Long-term follow-up and cross-over of treatment with high-density micropulse laser and half-dose photodynamic therapy in participants of the PLACE trial for chronic central serous chorioretinopathy.

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.
This study follows the PLACE trial, which was the first prospective randomized
controlled trial in chronic CSC. In this trial the long-term effect of
treatment with either PDT or ML will be investigated. Also, a possible
additional effect of applying a cross-over treatment (PDT in patients who
received ML during the PLACE trial, and vice versa) will be studied.

Primary objectives:
- To investigate the long-term outcome after successful treatment (no
subretinal fluid on OCT) in the PLACE trial.
- To investigate whether a cross-over treatment of half-dose PDT to HSML in
cCSC patients who either did not respond or who showed recurrence of subretinal
fluid in the PLACE trial, and vice versa, results in an absence of subretinal
fluid on OCT.

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

Prospective open-label follow-up and cross-over trial.

Patients who will be included in the cross-over study, will receive an
intervention. If a patient received half-dose photodynamic therapy during the
PLACE trial, high-density subthreshold micropulse laser therapy will be
executed. If a patient received high-density subthreshold micropulse laser
therapy during the PLACE trial, half-dose photodynamic therapy will be
executed.

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 midphase (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.