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New treatments provide hope for posterior pole diseases
The emergence of new posterior pole treatments holds promise for managing several retinal diseases, including posterior uveitis, diabetic macular edema and age-related macular degeneration.
New data on treatments such as rheophoresis and photodynamic therapy (PDT) with Visudyne (verteporfin for injection, Novartis), as well as “in the eye” medications such as Retisert (fluocinolone acetonide implant, Bausch & Lomb) and anecortave acetate (Alcon), may hold the key to combating some of the most perplexing ocular diseases.
Photodynamic therapy: new uses
Approved for the wet form of AMD, PDT treats abnormal blood vessels that grow beneath the retina, secondary to AMD and other retinal diseases. Although PDT continues to be useful for treating this condition, clinicians are exploring other areas in which it might be useful.
“When this was first approved by the FDA, there was a lot of hope that this treatment would finally reverse a lot of the damage from AMD,” said Steven Rose, MD, a practitioner in Rochester, N.Y.
Dr. Rose said during the past 4 years, he and his colleagues discovered that while PDT does slow the progression of AMD in a majority of patients, it is unlikely to reverse vision loss. However, it allows some to continue driving.
Dr. Rose said he has begun to use PDT for patients who have subretinal neovascular growth due to histoplasmosis, myopia and in those cases described as “idiopathic.” He said that younger patients who suffer from these conditions seem to reap more of a benefit from PDT.
“This is a drug that circulates through the bloodstream and binds to receptors in abnormal blood vessels,” he said. “There is a sense that younger patients may have more receptors for this drug to bind; therefore, the treatment effect may be greater in younger patients vs. older patients with AMD.”
Dr. Rose said he has been very encouraged by the results of the treatment of patients with subretinal neovascular growth. “The results in these younger patients, compared to the macular degeneration patients, are more impressive, both from a vision-preserving standpoint and the shorter course of treatment that’s required,” he said.
New data on rheophoresis
Rheophoresis blood filtration has shown great potential in treating certain forms of AMD. Rheophoresis is the subject of an FDA clinical trial sponsored by Vascular Sciences Corp. based in Tampa, Fla.
“There may be a significant subjective improvement in vision for some people who undergo rheophoresis,” said John Potter, OD, a practitioner in Dallas. “They have better distance vision, better peripheral vision and better scores on reading tests.”
Dr. Potter cited a study published in the Transactions of the American Ophthalmological Society, 2002;100:85-108. This multicenter, prospective, randomized, double-masked placebo study evaluated the safety of rheophoresis blood filtration to treat intermediate- to late-stage preangiogenic AMD with soft drusen.
The participants included 43 randomized patients (28 to rheophoresis and 15 to placebo) with available baseline and 3-month postbaseline best-corrected visual acuity (BCVA) measurements and intermediate- to late-stage preangiogenic AMD with multiple large soft drusen.
Patients were randomly assigned to receive eight rheophoresis or eight placebo procedures over 10 weeks. The main outcome measures were ETDRS [Early Treatment Diabetic Retinopathy Study] BCVA measurements at baseline and at 3, 6, 9 and 12 months post-baseline.
The study found that, in primary eyes, the mean logMAR line difference between rheophoresis and placebo-controlled eyes was 1.6 lines at 12 months post-baseline; the difference was significant throughout the first post-treatment year. Thirteen percent of rheophoresis-treated eyes compared with 0% of placebo-controlled eyes had a more than three-line improvement in BCVA at 12 months post baseline.
Four percent of rheophoresis-treated eyes compared with 18% of placebo-controlled eyes had a more than three-line loss in BCVA.
The subgroup of patients whose primary eyes had baseline BCVA worse than 20/40 demonstrated a logMAR difference between rheophoresis and placebo-controlled eyes equaling 3.0 lines at 12 months postbaseline; the difference was significant throughout the first post-treatment year.
“The easiest way to think about this is, at the end of 12 months, one of four people who were randomized to no treatment in the clinical trial lost three lines or more,” Dr. Potter said. “Of those who were treated, one out of 20 lost three lines or more.”
Dr. Potter said the study showed primarily that rheophoresis slows the progression of vision loss. “These trials have shown two things: number one, it does slow the progression of vision loss,” he said. “Number two, some patients actually get an improvement in their vision.”
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One of the primary benefits of rheophoresis, Dr. Potter said, is that it significantly reduces the distortions of central vision associated with macular degeneration. “We know that if you have AMD, straight lines appear jagged and irregular,” he said. “Rheophoresis reduces that.”
Dr. Potter recalled a patient who claimed that rheophoresis had helped with her arthritis. "Before treatment, she was insecure walking down stairs without a cane, because the stairs appeared jagged and distorted. After the treatment, the stairs were less crooked, so she didn’t rely on the cane."
In addition, he said, rheophoresis may enable some AMD patients to regain their driver’s licenses.
Retisert: “in the eye” steroid
Currently in phase 3 FDA clinical trials, Retisert is under development for the indications of posterior uveitis and diabetic macular edema.
“The Retisert product is designed to deliver drug to the eye over a 3-year period,” said Gary Phillips, MD, vice president of global pharmaceuticals for Bausch & Lomb. “Essentially, it is a high-potency steroid for implantation in the posterior chamber. Right now, we have global clinical trials ongoing for the product for both indications.”
The first indication expected to receive approval is non-infectious uveitis, Dr. Phillips said. “It makes sense pharmacologically that a steroid would work in the treatment of uveitis,” he said. “Uveitis basically is the inflammation of the uveal tract and can have a variety of causes. It’s a common final pathway.”
Dr. Phillips emphasized that Retisert should be considered only for the non-infectious form of the disease. “For other forms, you would want to eliminate the infection with an antibiotic or other microbial therapy, rather than using a steroid,” he said.
Another indication for Retisert currently in clinical trials is diabetic macular edema, Dr. Phillips said.
“It is current clinical practice for the retinal physician to inject a short-acting steroid into the eye to resolve macular edema,” he said. “Doctors are currently using Kenalog (triamcinolone acetonide, Squibb).
“Steroids seem to cut back on the leakiness of blood vessels,” he continued. “They help resolve the inflammatory aspects of the disease. Steroids seem to work at multiple points, at least in animal models. So, hypothetically, it makes sense. When the phase 3 trials are completed we will see what the data show.”
Anecortave acetate: positive results
Another drug currently in FDA clinical trials for the wet form of AMD is anecortave acetate. Phase 2 clinical trials have shown that anecortave acetate maintains or improves vision.
These results, based on a 12-month analysis of an ongoing 24-month trial, were presented by Jason Slakter, MD, at the 2002 annual meeting of the American Academy of Ophthalmology. Dr. Slakter is a retinal specialist at Vitreous-Retina-Macula Consultants of New York and clinical professor of ophthalmology at the New York University School of Medicine.
Alcon Research, Ltd., has been involved in two phase 2 studies in the United States and Europe to assess the safety and efficacy of anecortave acetate for the treatment of AMD as a single therapy or with PDT.
Both studies are double-masked, randomized, placebo-controlled, dose-response clinical trials and are similar in patient demographics, baseline logMAR visual acuity and lesion location (sub-foveal). The single-therapy trial is being conducted at 18 sites with 128 patients enrolled for 24 months. Anecortave acetate is delivered in the back of the eye, where it diffuses across the sclera and choroid into the macular portion of the retina. In the single-therapy study, anecortave acetate treatments were administered every 6 months.
The 12-month intent-to-treat analysis of the single-therapy study demonstrated that anecortave acetate 15 mg had a better visual outcome than placebo, based on mean change from baseline in logMAR visual acuity (p=0.0131). Patients receiving anecortave acetate (15 mg) as a single therapy experienced 25% less loss of visual acuity (VA) than did patients receiving placebo (79% vs 53%, p=0.0323). The benchmark for VA was the avoidance of loss of more than three lines of vision (15 letters by logMAR visual acuity). Patients treated with anecortave acetate 15 mg also demonstrated a smaller change in lesion growth, including choroidal neovascularization, than patients treated with placebo (133% vs. 249%).
“These data suggest the potential of anecortave acetate to provide us with a major new form of therapy to stabilize or even improve vision in patients with exudative macular degeneration,” Dr. Slakter said in his conclusion for the study. “In addition, this study showed that the drug significantly reduced lesion growth, which is highly correlated with the progression of the disease and loss of functional vision.”
For Your Information:
- Steven Rose, MD, is in private practice and teaches at the University of Rochester. He can be reached at 890 Westfall Rd., Rochester, NY 14618; (585) 442-3411; fax: (585) 442-9550; e-mail: srose@rochester.rr.com.
- John Potter, OD, is a member of the Primary Care Optometry News Editorial Board. He can be reached at 18352 Dallas Parkway, Dallas, TX 75287; (972) 818-1239; fax: (972) 818-1240; e-mail: john.potter@tlcvision.com.
- Neither Dr. Rose nor Dr. Potter has a direct financial interest in the products mentioned in this article, nor is either a paid consultant for the companies mentioned.
- Gary Phillips, MD, can be reached at 1400 North Goodman St., Rochester, NY 14609; (800) 344-8815; fax: (585) 338-0142. He is vice president of global pharmaceuticals for Bausch & Lomb.
- Jason Slakter, MD, is a vitreal/retinal specialist in New York. He can be reached at 519 East 72nd Street, Suite 203, New York, NY 10021; (212) 861-9797; fax: (212) 628-0698. Dr. Slakter has no direct financial interest in the products mentioned in this article. He receives grant research support, honoraria and travel support from Alcon.