The relationship between foveal outer nuclear layer thickness in the active and resolved phases of central serous chorioretinopathy treated with half-dose photodynamic therapy

The clinical diagnosis of CSC was based on the following symptoms: reduced visual acuity, with or without metamorphopsia or micropsia; the presence of serous retinal detachment on both fundus and OCT examinations; the presence of active angiographic leakage on FA (TRC-50IX; Topcon Corp.,Tokyo, Japan); and/or abnormally dilated choroidal vasculature and other features on indocyanine green angiography (ICGA) (Spectralis HRA + OCT; Heidelberg Engineering, Heidelberg, Germany), consistent with the diagnosis of CSC [17, 18].

The data of the affected eyes were collected, including the symptom duration, best corrected visual acuity (BCVA), measured with a standard Snellen chart and converted to the logarithm of the minimum angle of resolution (logMAR) for statistical analysis, intraocular pressure, using a noncontact tonometer, central retinal thickness, half-dose PDT spot size, as well as the physical examination information of slit-lamp biomicroscopy.

The subjects included were those with clear and detailed medical records; symptom duration of 6 weeks or more; no amblyopia in the CSC eye; spherical equivalent between −2D and + 2D; no history of refractive surgery; subretinal fluid resolution within 2 months of half-dose PDT; no recurrence within 12 months of half-dose PDT; subretinal fluid involving the fovea; and a continuous external limiting membrane (ELM) at the fovea on all OCT images.

The exclusion criteria were: fragmentary medical records; symptom duration of less than 6 weeks; either clinical signs or a history of any other intraocular disease in the affected eye; any steroid use; inability to define the symptom duration before half-dose PDT; amblyopia in the CSC eye; spherical equivalent < −2D or > +2D; a history of refractive surgery; any residual subretinal fluid for up to 2 months after half-dose PDT; any recurrence within 12 months of half-dose PDT; any of staphyloma, choroidal excavation, or retinal dipping; RPE abnormality involving the fovea; subretinal fluid only at extra fovea; and an ELM interrupted at the fovea on any OCT image.

The half-dose PDT protocol for CSC was performed with half the normal dose of verteporfin (Visudyne; Novartis AG,Bülach, Switzerland), that is, 3 mg/m²verteporfin, based on the rationale that a lower dose has less-severe collateral damage effects to the retina and choroid. Verteporfin was infused over 8 min, followed by delivery of laser at 689 nm at 10 min from the commencement of infusion to target the area of choroidal dilation and hyperpermeability [19‐21]. A total light energy of 50 J/cm²over 83 s was delivered to the angiographic leakage sites shown in FA or the area of choroidal hyperperfusion observed in ICGA [19‐21].

All OCT images were obtained through a dilated pupil with a line scan protocol (line scans of 30°, composed of 100 averaged images; Heidelberg Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany). In each subject, this protocol was applied both vertically and horizontally and centered on the fovea in the CSC eyes. The OCT images (vertical and horizontal) that passed through the central fovea were selected for the measurement of the ONL thickness, as well as the height of retinal detachment, and the width of the subretinal space. OCT images taken within 1 week before half-dose PDT, 2 months (±2 weeks) after half-dose PDT, and 12 months (±2 weeks) after half-dose PDT were analyzed.

The foveal ONL thickness was the average of the distances between the internal limiting membrane and the ELM at the center of the fovea measured from the horizontal and vertical scans respectively. (Figure 1a) The difference in the foveal ONL thickness was defined as the difference between the foveal ONL thickness measured at 12 m after half-dose PDT and that measured before half-dose PDT. The width of the subretinal space was defined as the distance between the vertices on the bottom side of the subretinal space on an OCT image(Figure 1b); and the height of the detached retina was defined as the average of the vertical distance between the ELM and RPE at the center of the fovea measured from the horizontal and vertical images respectively.(Fig. 1c) These measurements were made manually with the supplied caliper measurement tool (in 1:1 μm mode; HRA/Spectralis Viewing Module 6.0.9.0, Heidelberg Engineering). All the scans and measurements were made by Y.J. The repeatability of the measurements, including the foveal ONL thickness, the width of the subretinal space, and the height of the retinal detachment in the CSC eyes, were calculated from two horizontal scans taken of each eye during a single visit; 20 CSC eyes were included. Intraclass correlation coefficients (ICC) were used to assess the repeatability of the measurements (ICC values of 0.81–1.00 indicated almost perfect agreement between repeated measurements; values < 0.40 indicated poor to fair agreement) [22].

The data were analyzed with SPSS for Windows version 21.0 (SPSS, Chicago, IL, USA). Descriptive statistics were calculated, including medians, means, proportions, and frequencies. The Kolmogorov–Smirnov test was used to confirm the normality of the data. Either Pearson’s correlation coefficient or Spearman’s correlation coefficient was used to examine the correlation between symptom duration and the foveal ONL thickness 12 months after half-dose PDT. A paired t test was used to examine the difference between the foveal ONL thickness 12 months after half-dose PDT and that before half-dose PDT. The associations of the foveal ONL thickness difference (dependent variable of interest) with the ratio of the retinal detachment height to the subretinal space width (independent variable) was assessed with generalized linear models. Factors such as sex, age, BCVA before and after half-dose PDT, and symptom duration before half-dose PDT were included in a multivariate model to adjust for potential confounding. A P value of < 0.05 was considered statistically significant.