corticosteroid or a combined treat-
the treatment of the patients. It is nice to have the addi- ment, mainly if the patient is pseudophakic.
6 SUPPLEMENT TO RETINA TODAY MAY/JUNE 2015
NEW PARADIGMS IN DME DIAGNOSIS AND MANAGEMENT
Prof. Loewenstein: I usually start with an anti-VEGF Dr. Singh: My presentation at the Macula Society
and, unless a specific patient cannot come for frequent, meeting was a post hoc analysis of the RISE and RIDE
monthly dosing for those first few months. If I do studies with regard to the treatment response of
not see any improvement, I usually do not wait the 6 patients with anti-VEGF therapy in light of their base-
months suggested in the DRCR.net Protocol I.4 If I see line factors.6 The study demonstrated that there was no
that there is no response after 3 months, I may switch difference in patients within the trial, with no change
to another anti-VEGF, but I would tend to immediately noted in hemoglobin A1c from the time they entered
prescribe a steroid. And we get very good results using the trial until the end. So, 2 years later, after all the
this strategy. intervention, they did not realize any difference in their
A1c values.
Prof. Soubrane: If we find a serous retinal detachment
on OCT, it would be a good sign to prescribe a steroid. Prof. Lanzetta: We are also learning that A1c, renal
function, or blood pressure do not influence visual
Dr. Singh: Serous retinal detachment on the OCT improvement after anti-VEGF treatment. This is different
is an indicator that VEGFs are present. There is much from the common observation that patients with most
more inflammatory stimulus than you would see with difficult to control disease have worse outcomes after
use of a corticosteroid. laser treatment.
Prof. Soubrane: A retinal serous detachment is a sign Prof. Midena: At a certain point in DME, more
of rupture of the outer retinal barrier. This breakdown is advanced retinopathy appears in the patient, which this
not VEGF-dependent and suggests inflammatory players. is not really related to the patient’s general situation.
Improved glycemic and systemic hypertension control is, There are a lot of hard exudates all around the posterior
therefore, a part of our treatment. pole, or perhaps numerous cotton-wool spots. At this
point, none of our treatments is effective.
Prof. Lanzetta: This year at the Macula Society meet-
ing,5 an interesting presentation showed that the addition Prof. Soubrane: Ophthalmologists need to intervene
of personalized education and risk assessment during much, much earlier. By the time the patient presents
retinal ophthalmology visits do not result in improved with DME or proliferative DR, it is already too late. In our
diabetes control. However, during my first visit with dia- department, the waiting room chatter among patients
betic patients, I still extensively discuss the role of optimal with various levels of DR is what clicks for those with
disease control with the aim to limit DR progression. In milder disease. They hear how much worse their vision
selected patients with DME with very good visual acuity can become and start to realize that systemic control of
and minor thickening at OCT, I may consider observation their disease is necessary.
at first, trying to improve metabolic control.
Dr. Singh: Your first-line treatment for patients is
Dr. Singh: Would you summarize that presentation? anti-VEGF therapy, and you would consider anti-VEGF
in patients with serous retinal detachment and pseudo-
Prof. Loewenstein: Basically, Protocol M from the phakia. Are there any situations in which anti-VEGFs are
DRCR.net looked at the influence of the ophthalmolo- not your first-line therapy? For example, how would you
gists to educate the patient on the control of the disease. treat a patient with clinically significant DME but did
And unfortunately, the ophthalmologist’s education was not involve the fovea?
not very helpful. And it did not cause any difference in
patients’ blood control or their glucose control. Prof. Lanzetta: I am not fully convinced that anti-
VEGF is the first-line therapy in patients with diabetes
Prof. Lanzetta: There were a number of questions now that we have dexamethasone implant 0.7 mg
from that presentation that need to be answered. One (Ozurdex, Allergan) approval.
must ask why ophthalmologists are less efficacious in
guiding the patient toward a better management of Prof. Midena: I agree—it depends on the population.
diabetes compared with diabetologists. In other words,
which instruments should we use to “convince” our Prof. Lanzetta: To be honest, I do not know what
patients on the importance of improving their A1c is first-line therapy. I use both approaches. There are
levels? advantages and disadvantages to both treatments.
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NEW PARADIGMS IN DME DIAGNOSIS AND MANAGEMENT
Dr. Singh: Do you have the fluocinolone implant Prof. Loewenstein: We are not using both simultane-
(Iluvien, Alimera) approved in your countries? In the US, ously right now. I do know some groups in Germany are
it is approved for treatment of DME in patients who investigating simultaneous dosing, but we are not. We
have been previously treated with a course of corticoste- will use one, and if there is no response after a month or
roids and did not have a clinically significant rise in intra- so, we will consider the other, but that is not quite the
ocular pressure (IOP).7 same as simultaneously dosing.
Prof. Midena: I do not think that Iluvein is a good Dr. Singh: If we term it “multimodality,” then, how are
option for patients because it is coming from purely pre- you incorporating that into your treatments?
specified analysis.8 The 3-year cut-off is theoretical. I have
asked different clinicians presenting these data how one Prof. Lanzetta: I think in Europe many people still use
can be sure about the duration of DME. In the UK, where intravitreal therapy plus laser, even though we are lack-
there is a 1- or 2-year screening process in all diabetic ing evidence that using a laser adds anything beneficial
patients, they know the duration of disease. But in most to a drug regimen. Obviously, today, we are using the
of the other countries, we do not. We do not know the laser very differently than how we have used it in the past.
duration before presentation. We are treating less invasively and less destructively by
applying less energy or by using subthreshold modalities.
Prof. Soubrane: In France, there is strict record-keep-
ing about the exams, so physicians will know within a Prof. Soubrane: I use photocoagulation laser for
certain time frame when the DME began. lesions not involving the center of the macula.
Prof. Lanzetta: The problem is what we see in clinical Prof. Midena: I began using subthreshold micropulse
trials does not really correspond to what we obtain in (diode, and then yellow) laser in the past 8 years to avoid
real-life scenarios. If you look at the RISE and RIDE trials,9 the possibility of damaging the retina.
36 months of continuous monthly anti-VEGF injections
result in the best outcomes in terms of 3-line or more Dr. Singh: What are some of its benefits of using a
improvement in visual acuity. Although this is remarkable, micropulse laser, aside from not being photodestructive?
few clinics may have the capacity to inject on a monthly
basis for 3 years. Real-life management is a different story, Prof. Midena: From a dosing frequency, it is the same
with fewer injections and visits. Therefore, outcomes are as with standard laser (every 3 months), even though the
usually less favorable. The possibility to use a long-lasting likely pathophysiology of the micropulse laser is likely dif-
drug such as the dexamethasone implant 0.7 mg may ferent. We have worked on this topic for years, and now,
allow fewer injections still with reasonable outcomes. we are trying to show this clinically.
Dr. Singh: Are you finding your therapy outcomes Prof. Loewenstein: I have used the Lumenis Novus
haven’t matched what they’ve found in the studies or Spectra (Sigmacon) micropulse laser, but I have a pro-
that you need to inject more frequently to continue the totype. So there is a relatively large spot size of 200
outcomes? In other words, how are your real-life expecta- microns, which means I will limit the use to extrafoveal
tions/experiences differing from the clinical study results? lesions. In the few dozen or so patients in whom we have
used it, however, we have had excellent responses..
Prof. Loewenstein: We know that we have to inject
more frequently than was done in all the Ozurdex Prof. Midena: Even today, when there are poor or
clinical trials. Ozurdex does not hold for 6 months. The limited results, we deem it the ceiling effect. Even in the
COMO study is the first head-to-head comparison of RESTORE study, there did not seem to be much benefit
ranibizumab (Lucentis, Novartis and Roche/Genentech) to adding laser.11
to Ozurdex, but that was in patients with retinal vein
occlusion.10 There is also a study comparing the two Prof. Soubrane: I used micropulse lasers a long time
drugs in DME, but these results are not yet available. ago (and with the caveat that it is not the same technol-
ogy as we have today), but I was not really overwhelmed
Dr. Singh: It sounds as though some of us here are by their efficacy.
evaluating combining an anti-VEGF with a steroid. How
do you manage that? Prof. Lanzetta: I have been using subthreshold irradia-
8 SUPPLEMENT TO RETINA TODAY MAY/JUNE 2015
NEW PARADIGMS IN DME DIAGNOSIS AND MANAGEMENT
tion since the early 2000s with various modalities, such as monthly basis, after the loading phase and even with cor-
micropulse, or continuous wave and low energy. I am fully ticosteroid implant. I typically like to see these patients
convinced that this is the way we should use lasers today. within 1 month to check for IOP changes. After the first
Up to now, only a single study has shown that micropulse month, I might check these patients between 2 to 3
subthreshold high-density laser irradiation may provide months.
outcomes similar or superior to anti-VEGF therapy.12
What should be known is that a subset of patients Dr. Singh: If you are bringing the patient back to
with DME may benefit from laser, that it takes time for check the IOP, what is your ideal time frame?
the beneficial effect to manifest, and that multiple treat-
ment sessions may be necessary. Prof. Loewenstein: Ozurdex peaks in 6 weeks. But I
also think that the patients need to have the pressure
FOLLOW-UP checked after 2 weeks to determine if there is an increase
Dr. Singh: How are you managing your follow-up? Let in IOP.
us presume the patient has center-involving DME with
elevated retinal thickness, and you have initiated anti- Prof. Lanzetta: I do not think IOP increases are a dra-
VEGF therapy, with the multimodal therapy with combi- matic problem for most patients treated with dexameth-
nation Ozurdex. asone implant 0.7 mg but can be for some, probably the
younger individuals. I do not want to miss those patients,
Prof. Soubrane: It is pre-planned every month, with so I usually ask them to come back and have their IOP
Ozurdex every 4 to 6 weeks and every month for anti- checked after 2 weeks.
VEGFs.
Dr. Singh: How do you treat/manage the patient with
Prof. Midena: We do not see the patient even after the an IOP spike?
loading phase. I see the patient at baseline, they have three
injections promptly, and then I see them at 4 months. Prof. Loewenstein: I consult with my glaucoma special-
ist if the patient does not improve on topical medications.
Dr. Singh: Is someone else doing the injections for you? I prescribe beta-blockers, or perhaps a prostaglandin.
Prof. Midena: Yes, and I see the patient in 6 months Prof. Soubrane: If there is a huge rise—up to 50 mm Hg,
because I perform the loading phase and then I see the despite three IOP-lowering drops—I will try to push for a
patient. I never see the patient monthly. vitrectomy to remove the implant rather than having a
trabeculectomy performed.
Dr. Singh: Another ophthalmologist is doing the
injections? Dr. Singh: Would anyone else remove the Ozurdex
implant rather than perform incisional glaucoma surgery?
Prof. Midena: Yes, absolutely an ophthalmologist. In
my case, if I prescribe a steroid, and someone else is check- Prof. Loewenstein: I would not. I have one such
ing the pressure, then I am completely comfortable for 2, patient who had a trabeculectomy and then needed
even 3 months—unless I did not see any response from Ozurdex, and I was completely comfortable prescribing
previous injections. With anti-VEGF, I do give monthly Ozurdex.
injections for 3 months, and then I see the patient the
month after the third injection. However, the person who Prof. Lanzetta: I had a female patient who spiked up
is providing the injections has make sure there is no endo- to 50 mm Hg. She did very well immediately after dorzol-
phthalmitis, detachment, or other complications. amide and timolol and prostaglandin analog drops.
Prof. Soubrane: While I may not personally see my Prof. Soubrane: I had one patient who did not
patients every month, I want them to be seen just to improve with medical treatment and went onto under-
ensure that the treatment is working.. Just to be sure the going a trabeculectomy. This patient now has a severe
treatment the working. hypotensive globe.
Prof. Midena: Theoretically speaking, I would like Prof. Midena: If you have a patient whose IOP spikes
to see the patients receiving anti-VEGF therapy on a and still has recurrent edema after 5 or 6 months, are
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NEW PARADIGMS IN DME DIAGNOSIS AND MANAGEMENT
you comfortable injecting again with Ozurdex, or do you Prof. Loewenstein: The most important take-away
change your treatment? point was that the three treatments worked very well.
We now have data on as needed p.r.n. regimens that we
Prof. Lanzetta: I probably would consider switching. did not have before. Finally, we now know when afliber-
cept 2.0 mg will work better than ranibizumab 0.3 mg.
Prof. Loewenstein: So would I.
Dr. Singh: Did that surprise you?
Dr. Singh: What about the patient with an IOP rise but
improvement in the edema, who then has a recurrence? Prof. Loewenstein: Yes—all the other trials had
shown no differences between the two compounds.
Prof. Loewenstein: If his or her IOP is really easy to con- However, Protocol T used 0.3 mg.13 It is unclear what
trol, and for some reason the patient is more comfortable the results would have been if they had studied 0.5 mg.
with receiving Ozurdex, it would not be a big, big problem. In RIDE and RISE,7 there was a small difference in effi-
cacy between those two concentrations. But again, in
Dr. Singh: By “easy to control,” we mean one or two Protocol T it was a p.r.n. regimen, even if it was a very
topical drops? strict p.r.n. regimen. So, for me, in lower visual acuities if
the cost is the same between the two compounds, I have
Prof. Loewenstein: Yes. to lean toward the more efficacious one.
OTHER TREATMENTS Prof. Soubrane: I am also frustrated we do not have
Dr. Singh: What are your thoughts on some of the results with the 0.5-mg concentration. However, it is
newer agents we have been hearing about? Should we obvious that our patients do not lose their chance for
be considering these as another potential therapy? Are improvement if we inject aflibercept. To me, that is a
there other DME therapies you are looking forward to major point.
hearing about in the future?
Prof. Lanzetta: I fully agree. One other observation is
Prof. Loewenstein: I am not convinced any other from a practicality perspective—we do not really have to
treatment will replace what we have now. There is very give five initial monthly injections before moving to a dif-
little data on the angioinhibitors, for example, even ferent regimen. We can probably start p.r.n. much sooner.
though they are higher up on the VEGF pathway.
Prof. Midena: There are three main points from
Dr. Singh: I agree—very little data. How about phar- Protocol T.13 The number of injections of aflibercept in
macological vitreolysis? One of the theories is that vit- the p.r.n. regimen was the same as in VISTA.14 So we do
reolysis in those patients (without traction) can actually not need a p.r.n.; a fixed regimen is much simpler for my
prevent DR/DME from progressing. patients. The working population does not like to be
checked every month; it is a lot of time away from work.
Prof. Midena: It is a very nice idea. Physiologically, Second, we need to stop considering aflibercept as a
it is a very consistent concept. Vitreolysis is not useful pure anti-VEGF. It is a completely different molecule. If
when thickening of internal retinal membrane or epireti- pharmacologists consider it a different drug, we should,
nal membranes are present in patients with diabetes, too. And I think that is the story behind why the results
because the membranes are not purely collagenous are much better—aflibercept also has another property.
material, but neurites or glial cells are present in the Third, there was an astonishing number of laser treat-
epiretinal/retinal thickened area. ments. More than 30% of patients underwent some type
of laser therapy in each eye? Laser is not dead!
Prof. Loewenstein: I think the most important thing
recently has been the Protocol T trial13 results that have Dr. Singh: What does everyone else think? After read-
just been published. ing Protocol T, is laser dead?
Prof. Soubrane: I think laser may still have a role in
TAKE-AWAY POINTS FROM PROTOCOL T treatment of DME, but not everywhere. In France, afliber-
Dr. Singh: What was your take-away point from the cept is presently an acceptable treatment for DME and
Protocol T study? will be reimbursed soon, but not yet.
10 SUPPLEMENT TO RETINA TODAY MAY/JUNE 2015