Laser therapy and PDT: history, current events and perspectives

The use of light for therapeutic purposes dates back as far as 3,000 years and there are currently two different approaches:
1) The phototherapywhich is based on the simple application of light to the tissue to be treated, as the absorption of light rays by endogenous molecules generates the treatment.
2) The photochemotherapywhich involves the administration of an exogenous photosensitising agent, or its precursor, prior to exposure to light.
In ophthalmology, the first important application dates back to 1949 with the publication of clinical results of retinal photocoagulation by Gerd Meyer-Schwikerath, while the first photochemotherapy, represented by photodynamic treatment, is due to a study by Raab in the early 1900s.
Today, with the advent of anti-VEGF therapies, different types of laser treatments may still be a viable alternative for some particular clinical hypotheses.

Classic photocoagulation
In the classic photocoagulation The energy delivered to the tissue generates a significant temperature rise (above 65° C), which results in protein denaturation and coagulative necrosis of the tissue. This effect depends on the wavelength used and the intensity and duration of exposure.
Laser photocoagulation is widely used in retinal pathologies, such as diabetic retinopathy or venous occlusions, for the elimination of ischaemic areas, whereas it is now less likely to be used in the treatment of exudative AMD. The direct effect of the treatment is, in fact, the death of the affected cells and the invariable loss of function of the target tissue; this side effect represents an acceptable duty if the treated retinal area does not correspond to central areas of the visual field, but results in an invariable drop in visus in the case of central treatments.

Transpupillary thermotherapy (TTT)
The transpupillary thermotherapy (TTT) is a technique used today only for the treatment of intraocular neoplasms. It is based on a principle similar to that of classic photocoagulation, but generates a lower rise in choroidal temperature, albeit above 45°C. The resulting cellular damage is not instantaneous, but results in delayed necrosis due to degradation of cellular constituents and dysregulation of the cell's biochemical cycles.
TTT has shown some utility in the treatment of neovascular lesions, in particular occult membranes; however, randomised clinical trials irrefutably demonstrating its efficacy are lacking. It is a therapy that is easy to perform and inexpensive, but the calculation of useful treatment parameters and the dramatic side effects that result from overtreatment remain an unsolved problem that limits its use in clinical practice.

Photodynamic therapy (PDT)
The procedure is divided into steps: first a photosensitising agent is injected into the vein; after a period of time for the drug to accumulate at the level of the neovascular lesion, it is activated by laser irradiation. The wavelength is chosen according to the absorption peak of the photosensitising agent.
Once activated, the drug molecules generate free radicals and reactive forms of oxygen; the result is photochemical damage to endothelial cells at the level of the neovascular lesion, leading to thrombosis.
In 2000, PDT was approved by the FDA for the treatment of predominantly classic neovascular lesions in AMD, as well as myopic lesions and those related to other causes (such as presumed histoplasmosis). Compared to classic photocoagulation, it represents a huge step forward; however, on average, treated patients still tend to worsen, albeit at a slower rate of progression; furthermore, the improvement in visual acuity, if any, is limited. With the advent of pharmacotherapy (anti-VEGF), capable not only of halting the progression of the neovascular form of AMD, but also of ensuring, in a good percentage of cases, an improvement in visual acuity, the use of PDT has decreased considerably. However, anti-angiogenic + PDT combination therapy now offers new insights and treatment possibilities that, in some cases, allow an improvement in the clinical condition comparable to that achieved by drug therapy alone with fewer injections.

Feeder Vessel Treatment
The technique called 'Feeder Vessel Treatment' is a conservative variant of laser photocoagulation and was proposed in 1998 by Giovanni Staurenghi. The therapy involves a laser treatment targeted on the afferent vessel of the neovascular membrane, which should, if successful, obliterate the lumen of the collector that carries blood to the entire neovascular frond and consequently cause its closure. To date, however, this therapeutic option remains available only in a few highly specialised centres, which possess adequate instrumentation for identifying the afferent vessel (angiography with dynamic indocyanine green), as well as particularly experienced operators, capable of performing the treatment even with traditional laser instruments.

In conclusion, we list some specific clinical pictures in which the use of laser or combination therapy may still be a better option than intravitreal anti-VEGF:
- Polypoidal lesions
- Retinal Angiomatous Proliferations (RAP)
- Neovascular lesions with Feeder Vessel evident