Clinical spectrum of severe chronic central serous chorioretinopathy and outcome of photodynamic therapy

Figures & data

Table 1 Demographic characteristics in severe chronic CSC patients (cases) and nonsevere chronic CSC patients (controls)

Characteristics	Cases	Controls	P-value
Patients (eyes)	66 (81)	35 (37)	n/a
Male, n (%)	69 (85)	28 (76)	0.210
Caucasian ethnicity, n (%)	72 (89)	27 (73)	0.029
Mean age at diagnosis in years (range)	49 (29–78)	47 (30–72)	0.243
Mean time from CSC diagnosis to final visit in years (range)	6 (0–30)	2 (0–7)	<0.001
Subjects with recent use of steroids,a n (%)	17b (21)	13 (35)	0.110

Notes:

a Within 3 months prior to the diagnosis.

b One patient was diagnosed with Cushing syndrome. Bold font indicates data were considered statistically significant.

Abbreviations: BCVA, best-corrected visual acuity; CSC, central serous chorioretinopathy; n/a, not applicable.

Table 2 Treatment specifications in severe chronic CSC (cases) and nonsevere chronic CSC (controls)

PDT	Treatment characteristics	Cases	Controls	P-value
Before study PDT treatment	Treatment-naive eyes (%)	63 (78)	37 (100)	0.002
	Eyes with previous treatments (%)	9 (11) conventional thermal laser 4 (5) anti-VEGF injectionsa 1 (1) PDT 2 (2) multiple treatments	n/a	n/a
Regarding study PDT treatment	PDT settings (%)	72 (89) half-dose 7 (9) half-time 2 (2) half-fluence	31 (84) half-dose 5 (13) half-time 1 (3) unknown	0.454
	Median time from diagnosis until the study PDT in weeks (range)	5 (0–234)	31 (3–354)	<0.001

Note:

a None of the treated eyes had evidence of choroidal neovascularization, and injections were given before referral. Bold font indicates data were considered statistically significant.

Abbreviations: CSC, central serous chorioretinopathy; n/a, not applicable; PDT, photodynamic therapy; VEGF, vascular endothelial growth factor.

Table 3 Additional treatments after initial PDT in severe chronic CSC (cases) and nonsevere chronic CSC (controls)

Treatment characteristics	Cases	Controls
Total number of eyes that received additional treatments (%)	25a (31)	6a (7)
Number of eyes that received additional PDT treatments (%)	25b (100)	6b (100)
Number of eyes that received additional conventional laser (%)	1 (4)	0 (0)
Reason for additional treatment (%)	11 (44) recurrence of SRF	1 (17) recurrence of SRF
	14 (56) insufficient response to PDT	5 (83) insufficient response to PDT

Notes:

a Some eyes received more than one type of additional treatment.

b Range of extra PDTs needed in cases: 1–2, and in controls: 1.

Abbreviations: CSC, central serous chorioretinopathy; PDT, photodynamic therapy; SRF, subretinal fluid.

Figure 1 Multimodal imaging of a 71-year-old male patient with severe bilateral chronic central serous chorioretinopathy (A–F: right eye, G–L: left eye).

Notes: On color fundus photography, atrophic RPE alterations were seen in the inferotemporal quadrant of the left eye (G). Multifocal “hot spots” of leakage (H) and extensive areas of atrophy were seen on fluorescein angiography (B, H). Fundus autofluorescence showed large areas of hypo- and hyper-autofluorescent abnormalities corresponding to the RPE changes, extending to outside the macula (D, J). Indocyanine green angiography images (C, I) showed multifocal areas of diffuse choroidal abnormalities and leakage. OCT revealed in both eyes epiretinal membrane and subretinal fluid centrally in the macula (E, K). Posterior cystoid retinal degeneration was seen in the outer nuclear layer of the nasal macula of the left eye (K). Ten weeks after half-dose photodynamic therapy, which was only performed in the left eye, both subretinal fluid and posterior cystoid retinal degeneration had disappeared (L). The black arrows on the color fundus photography images correspond to the scanning plane on the OCT scans (E, F, K, L).
Abbreviations: OCT, optical coherence tomography; RPE, retinal pigment epithelial.

Table 4 Clinical outcome after PDT with reduced settings in severe chronic CSC (cases) and nonsevere chronic CSC (controls)

Clinical outcome measures	Cases	Controls	P-value
BCVA before initial PDT in ETDRS letters±SD	66±19	78±11	<0.001
BCVA at first follow-upa in ETDRS letters±SD	72±18	82±9	<0.001
BCVA at final follow-upb in ETDRS letters±SD	72±21	82±11	0.001
Resolution of SRF at first follow-up,a n (%)	56 (70)	28 (78)	0.386
Resolution of SRF at final follow-up,b n (%)	71 (88)	35 (95)	0.247
Resolution of SRF in treatment-naive eyes at first follow-up,a n (%)	43 (70)	28 (78)	0.368
Resolution of SRF in treatment-naive eyes at final follow-up,b n (%)	55 (87)	35 (95)	0.241
Presence of PCRD before initial PDT, n (%)	25/81 (31)	n/ac	n/a
Resolution of PCRD at first follow-up examination,a n (%)	11/25 (44)	n/ac	n/a
Resolution of PCRD at final follow-up examination,b n (%)	13/25 (52)	n/ac	n/a

Notes:

a The average time between initial PDT and first follow-up was 7 weeks.

b The average time between initial PDT and final follow-up was 90 weeks.

c Posterior cystoid retinal degeneration was only present in the case group. Bold font indicates data were considered statistically significant.

Abbreviations: BCVA, best-corrected visual acuity; CSC, central serous chorioretinopathy; ETDRS, Early Treatment of Diabetic Retinopathy Study; n/a, not applicable; PCRD, posterior cystoid retinal degeneration; PDT, photodynamic therapy; SRF, subretinal fluid.

Figure 2 Kaplan–Meier curve showing the cumulative fraction of patients treated for chronic central serous chorioretinopathy (cCSC).

Notes: Endpoint: “Complete resolution of subretinal fluid (SRF) after photodynamic therapy”; the median duration to SRF resolution in cCSC patients with a severe phenotype of the disease (cases) was 8 weeks (95% CI: 7–9). In cCSC patients who did not meet the criteria of severity (controls), the median duration was 7 weeks (95% CI: 7–8; log-rank test; P=0.281).

Figure 3 Clinical features on multimodal imaging of the right eye of a 63-year-old female patient with severe chronic central serous chorioretinopathy (A–C). Black arrow on color fundus photography image (A) shows the scanning plane, which is depicted on the SD-OCT scans (D, E). FAF shows multiple speckled hyperautofluorescent changes in the macula together with an irregular surface of hypoautofluorescence, expanding from the fovea to the superior and inferior vascular arcades (B). Fluorescein angiography imaging (C) revealed a limited area of fluorescein leakage with a clear central focus. The areas of hypofluorescence were located more temporal from the fovea and were smaller than on FAF. An SD-OCT scan (D) at first presentation and prior to treatment revealed a subretinal serous fluid accumulation together with a posterior cystoid retinal degeneration in the outer nuclear layer of the retina. At ~2 months after half-dose photodynamic therapy, both subretinal and intraretinal fluid on OCT had resolved completely (E).

Abbreviations: FAF, fundus autofluorescence imaging; SD-OCT, spectral-domain optical coherence tomography.

Figure 4 Four categories of eyes with severe chronic central serous chorioretinopathy with active fluorescein leakage on fluorescein angiography.

Notes: This figure illustrates different fluorescein leakage locations (arrows) in relation to the largest area of DARA (dotted line). (A) Category 1 concerns a leakage point inside the largest area of RPE alterations. (B) Category 2 concerns 1 or more leakage points located on the edges of the largest region of RPE alterations. (C) In category 3, leakage points causing macular subretinal fluid are outside the largest zone of RPE alterations. (D) Category 4 concerns cases with multifocal leakage points in several of the aforementioned locations in relation to the area of RPE alterations.
Abbreviations: DARA, diffuse atrophic RPE alterations; RPE, retinal pigment epithelium.