Wrapping Up a Year in Retina

A final sampling from our 2011 annual meeting offers guidance on imaging, surgical technique and the status of several investigational therapies.

Andrew E. Mathis, PhD, Medical Editor • Robert Murphy, Contributing Editor

Each year, the Retinal Physician Symposium presents many of the latest findings in clinical research and expert recommendations for surgery. At the seventh annual meeting, held earlier in 2011, leaders in the field of retina spoke about a diverse range of topics in medical and surgical care. As we look forward to the 2012 meeting (March 28-31 in Miami Beach), we conclude our coverage of the 2011 RPS with the following highlights.

DAVID BOYER ON NEUROPROTECTION AND VISUAL CYCLE MODULATION

A presentation given by David Boyer, MD of Los Angeles, focused on two approaches, neuroprotection and visual cycle modulation. Currently, at least three drugs have been designed and are being tested for neuroprotection. One is a ciliary neurotrophic factor (CNTF), presently called NT50. Another is intravitreal brimonidine tartrate. A third is topical tandosporine.

• CNTF. This growth factor is capable of rescuing dying photoreceptors and protecting them from degeneration. A minor surgical procedure is required to implant the drugde livery system and enable long-term dispersion of biologics. A small incision is made and a tube is sutured into the wound, after which the wound is closed. The implant is well tolerated. Within this chamber, pigment epithelial cells that have been modified by CNTF are then released while oxygen and other nutrients enter the implant.

Two phase 2 studies have been undertaken. One study looked at its effect in retinitis pigmentosa, another in geographic atrophy.

Patients in the geographic atrophy study were at least 50 years old, with vision from 20/50 to 20/200. No significant safety events occurred. The procedure and implant were well tolerated. There was no retinal detachment, endophthalmitis, increased intraocular pressure or choroidal neovascularization. No CNTF was detected in the systemic circulation, nor were antibodies found.

OCT revealed a dose-dependent retinal thickness increase in terms of total macular volume. Increased retinal thickness appeared at month four and continued through month 18 (Figure 1). This was associated with a trend toward an emerging visual acuity benefit at months 12 and 18. But the numbers were very small, casting doubt on the apparent visual stabilization.

Figure 1. Increased retinal thickness appeared at month four and continued through month 18.

However, if you look at the subset of patients with good baseline vision — 20/50 to 20/63 — those receiving the high dose apparently enjoyed visual improvement compared with those getting the low or sham dose (Figure 2). Even those with 20/80 at baseline had visual improvement with the high dose.

Figure 2. Patients receiving the high dose enjoyed VA improvement compared with those getting the low dose.

But once central vision is lost, there is no improvement. This makes sense, Dr. Boyer observed. This treatment will not necessarily restore vision in a patient who has lost it, as those cells are nonfunctioning. However, if you treat a patient who hasn't quite lost his vision, it may prevent future vision loss to the viable remaining photoreceptors.

Concerning progression of geographic atrophy, the change from baseline in the treated group was insignificant. There appeared to be no change in the lesion size with treatment; however, the sham control arm did not show progression either.

The implanted devices showed no signs of inflammation. There was long-term viability. The implants were removed at 24 months (Figure 3). Some patients requested that they not be removed and thus still have them in their eye.

Figure 3. The explanted devices demonstrated the long-term viability of CNTF.

• Brimonidine tartrate. This alpha-2 adrenergic receptor agonist is virtually the same compound used to treat glaucoma. It is also neuroprotective in animal and other experimental models. It protects retinal ganglion cells — obviously good for glaucoma — as well as bipolar cells and photoreceptors.

Brimonidine's effects were noted in numerous insults. Crush injuries, ischemic changes, ocular hypertension and phototoxicity all showed protection with brimonidine.

It's administered the same as the dexamethasone long-acting implant (Ozurdex): delivery through an injector system in the office. The trial was a primary comparison of treated and untreated eyes.

• Tandosporine. Code named AL-8309b, this compound is a topical selective serotonin 1A agonist, already approved in Japan for systemic use. Early trials here show that it is neuroprotective in animals. Investigators found a dose-dependent protective effect on photoreceptors and RPE cells in photo-oxidative stress.

Tandosporine is mediated by an unusual avenue; namely, the survival pathway. Therefore, it induces increased resistance to oxidative stress. It also instigates expression of antiapoptotic proteins and blocks cell death. Tandosporine's protective effects are receptor-mediated, and require both genetic transcription and translation. Its oxidative byproducts — carboxymethylpyrrole adducts and antibodies — which are elevated in AMD, seem to be reduced with this drug.

Tandosporine is currently in a fairly large phase 2 trial with three groups of 180 each.

Visual cycle modulation is a different way of approaching the problem of photoreceptor and RPE loss. The visual cycle can be illustrated by turning on rhodopsin and observing it all the way through the 11-cis-retinol production. Here, you can block formation of A2E and other stable toxic metabolites, thereby slowing down the visual cycle, avoiding the build-up of A2E and perhaps blocking some of the atrophic progression that might otherwise occur.

Associated with photoreceptor death and A2E retinal accumulation, you also see accumulation of autofluorescence. If you can reduce this, Dr. Boyer, noted, you may also be able to limit the lesion's progression. A2E destabilizes the cell membranes, while interfering with metabolism and downstream complement activation.

Two drugs for visual cycle modulation are worth mentioning. Visual cycle modulation generally slows the activity of the rods. It reduces the metabolic load on the cones and the rod cell deterioration that commonly comes with aging. Visual cycle modulation also reduces the accumulation of toxic fluorophores and prevents photoreceptor and RPE cell loss.

• Acucela (ACU-4429). This drug prevents the conversion of 11-cis-retinol by blocking RPE-65. It's a small molecule that is selective for rod photoreceptors. This is important, because the rods seem to cause most of the A2 accumulation, Dr .Boyer noted. It has been shown to be effective in animal models with retinopathy of prematurity. Acucela is designed to prevent or inhibit the generation of toxic byproducts by slowing the rod visual cycle.

In phase 1 and 2 studies, 125 healthy subjects received a well-tolerated dose. No significant adverse events occurred. Patients showed a good pharmacologic response even at low doses. There was no change in cone energies, only in rod suppression, a response that was clearly dose-dependent. Obviously, this would lead to night blindness, so one has to temper the dose. Phase 2 continues with 83 patients.

• Fenretidine. This derivative of vitamin A has numerous properties: chemo-preventative, apoptotic, antiandrogenic and anti-inflammatory. Johnson & Johnson developed fenretidine many years ago as an adjunctive treatment for metastatic breast cancer, but it proved ineffective. Its adverse events coincide with those of the retinoids and diminish over time. Its primary mechanism blocks all-trans-retinol from going up to the cycle and prevents its formation.

Some background, in brief: In a normal eye, retinal vitamin A is, of course, used to produce vision. It is recycled and then regenerated by the liver. Beyond that, it is the retinol binding protein that retrieves retinol from the liver. Transthyretin transports retinol to the retina, and the cycle continues. In patients genetically predisposed to AMD, and certain others, the recycling process is compromised. A build-up of waste products damages RPE cells, with eventual loss of pigment epithelial cells.

This is where fenretidine comes in. The retinol-binding protein grabbing the retinol and transthyretin is a large molecule, and because it cannot be excreted through the kidneys, it persists in the system. Meanwhile, there is no loss of transthyretin or retinol-binding protein. When you add fenretidine, it “grabs” the retinol-binding protein yet doesn't allow the retinol to bind. Fenretidine is a smaller molecule, which allows the retinol-binding protein to excrete in the urine. The level of retinol-binding protein is now reduced, just as the amount of retinol grabbed from the liver is diminished. This process in turn down-regulates the visual system.

The theory was that if you reduce the serum retinolbinding protein, you'll slow the growth of geographic atrophy. Work with a Stargardt mouse model showed some improvement. A study in human subjects included three groups, a placebo, 100 mg of fenretidine and 300 mg of the drug. The study enrolled 246 subjects, of whom 68 withdrew early.

Median lesion growth was one endpoint. At 18 months, the high dose seemed to show improvement in lesion size, but this was not carried out to 24 months. The study administrators discovered a change in the formulation occurring around the 12-month point. By this point, some subjects already had gone out to 18 months and received the regular dose. Some subjects had even extended out to 24 months.

When you looked at people who had started the study with the original formulation and completed the regimen, they showed a decrease in lesion growth. These were people who received the same drug all the way through 24 months. The rest received the modified drug, which was not as bioavailable and had a large particle size.

Looking at patients who received the same dose all the way through (“early enrollers”), they actually had retinol-binding protein that was lower throughout the study. But this effect was lost at about 18 months in patients who received the modified medication. The same goes for vision. The early enrollers maintained their vision, yet was lower than the late enrollers who received a different dose in the last part of the study.

The most interesting and surprising outcome is that fenretidine reduced the incidence of choroidal neovascularization by 50%. Of the placebo group at 24 months, 22% developed choroidal neovascularization. Of those receiving fenretidine 100 mg or 300 mg, 13.5% and 13.8% displayed CNV — roughly half in both treatment groups compared with the placebo group.

Twenty-two of the placebo group with CNV seemed high in a 24-month study of geographic atrophy. But it makes sense when you think about it. Fenretidine was originally tested as an adjunct for patients with meta static breast cancer, owing to the drug's anti-VEGF properties. Likewise, in this study it showed reduction in VEGF expression. It makes sense that if the drug is given early, before CNV develops, it may suppress new vessel growth.

Adverse events deserve mention. Patients with geographic atrophy and other forms of dry AMD have a high incidence of dark-adaptation problems. They have trouble driving at night even though their vision may be 20/20 or 20/30. Researchers and companies are looking at dark-adaptation problems as one of the earliest signs of developing age-related macular degeneration. In this study, nearly 30% of the placebo group was symptomatic, while 37% of the treated groups experienced dark-adaptation problems at night. Some of these were rather severe, meaning patients could not drive home after the study. In other settings, they could not drive home from the office after working later than sunset.

From this study, we can conclude that fenretidine slowed the lesion growth in some patients with geographic atrophy, and seemed to correlate with decreased levels of retinol binding. Fenretidine reduced the incidence of CNV in both treatment arms, and was generally well tolerated. The drug's developers are moving onto a phase 3 trial.

JAY DUKER ON DIABETIC RETINOPATHY IMAGING

Retinal imaging expert Jay Duker, MD, director of the New England Eye Center, spoke about the use of imaging in diabetic retinopathy (DR). Dr. Duker gave a comprehensive overview of imaging in DR, with a special emphasis on how the use of optical coherence tomography has evolved over the last several years and how it should and should not be used.

Dr. Duker discussed all four types of imaging available: fundus photography, fluorescein angiography, B scan ultrasonography and OCT, including the four types of fundus photos (central, widefield, stereo and ETDRS standard field) and two types of FA (standard and widefield). These imaging modalities help the clinician in documenting disease, including the progression or regression of DR, and make the diagnosis of proliferative DR or retinal detachment, particularly in the case of cloudy media or shallow fluid.

According to Dr. Duker, FA is becoming less and less important in following diabetic retinopathy patients. Dr. Duker then turned to a more specific discussion of fundus photography. Reiterating the four subtypes of fundus photos, Dr. Duker briefly asked the audience how many used the DR levels (10 to 53) established by the Early Treatment of Diabetic Retinopathy Study. Seeing few hands, he said, “I think it's just not something we use clinically,” although he submitted that, for research purposes, the levels are useful.

As far as “standard” macular fundus photography is concerned, Dr. Duker said, its advantages are that it is easy and readily available and that certain morphological features, such as hard exudates, are most easily seen with fundus photos. However, it cannot confirm clinically significant macular edema (CSME), and its usefulness when there is media opacity is limited.

Here, Dr. Duker made an important point about compensation for imaging studies, noting that Medicare will only cover one ancillary imaging test per patient visit. If there are two or more different diagnoses in a patient, then that patient may be a candidate to undergo more than one modality and they may be reimbursed. However, he said, going forward, doing so will be more difficult, so it is most important that the best modality be chosen and that extraneous imaging studies not be done. At this point, Dr. Duker showed the first of several case study slides. The case he showed was of a patient with diabetic macular edema whose case resolved in two years' time without treatment (Figure 4).

Figure 4. Dr. Duker's first case study was of a patient with DME whose case resolved in two years' time.

Regarding stereo fundus photography, Dr. Duker noted that, while this type of photography has been useful in landmark studies to document progression of DR over time, it is almost never used clinically. This lack of use is a result of its time-consuming nature and the requirement of a trained reader to interpret the results. Furthermore, it cannot replace a comprehensive eye exam, and other types of imaging studies are more accurate in diagnosing DME.

Next, Dr. Duker very briefly discussed B-scan ultrasonography, which is very useful in the presence of media opacity and is a particularly good aid in diagnosis retinal detachment and determining the need for surgery. Then, Dr. Duker moved on to FA, which he characterized as the best imaging modality for highlighting microaneurysms and showing ischemia, as well as diagnosing PDR, although it is possible to diagnose PDR without FA.

A slide Dr. Duker showed here (Figure 5) provided a particularly good demonstration of how FA can image macular ischemia. “I think it's nice to know if macular ischemia is present,” Dr. Duker said, conceding that it is not always correlated with visual outcomes. The downsides to FA are that it was not used in the ETDRS (hence not useful in diagnosing CSME) and that it is also not particularly useful in DME, regarding either treatment parameters or outcomes.

Figure 5. Another of Dr. Duker's slides demonstrated how well FA can image macular ischemia.

There are widefield FA systems that can provide some useful information, Dr. Duker said. For instance, the ability to provide montage images (Figure 6) can be helpful in meeting certain diagnostic criteria, and it shows the peripheral retina much better. However, its value in altering outcomes tends to be anecdotal thus far.

Figure 6. FA is also versatile in its ability to provide montages of retinal images.

The remainder of Dr. Duker's presentation dealt with the use of OCT in DR. First, he provided a brief overview of DME and its subtypes (cystoid, focal and diffuse). Clinical diagnosis is still made at the slit lamp, and no ancillary testing is involved in the diagnosis.

What has changed, Dr. Duker said, is that newer medical treatments are available, and OCT can visualize and quantify macular thickening. Then, in bringing his presentation of OCT utility up to date, Dr. Duker stated that OCT is now the critical test to determine proper treatment of DME and the gold standard for the diagnosis of vitreomacular traction and taut posterior hyaloid and whether surgery is indicated. OCT can also distinguish between CSME and subclinical macular edema.

Here, Dr. Duker provided two case studies to demonstrate the principles discussed thus far. In the first (Figures 7 and 8), a 32-year-old diabetic woman with no light perception in the right eye after a vitrectomy had greatly reduced vision (from 20/30 to 20/200) in the left eye. To determine whether she had a retinal detachment, OCT was performed, which concluded that she did not have a detachment but instead a subhyaloid hemorrhage that would not require a vitrectomy. The second case (Figures 9 and 10) was of a 66-year-old diabetic man who had been treated with focal laser five years earlier. There was definite hard exudate, but the OCT did demonstrate cystic spaces without thickening, which required closer follow-up without further therapy.

Figure 7. A 32-year-old diabetic woman with NLP OD had reduced VA in the OS.

Figure 8. Vision in the right eye had decreased from 20/30 to 20/200.

Figure 9. A 66-year-old diabetic man had hard exudate in an eye previously treated with focal laser.

Figure 10. OCT demonstrated cystic spaces without thickening.

So what is the benefit of OCT in diagnosis and screening, Dr. Duker asked? In short, he said, “What if we took all the diabetics out there and threw them in an OCT and looked to see if they had macular edema. Is that a good idea or a bad idea?” There is no clinical evidence, Dr. Duker said, to indicate OCT is an effective screening tool. In a study done by the DRCR.net, OCT detected subclinical DME in 4% of cases in which it had not been seen clinically, which Dr. Duker called a surprising low number, probably indicating how well the earlier study had done in detecting subclinical DME.

Here, Dr. Duker turned to a case of a completely asymptomatic diabetic patient whose OCT showed some retinal thickening (Figures 11 and 12). This was the fellow eye of an eye with macular edema, and the ability to visualize sub-clinical macular edema in this patient led to a shorter period before the next follow up.

Figure 11. Another patient with macular edema in the fellow eye presented without symptoms.

Figure 12. The OCT showed some retinal thickening, and the ability to visualize this thickening shortened treatment time.

Dr. Duker quickly reviewed Peter Kaiser's four types of macular edema by their prevalence (focal/diffuse, 60% to 90%; cystoid, 50%; serous macular detachment, 15%; mechanical, with hyaloid traction or epiretinal membrane, 16%). Cases of mechanical retinal detachment are resistant to laser but may respond to surgery.

To demonstrate, Dr. Duker provided a case of a 76-year-old woman with 20/400 visual acuity in the left eye and ERM in the right eye. An OCT of the left eye revealed a “volcano-like” vitreomacular detachment that was treated with vitrectomy. One year later, she had 20/40 vision OD.

After providing two more cases of patients treated for DME who were followed with OCT, demonstrating, he said, that “laser works — but it often works slowly,” Dr. Duker suggested that the future may hold a redefinition of CSME based on OCT data, as well as its use in the treatment of subclinical DME. It may also provide anatomic landmarks, such as the IS/OS junction and photoreceptor mosaic, to link structure to function.

PRAVIN DUGEL ON MICROINCISION VITRECTOMY SURGERY

In a presentation on microincision surgery, Phoenix retinal surgeon Pravin Dugel, MD, described dissection techniques with new instrumentation designed to improve and simplify the way surgeons perform surgical dissection. As a consultant to Alcon, Dr. Dugel's experience and presentation are limited to the Alcon Constellation system, although the concepts he described do apply to other instruments as well.

Dr. Dugel noted in his lectures that his most difficult cases are diabetic tractional retinal detachments. These he divides according to the type of dissection used. Some 75% of cases call for the proportional reflux hydrodissection technique. The volume of these cases has expanded, as Dr. Dugel has become more familiar with the technique, one that he says is efficient and easy to use. Another 15% of his cases are best suited for proportional viscodissection. The final 10% are the most difficult cases, for which Dr. Dugel uses bimanual dissection.

Beginning with the last and working backward, Dr. Dugel stated that bimanual dissection techniques remain largely unchanged from conventional methods. The biggest change is the illumination, which he noted has greatly improved in recent years. The instrumentation is now more advanced as well. Proportional viscodissection offers significant advances over previous viscodissection techniques. Dr. Dugel said that he always found the concept of viscodissection appealing — to separate good tissue from bad and have a plane that clearly demarcates the two, separated by a layer of viscoelastic. What he does not like is having to inject posteriorly and trying to find a plane underneath the affected area. And there is no way to do this without having to inject it.

Instead, Dr. Dugel said, the surgeon can attach a 26-gauge lacrimal cannula to the vitreous fluid control port and fill it up with viscoelastic. Dr. Dugel uses Viscoat because he likes how it coats the vessels and stops the bleeding, although other viscoelastics are also indicated as the surgeon's discretion and experience level allows. The surgeon can control this very easily.

Most of Dr. Dugel's discussion, however, focused on the technique he uses most often and finds most exciting: proportional reflux hydrodissection. When removing tissue using this technique, he works toward two basic goals: safety and efficiency.

Safety brings up two key concerns. One has to do with the ultrahigh cut rate used in this procedure; the other issue is the so-called sphere of influence of the surgical instrument used at any given time. Also worth mentioning is why Dr. Dugel prefers 25-gauge surgery vs a larger-gauge procedure.

Concerning the cut rate, note that the cutter's suction force is roughly conical, Dr. Dugel said. The volume re moved is therefore consistent. What varies is the amount of pull based on the length of collagen pull. Vitreous in closer proximity to the cutter experiences greater pull.

If you go to a higher cut rate, Dr. Dugel continued, everything shrinks. If you compare a higher cut rate with a lower one, at all distances from the cutter's tip, the length of the collagen fiber pull will always be less with a higher cut rate. This means the higher cut rate will always be safer than the lower one.

Next, Dr. Dugel discussed the sphere of influence, an important new concept that came to him when he and colleagues set up a simple cantilever experiment. A needle attaches to what looks like tissue, while a probe can be placed at any distance. The probe can be set at any parameter. Using high-speed cinematography, the surgeon measures when the cantilever moves and attracts tissue.

Dr. Dugel and colleagues found that, looking at any distance, a larger gauge requires a higher flow to attract tissue than does a smaller gauge at the same distance. To cause tissue attraction at the same distance, the amount of flow required is almost twice as much with a 20-gauge probe vs a 25-gauge. The larger the gauge, the higher the required flow from the same distance.

What Dr. Dugel calls “the vacuum cleaner experiment” illustrated the concept of reduced sphere of influence. “Pretend there's a pile of M&M candies on a table,” Dr. Dugel told the audience. “Imagine the green ones represent fibrous tissue and the others healthy retina. Your goal in surgery is to remove fibrous tissue yet not incarcerate retina. Now envision large-gauge surgery as a vacuum cleaner that picks up not just the green candies (fibrous tissue) but all the others too (healthy retina). Now look what happens if you change to a smaller gauge. You can pick up the green candies without incarcerating normal retinal tissue.” This is why Dr. Dugel uses a smaller gauge — because he requires less flow, and it is much more accurate.

Pivoting from safety to efficiency, Dr. Dugel came next to duty cycle control. Duty cycle is the percentage of time the cutter remains open at a given rate. Adjusting the cutter's duty cycle means the surgeon can use it as a multifunctional tool. Duty cycle is expressed it in terms of bias, so duty cycle can be at a shave bias or closed, where the flow is decreased. It can be 50-50, an open bias, or a core bias, where the flow is increased.

Duty cycle for Dr. Dugel is not important in the vitreous because there he wants to use highest possible cut rate. Duty cycle does not matter much when the surgeon is using the highest cut rate. But duty cycle is extremely important when there is no vitreous, because the surgeon can then morph his or her cutter into a horizontal scissors, or vertical scissors, or even a phacofragmatome.

Dr. Dugel went on to describe the proportional reflux hydrodissection technique. The old cutters had an impulse reflux. The idea was that, if the surgeon inadvertently incarcerated retina, he or she could click the foot pedal to the left or right as needed, and a pulse of water would come out and disincarcerate the retina.

The new device uses proportional reflux. Instead of just having a pulse, the surgeon has a controlled stream of fluid. Pressing down on the pedal, the surgeon can control exactly how much fluid disperses.

Dr. Dugel described several clinical applications for proportional reflux hydrodissection, which can be used to create a small amount of separation and a reduced sphere of influence in a traction retinal detachment case.

In a case highlighting sphere of influence, the surgeon can easily control a wayward piece of tissue by removing it from the retina, thanks to a small sphere of influence. You can therefore take it away without incarcerating retina.

There is also a peel-back technique that surgeons can use with proportional reflux hydrodissection. The surgeon approaches the tissue from reverse angle and has it folded back into the cutter at a high cut rate. If the cut rate is high and the surgeon's sphere of influence is small, then the surgeon will not incarcerate retina and will only incarcerate fibrous tissue. Outside-in peeling creates an epicenter, which the surgeon can remove because you sphere of influence is small.

Another application is a combined traction rhegmatgenous retinal detachment. Clicking the foot pedal, fluid emerges and creates a separation. Not only does it separate good tissue from bad, it also pushes back the detached retina. Then you go underneath and peel outside-in toward the epicenter. The tissue bunches up toward the epicenter. This you can easily remove, because the sphere of influence is small, and the surgeon does not have to worry about incarcerating retina.

With the fold-back technique, the surgeon approaches from the reverse, rather than the front angle. There, the surgeon can fold back the tissue nicely to its proper location. “Use this fold-back technique with an ultrahigh cut rate,” Dr. Dugel recommended.

“Imagine a severely ischemic eye with a combined traction rhegmatogenous retinal detachment,” Dr. Dugel continued. “Proportional reflux hydrodissection creates little spaces, allowing you to get underneath and then peel from the outside in. Locate your epicenter, and remove it knowing that your sphere of influence is small.”

Normally, in a case involving two epicenters, Dr. Dugel explained, the surgeon can just leave this alone. However, if the surgeon is confident that he or she can remove everything, then there is no reason to leave behind epicenters when the surgeon can remove them without incarcerating retina.

The surgeon can also use the cutter as a phacofragmatome. Consider a piece of lens material that could not be removed with a 25-gauge alone. If the surgeon reduces the cut rate to 100 — since there is no vitreous — he or she can now use a core (rather than shave) duty cycle and can then fully incarcerate the lens material into the port.

With this device, there are three folders: horizontal scissors, vertical scissors and phacofragmatome. Each has built-in flow control and other parameters. What no one should be doing in a stressful situation, Dr. Dugel said, is trying to think of numbers. Therefore, the surgeon works at 5,000 cuts per minute for a core vitrectomy. Then, the surgeon recognizes the situation — for instance, lens material — and then clicks to obtain the proper parameters.

This is an evolving technology about which surgeons are learning more and more, Dr. Dugel said in conclusion. He uses proportional reflux hydrodissection with increasingly greater frequency. Ultimately, surgeons are looking for maximum safety and efficiency. Safety comes largely from an ultrahigh cut rate, as well as a reduced sphere of influence. Efficiency comes from understanding duty cycle control, using the cutter in multifunctional ways and comprehending new dissection techniques.

LOOKING AHEAD

The eighth Retinal Physician Symposium will be held this March 28 to 31 in Miami Beach. Lectures that are both comprehensive and candid will again be the hallmark of the education. Information on this year's panel can be found all below. RP

Program Topics Will Include*: • Choosing the best anti-VEGF for age-related macular degeneration • Classification of CNV: Do we need a new standard? • CNV masquerade syndromes: Diagnosis and management • Treatment algorithms for diabetic macular edema • Tricks for spectral domain OCT • Anti-VEGF, steroids, laser: What is best for retinal vein occlusions?

Expert Faculty Will Include*: EDUCATION DIRECTOR Jason S. Slakter, MD Vitreoretinal Surgeon and Macular Disease Specialty, Vitreous-Retina-Macula Consultants of New York, New York, NY EDUCATION COORDINATOR Peter K. Kaiser, MD Vitreoretinal Specialist, Cole Eye Institute, The Cleveland Clinic, Cleveland, OH FACULTY: David M. Brown, MD, FACS Clinical Associate Professor, Methodist Hospital, Houston, TX Pravin Dugel, MD Clinical Associate Professor, Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA Managing Partner, Retinal Consultants of Arizona, Sun City, AZ Justis P. Ehlers, MD Physician, Cole Eye Institute, The Cleveland Clinic, Cleveland, OH Bailey Freund, MD Retinal Specialist, Vitreous-Retina Macula Consultants of New York, New York, NY Clinical Associate Professor of Ophthalmology, New York University School of Medicine, New York, NY Staff Member, New York-Presbyterian Hospital, Eye, Ear & Throat Hospital, and Lenox Hill Hospital, New York, NY Jeffrey S. Heier, MD Retina Specialist, Ophthalmic Consultants of Boston, Boston, MA Carol Shields, MD Co-Director, Oncology Service, Wills Eye Institute, Philadelphia, PA Professor of Ophthalmology, Thomas Jefferson University, Philadelphia, PA Jerry Shields, MD Director, Oncology Service, Wills Eye Institute, Philadelphia, PA Professor of Ophthalmology, Thomas Jefferson University, Philadelphia, PA Sonia H. Yoo, MD Professor of Ophthalmology, Bascom Palmer Eye Institute, Miami, FL

Eden Roc Renaissance, Miami Beach, FL Overlooking world-renowned Miami Beach, on prestigious Millionaire's Row, the Eden Roc Renaissance embraces its role as a timeless treasure, blending iconic style, modern architecture and contemporary glamour. Famous for being host to Hollywood greats like Elizabeth Taylor, Katharine Hepburn, Lauren Bacall and Humphrey Bogart since 1956, Eden Roc continues to enchant guests and celebrities alike. Experience breathtaking views of Miami Beach from the comfort of spacious guest rooms, suites and bungalows. Eden Roc Renaissance • 4525 Collins Avenue • Miami Beach, FL 33140 • 800-468-3571 • www.edenrocmiami.com Room Rate: $299 Reservations must be made by February 28, 2012. Please refer to Retinal Physician Symposium to receive the special rate. Rooms not reserved by this date are subject to the hotel's availability and prevailing rate. Please make reservations as early as possible as the group room block may sell out before the actual cutoff date.

RPS Keeps You in Touch with the Trends — and the Trendsetters Peter K. Kaiser, MD, Education Coordinator

The 8th Annual Retinal Physician Symposium will take place from March 28-31, 2012 at the awesome Eden Roc Renaissance Resort in Miami Beach, FL. The resort is located on Collins Avenue directly on the beach with four pools to relax in, a wonderful spa, and close proximity to excellent restaurants and shopping when you don't want to relax. RPS is a meeting for you and your whole family to enjoy and rejuvenate from the winter blues. From an educational front, for those of you who have not made it to RPS, it is unlike any other meeting you may have attended in the past. The “lectures” are designed so that the speaker has less time than the questions afterward so each topic is explored in depth. The discussions are truly the best part of this meeting with everyone taking part in the discussion. Other meetings let you listen to great speakers, at RPS we want the audience to interact with our faculty. This year we return an incredible faculty list culled from the editorial board of Retinal Physician including Drs. Brown, Shields (both!), Murray, Flynn, Freund, Srivistava, Dugel, Slakter, Ehlers, Moshfeghi and Heier. Topics germane to your practice will be explored in great detail including: management of AMD masquerade syndromes, diagnosis and differential management of various CNV subtypes, updates on all the approved drugs, implications of CATT on clinical practice, new imaging tricks and techniques, diabetic surgery, uveitis cases, tumor cases and the latest updates from clinical trials. On Wednesday evening, we will once again hold the pre-conference Drug Development Forum chaired by Emmett Cunningham and Quinton Oswald. This exciting format brings together Wall Street analysts, venture capital, preclinical companies, clinical companies, and CROs to discuss drug development strategies. We hope you will bring your talent to Miami Beach and join us at RPS 8.