Age related macular degenerationBMJ 2000; 321 doi: https://doi.org/10.1136/bmj.321.7274.1425 (Published 09 December 2000) Cite this as: BMJ 2000;321:1425
New hope for a common problem comes from photodynamic therapy
- Neil M Bressler, physician,
- James P Gills, professor of ophthalmology ()
Age related macular degeneration is the commonest cause of severe loss of central vision in people aged over 50 in the Western world.1 The vision loss results from loss of function of the macula, the centre of the retina, which is responsible for central visual tasks such as reading, driving, and recognising faces. Macular degeneration has until recently been untreatable, but laser treatments have become available within the past few years that can halt progression of the disease and the consequent loss of vision in some patients.
The early stages of macular degeneration (usually without significant vision loss) include the formation of drusen,2 which can be seen with the direct ophthlamoscope (after dilatation of the pupil) as small yellow deposits in the centre of the retina. Drusen are extremely common, detected in at least 10% of everyone over 65.1 Although their cause is unknown, their progression is well documented.
Significant vision loss may occur from neovascular or non-neovascular abnormalities. In neovascular (sometimes termed “wet”) age related macular degeneration, abnormal new blood vessels from the choroidal layer of the eye that nourishes the outer retina grow and proliferate with fibrous tissue within drusen material.2 This choroidal neovascularisation causes acute loss of vision as transudate or haemorrhage accumulates within and beneath the retina, with permanent loss occurring as the outer retina (including the photoreceptors) becomes atrophic or replaced by fibrous tissue.2 Although the haemorrhage, fluid, or scar tissue from the choroidal neovascularisation may be seen, the abnormal blood vessels themselves and early stages of fibrosis may not be seen easily on ophthalmoscopy but may be visualised on fluorescein angiograms of the retina.
In non-neovascular (or “dry”) degeneration the pigmented layer of the retina and the photoreceptors overlying drusen become atrophic, and this is accompanied by slow loss of central vision, usually over a decade or two.3 Most people who lose vision from age related macular degeneration, however, lose vision from neovascular complications.1
Two types of treatments have been shown to reduce the risk of vision loss in selected patients with neovascular complications. One, laser photocoagulation, uses thermal energy delivered under topical anaesthesia to burn the area of the retina occupied by choroidal neovascularisation. Several randomised clinical trials sponsored by the National Institutes of Health4–6 have shown that photocoagulation could reduce the risk of severe vision loss for about 15% of patients. 7 8 The treatment is usually applicable to choroidal neovascular lesions that do not extend under the centre of the retina since photocoagulation will usually destroy any viable photoreceptors overlying the abnormal vessels.
However, most patients with neovascular macular degeneration present to an ophthalmologist with new vessels extending under the centre of retina. In such cases a new technique, photodynamic therapy using the drug verteporfin, has recently been shown in randomised trials to reduce the risk of moderate and severe vision loss. 9 10 Photodynamic therapy is a two step process. Firstly, a photoactivator, verteporfin, is infused intravenously. Then a laser is applied over the entire neovascular lesion. This activates the drug, which has concentrated within the neovascular lesion. The photoactivation presumably selectively destroys the lesion by creating reactive intermediates of oxygen such as superoxide and hydroxide radicals without damaging viable retinal tissue overlying the neovascularisation.11
Retreatment as often as every three months, averaging five to six treatments over two years, is needed to prevent significant growth. Tests using higher doses of light failed to stop regrowth but instead caused photoactivation in normal retinal blood vessels, leading to loss of vision. The clinical trials showed that photodynamic therapy with verteporfin could reduce the risk of moderate and severe vision loss from 61% to 33% at one year and from 69% to 41% at two years in patients with neovascularisation extending under the centre of the retina and predominantly classic appearances on fluorescein angiography — an appearance that has a high likelihood of growth and vision loss within months if left untreated. Fortunately, the drug appears to be safe. Some patients may notice some transient fluctuations in vision for a few days after treatment, and all patients need to avoid prolonged exposure to bright sunlight during the two day period of potential photosensitivity.
Perhaps 20% to 30% of the 200 000 cases of neovascular macular degeneration that present to ophthalmologists in the United States each year are candidates for prompt photodynamic therapy. Once extensive vision loss has occurred the treatment is no longer beneficial. It is important therefore to teach older patients with drusen who are at risk of developing neovascular macular degeneration to screen for the possible development of neovascularisation. The primary care physician has an important role here since drusen are usually asymptomatic.
Specifically, the physician needs to evaluate the retina for the presence of drusen or refer the patient to someone who can screen for drusen each year. Once drusen have been discovered the patient needs to be told to screen one eye at a time often, perhaps as often as each day, for possible signs of developing neovascularisation so that if it develops the patient can seek help quickly. Such screening includes checking straight lines, as on a piece of graph paper or between tiles in a bathroom. Any sudden development of blank spots or distortion of the lines may be a sign of neovascularisation. Since the development of neovascularisation in one eye is associated with a 50% chance of developing a similar lesion in the other eye,12 it is critical to try to save vision in either eye since one does not know which eye will end up being the better seeing eye.
The advent of effective photodynamic therapy makes even more important than before the need for primary care physicians to identify and educate the many people aged over 50 who have drusen about the risk of developing choroidal neovascularisation. As the number of people in this age group will double over the next 25 years, the public health importance of age related macular degeneration will continue to grow.
This work is supported by the Wilmer Retinal Vascular Center Research Fund and the Michael A Panitch Fund to Stop Age-Related Macular Degeneration. NMB has been reimbursed by CIBA Vision for attending symposiums and organising educational programmes on age related macular degeneration. He has also been paid for consulting for CIBA Vision and QLT Inc.