Institutionen för klinisk neurovetenskap / Department of Clinical Neuroscience
Abstract
Age-related macular degeneration (AMD) is the leading cause of
irreversible blindness among elderly in industrialized nations, and
promises to extract an even greater toll with the imminent demographic
shift. Neovascular AMD (wet AMD) often develops quickly and involves the
growth of new blood vessels under the retina (choroidal
neovascularization, CNV). These new blood vessels tend to be fragile and
often leak blood and fluid. The blood and fluid elevates the macula, the
central part of the retina, causing rapid visual loss. Without treatment
the prognosis is poor with profound impact on an individual s ability to
perform daily tasks.
Photodynamic therapy (PDT) has been the most common treatment for
neovascular AMD. PDT uses a cold laser to seal the leaking blood vessels.
This involves injecting a lightsensitive drug that reaches and coats the
abnormal blood vessels via the blood stream. The drug is then activated
by light leading to a local occlusion of new vessels.
Transpupillary thermotherapy (TTT) is technique in which a laser-induced
subretinal vascular occlusion can be created through a small temperature
elevation but without any photosensitive drugHowever, there has been a
controversy about the optimal TTT laser intensity and controlled clinical
trails demonstrating efficacy in neovascular AMD have been lacking.
The first two studies of the thesis demonstrate that PDT as well as TTT
can reduce experimental CNV, without causing damage to the surrounding
tissue. A cellular damage in surroundning tissues was however seen at
higher dosage. The therapeutic window is thus narrow for both treatments
underscoring the importance minimizing treatment doses. We also found
that both TTT and PDT induce an immediate thrombosis and cessation of
perfusion in CNV areas, but after PDT some areas remained vascularised
while after TTT the closure of the abnormal vessels proceeded for at
least one week.
The third and fourth studies of the thesis were on a prospective clinical
study, randomizing 98 patients with neovascular AMD (occult CNV) to
either low-dose TTT or PDT. During a follow-up of 12 months, no
significant differences between the two groups emerged. The proportion of
patients with stabilized visual acuity was approximately 75% in both
groups and the two treatments were equally potent at stabilizing
patient-reported visual function.
Recently intravitreal anti-VEGF has become the first line treatment for
neovascular AMD demonstrating superior efficacy for all forms of
neovascular AMD. However, anti-VEGF is expensive and requires repeated
injections. The use of PDT as an adjuvant to anti-VEGF therapy has been
suggested to decrease both the cost and the need for repeated injections.
Also this combination may prove beneficial regarding control of lesion
growth. The results of this thesis, showing that low dose TTT may be
equipotent to PDT, suggests that TTT may be a cost-effective adjuvant to
intravitreal anti-VEGF treatment