Steroids and PDT still play a role in AMD treatment Retina

By Nadja Geipert fast-moving field and an exciting one to work improved PDT’s outcome (Augustin AJ et al; (TAP) showed that 69 per cent of patients in San Francisco in,” she said. Ophthalmology; Jan 2006;113).The visual with classic neovascularisation who received acuity improved in the majority of patients PDT avoided losing three or more lines of BOTH steroids and photodynamic therapy Retaane monotherapy for dry AMD and the re-treatment rates were lower. vision. (PDT) might continue to play a role in The development and logic behind “Although almost none gained vision, at combination treatments for age-related is also being evaluated treating AMD with steroids first began 20 least we were able to increase the number despite the recent as a monotherapy option.Alcon is years ago when an experiment in an animal of people who avoided vision loss, and so arrival of “wonder drugs” conducting the Anecortave Acetate Risk model of AMD demonstrated that infusing people started incorporating PDT in the (Macugen, Pfizer), (Lucentis, Reduction Trial (AART), which will evaluate steroids through an indwelling cannula management of AMD. But now the bar has Genentech), and (Avastin, if the steroid alone can reduce the risk for system reduced the frequency of subretinal been raised,” said Dr Bressler. Genentech), say clinical researchers. neovascularisation in patients with dry neovascularisation (Ishibashi T et al.Arch The FOCUS trial tested ranibizumab in “Steroids are likely to play a part in the AMD. Ophthalmol, May 1985; 103). combination with photodynamic treatment of AMD, but as a component of Starting in June 2006, patients age 50 The findings suggested to researchers that therapy in subfoveal neovascular AMD and multimodality therapy instead of years or older with dry AMD in the study inflammation or macrophage infiltration compared it to PDT alone in patients with monotherapy for active choroidal eye and wet AMD in the non-study eye will might play an important part in subretinal predominantly classic choroidal neovascularisation (CNV),” said Julia Haller, receive the steroid or placebo every six neovascularisation.To test steroids for the neovascularisation. MD, professor at Johns Hopkins Hospital in months for four years. treatment of choroidal neovascularisation, More than 90 per cent of the patients Baltimore, Maryland. Another steroid tested and used in AMD researchers needed a much better who received the combination treatment The modified steroid anecortave acetate treatment is triamcinolone whose anti- understanding of the steps involved in avoided losing three lines of vision or more (Retaane,Alcon) has been shown to be as angiogenic effects were first confirmed in angiogenesis. compared to 68 per cent receiving PDT safe and effective as PDT with verteporfin animal models. However, human trials on While VEGF plays an important role, alone. In addition, 24 per cent gained three (Slakter JS et al; Ophthalmology; Jan 2006; 113). monotherapy with triamcinolone yielded steroids also influence the progression of or more lines of vision compared to five per The medication does not have anti- conflicting results. new blood vessel growth.And, steroids have cent who received PDT alone. inflammatory properties because it has been An Australian randomised clinical trial in inherent anti-angiogenic properties, which Meanwhile further studies showed that a chemically stripped of glucocorticoid activity 151 eyes using a single dose of intravitreal can be enhanced.Anecortave acetate was few ranibizumab treatments alone prevented to reduce pressure increase effects. triamcinolone acetonide for neovascular chemically altered to make it more anti- vision loss in 95 per cent of patients. Anecortave acetate is also being tested age-related macular degeneration found no angiogenic and to remove the anti- “For these predominantly classic lesions, and used in combination with PDT (Eter N, difference in visual loss between the placebo inflammatory component, which reduces its when ranibizumab is available we should Biodrugs, 2006: 167-79).A study combining and the treatment group after 12 months. effect on IOP and its tendency to create recommend that as the first therapy,” said PDT and anecortave acetate showed that Yet, closer examination revealed that the cataracts. Dr Bressler. Ranibizumab was FDA-approved visual acuity of patients receiving the change in size of the neovascular in the US on June 30, 2006. combination therapy remained stable more membranes was significantly less in the Genetics play a role in AMD Despite these results, PDT continues to than in patients who received monotherapy. treatment group after three months, a inflammation be investigated in combination therapies. A small group of patients receiving the difference that had disappeared by the “You might get better visual acuity combination treatment even showed twelfth month.The researchers also But nothing has fuelled the continuing outcomes if you combine it, or it might be improved vision. In addition, the researchers discovered that eyes receiving triamcinolone interest in treating AMD with steroids like safer and we may be able to get away with discovered that the patients who received faced an increased risk for elevated last year’s groundbreaking discovery that fewer injections,” he said. the steroid needed fewer PDT treatments. intraocular pressure (IOP) (Gillies MC et al; there is a powerful genetic association A randomised, double blind trial by Pfizer Even though anecortave acetate is a Arch Ophthalmol.; May 2003; 121). between AMD and inflammatory pathways is enrolling patients to compare whether steroid, it appears to work as an anti- “Steroid monotherapy seems more (Klein et al; Science;April 2005; 308; 385-389), Macugen in combination with PDT with angiogenic agent, blocking vascular promising in experimental models than (Edwards et al; Science;April 2005; 308; 421- verteporfin is safe and effective in slowing endothelial growth factor (VEGF) activity and clinical situations for humans,” said Dr 424), (Haines et al; Science;April 2005;308; down fluid leakage within the eye and thus interfering with neovascularisation.VEGF Haller. 419-421), (Hageman et al; PNAS; May 2005; stabilising and/or improving vision.The is a significant player in the angiogenic Yet, a small Spanish study found 102; 7227-7232).The genetic connection results will then be compared to patients cascade that leads to the growth of blood triamcinolone to be effective in combination appears to exist for both neovascular and who received only Macugen.The study is to vessels. with PDT in keeping visual acuity stable in non-neovascular forms of AMD. be completed by October 2008 and One big difference between the steroid patients with CNV (Ruiz-Moreno et al; “It is too early to tell if we may want includes patients with CNV due to AMD and the other two medications is the route Ophthalmol, May 2006; 16). both anti-angiogenic and anti-inflammatory with predominantly classic lesions of delivery. A much larger study testing this particular properties in steroids in light of the composition. Anecortave acetate is administered via a combination found that its main benefit was complement factor H story.There is also PDT might also still be a good alternative posterior juxtascleral depot route every six that the steroid reduced the amount of more and more being done to develop new for patients who cannot tolerate the months. Researchers can visualise the drug’s required verteporfin treatments (Ergub E et steroids and to modify old steroids,” she intraocular injections, or are at a high risk position behind the eye in the subTenon's al;Am J Ophthalmol 2006 Jul;142(1):10-16). said. for infections, according to Dr Bressler. space on the scleral surface over the macular Combination therapies appeal because PDT was first approved by the FDA in All of this is good news in the fight region with high-resolution ultrasonography. usually more than one molecule or step is the US in 2000 and slowly approved by against one of the world’s leading causes of The six-month administration schedule and involved in disease progression. Using European countries in the ensuing years.An blindness leaving ophthalmologists with route of delivery make the medication a several agents to attack a disease cascade article in the British Journal of Ophthalmology more options to provide the best possible good candidate for chronic therapy. It appeals might yield a stronger effect, researchers in 2004 stated that PDT is the only available care for their patients. to patients because it requires fewer office reason. treatment for some forms of neovascular Dr Haller and Dr Bressler spoke at the visits. By combining PDT with a steroid AMD (Hopley et al; Br J Ophthalmol,Aug ASCRS annual meeting in San Francisco, “Extended delivery of somebody’s new treatment, investigators hope to reduce the 2004;88).With the arrival of the anti-VEGF California last March. promising drug is certainly the Holy Grail; I inflammatory effect and free radical damage drugs, this is no longer true. caused by PDT (Spaide et al; Ophthalmology “AMD treatment is moving fast and don’t think there is a single drug company [email protected] 2003). furiously,” said Neil Bressler MD, professor that doesn’t have that as part of its product [email protected] development,” said Dr Haller. One study investigating verteporfin of ophthalmology at Johns Hopkins Hospital “Exciting technological developments in therapy combined with intravitreal in Baltimore, Maryland. drug development and delivery make this a triamcinolone in different types of CNV due One-year results of the treatment for to AMD concluded that the steroid age-related macular degeneration with PDT

18