Comparing half-dose photodynamic therapy with high-density subthreshold micropulse laser treatment in patients with chronic central serous chorioretinopathy (the PLACE trial): study protocol for a randomized controlled trial

Abstract

Background: Chronic central serous chorioretinopathy (cCSC) is an eye disease characterized by an accumulation of serous fluid under the retina. It is postulated that this fluid accumulation results from hyperpermeability and swelling of the choroid, the underlying vascular tissue of the eye, causing a dysfunction of the retinal pigment epithelium. This fluid accumulation causes neuroretinal detachment. A prolonged neuroretinal detachment in the macula can lead to permanent vision loss. Therefore, treatment is aimed primarily at achieving resolution of subretinal fluid, preferably within the first 4 months after diagnosis of the disease. A broad spectrum of treatment modalities has been investigated in cCSC, but no consensus exists on the optimal treatment of cCSC. Currently, photodynamic therapy (PDT) and high-density subthreshold micropulse laser treatment (HSML) are among the most frequently cited treatments in obtaining successful neuroretinal reattachment.

Methods/design: This is a randomized, controlled, open-label, multicenter trial comparing the efficacy of half-dose PDT to HSML in treating patients with cCSC. A total of 156 patients will be recruited, 78 patients in each treatment arm, with a maximum follow-up duration of 8 months after the first treatment. A complete ophthalmological examination with vision-related quality of life (NEI VFQ-25) and stress questionnaires, will be performed at baseline, 6 to 8 weeks after the first treatment, 6 to 8 weeks after a second treatment (if necessary), and at the final follow-up visit at 7 to 8 months after the first treatment. Treatment visits will be scheduled within 3 weeks after the baseline visit, and within 3 weeks after the first control visit, if a second treatment is required.

Discussion: Both half-dose PDT and HSML may be effective treatments in cCSC, but because of the lack of prospective randomized controlled trials, which treatment should be the first choice remains unclear. The aim of this study is to compare the efficacy of half-dose PDT to HSML. The primary endpoint to evaluate efficacy will be a complete absence of subretinal fluid on optical coherence tomography after treatment. Secondary functional endpoints include change in Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity, retinal sensitivity on microperimetry, and NEI VFQ-25 questionnaire of visual functioning. Registration number Institutional Review Board (CMO Arnhem-Nijmegen, the Netherlands): 2013/203 NL nr.: 41266.091.13 TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01797861 . Date of registration: 21 February 2013.

Fig. 1

Multimodal imaging in chronic central serous chorioretinopathy. Examples of fluorescein angiography (FA), indocyanine green (ICG) angiography and spectral-domain optical coherence tomography (SD-OCT) in chronic central serous chorioretinopathy (cCSC). (a-c) Right eye of a patient with cCSC with more widespread leakage on FA (a) corresponding with hyperfluorescent areas on ICG angiography (b) and SRF on SD-OCT (c)

Fig. 2

Study flow chart

Fig. 3

Examples of areas treated in photodynamic therapy and micropulse laser treatment. Examples of imaging features on fluorescein angiography (FA) and indocyanine green angiography (ICG) angiography in chronic central serous chorioretinopathy (cCSC), and the corresponding treatment areas for photodynamic therapy (PDT) and high-density subthreshold micropulse laser treatment (HSML). a-b FA of the right eye of a patient showing hyperfluorescent “hot spots,” indicating leakage inferior of the fovea (a). On ICG angiography, an area of hyperfluorescence, which corresponds to the hyperfluorescent area on the FA, is seen (b). c-f An example of a PDT spot (white circle) overlapping the hyperfluorescent area on the ICG angiography plus 1 mm as described in the protocol (c). HSML treatment scheme that would apply to the same eye, in which only the central foveal area is excluded for treatment (white circle). The hyperfluorescent area on the ICGA is treated with numerous, nonoverlapping adjacent laser spots (white area) (d)