Macular Degeneration Treatment

Treatment of macular degeneration has been disappointing to date. At best, most available treatments help to avoid further vision loss rather than improve vision. Lucentis (recently approved by FDA) is the only drug that has been shown to improve vision in the settings of a controlled clinical trial. Currently, there is no treatment that can 'cure' the disease or reverse its course. There is hope however, that with all the research that is underway to define the disease process at a molecular and genetic level, future treatments will offer more promise. In the meantime it is reasonable to modify the lifestyle to reduce the likelihood of developing macular degeneration and if indicated, to consider laser or drug treatment of established macular degeneration to avoid further vision loss.

Most patients diagnosed as having macular degeneration have the mild or intermediate forms of the disease (also referred to as age-related maculopathy). Approximately 30% of individuals 75 years or older have this form. Based on the published literature to date, ophthalmologists can inform individuals with non-advanced macular degeneration that their eye disease most likely will not progress substantially. It is important to understand that the presence of mild or intermediate form of age-related maculopathy does not mean that it's progression to blindness is inevitable. If you have been told that you have beginnings of macular degeneration or early changes like pigment changes & small drusen, then do not unnecessarily worry that it will soon progress to advanced form and vision loss. AREDS showed that there is more than 98% probability that early macular degeneration changes will not progress to advanced macular degeneration over a period of 5 years.

Only 6%-8% of individuals who are 75 years or older have the advanced form of macular degeneration. Only very few individuals will have irreversible and largely untreatable visual loss and reduced quality of life due to macular degeneration. It is important to understand that even in these patients 'vision loss' or 'blindness' refers to the loss of 'central vision' only. The peripheral vision is preserved. Blindness in macular degeneration does not mean 'inability to see light' and even with far advanced macular degeneration the peripheral retina allows for useful vision.

At present, there are 2 main interventions. The first is an attempt to slow the progression of macular degeneration by high dose antioxidant + zinc supplements. The AREDS showed that treatment with antioxidants + zinc reduces the probability of developing advanced macular degeneration

as well as moderate vision loss

. As can be seen, the beneficial effect of vitamin supplements is at best of modest proportions and not as dramatic as the manufacturers of vitamin supplements will have you believe.
For more information read our Nutrition, Vitamins & Vision

article.
NEI is currently conducting a clinical trial, AREDS2

to study whether increasing the intake of xanthophylls (lutein and zeaxanthin) and fish oil (omega-3 polyunsaturated fatty acids) will help to prevent development of advanced AMD. The evidence base suggests that increasing the intake of lutein and zeaxanthin and omega-3 fatty acids may prevent AMD progression.

The recommended laser treatment for wet macular degeneration depends upon the location of CNV relative to the fovea (i.e. whether subfoveal or juxtafoveal/extrafoveal). Laser treatment works best if CNV is well-demarcated (i.e. classic CNV) as determined by fluorescein angiography. Thermal photocoagulation (using Argon or Krypton laser) is effective treatment for extrafoveal CNV and to a lesser extent for juxtafoveal CNV. Although thermal photocoagulation of subfoveal CNV does provide a long-term benefit by reducing the likelihood of moderate and severe vision loss, it does lead to an immediate reduction in vision following the treatment. Because thermal laser photocoagulation causes immediate reduction in vision as well as scarring of the retina, there has been a search for a better treatment for subfoveal CNV. The ideal laser treatment for subfoveal CNV would eradicate the CNV and yet preserve the overlying retina. Photodynamic therapy (PDT) represents a step forwards in this direction. Treatment outcomes with PDT can be summarized as being about twice as good as those with thermal laser. "Twice as good, if vision loss is still the typical outcome, is not good enough." (editorial, Ophthalmology. 2005;112:531-2).

Photodynamic therapy (PDT) using a photosensitizer drug verteporfin (VISUDYNE

) is a two-step treatment process. It is relatively painless, takes about 20 minutes, and can be performed in a doctor's office. First, Visudyne is injected intravenously into the patient's arm. It travels throughout the body including the abnormal vessels in the eye. Next, the drug is activated by shining a laser light into the patient's eye for approximately 90 seconds. Once activated, it affects the blood vessels in the area of the treatment which leads to a slower rate of vision decline. Visudyne therapy slows retinal damage, but it does not stop the vision loss or restore vision in eyes that have been damaged by AMD.

Visudyne Photodynamic Therapy (PDT) Treatment

In order to have realistic expectations regarding the visual outcome after PDT, it is very important to understand the results of the PDT clinical trials. At best one can hope to have a similar outcome. The Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study showed that PDT slows the vision loss

due to subfoveal CNV and thus preserves the baseline vision

especially in those patients who have predominantly classic subfoveal CNV.

The Verteporfin In Photodynamic Therapy Study (VIP) was performed to determine vision outcomes after PDT for 'occult' subfoveal CNV. After 2 years of follow up, the study reported that PDT with visudyne reduces the risk of severe vision loss

Macugen (Pegaptanib) Treatment

In 1971 Judah Folkman first proposed the targeting of a specific angiogenic factor (like VEGF) as a way to treat disease, and specifically a way to treat cancer and ophthalmic disease. VEGF which is an acronym for vascular endothelial growth factor makes blood vessels very leaky and also makes them grow. In the late stages of wet macular degeneration - the neovascular phase - abnormal new vessels begin to grow up towards the retina. These vessels leak fluid, lipid and blood, and they damage the photoreceptors which sense light. This process, the angiogenic process, is VEGF driven. Macugen

(Pegaptanib) is a selective Vascular Endothelial Growth Factor (VEGF) antagonist to VEGF isoform 165. Macugen blocks VEGF actions and prevents the growth of abnormal new vessels and prevents leakage of fluid and blood in the retina. Macugen was approved by the FDA for use in wet macular degeneration in December 2004.

The recommended dose of Macugen is 0.3 mg of intravitreous injection administered once every 6 weeks. In the clinical trials, after 1 year 45% eyes developed moderate vision loss and 22% developed severe vision loss if no treatment was given. If treated with Macugen, the probability of developing moderate vision loss

over a period of 1 year is reduced by about 15% and the probability of developing severe vision loss

is reduced by about 50%. This implies that the rate of vision decline with Macugen treatment is slower than the rate in patients who do not receive macugen treatment. Serious adverse events related to the intravitreal injection procedure included endophthalmitis (1.3%), retinal detachment (0.7%), and traumatic cataract (0.6%). Other frequently reported adverse events in patients treated with Macugen were eye irritation, eye pain, hemorrhage under the outer membrane of the eye (conjunctiva), and blurred vision. Macugen is contraindicated in patients with ocular or periocular infections.

We know from the Macugen trial data that there seems to be no adverse reactions in giving PDT to patients receiving Macugen. However, we do not know whether there is an additive beneficial effect on vision after combining Macugen and PDT.
For more information read our article on Macugen

Lucentis (Ranibizumab) Treatment

Lucentis (ranibizumab) is a humanized anti-VEGF antibody fragment that inhibits VEGF activity by competitively binding with VEGF. Lucentis (ranibizumab) is derived from Avastin (bevacizumab), a full-length humanized monoclonal antibody against VEGF. Genentech has developed Lucentis with a marketing tie-up with Novartis Ophthalmics.

Lucentis is injected inside the eye (intravitreous injection) as an office procedure that is best performed by Ophthalmologists with specialty training in Retina and Vitreous surgery. FDA has approved Lucentis treatment for wet macular degeneration patients.

� About 95% patients with wet macular degeneration maintain their baseline vision after 12 months of treatment with Lucentis. The vision loss, if any, is less than 15 letters of visual acuity. This level of vision loss is considered to be not clinically significant. This is an important treatment effect because to date all other available treatment options (vitamins, PDT or Macugen) at best delay the inevitable vision loss but importantly, do not prevent ongoing vision loss. The results from Lucentis clinical trials support its use to prevent further vision loss from wet macular degeneration.
� About one-third patients (34%-40%) GAIN vision after 12 months of treatment with Lucentis. This vision gain is clinically significant - defined as gaining more than 15 letters of visual acuity. This is perhaps the most significant reason for initiating Lucentis treatment in wet macular degeneration. The vision gain after Lucentis treatment makes it possible for patients to look forwards to doing things like reading again, however not everyone will get such a positive outcome. There is no other macular degeneration treatment that has been shown to improve vision in the settings of a FDA controlled clinical trial.
� Long term data is still awaited to fully assess Lucentis efficacy.
For more information read our article on Lucentis

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