Photodynamic therapy (PDT) is a treatment that involves intravenous administration of a photosensitizer (photosensitizing agent) and irradiation of the target lesion with a specific wavelength of laser light to selectively occlude blood vessels.
In ophthalmology, PDT was introduced in the 1990s, and PDT using verteporfin (brand name: Visudyne®) was approved by the US FDA for age-related macular degeneration in 2000. In Japan, it became covered by insurance in 2004.
PDT was initially widely used as a primary treatment for age-related macular degeneration, but with the advent of anti-VEGF drugs, its role in AMD has shifted to second-line or combination therapy with anti-VEGF agents. On the other hand, it remains one of the main treatment options for central serous chorioretinopathy, although it is not covered by insurance in Japan.
PDT is also applied to choroidal ophthalmic tumors (e.g., choroidal hemangioma, choroidal melanoma), using a protocol with increased irradiation energy for tumors. 1)
In Japan, PDT for age-related macular degeneration is covered by insurance. On the other hand, PDT for central serous chorioretinopathy is not covered by insurance and may be a financial burden for patients. It is important to confirm with the attending physician before treatment.
The clinical features of the main diseases for which PDT is indicated are shown below.
The subjective symptoms commonly observed in diseases for which PDT is indicated are as follows.
In central serous chorioretinopathy, the duration of symptoms is directly linked to visual prognosis. It is said that the chance of visual recovery decreases by approximately 4% for each week that symptoms persist. 3)
Important findings for evaluating the indication of PDT are shown by disease.
Age-related Macular Degeneration (Exudative Type)
Classic CNV: Shows well-defined early hyperfluorescence on FA (fluorescein angiography). It serves as the basis for GLD measurement in the TAP protocol.
Occult CNV: Shows ill-defined late leakage on FA. It accounts for the majority of age-related macular degeneration lesions.
OCT findings: Subretinal fluid, intraretinal fluid, and pigment epithelial detachment (PED) are observed.
Central Serous Chorioretinopathy
Polypoidal Choroidal Vasculopathy
Central serous chorioretinopathy mainly occurs in middle-aged men and is characterized by serous retinal detachment with choroidal hyperpermeability and thickening (pachychoroid). Age-related macular degeneration is more common in the elderly and primarily involves drusen, RPE abnormalities, and choroidal neovascularization. PDT is effective for both, but the indications and protocols differ. See the “Standard Treatment” section for details.
Central serous chorioretinopathy and polypoidal choroidal vasculopathy are now understood as a group of diseases (pachychoroid spectrum) that share choroidal thickening (pachychoroid) as a common basis. 2) This spectrum also includes polypoidal choroidal vasculopathy, pachychoroid choroidal neovascularization, and pachychoroid neovascularization.
An association between central serous chorioretinopathy and steroid use is known. Both systemic and local (eye drops, nasal sprays, intra-articular) administration can be a risk for onset or exacerbation. If symptoms suggestive of central serous chorioretinopathy appear while using steroids, it is important to promptly consult an ophthalmologist.
To determine the suitability of PDT, examinations combining multiple modalities are necessary.
To calculate the irradiation diameter according to the TAP protocol, measure the GLD of the entire choroidal neovascularization confirmed on FA. The spot diameter is basically GLD + 1,000 μm. The maximum irradiation diameter is limited to 6,000 μm.
In PDT for central serous chorioretinopathy, the target for irradiation is the area of choroidal hyperpermeability identified on ICGA. 3) Irradiation design covering the entire hyperpermeable area contributes to improved SRF resolution rate.
The main parameters of the standard PDT protocol are shown below. 1)
| Parameter | Standard Value |
|---|---|
| Verteporfin dose | 6 mg/m² (per body surface area) |
| Intravenous infusion time | 10 minutes |
| Laser wavelength | 689 nm |
| Irradiance | 600 mW/cm² |
| Irradiation time | 83 seconds |
| Total irradiation energy | 50 J/cm² |
| Tumor energy | 100 J/cm² (ocular tumors) |
For ocular tumors (e.g., choroidal hemangioma, choroidal melanoma), a protocol with increased irradiation energy of 100 J/cm² is used. 1)
To reduce the risk of vision loss associated with the standard protocol, the following modified protocols have been developed. They are widely studied especially for application to central serous chorioretinopathy.
Age-related macular degeneration (wet type)
TAP and VIP trials: Demonstrated efficacy for classic predominant choroidal neovascularization. 4)
ANCHOR trial: PDT monotherapy was shown to be inferior compared to ranibizumab. 4)
Current status: Anti-VEGF drugs are first-line. PDT is used as second-line or in combination for cases unresponsive to anti-VEGF and for certain types of choroidal neovascularization. 5)
Central Serous Chorioretinopathy
PLACE randomized trial: Half-dose PDT group had SRF resolution rate of 67.2% vs. 28.8% in the HSML laser group (p<0.001). 3)
SPECTRA trial: Half-dose PDT group had SRF resolution of 78% vs. 17% in the eplerenone group. 3)
REPLACE/SPECS trials: Support the high efficacy of half-dose PDT. 3)
Polypoidal Choroidal Vasculopathy
EVEREST trial: ICGA-guided PDT alone or in combination with ranibizumab is effective for polypoidal choroidal vasculopathy regression. 2)
Current status: Combination PDT with anti-VEGF drugs is recommended. 5)
Asian data: Evidence specific to polypoidal choroidal vasculopathy, which differs from Western age-related macular degeneration, has been accumulating. 2)
The Japanese clinical practice guidelines for age-related macular degeneration stipulate the following. 5)
PDT for central serous chorioretinopathy is not covered by insurance in Japan, but its efficacy for chronic central serous chorioretinopathy has been established by multiple high-quality RCTs. 3) The half-dose PDT protocol (3 mg/m²) is widely used as the standard.
The effect is evaluated by OCT etc. 3 months after the initial PDT, and retreatment is performed as needed. In age-related macular degeneration, evaluation is usually performed every 3 months. In central serous chorioretinopathy, SRF disappears in many cases after a single half-dose PDT, so repeated treatments are relatively rare. 3)
PDT induces vascular damage through a photochemical reaction, not a thermal effect. This is a fundamental difference from conventional thermal laser photocoagulation. 1)
The sequence of action is as follows.
While thermal laser coagulates all layers including retinal photoreceptors, PDT selectively acts on neovascular endothelium, causing less thermal damage to the surrounding neural retina. 1)
The main target of PDT for central serous chorioretinopathy is the choroidal vessels. 3)
Polypoidal choroidal vasculopathy, like central serous chorioretinopathy, develops on a background of pachychoroid (choroidal thickening and dilated large choroidal vessels). 2) Polypoidal lesions confirmed on ICGA are sources of bleeding and exudation from abnormal choroidal vessels. PDT exerts a direct occlusive effect on these polypoidal lesions.
Verteporfin (Visudyne®) has been experiencing a global supply shortage since around 2021, limiting opportunities for PDT treatment. This has affected treatment opportunities for central serous chorioretinopathy and polypoidal choroidal vasculopathy, relatively increasing the role of alternative treatments (such as anti-VEGF drugs and mineralocorticoid antagonists).
The Japanese clinical practice guidelines for age-related macular degeneration recommend combination PDT with anti-VEGF drugs in some cases. 5) Particularly in polypoidal choroidal vasculopathy, combination therapy has been shown to improve polyp regression rates compared to anti-VEGF monotherapy.
In a 2023 comprehensive review of polypoidal choroidal vasculopathy, Sen P et al. reported that the widespread use of OCT-based diagnostic modalities (including OCT-A) has improved diagnostic accuracy for polypoidal choroidal vasculopathy. They also emphasized accumulating evidence that the combination of anti-VEGF drugs and PDT shows superior effects in both polyp regression and visual acuity maintenance. 2)
In polypoidal choroidal vasculopathy and pachychoroid spectrum diseases, non-invasive OCT/OCT-A-based diagnosis without ICGA is advancing. 2) This is making it possible to plan diagnosis and treatment even for patients at risk of contrast agent allergy.
Research on novel photosensitizers using nanocomplex technology aimed at more efficient targeted delivery and lower toxicity is progressing. 1) Expansion of PDT applications in ophthalmic oncology is also being considered, and evaluation of the efficacy of high-energy PDT (100 J/cm²) for choroidal melanoma is ongoing. 1)
In a 2025 review, Cheung CMG et al. summarized that four RCTs (PLACE, SPECTRA, REPLACE, SPECS) consistently demonstrated the superiority of half-dose PDT for central serous chorioretinopathy. The finding that the likelihood of visual recovery decreases by approximately 4% for each week of symptom persistence is noteworthy as it suggests the importance of early intervention. 3)
