My first choice treatment is vitrectomy. 2nd choice is grid laser. Other treatments can not rescue permanently.

In my opinion vitrectomy is more expensive and long term in recovery after the surgery, moreover is useful mainly in edema due to a tractional strands on the retina. there is no clinical evidence in efficacy in CME due to a barrier defect, alternative procedure in my opinion may be steroid inserts

When the total volume of macula no more than 8 mm3 the micropulse panmacular coagulation is effective. But in case of high macular oedema only remuving of posterior hyaloid membrane and peeling op ILM is effective

But anti Vega or implants play a Role in diabedic csme?

Injection should be tried first before grid treatment because if retinal edema is diminished less power of laser energy will be required & absorption of laser energy is better with more effective ttt. But still remaining a question , Is antiVEGF ttt is ideal as pre laser ttt ? what about the role of IVTA Now ?

Difinetly IVTA has its known complication but still more effective than AntiVEGF with respect to DME.In experimental studies, bevacizumab did not prevent or reverse vascular dilatation and tortuosity completely compared with its effects on

neovascularization

And what about severe side effects of IVTA? As glaucoma drugs resistent, cataract formation, and retinotoxicity?

So this is the point, I have used intravitreal diclofenac prior to laser therapy & compare its effects to IVTA. The initial results on retinal thickness are promising. In addition, no cataract or Elevated IOP.

Hello, I want to ask the previous participant. How have you done the intravitreal injection of diclofenac? What concentration of diclofenac have you used? Are there any literature data about an ability of intravitreal using of non-steroid anti-inflammatory medications for DME tretment? Нave you notify your patients about a fact that diclofenac is not the medication assigned for intravitreal injection? Thank you.

Diclofenac is given in adose of 500 microgm/0.1 mL. This was based on expermintal studies that show that non toxic doses of NSAI is not associated with cataract or elevated IOP.Also based on a clinical pilot study that reveal the effect of diclofenac on macular edema due to variable etiology including DME. All patients signed a consent indicating that this is a research work. we got initial promizing results & puplished this data in the retina journal

usually there is no need of intravitreal administration of diclofenac because, on the matrket, there are two different NSAI molecules that could be used without risk and are on label for DME: Nevamfenac and Bromfenac that pass corneal barrier because are lipofilic. Bromfenac acts directly while nevamfenac is a precursor of amfenac that acts inside the eye.

several papers discuss this topic suggesting a positive effects of boths associated with anti VEGF injections

Dear Vingolo,

Diabetic macular edema is not a single entity. it migt be due to macular ischemia for whic no treatment works. second cause is diffuse leakage from perifoveal capillaries. in this case macular grid is the first line of treatment, if it fails then we consider Anti VEGF. Macular edema might be due to leakage from a few micro aneurysms. in this entity, focal laser is the best . we mst consider the posibillity of vitreo macular traction for whic vitre-retinal surgery is the answer to relieve the traction. Any combination of these therapy can be considerered depending upon the findings of FFA.

One important point nowadays is to make less damage to the retina ; and we know that in the first year after macular photocoagulation the scars grow 50% and they continue growing with much less speed even later ... I have seen many patients in whom the scar has reached the fovea which is a disaster, even if this doesn't happen they develop permanent scotomas, so it is better to go toward anti-VEGF therapy...

one important point in treatment success is good metabolic control ; otherwise it will recur and in patients with persistant macular edema don't forget to do a wide-field F/A to rule out peripheral retinal capillary non-perfusions which in some studies were shown to be the source of VEGF and continued macular edema ; in these cases targeted PRP in the ischemic parts also may be helpful .

So, I prefer Avastin .. if there is a prominent component of CME on OCT , combination of Avastin and triamcinolone specially in pseudophakic ptients ( it was shown that if edema is cystoid it does not respond as well to Avastin)

Sydney it is a very intersting idea.. we can try it as Vit C has no harm and ater soluble...

Ofcourse what I told before, is what I already am doing except for those which the cause is macular ischemia which it dosn't work ...

I have used vitamin C but despite high doses (we have used also 1gr twice a day) in the eye concentrations are very low so the effects are often not well identifiable.

sometimes instead ascorbic acid alone we also tried ascorbate glicerol 10% and was effective even if with effects on intraocular pressure. What do you think about it?

for niloofar, in my opinion triamcinolone is too dangerous...I prefer to perform laser at correct energy (100-200 mW). unfortunately in italy use of avastin now is not allowed but my experience is that lucentis and avastin have overlapping effects

moreover I prefer OCT measurement to FA....

My choice is only intravitreal Anti-VEGF as a first line of therapy.May be sometimes repeated injections. Lasers to be done in non-responders. And steroids at the most for pseudo-phakic DME.

NON RESPONDERS TO ANTIVEGF usually are non responders to laser too

I also prefer antiVEGF as first line therapy for CSME. Some non-responder still respond to steroid injection, especially if you suspect an inflammatory component.

And what do you think about vitrectomy

both treatments required for the diabetic macular oedema. some patients also required PRP treatment

Depends on FA and OCT findings-Anti-vegfs first line ;surgery -lasers when indicated

I would have laser as the first line, but only if CRT allows. If you have a massive oedema, laser will not work; in that case anti VEGF will be the first line. Also if DME reoccurs after grid, I would not repeat grid, but move to anti VEGF.

1) Only relevance of FA for evaluation and treatment of DME is to look for macular ischemia if VA poor. The ETDRS (many years ago) showed no correlation of FA leakage to thickening or treatment outcome. Nothing has changed since in this regard. 2) Treatment should be preventative (early) rather than therapeutic (late). SDM allows early treatment, macular and PRP, including transfoveal treatment, even in eyes with 20/20 VA to prevent DME, arrest and reverse retinopathy harmlessly while at the same time improving retinal function. Because SDM is harmless, it can be repeated ad infinitum if necessary. "Paleophotocoagulation" (mETDRS, PASCAL, etc) is limited by inherent tissue damage. SDM does absolutely no damage, more effective. Come to my courses at the ASRS in Toronto and Euretina in Hamburg! Early treatment with SDM not only prevents progression, visual loss, worsening of retinopathy, but thus precludes the need for more expensive and risky treatments including intravitreal anti-VEGF injections. We no longer do intracapusular cataract surgery or open-sky vitrectomy. Why do we continue to burn retinas? Harmless and effective treatments like SDM now make prevention possible for the first time.

THanks Paul;

What is SDM.

Sorry for the ignorance.

yog

Subthreshold diode micropulse laser (SDM). Full-text downloads avail on site. CDR review article and "Long-term safety" paper most informative.

Actually subthreshold micropulsed laser are useful in treating very mild phases of CME in short number of cases and need to be confirmed by more long term studies. We know non that virtually safe photodynamic therapy cases chorioretinal atrophy after years...

Not so. Useful for all degrees of DME, PDR, CSR, RVO, etc. Harmless without retinal damage or injury in published 10 year follow up.

i preffer to rule out traction with oct (in that case I make PPV with ilm peeling), and FA to rule out macula ischemia (in that case i preffer intravitreal steroids), the FA show me focal edema that can be treated with focal laser, if the edema is diffuse or with central comprimise I preffer Anti VEGF. I don´t have SDM. Macular Grid laser is reserved for multifocal edema after 3 to 10 days after anti VEGF treatment.

anti VEGF treatment is the present gold standard and I agree, however, steroidal inserts, when possible, are also a valid alternative

Problem: Intravitreal injections and conventional laser have no application in eyes with good VA. Once DME develops and VA is affected, treatment is difficult, prolonged, expensive, and unlikely to restore normal vision. Ideally, treatment should be given BEFORE vision loss, and thus before significant fovea-involving DME develops. Only SDM is sufficiently safe and effective for this task. It is also clinically harmless and effective for treatment of significant DME, and PDR, and can arrest and reverse DR (as can any therapeutically effective treatment for DR, including conventional laser and drugs). However, only SDM is sufficiently safe to use BEFORE high-risk or clinically significant disease develops to prevent vision loss. Even if asymptomatic diabetic patients with 20/20 vision would allow you to stick needles in there eyes every few months for years the world does not have enough retina doctors or money to do this. Sorry, Genentech.

(Sorry "you" doesn't mean you, it means any of us!! (And "there" should be "their"!!!)

I strongly agree with jeffery anti vegf are useful only in early phases of DME while steroid implants are useful in severe and refractory to others treatment DME. in my opinion only laser either subthreshold or focal grid are the gold standard!

there is emerging evidence that subthreshold micro pulse diode laser therapy is a valid treatment option. However, Vujosevic et al in 2010 in a prospective trial compared SDM to modified ETDRS photocoagulation for diabetics macular evaluating microperimetry and FAF. They report no significant difference in BCVA or central retinal thickness. Although SDM preserved better central retinal sensitivity. Therefore, I agree with you in that it is less aggressive. However, in clinical practice various issues exist; laser equipment and laser operator (experience and clear treatment parameters are necessary). As regards antivegf these can be used with retinal thickness above 250 and VA between 78 and 24 letters. While it is certainly true that we do not want to inject pts with 20/20 of vision, but is also true that without optimal equipment for SDM, standardized protocols and expertise......attempting this in 20/20 eyes is also arguable. The costs of Antivegf are certainly a problem and steroidal inserts are promising ongoing trials.

Safe and effective parameters for SDM have been developed thru over 14 years of clinical experience, corroborated by empirical models like the American National Standards Institutes "Maximum Permissible Exposure" standards, and computational tissue temperature modeling, the results of which all agree. You are correct - safe and effective SDM can only be done with certain laser parameters and certain lasers. It is not possible with CW lasers (which have too narrow a therapeutic range), and is less safe with short wavelength micropulsed lasers (532 and 577nm which also narrow the therapeutic range and are affected by media) However, unlike all other retinal laser procedures, a single set of known SDM laser parameters can be used on all eyes without individual adjustment for lens status, media opacity, fundus coloration, retinal hemorrhage, or degree of retinal thickening. This is the result of the unique attributes of the 810nm laser and a low (5%) micropulse duty cycle. We have just presented transfoveal SDM of eyes with 20/20-20/40 and fovea-involving DME, showing improvement in VA and macular thickness even tho these eyes were "normal" or near normal before treatment. Nothing else can do this safely. For laser parameters see "Information for Retina Specialists" at www.venturacountyretina.com.

Finally, in an RTC Lavinsky et al showed marked superiority of high-density SDM compared to mETDRS in treatment naive eyes with respect to DME reduction and VA improvement. "Less aggressive" suggests SDM if less effective. Overall it is more effective, and likely works exactly the same way as conventional laser, absent tissue damage, inflammation, and functional loss. Thus, SDM presents itself as the first reasonable candidate for preventative treatment of DR.

Jeffery, I read your recent 2012 articles and the OCT images of no damage with reduction of macular edema are impressive. Indeed, this together with promising future uses of SDM in other retinal pathologies involving the RPE is extremely interesting and challenging. Question to all: if the appropriate equipment is not available would antiVEGF be the treatment of choice considering the irreversible damage produced by "conventional grid" in all it's classifications?

Conventional grid if well done does not cause irreversible damage of the retina!!!!

I meant "damage" or better "alterations" on OCT images with respect to SDM and long term adverse effects!

I would have to take exception to Dr. Vingolo's statement. Please define what you mean by "irreversible damage"? Conventional laser photocoagulation is by definition inherently thermally irreversibly damaging to the retina. Indeed, the therapeutic range of CW lasers is so narrow that a therapeutic effect cannot be obtained in any practical terms absent the association with thermal retinal damage. Even low-energy short-pulse CW laser ("subthreshold" al la PASCAL) causes irreversible damage healed by filling-in from adjacent RPE and retinal cells. The acute laser lesions are easily seen by appropriate imaging, as is the healing process. As cells are destroyed and not replaced except by filling-in, and because cellular damage and death is caused resulting in inflammation and loss of functional tissue, the changes are certainly irreversible as I would define them.

PS: Most sensitive indicators of laser-induced retinal damage are fluorescein angiography and fundus autofluorescence or retrograde autofluorescence photography. SD-OCT can miss more easily and is less reliable. Biomicroscopic clinical exam and color fundus photography are by far the least sensitive indicators retinal damage and commonly will miss and underestimate laser-induced retinal damage significantly.

Jeffery consideration addresses crucial point of the question in my opinion autofluorescence is the best way to recognize every damage on the retina even if minimal

For me the anwer today is clearly the combination of inital anti-VEGF and, after flatening of the Retina, an additional (modified!) grid laser Treatment.

I agree with the marco's answer and I follow that strategy but in most of cases my opinion is that the resolutive action is performed by laser grid even in subtreshold way

I premise behind pre-treatment with a drug prior to laser is that, by reducing macular thickness, conventional ("paleo") laser can be performed more effectively at lower energies and is thus less damaging. This is not relevant to SDM because the 810nm laser is unafffected by media opacity, including degree of macular thickness. Done correctly, does not do any retinal damage. My approach is simple: If VA is 20/40 or better, I use only laser. Due to treatment risks, there is no indication for injections with good VA. I am able to successfully manage 90% of eyes with DME and presenting VA of 20/40 with SDM laser alone. If presenting VA is 20/50 or worse, I start with anti-VEGF. This is not to reduce retinal thickness; this is simply to hasten VA improvement. Then I do SDM laser. Overall I am able to successfully manage 70% of DME eyes without any injections using clinically harmless SDM. The safety of SDM allows much earlier treatment, even transfoveal in 20/20 eyes, to prevent worsening and preclude the need for more invasive and risky treatment.

From my point of you even those patients with pretty good VA (but with center involvément, profit from the inital anti VEGF. However, longterm stabilisation may be achieved better by adding the laser...

I agree with jeff

In my opinion anti-VEGF injection into vitreous cavity to reduce macular edema and once macular edema is less this is followed by laser treatment helps to improve the effectiveness of laser and reduce laser energy and damage.

Thats a very important point! I have personally very good experience with navigated laser after anti-VEGF, as its high accuracy and the possibility to plan the treatment on FA images seems to improve outcomes

See above. Focal photocoagulation of microaneurysms requires high energies and short wavelengths which are inherently damaging to the retina and RPE. The value of focal treatment over grid application has never been demonstrated; instead the effectiveness of grid - even more so in the case of SDM which involves "low-intensity/high-density" confluent and contiguous laser application to the areas of pathology - has repeatedly shown effectiveness in the absence of focal treatment. Thus, the risks and adverse effects of focal treatment are unnecessary. FA leakage in DME was shown as early as the ETDRS to have no correlation with retinal thickening, VA, or treatment outcome and is thus of no practical importance. SDM guided by SD-OCT allows more effective and absolutely clinically harmless management of DME without regard to degree of macular edema / thickness or location of swelling as transfoveal treatment of center-involving DME can be performed. SDM increases retinal sensitivity by microperimetry where the laser is applied as opposed to conventional laser like NAVILAS that is destructive and reduces retinal function. Most importantly, the safety of treatments like SDM allow early treatment before visual loss, even in the fovea of center-involving DME, so that visual loss and the need for long-term drug injections, etc, can be avoided and normal visual function preserved. The world is changing. For the better.

This is a dicussion about laser yes/no. subthreshold may be an issue, but to date there is a significant higher level of evidence for the vision stabilizing effect of conventional laser, compared to subthreshold. In addition, the up and down while only injecting may lead in some how to retinal fibrosis too..

Yes. There is far more data on conventional laser because we have done that way for 50 years. But we no longer do intra capsular cataract surgery, open-sky vitrectomy, or implant Leiske lenses, etc. They all worked, too. With all the progress we have made in so many other areas is it not interesting that the concepts and techniques of retinal laser treatment are essentially unchanged in most minds since the 1960s? If we depend on the preponderance of data regarding anything, we will never make progress. We now know unequivocally that we can do effective laser treatment for DME and other disorders harmlessly. Thus the burden of justification now lies with those who continue to do harm. What added important actual benefit can be demonstrated from the retinal damage by conventional laser? Evidence suggests there is none. However, the adverse effects and limitations of conventional laser are many and well-known. Absent evidence otherwise, to answer "we have always done it this way and know it works" falls short.

Because of the risks and adverse effects of conventional laser and intravitreal drugs we must delay treatment until the disease (DME) is bad enough to justify the risks of treatment. We then intervene late in the disease and spend vast amounts of time and money unsuccessfully trying to eliminate the disease and restoring normal visual function. This is the future: to intervene preventatively much earlier before anatomic derangement and visual loss occur to maintain normal visual function and prevent visual loss.

We know that all treatments therapeutically effective for DR treatment also stop, slow, or reverse retinopathy. We know that early treatment of chronic progressive diseases eases management and improves final outcomes. Only treatments as safe as SDM, however, are suitable as early preventative treatment. Chronic physiologic dysfunction (DM) always preceded anatomic derangement (DR, DME, PDR). "Mild" NPDR thus represents not early disease, but advanced disease with end organ damage. When I was a resident I was taught that Kelman's phaco was a crime that blinded people. The preponderance of evidence favored extracapsular surgery. Indeed.

Finally, where do we get "high-level" evidence these days? From big pharma willing and able to pay the bills that they anticipate will help sell their products. Maybe we can convince Novartis to do a multicenter RTC comparing SDM to drugs to see if all of those drug injections are really necessary. But I doubt it.

Jeff, when you treat the macula with SDM, what are you pretending to do?, a RPE photo-stimulation, an inhibition of its VEGF production?, what about the VEGF produced by the Muller cells, and the vascular permeability because of the loss of endothelial and pericits cells? how long does the SDM works?

Camilo, what ever it is I am pretending to do, it works. How, we can only surmise by exclusion. SDM causes no retinal damage, so the old theories regarding laser effects that invoke the therapeutic benefit of retinal scars don't hold. SDM selectively treats the RPE, so SDM does not likely directly affect VEGF production by neuroretina. But it might indirectly, via influence on the RPE. The effect of SDM appears to be as long-lasting as conventional photocoagulation. Therefore, mechanistically while SDM appears to have a drug-like effect via laser photo-stimulation of the RPE - which could be transient - the lasting effect suggests that SDM may be "reprogramming" the RPE, like a computer "reset" or "reboot". I call this the "switch theory". Along this line it is interesting to note that low-duty cycle SDM appears to work clinically equally well throughout a very broad therapeutic range from 18-55xMPE (ANSI 2000). Thus, rather than the laser-intensity dose-response mode we have traditionally associated with conventional laser, SDM seems to produce a given response at the RPE cellular level, which is then amplified and maximized by confluent treatment and recruitment of the RPE in the pathologic area. The dose/response idea applied to SDM then is via treatment density, not treatment intensity. If you think about it, I think you will see this concept fits very well with our current concepts of the pathophysiology of DR. Finally, I am aware of unpublished data from in-vivo hyperspectroscopy that demonstrates intra-RPE metabolic changes elicited by SDM in the absence of any laser-induced morphologic RPE cellular change (thus the absence of detectable laser-induced retinal damage by other imaging modes). In sum, SDM appears to normalize RPE function, and the cascade of effects which follow.

The best treatment will be in the near future, since the laser and specifically anti-VEGF have pros and cones (ocular side effects, systemic side effects , particularly in diabetic patients, tachyphylaxi, etc)

I hope so but at the moment our goal is to improve retinal function/anatomy and spare as more is possible retinal cells for future treatments

Anti-VEGF has completely changed my strategy of treatment in cases with non-proliferative retinopathy and macular edema. First line I start with ant-VEGF and use it for 6-12 months on a PRN base. I use macular grid or focal laser treatment then second line if persistent or recurrrent macular edema is present. By this strategy the structural damage to the retina can be minimized.

Or, you can begin with SDM as clinically harmless, completely non-damaging true subthreshold laser treatment, treat early, prevent rather than treat vision loss, and largely eliminate the need for injections altogether. I prefer this strategy.

www.venturacountyretina.com "Information for Retina Specialists"

I agree with Heinrich anti-VEGF revolutioned treatment of DR.

Certainly, no one would disagree. With respect to science, this site is dedicated to research, and thus gaining new knowledge. As physicians treating patients, rather than the new, our overriding interest in treating our patients is not the new, or the agreed upon (consensus placing us at the peak of the bell-curve at the point of maximum mediocrity and minimal learning), but what is best - what is Ideal. If I am the patient, the Ideal treatment looks like this: Absolutely harmless. Painless. Simple. Easy Quick. Totally effective. Non-invasive. And good once and for all. Thus, the ideal treatment for any disease is the thing that most resembles no treatment at all - but is perfectly effective. Of course, this does not exist. But our interest as doctors is not professional consensus, but what measures are available to us to allow us to treat the patient in the most ideal way. While intravitreal drugs are indeed fabulous, their extreme burden of cost, risks, short action, cause of patient fear and anxiety, and side effects (from VEGF suppression) make them far from ideal. Thus, to provide the most excellent and ideal care for our patients we should be striving to minimize, not maximize, our use of these drugs. Clearly, they are indispensable in advanced disease. However, Ideal disease management is prevention. We know that seat belts and airbags have improved trauma outcomes far more than advances in trauma surgery. Since the dawn of DR in the 60's we have engaged in late intervention for end stage disease. This has been dictated by the risks and adverse effects of existing treatments (retinal photocoagulation, and now intravitreal anti-VEGF agents). This is far from Ideal. Now, we can do better. SDM is all things Ideal except perfectly effective. But it is more effective than conventional photocoagulation, and can be as effective as drugs used correctly. More importantly, because of the safety of SDM it can be used preventively, treating very early to prevent vision loss and prevent difficult to irradiate DME and PDR. When used in this way, use of remarkable but less-than-ideal intravitreal drugs is almost never necessary. So, yes, these drugs are great. But even better is not having to use them at all.

Anti VEGF to decrease edema followed by grid laser to prevent recurrence.