A prospective randomised controlled multicentre trial comparing half-dose photodynamic therapy (PDT) with high-density subthreshold micropulse laser treatment in patients with chronic central serous chorioretinopathy (CSC).

Chronic central serous chorioretinopathy (CSC) is a relatively frequent eye
disease that often occurs in patients in the
professionally active age range. In this disease, there is pooling of fluid
under the central retina (the macula). This
specific form of macular degeneration can cause permanent vision loss, image
distortion, loss of color and contrast
vision due to this fluid under the retina. An early diagnosis and treatment may
improve the visual outcome and quality of
life. To date there is no international consensus on the optimal treatment of
chronic CSC. Many retrospective studies
suggest that treatment with photodynamic therapy (PDT) is effective in chronic
CSC. Micropulse laser (ML) therapy may
also be effective in this disease.
The proposed study is the first prospective randomized controlled trial in
chronic CSC. In this study, participants with chronic CSC will be randomized
into two treatment groups, PDT or ML treatment. The trial is a superiority
study,
because retrospective studies suggest that PDT treatment may be more effective
than ML treatment. Therefore, PDT
treatment is challenged against ML treatment.

Primary Objective
To investigate whether half-dose PDT treatment leads to a higher percentage of
chronic CSC patients with subretinal fluid on OCT achieving an absence of this
subretinal fluid on OCT as compared to HSML treatment.

Secondary Objectives
To investigate the clinical outcome comparing half-dose PDT treatment with HSML
treatment in patients with subretinal fluid due to active leakage in chronic
CSC, based on evaluation of best-corrected visual acuity (BCVA), retinal
sensitivity on microperimetry, and subjective success score on the NEI VFQ-25
questionnaire.

This study is a multicentre, prospective, randomized, controlled, open-label
study that will compare the efficacy and safety of two treatments in patients
with chronic CSC.

Half-dose PDT treatment
For this intervention the patients need dilated pupils (with 1.0% tropicamide
and 2,5% phenylephrine). All patients will get an intravenous drip through
which 3 mg/m2 verteporfin (Visudyne ®) (half-dose) is administered, with an
infusion time of 10 minutes. At exactly 15 minutes after the start of the
infusion, an anesthetic eye drop is given (oxybuprocaïne 0.4% or equivalent), a
contact glass (a Volk® PDT lens, magnification of 1.5x) is positioned on the
affected eye, and the aiming beam of the laser is focused on the treatment
area. The magnification factor is taken into account in the settings of the PDT
machine. The area of treatment is chosen, with the area of the aiming beam
corresponding to the area of the subsequent laser spot area. The area that has
to be treated is determined based on those hyperfluorescent area(s) on
mid-phase (approximately 10 minutes) ICG-angiography that correspond to
subretinal fluid accumulation in the macula on the OCT scan and
hyperfluorescent *hot spots* on the mid-phase (approximately 3 minutes)
fluorescein angiogram. The spot size will be defined based on diameter of the
hyperfluorescent area on ICG angiography plus 1mm. The treatment is performed
with standard 50 J/cm2 fluency, a PDT laser wavelength of 689 nm, and a
standard treatment duration of 83 seconds. Care must be taken to treat at
exactly 15 minutes after the start of the infusion, to maximize the
localization of the effect of treatment to the choroid and minimize possible
damage to the adjacent retinal structures. The PDT treatment must take place at
least 45 minutes after ICG angiography has been performed.

High-density subthreshold micropulse laser (HSML) treatment
For this intervention the patients need dilated pupils (with 1.0% tropicamide
and 2,5% phenylephrine). An anaesthetic eye drop is given (oxybuprocaïne 0.4%
or equivalent), and a contact glass (for instance a Volk® Area Centralis lens)
is positioned on the affected eye. HSML treatment with an 810 nm diode laser
(Iridex, Mountain View, United States) will be performed of the areas
identified on mid-phase ICG angiography. Multiple confluent, adjacent
(non-overlapping) laser spots will be applied, covering the leakage area on
mid-phase ICG angiography. The number of spots and number of zones treated
depend on the extent of the leakage area(s) on mid-phase ICG. The area that has
to be treated is determined based on those hyperfluorescent area(s) on
mid-phase (approximately 10 minutes) ICG-angiography that correspond to
subretinal fluid accumulation in the macula on the OCT scan and
hyperfluorescent *hot spots* on the mid-phase (3 minutes) fluorescein angiogram.
The following HSML treatment settings will be used: a power of 1800 mW*, a duty
cycle of 15%, frequency of 500 Hz, exposure time of 0.2 s per spot, spot size:
125 µm, minimal distance of spot from fovea: 500 µm.
* Subthreshold treatment is desired, meaning that no visible reaction due to
laser treatment has to be seen in the retina. In virtually all patients, a
power of 1800 mW wil not produce a visible discoloration of the retina after
application of a laser spot with the aforementioned settings. If retinal
discoloration is seen at a power of 1800 mW (corresponding to suprathreshold
treatment), for instance in patients with darkly pigmented fundi, the power
will be reduced with steps of 300 mW until there is no visible reaction. The
first laser *test* spot will always be applied juist outside the macular area.

It is possible that by exception extra visits may be necessary in addition to
standard clinical care, because in some cases not all examinations may be
possible on the same day. This may for instance be the case if an extra visit
is necessary to complete the clinical examinations that are required to judge
eligibility.