Overview of Photodynamic Therapy for the Eye
Photodynamic therapy (PDT) is a kind of treatment that usually involves adding a special compound to the affected part of the body or injecting it. The compound, also known as a photosensitizing compound, sticks onto the cells that need to be targeted. Then, a specific type of light is used to illuminate this area. This treatment approach was first introduced by a German professor Hermann von Tappeiner in the 1900s. His student Oscar Raab had shown that a photosensitizing agent called acridine orange could harm certain organisms in water, but only if both the agent concentration and light exposure were high.
When using photodynamic therapy, three things are needed: the photosensitizer (the special compound), a source of light, and oxygen. The therapy begins with applying the photosensitizer on the affected region. This agent is then activated with light. In presence of oxygen, this leads to the production of reactive oxygen intermediates, which are substances that attack vital parts of the cells causing cell death due to irreversible oxidation. It’s a technique that’s been known for over a hundred years, but only gained popularity in treatment after the 1970s. It’s currently used to treat several skin-related health conditions.
Its use in treating eye conditions is somewhat limited but has been in practice for the last 30 years. The first use of PDT in ophthalmology was to treat a condition where new, abnormal blood vessels form beneath the part of the retina responsible for sharpest vision. A photosensitizing agent called verteporfin is commonly used in ophthalmology because it is easily absorbed in the body, does not stay for long (reducing the chances of skin sensitivity) and is good at absorbing light.
Anatomy and Physiology of Photodynamic Therapy for the Eye
Photodynamic therapy is a treatment method that involves putting a special substance that reacts to light, called a photosensitizing agent, over the area to be treated. Once the agent is activated by shining a light on it, it starts a process which creates what are called reactive oxygen intermediates. These are molecules that interact with the key parts of cells and causes them to self-destruct and die due to a process called oxidation.
When used for eye-related issues, the growth of abnormal blood vessels selectively take in a substance called verteporfin. The next step involves starting a controlled chemical reaction by using a light at a specific wavelength of 689 nm. This particular light is chosen because it can reach the problematic cells within a layer of the eye known as the choroid, even with tissues and other cells potentially blocking its way. This specific light is very good at getting deep into the tissue.
When the light hits the verteporfin, it excites the molecules and they react with nearby oxygen molecules. This creates damaging free radicals, which are unstable molecules that can cause harm to cells. They bring about the destruction and death of the affected cells. This process also triggers what’s known as a clotting cascade and platelet aggregation – a series of reactions that results in the formation of small blood clots, effectively blocking the abnormal blood vessels.
Why do People Need Photodynamic Therapy for the Eye
Photodynamic therapy (PDT) is a type of treatment used in several areas of medicine, including skincare (dermatology), cancer care (oncology), eye care (ophthalmology), and heart health (cardiovascular). It’s used to treat a variety of conditions, and this is how it works:
For skin conditions, PDT is approved to treat specific problems, such as Actinic Keratoses, a type of skin growth caused by sun exposure. Doctors use a FDA-approved substance, called Aminolevulinic acid (ALA), and light to treat only the affected areas of the skin. But, in some cases, they may need to treat a larger area if multiple skin growths have formed. PDT can also be used to treat Basal Cell Carcinoma, a type of skin cancer, and Bowen disease, a skin condition that can lead to cancer, but these uses are approved only in Europe.
Even though there are FDA-approved uses for PDT, it’s also used “off-label” for other skin conditions. This includes skin conditions that are pre-cancerous or cancerous, inflammatory disorders such as psoriasis and acne, skin infections, anti-aging treatments, and even tumor prevention.
Photodynamic therapy can also be used in ophthalmology or eye care. For example, it has been used to address age-related vision loss due to an eye condition called Neovascular age-related macular degeneration. Although injections have become the main treatment for this condition, PDT can still be used in cases when injections don’t work or used alongside injections. Also, PDT has been utilized to treat a condition causing bleeding and leaking in the eye called Polypoidal choroidal vasculopathy (PCV). There are specific guidelines followed by doctors, as studied and found in the EVEREST Trial. Other eye conditions treated with PDT include Non-AMD choroidal neovascularization, Central serous chorioretinopathy (CSCR), and Choroidal hemangioma.
The uses of PDT can vary widely, and it depends on the specific problem and the discretion of the healthcare provider. Consult with your doctor to understand the best possible treatment for your condition.
When a Person Should Avoid Photodynamic Therapy for the Eye
There are some situations where it’s not safe to use photodynamic therapy, a type of treatment that uses light to activate drugs that can kill cancer cells:
– If the tumor isn’t responding to treatment, photodynamic therapy might not be effective.
– Some skin diseases, like porphyria and SLE (Systemic Lupus Erythematosus, an autoimmune disease), can make a person more sensitive to light, which would make photodynamic therapy a bad choice.
– If a person is allergic to any of the components of the therapy, it can’t be used.
– Finally, the drugs used in this therapy should be avoided by pregnant women because they may have negative effects for the baby.
Equipment used for Photodynamic Therapy for the Eye
At present, the FDA has given approval for the use of two certain skin treatments, called aminolevulinic acid (ALA) and methyl aminolevulinate (MAL). MAL is a variant of ALA, where an extra methyl group is added to the structure.
ALA is a sensitive compound and doesn’t mix well with fat. This stops it from getting through skin or cell boundaries. As a result, it needs more time to work and is only useful for treating skin diseases that affect the surface layers of the skin. Some newer versions of ALA have been created that can penetrate deeper into the skin and are more stable as a molecule.
MAL, on the contrary, is more stable and can mix with fat, meaning it can penetrate deeper into the skin compared to ALA.
The effectiveness of these treatments is dependent on light exposure. Protoporphyrin 9, an active component of the treatments, can be activated by visible light that falls in two ranges: 404 to 420 nm, known as blue light, and 635 nm, known as red light.
Light with longer wavelengths can penetrate deeper into the skin. That’s why blue light is used for thin actinic keratoses (a type of skin disease caused by sun damage) and red light is used for deeper, thicker skin lesions and to target deeper tissues like oil-producing glands in the skin.
Light for these treatments can be provided from sources like xenon lamps, halogen lamps, lasers (including PDL, LP, Argon, Diode types), Intense Pulsed Light (IPL), LED lights, and fluorescence diagnosis systems.
Reflecting on the use of these treatments for eye conditions, a substance called verteporfin is injected into the bloodstream and allowed to circulate for about 10 minutes. It’s good to wait an extra 5 minutes to allow these molecules to build up in the sick cells. Following this wait, the patient’s eye is exposed to a special PDT laser that emits light with a wavelength of 689 nm. The standard procedure using PDT involves exposure to an irradiance (light intensity) of 600 mW/cm, a fluence (light energy) of 50 J/cm, for a duration of 83 seconds.
Preparing for Photodynamic Therapy for the Eye
Before starting the treatment, the doctor will clean the skin area with a special lotion and an alcohol swab. If needed, they will remove the surface layer of the skin’s affected area, this process is known as “debriding”. If the treatment is for the eye, the doctor will carefully measure and map the size of the eye’s affected area with a special technique called indocyanine green (ICG) angiography. The patient’s eyes need to be dilated or widened using a specific eye drop that contains tropicamide and phenylephrine before the procedure begins. The size of the treatment area, also known as the laser spot size, is determined by the largest part of the eye’s affected area, which was mapped out using the ICG. The size of the treatment area needs to be slightly larger, generally more than 500 micrometers, than the largest part of the affected area. This is done to ensure that all affected areas are adequately treated.
How is Photodynamic Therapy for the Eye performed
If you’re having a photodynamic therapy (PDT), a method used to treat various diseases using light to activate a drug inside the body that kills harmful cells, there should be no bleeding before the treatment. Once the light-activated drug, known as a photosensitizer, is applied, it needs to sit for a while. The amount of time it sits on your skin depends on the drug used and the reason for your treatment. If you’re using a photosensitizer called ALA, it will need to soak into your skin for 30 minutes to 18 hours, while another one called MAL-PDT needs 3 hours. During this time, your skin should be protected from natural light using something like aluminum foil.
After the needed time, the drug is wiped away using a dry cloth or a saline solution. The next step depends on the photosensitizer you’re using: ALA-PDT can use various light sources, but MAL-PDT uses a specific red light (635 nm).
After the procedure, it’s essential to protect your skin from the sun and other light sources.
If you’re having PDT for an eye condition, a photosensitizer called verteporfin is used. This is injected into your body’s veins and spreads all over your body. To allow the verteporfin to gather in the eye’s abnormal cells, there’s a 5-minute wait after the injection. Then the doctor will aim a PDT laser, which uses a 689 nm light, at the eye to be treated. This laser is attached to a special device that helps the doctor see the back of your eye.
The size of the laser targeted area is based on the size of the abnormality in your eye, as seen in tests like an angiography. Usually, the laser covers an area a bit bigger than the actual abnormal spot. The normal laser strength used is 600 mW/cm for 83 seconds; however, a milder version of PDT used to lessen possible side-effects, like eye bleeding, only uses a laser strength of 25 J/cm.
At times, the drug dose is also lessened to improve safety. Instead of 6mg/m, only 3mg/m is used. However, it’s not always clear which approach works best for different eye conditions because there isn’t enough research on this topic.
Possible Complications of Photodynamic Therapy for the Eye
Photodynamic therapy, a type of treatment that involves light-based therapy, can sometimes lead to unwanted side effects and complications. These can occur right after treatment, or develop over a longer period of time.
Soon after receiving photodynamic therapy some patients may experience pain, redness and swelling, itchy skin, hives, skin rashes, and possibly scalp rashes. In rare cases, there might even be a decrease in the body’s immune response. Also, if a lot of the drug used in the therapy gets absorbed into the body, it could potentially result in a reaction to light not only on the treated area but throughout the body.
Over time, some long-term side effects of the therapy can surface. These include changes in skin color, and scarring. Sometimes, a rare skin condition known as bullous pemphigoid, which causes large, tight blisters to form on the skin, can occur, though we’re not quite sure why this happens.
There have been some instances where skin tumours like keratoacanthomas, basal cell carcinoma, invasive squamous cell carcinoma, and melanomas have developed after treatment. However, it’s not clear yet whether photodynamic therapy is directly responsible for causing these tumours, and more research is needed in this area.
The use of photodynamic therapy in eye treatments has declined over time due to possible complications. The most common problem is a decrease in vision caused by bleeding beneath the retina, a layer at the back of the eye. Also, people receiving the therapy often experience light sensitivity after getting an injection of a drug called verteporfin. Because of this, it’s recommended that patients avoid sunlight and cover their skin to avoid light exposure for a couple of days post-injection.
In rare cases, while injecting verteporfin, the drug might leak into the tissue surrounding the blood vessels. If this isn’t treated promptly, it can lead to skin death. Some people have also reported back pain after getting an infusion of verteporfin.
What Else Should I Know About Photodynamic Therapy for the Eye?
Photodynamic therapy (PDT) is a treatment method often used for actinic keratosis (a skin condition caused by sun damage) and some non-melanoma skin cancers. PDT is non-invasive—meaning it doesn’t involve surgery—and is typically less painful than other treatments. It is known for leading to good cosmetic outcomes and preserving healthy skin tissue. Interestingly, PDT is also starting to be used for other skin conditions. Recently, there have been improvements in how the treatment is delivered, and ongoing research is finding new photosensitizers (compounds that make cells sensitive to light).
During PDT, a photosensitizer is activated by light of a particular wavelength (470-700 nm). This results in a series of biochemical changes that produce reactive oxygen species—highly reactive molecules. These reactive molecules cause cytotoxic (cell-damaging) effects.
The agents used in PDT are prodrugs—a type of medication that, after being administered, is metabolized into an active form within the body. In the case of PDT, these prodrugs are converted into protoporphyrin 9, a compound that acts as the photosensitizer. The protoporphyrin 9 mainly builds up in the fast-growing cells of pre-cancerous and cancerous lesions due to their quick division process and lack of an enzyme called ferrochelatase. It also builds up in other structures like blood vessels, melanin, and sebaceous (oil-producing) glands. When light of the right wavelength shines on the protoporphyrin —activated via the photosensitizer—it triggers chemical reactions that eventually produce free oxygen radicals. These radical molecules cause cell damage and vascular damage (damage to blood vessels), leading to inflammation and immune responses that cause further damage to the target tissue.
It’s important to note that protoporphyrin 9, generated from the photosensitizers, gets fully broken down into heme (a component of hemoglobin in red blood cells) within 24 to 48 hours. This short lifespan reduces the chance of long-lasting skin sensitivity to light, a side effect of PDT.
The use of topical photosensitizers—those applied on the skin—has an added advantage of minimizing the risk of photosensitivity (light sensitivity) across the whole body.
Currently, PDT’s role in eye-related medical treatments (ophthalmology) is fairly limited due to its high cost and availability issues. Alternative treatments such as anti-VEGF injections and laser photocoagulation, which have a safer profile, are frequently chosen instead of PDT.
