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Room for improvement in anti-VEGF treatment of AMD
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George A. Williams |
LAS VEGAS — The advent of anti-VEGF agents has bolstered the fight against wet age-related macular degeneration, but several unanswered questions remain, according to OSN Retina/Vitreous Section Member George A. Williams, MD.
Dr. Williams posed many of those questions in the retina keynote address at the OSN Las Vegas 2007 meeting. He also presented an overview of the U.S. clinical trials that are evaluating anti-VEGF agents for AMD.
“Our new goal is now visual improvement. We expect patients are going to get better,” Dr. Williams said. “But we still need more information about long-term follow-up and safety.”
Lucentis (ranibizumab, Genentech) is now the “standard of care,” but the current dosing regimens and delivery techniques are less than ideal, he said.
“We also need to improve efficacy for the 60% of patients that do not have that three-line improvement. So we need to identify the adverse predictive factors and investigate combination therapies,” Dr. Williams said.
Surgeons must take into account their patients’ overall quality of life by considering the visual acuity in the non-treated eye as well as the logistical factors and costs associated with treatment, he said.
Other unanswered questions concern the length of treatment, the role of re-treatment and the role of imaging, such as optical coherence tomography and fluorescein angiography, he noted.
“In ophthalmology, we must take the lead in providing these answers to ensure we’re going to have access to this technology for our patients,” he said.
Dr. Williams’ keynote address was one of several new features of the OSN Las Vegas meeting.
Attendees also found a new focus on interactivity, with the use of audience response surveys, the Glaucoma Journal Club and a case-presentation-driven Grand Rounds session.
Led by co-course directors Richard L. Lindstrom, MD, OSN Chief Medical Editor and Louis B. Cantor, MD, OSN Glaucoma Section Member, the new format was designed to offer the comprehensive ophthalmologist the focus on glaucoma that the meeting is known for, with an additional emphasis on cataract and refractive surgery and retina.
Presentations from the OSN Las Vegas meeting are highlighted in the remainder of this article. These items first appeared as daily reports on the OSN SuperSite. Look to upcoming issues of OSN for expanded coverage of selected items.
Glaucoma
Gonioscopy necessary before initiating glaucoma therapy
Gonioscopy is an essential tool for making an accurate diagnosis and understanding the biological mechanisms at work in glaucoma suspects, according to a specialist.
“Gonioscopy is the most important factor in making a correct diagnosis,” said Alan L. Robin, MD, an OSN Glaucoma Section Member.
According to Dr. Robin, less than half — or 45.9% — of respondents to a practice patterns survey conducted by the American Academy of Ophthalmology said they perform gonioscopy at the initial patient consultation.
As for which device is best to use, Dr. Robin said: “I don’ t care as long as you use it.”
He said the Goldmann goniolens and the Zeiss four-mirror goniolens — which are indirect goniolenses — are both excellent. The Zeiss four-mirror device has a small-diameter lens and is ideal for narrow angle indentation, although it is not optimal for visualization of the corneal wedge sign.
Dr. Robin laid out a few tips for properly performing gonioscopy. These include starting with visualization of the interior angle, which is the deepest and most pigmented, having the patient look “over the hill” toward the mirror to obtain a better view of the angle, looking for the corneal wedge and performing indentation gonioscopy.
“By pushing, you can tell the difference between something that is closed and is totally zippered shut and something that has the opportunity to be opened,” Dr. Robin said. “It gives you an idea of the pathology beneath.”
Other gonioscopy tips include examining the other eye for recession or angle-closure disease and using topical glycerin to assist in visualization of factors such as debris, angle closure and peripheral anterior synechia.
Dr. Robin concluded that “gonioscopy is very important, and hopefully by learning these simple tricks … you will learn how to do it much more effectively.”
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Images: Wolkoff L, OSN |
Avoid specific benchmarks when using CCT to determine glaucoma risk
When assessing a patient’s risk of developing glaucoma, clinicians should categorize corneal thickness as “thick, thin or average,” rather than attempting to use an absolute number, a speaker said.
Central corneal thickness (CCT) can be affected by numerous factors, and therefore the use of a specific benchmark could be misleading, Odette V. Callender, MD, said.
“With all the things that can affect the actual measurement and number, it is probably best to look at it as a category of thick, thin or average and not focus on the exact pachymetry number you’re getting,” Dr. Callender said.
For example, it has been found, notably by the Ocular Hypertension Treatment Study (OHTS), that black patients tend to have thinner corneas than white patients. Other studies have found that factors such as corneal drying, diurnal variation, long-term variation, previous refractive surgery and contact lens use can all have a significant impact on CCT.
Race can also play a role in the measurement of cup-to-disc ratio, she said.
“African Americans have larger optic nerves. We know that the cup-to-disc ratio varies with the size of the nerve. All of this says it’s important to assess the size of the disc itself and not just the ratio,” she said.
Dr. Callender recommended using the ISN’T rule when evaluating the optic nerve because it does not vary according to racial characteristics.
“In OHTS, it was found that race is not really the issue, just that black [patients] have thinner corneas and larger optic nerves,” Dr. Callender said. “Look at the ocular characteristics of your patients and not so much the racial characteristics.”
Underlying causes shape secondary glaucoma treatment
The treatment of secondary glaucoma requires an understanding of the underlying causes so that therapies can be tailored to both the reduction of IOP as well as the secondary pathology, according to a presenter.
Eydie Miller-Ellis, MD, spoke on the various causes of secondary glaucoma.
Underlying causes include pseudoexfoliation, pigment dispersion syndrome, steroid-induced pressure spikes, lens-induced pressure spikes, trauma, uveitis and neovascularization, she said.
“There is overlap in medical and surgical therapy for secondary and primary glaucomas, and there are diagnosis- specific interventions,” she said.
One of the newest therapeutic interventions is aimed at neovascular glaucoma due to retinal ischemia. The most common causes of this condition are proliferative diabetic retinopathy, central retinal vein occlusion and carotid artery occlusive disease.
Because several angiogenesis factors have been identified with these pathologies, the off-label use of anti-VEGF agents has emerged as a promising treatment option, Dr. Miller-Ellis said.
“These agents, alone or in combination with PRP [panretinal laser photocoagulation], decrease anterior segment neovascularization,” she said.
Dr. Miller-Ellis explained that, if the angle is open, IOP may improve after regression of the fibrovascular membrane. If the angle is closed, neovascular regression decreases hemorrhagic risk, as well as the risk of inflammation that can accompany glaucoma surgery.
Adjunctive therapy ‘alive and well,’ but individual regimens should be tested
The obvious truths of adjunctive therapy — that patients are less compliant and there are more side effects with more medications — should encourage ophthalmologists to rethink fundamental approaches to it, said a glaucoma specialist. He offered strategies to improve therapeutic outcomes.
“Adjunctive therapy is alive and well,” said Steven T. Simmons, MD, at a CME symposium. The symposium was supported by an unrestricted grant from Allergan. “We can do better with what happens to a lot of our patients with this disease.”
The primary goal when adding a second or third medication is to achieve a 15% IOP reduction, Dr. Simmons said. If that does not occur, he said to try another combination.
In choosing appropriate adjunctive therapy, one major problem is that there are few studies that have been conducted that give insight into what are the best combination therapies.
Another problem that might jeopardize the effectiveness of combination therapy is that a therapeutic regimen might initially work but might not continue to work.
“When was the last time you did a reverse one-eye trial to test whether that patient’s pressures were drifting because of the loss of efficacy or just worsening of the disease before you added a third medication or laser trabeculoplasty?” Dr. Simmons asked the audience.
He said a physician should not assume that a medical therapy foundation built for a patient does not fluctuate.
Cataract/Refractive Surgery
Intracorneal inlays an option for emmetropic presbyopes
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An emerging generation of small-diameter intracorneal inlays could be an excellent option for emmetropic presbyopes, according to a surgeon.
Dr. Lindstrom presented the latest study results for small-diameter intracorneal inlay devices manufactured by Chiron/Bausch & Lomb, Biovision, Intralens and AcuFocus, which was recently purchased by Bausch & Lomb.
While each device presents a different technological spin on the concept, they have all provided promising near and distance results in small patient groups, with patients experiencing significant improvements in distance and near vision.
He said the technology behind the implants is promising for treating presbyopia in this class of patient. In the United States, there are about 62 million emmetropic presbyopes who could benefit from these technologies, he noted.
“A lot of exciting things are coming,” he said. “You’re going to see these products launched outside the U.S. within the next year.”
Four keys help improve the success of cataract surgery
With patient expectations on the rise and cataract surgeons facing increasing pressure to provide near-perfect refractive outcomes, four fundamental keys to successful surgery should be adopted, according to Uday Devgan, MD, FACS.
To meet the needs of younger, more affluent patients with better preop best corrected visual acuity who expect better postop distance results, surgeons must first look to increase refractive accuracy, Dr. Devgan said.
“Patients won’t be happy if you don’t achieve the desired refractive results. Hone your lens [calculations],” he said.
Surgeons should choose an IOL calculation formula and be sure to determine the true K power, particularly in post-LASIK eyes. They should also be sure to “fix postop surprises,” he noted.
Postop remedies might entail an IOL exchange, a piggyback IOL, LASIK, PRK or another refractive procedure.
“If you are not comfortable doing this, it is easy to pair up with a refractive surgeon in your community,” he said.
The second key to successful surgery is addressing astigmatism. Surgeons should take topographic measurements and note the effect of the incisions on corneal flattening. Using paired incisions can reduce astigmatism by about 1 D, Dr. Devgan said.
Limbal relaxing incisions are another technique surgeons should learn to manage postop astigmatism, he added.
The third key to surgical success is to minimize complications and deliver clear corneas. Dr. Devgan advised using a phaco chop technique to minimize ultrasound energy, avoiding complications such as broken lens capsules and switching to silicone-coated phaco tips. He also advised employing an NSAID in every case to reduce the risk of cystoid macular edema.
The final key: “Exceed patient expectations,” Dr. Devgan said.
He advised determining what the patient wants by using a questionnaire or Dell survey and setting realistic postop expectations from the beginning.
“If you want to try new technologies or a new technique, choose your patients very carefully,” he said. The “right” initial patient is a hyperope with low astigmatism and an “easygoing personality,” he said.
These patients are generally not looking for perfect vision and are willing to take the time to adapt to their new vision, he said.
Retina/Vitreous
NSAIDs effective against retinal conditions
The ability of topical nonsteroidal anti-inflammatory drugs to penetrate the back of the eye and suppress retinal inflammation makes them effective potential therapies for stabilizing or improving vision in patients with a variety of retinal disorders, according to Ronald P. Gallemore, MD, PhD.
Dr. Gallemore discussed the use of NSAIDs at a CME symposium sponsored by Ista Pharmaceuticals.
He first pointed to a randomized controlled study of 546 patients with pseudophakic cystoid macular edema (CME). Researchers found that adding an NSAID to a steroidal regimen reduced the overall incidence of CME vs. steroids alone, he said.
A separate study of 85 patients with CME found that using NSAIDs alone resulted in a 12 to 16 letter gain in visual acuity, he said.
Additionally, “NSAIDs might provide an adjunctive therapy for DME (diabetic macular edema). You can put a chronic NSAID on the eyeball and stabilize the eye, and you might reduce the need for other treatments,” Dr. Gallemore said.
NSAIDs may also be effective against retinal vein occlusion, a condition that is known to recur despite treatment, Dr. Gallemore said.
“But in some patients, it can break the cycle and stabilize the eye, and the patients without corneal problems seem to tolerate it well and stay on this stuff for sometimes years,” Dr. Gallemore said.
Patients with epiretinal membranes and DME may respond to NSAIDs, he said. One patient who did not want to undergo vitrectomy improved from 20/50 to 20/30 on a once-daily NSAID regimen, he said.
“Ninety percent of the time they still go on to have surgery, but there are definitely some patients who respond pretty well to this regimen,” he said.
When choosing an NSAID to use as a retinal treatment, surgeons must consider potency, penetration, patient compliance and efficacy, he said.
“The jury is still out on relative efficacies … all these drugs seem to be beneficial in some settings,” he added. Larger studies of more retinal disorders are planned, he said.
A note from the editors:
To facilitate bringing news to readers rapidly, for OSN SuperSite articles and meeting wrap-up articles, OSN departs from its editorial policy and typically does not send these items out for source corrections.