Evaluation of anterior scleral thickness in eyes with central serous chorioretinopathy

Abstract

Purpose:

To compare the anterior scleral thickness in eyes with central serous chorioretinopathy (CSC) and healthy eyes.

Design:

Cross-sectional observational study.

Methods:

The study included patients with CSC and age and gender-matched healthy individuals. The subfoveal choroidal thickness (SFCT) and scleral thickness at 3 mm, 4 mm, and 8 mm posterior to the scleral spur were measured using swept source optical coherence tomography (Topcon DRI-OCT Triton plus).

Results:

The study included 35 eyes with CSC and 35 control eyes. In CSC group, 82.86% were simple and 17.14% were complex. There was no statistically significant difference in the scleral thickness in CSC and control groups. Though the sclera was thicker in the complex CSC group compared to simple CSC at 3 mm (nasal: 724.33 ± 180.53 vs 658.48 ± 57.63, temporal: 696.17 ± 212.91 vs 628.83 ± 107.7) and 4 mm (nasal: 656.67 ± 109.34 vs 621.62 ± 79.31, temporal: 640.17 ± 191.31 vs 616.48 ± 86.30), the difference was not statistically significant. A moderate negative correlation was noted between SFCT and scleral thickness at 8 mm (r -0.349) and 3 mm on the nasal side (r -0.388) in the control group. A moderate negative correlation was noted between SFCT and scleral thickness at 4 mm (r -0.377) and 3 mm (r -0.403) on the temporal side in CSC group.

Conclusion:

The anterior scleral thickness was similar in CSC and healthy eyes. As the study sample predominantly included simple CSC, the findings indicate that the anterior scleral thickness may not be involved in the pathogenesis of simple CSC.

Central serous chorioretinopathy (CSC) is now considered as a pachychoroid spectrum disease.[1] CSC is characterized by circumscribed serous detachment of the retina. The detachment is a result of leakage at the level of retinal pigment epithelium (RPE) as demonstrated by fundus fluorescein angiography (FFA). Other features include pigment epithelial detachments and granular changes in the pigmentation of the RPE.[2,3] Although the subretinal fluid (SRF) can resolve spontaneously, a few patients have significant clinical sequelae, including atrophy of the RPE, retina, and rarely choroidal neovascularization.[4]

The etiology and pathogenesis of CSC are yet to be completely understood. It was initially thought to be associated with infective pathology such as syphilis, tuberculosis, or Helicobacter pylori infection. Later, the theory of sympathetic overactivity gained popularity. Detection of delayed choroidal filling, choroidal vascular dilatation, and choroidal vascular hyperpermeability on indocyanine green angiography (ICGA) suggested that the choroidal circulatory abnormalities are key factors responsible for the development of CSC.[5] Studies using ultrawide field ICGA proposed that the presence of choroidal vascular dilatation may be related to congestion of choroidal outflow in the vortex vein.[6] Vortex vein dilatation was observed in 83.3% of cases with CSC.[7] Another mechanism proposed to be involved in pachychoroid spectrum diseases is asymmetric venous outflow, and eyes with CSC are known to exhibit vortex venous asymmetry.[7] Vortex vein which makes an exit from the eye through the sclera may be affected by the scleral thickness. Thickened sclera may result in hindrance to the venous outflow which can lead to venous overload.[8] Studies evaluating the equatorial and posterior scleral thicknesses using contact b-scan ultrasonography showed increased scleral thickness in eyes with CSC.[8]

In this study, we evaluated the correlation between anterior scleral thickness and choroidal thickness in eyes with CSC in comparison to the age-matched control group.

Methods

This was a cross-sectional, comparative study conducted at a tertiary eye care center in central Karnataka, India, between September 2022 and September 2023. The study was approved by the institutional ethics committee and was conducted in accordance with the principles of the Declaration of Helsinki. Informed written consent was obtained from all the participants.

Cases diagnosed as CSC based on clinical examination, optical coherence tomography (OCT), and FFA (whenever required) with the axial length in the range of 22–24 mm and age more than 18 years were included. Cases with less than two disc areas of RPE alterations were classified as simple CSC, and cases with more than two disc areas of RPE alterations were classified as complex CSC.[9] In eyes with bilateral disease, only right eye was included in the study. The control group included age and gender-matched healthy volunteers aged more than 18 years with normal ocular examination and an axial length in the range of 22–24 mm. Participants with past history of ocular inflammation, macular diseases other than CSC, prior retinal photocoagulation except focal laser for CSC, history of ocular surgeries, raised intraocular pressure, and scleral ectasia were excluded.

Participants underwent a detailed ocular examination. Axial length was measured using IOL Master 700 (Carl Zeiss Meditec, Jena, Germany). Subfoveal choroidal thickness (SFCT) and anterior scleral thickness were measured using swept source OCT [Topcon DRI-OCT Triton plus (Topcon corporation, Tokyo, Japan)]. 9 mm radial scan centered on the fovea was captured. Subfoveal choroidal thickness was measured manually using the inbuilt callipers from the Bruch’s membrane to the choroidoscleral junction at the foveal center in the well centered scan. Subfoveal choroidal thickness was measured by three independent readers.

Cross-sectional imaging of sclera was acquired using anterior segment OCT. Two separate ‘16 mm horizontal line scans’ were captured along the horizontal meridian in temporal and nasal quadrants. Scleral thickness was measured manually at three points posterior to the scleral spur: 3 mm, 4 mm, and 8 mm. Scleral thickness was measured as a perpendicular line from the outer surface (junction of compact sclera and episcleral vessels) to the inner surface of sclera (junction of compact sclera and pars plana/choroid) manually with the inbuilt calliper [Fig. 1].

Figure 1.

Representative image of a case of simple CSC. (a) Figure depicting measurement of subfoveal choroidal thickness from Bruch’s membrane to choroidoscleral junction in cross-sectional OCT. (b-d) Figures depicting measurement of scleral thickness at 3 mm (584 micron), 4 mm (600 micron), and 8 mm (380 micron) posterior to scleral spur, respectively

Statistical analysis

Statistical analysis was performed with SPSS software version 12.0 (SPSS, Inc., Chicago, IL). All values were expressed as mean and standard deviation. Mann–Whitney U test was used to compare the age, axial length, subfoveal choroidal thickness, and scleral thickness between cases and control eyes. Pearson correlation was used to assess the correlation between SFCT and scleral thickness. A P value less than 0.05 was considered statistically significant.

Results

The study included 35 eyes of 35 patients with CSC and 35 eyes of 35 age and gender-matched healthy subjects. Out of the 35 eyes with CSC, 29 (82.86%) were classified as simple CSC (25 primary, 4 recurrent) and 6 (17.14%) were classified as complex CSC (4 primary, 2 recurrent).

The mean age of the patients in CSC group was 41.51 ± 6.94 years, and the mean age of subjects in the control group was 41.68 ± 7.35 years. There was no statistically significant difference in the age distribution between the two groups (p-0.81). The study population predominantly included men accounting for 77.14% of patients in both the groups. The mean axial length in the CSC group was 22.88 ± 0.64 mm, and that in the control group was 23.12 ± 0.50 mm. The difference in the axial length between the two groups was statistically significant (p-0.48). Mean SFCT was 427.23 ± 68.99 microns in CSC group and 338.11 ± 85.68 microns in the control group. The subfoveal choroid was significantly thicker in CSC group (P value < 0.001).

Mean scleral thicknesses measured at 3 mm, 4 mm, and 8 mm nasally and temporally in CSC group and control group are summarized in Table 1. There was no statistically significant difference in the scleral thickness between the two groups. Sclera was significantly thinner at 8 mm compared to 3 mm and 4 mm (P < 0.00001) in both the groups.

Table 1.

Comparison of scleral thickness between the CSC group and control group

Scleral thickness		CSC group (Mean±SD) (microns)		Control group (Mean±SD) (microns)		P*
3 mm nasal		669.77±89.04		652.83±91.98		0.74
3 mm temporal		640.37±107.73		632.28±69.56		0.83
4 mm nasal		627.63±83.15		605.51±92.92		0.42
4 mm temporal		620.54±106.14		614.88±72.46		0.86
8 mm nasal		375.83±54.23		395.80±64.20		0.14
8 mm temporal		370.22±63.27		373.97±55.47		0.99

A subgroup analysis was performed to compare the scleral thickness between simple CSC and complex CSC [Table 2]. Though the sclera was thicker in the complex CSC group compared to simple CSC group at 3 and 4 mm, the difference was not statistically significant. The scleral thickness at 8 mm was similar between the simple and complex CSC. Measurement of choroidal thickness and scleral thickness in a case of simple CSC and complex CSC is represented in Figs. 1 and 2, respectively.

Table 2.

Comparison of scleral thickness between the simple CSC and complex CSC

Scleral thickness		Simple CSC (Mean±SD) (microns)		Complex CSC (Mean±SD) (microns)		P*
3 mm nasal		658.48±57.63		724.33±180.53		0.74
3 mm temporal		628.83±107.7		696.17±212.91		0.70
4 mm nasal		621.62±79.31		656.67±109.34		0.71
4 mm temporal		616.48±86.30		640.17±191.31		0.84
8 mm nasal		376.55±47.52		372.33±89.01		0.84
8 mm temporal		368.55±63.21		378.33±74.49		0.70

*Mann–Whitney U test was used to assess the difference in scleral thickness between two groups. CSC: Central serous chorioretinopathy

Figure 2.

Representative image of a case of complex CSC (recurrent). (a) Cross-sectional OCT showing subretinal fibrin, subretinal fluid, and serous PED. The figure depicts subfoveal choroidal thickness measurement. (b-d) Figures showing thicker sclera at 3 mm (699 micron), 4 mm (716 micron), and 8 mm (447 micron) posterior to scleral spur, respectively

Correlation between the scleral thickness and SFCT in CSC group and control group is summarized in Table 3. A moderate negative correlation was noted between SFCT and scleral thickness at 8 mm and 3 mm on the nasal side in control group. A moderate negative correlation was noted between SFCT and scleral thickness at 4 mm and 3 mm on temporal side in CSC group.

Table 3.

Correlation between scleral thickness and SFCT in the CSC group and control group

Parameter				R		P
SFCT and scleral thickness at 8 mm temporal		CSC group		-0.107		0.541
		Control group		-0.325		0.057
SFCT and scleral thickness at 8 mm nasal		CSC group		-0.329		0.053
		Control group		-0.349		0.040*
SFCT and scleral thickness at 4 mm temporal		CSC group		-0.377		0.025*
		Control group		-0.144		0.409
SFCT and scleral thickness at 4 mm nasal		CSC group		-0.087		0.619
		Control group		-0.302		0.078
SFCT and scleral thickness at 3 mm temporal		CSC group		-0.403		0.016*
		Control group		-0.162		0.352
SFCT and scleral thickness at 3 mm nasal		CSC group		-0.2693		0.118
		Control group		-0.388		0.021*

Pearson correlation was used to assess the correlation between SFCT and scleral thickness. SFCT: Subfoveal choroidal thickness, CSC: Central serous chorioretinopathy

A strong interobserver agreement was noted in the measurement of SFCT between the three graders (ICC-0.902).

Discussion

Impedance to choroidal venous outflow through the vortex vein is proposed to be a predisposing factor in eyes with CSC. Equatorial scleral thickness measured by contact B scan ultrasonography is noted to be significantly higher in eyes with CSC compared to the control eyes in a study.[8] Though equatorial scleral thickness is a better indicator of resistance to choroidal venous outflow as the vortex veins are located close to the equator, it can be measured noninvasively by imaging modalities with low resolution such as ultrasonography or magnetic resonance imaging. Anterior segment OCT is a better tool to measure the scleral thickness due to its better resolution. However, the limitation of ASOCT is that it can be used to measure the anterior scleral thickness and not the equatorial scleral thickness. A few studies have evaluated the anterior scleral thickness (sub lateral rectus,[10] 6 mm posterior to scleral spur,[11] at insertion of recti[12]) in eyes with CSC. In this study, we measured the scleral thickness at 3, 4, and 8 mm posterior to scleral spur in nasal and temporal horizontal meridian in eyes with CSC and controls.

In the present study, the scleral thickness was significantly lesser at 8 mm posterior to scleral spur compared to 3 mm and 4 mm in both CSC group and control, which correlates with the well-known observation that sclera is thin posterior to rectus muscle insertion. The subfoveal choroid was significantly thicker in eyes with CSC compared to control group, which is in agreement with the studies published in the literature. However, we did not find a significant difference in the anterior scleral thickness up to 8 mm posterior to scleral spur in eyes with CSC and control eyes. We noted a moderate negative correlation between anterior scleral thickness at a few regions and SFCT in both the groups.

To the best of our knowledge, two studies have evaluated the anterior scleral thickness using ASOCT in eyes with CSC. In a pilot study by Lee et al. comparing the scleral thickness between 15 eyes with CSC and 15 healthy eyes, the anterior sclera (sub lateral rectus) and choroid were significantly thicker in eyes with CSC compared to healthy eyes. In addition, a positive corelation was noted between scleral and choroidal thicknesses among both the control and CSC groups.[10] However, in the present study, a negative correlation was noted between anterior scleral thickness at a few regions and choroidal thickness. The study by Lee et al. included eyes with acute, recurrent, chronic, and inactive CSC with inactive cases constituting half of the sample;[10] however, most of the cases in the present study were primary simple CSC. In the present study, the axial length was significantly higher in control group than in CSC group. The anterior scleral thickness decreases with increasing degree of myopia.[13] So, it is expected that the scleral thickness would be lesser in control group. However, despite the longer axial length, the scleral thickness in control group was similar to that in CSC group, indicating that the anterior scleral thickness may not have a role in pathogenesis of simple CSC.

In a study conducted by Imanaga et al.,[11] sclera (6 mm posterior to scleral spur) was noted to be significantly thicker in eyes with complex CSC compared to simple CSC. The authors concluded that thick sclera may be associated with larger areas of RPE atrophy and recurrent and persistent SRF and may be a poor prognostic factor in CSC. It would not be possible to comment whether the sclera in eyes with simple CSC was thicker compared to healthy eyes in the study by Imanaga et al.,[11] as it did not have a control group. In a study by Yoneyama et al.,[14] complex CSC was exclusively seen in men, was mostly bilateral, and had thicker choroid and thinner central retina compared to simple CSC. These findings would indicate that other predisposing factors could be involved in the pathogenesis of complex CSC, but it would not be possible to conclude whether thicker sclera is one of the factors. Most of the cases in the present study were simple CSC. Though the sclera was thicker at 3 and 4 mm in complex CSC compared to simple CSC (not statistically significant), it would not be possible to draw a conclusion due to a small sample size.

In a study by Aoki et al.,[12] anterior scleral thickness was measured at the insertion of lateral, medial, and inferior recti and 6 mm behind the scleral spur in the superior quadrant in eyes with CSC and control. The sclera was noted to be significantly thicker in eyes with CSC compared to control eyes in temporal and nasal quadrants but not in superior and inferior quadrants. There is no mention of the type of CSC (simple/complex) recruited in this study.

Spaide et al.[8] conducted a study to measure the scleral thickness using contact B-scan ultrasonography in 40 patients with CSC and 23 controls. The mean subfoveal scleral thickness was 1.3 mm in CSC group and 0.86 mm in the control group (P < .001). The mean equatorial scleral thickness was 0.61 mm in CSC group and 0.42 mm in the control group (P < .001). They concluded that the scleral thickness in both equatorial and subfoveal regions is higher in eyes with CSC and scleral thickness is a potential predictor of CSC consistent with the proposed theory of venous overload choroidopathy. However, a direct comparison with this study is not appropriate as the imaging modality used and the region of sclera measured are different in both the studies.

Scleral thickness was measured using swept source ASOCT (CASIA2; Tomey Corporation) in the study by Lee et al.[10] and Imanaga et al.[11] The present study used swept source ASOCT (Topcon DRIOCT Triton plus) to measure scleral thickness. Data regarding the agreement in scleral thickness measurement between the two devices are not available. However, it is less likely that the difference in device used would have affected the results.

The strengths of the study are the inclusion of age and gender-matched control group, measurement of sclera as posterior as 8 mm from the scleral spur, and strong interobserver agreement between the three graders. The limitations of the study are a small sample size and a relatively small proportion of cases with complex CSC. Diurnal variation in anterior scleral thickness was not considered in the study. Though diurnal variation in scleral thickness is described in the literature, the maximum thickness is noted on waking up and the changes during the midday are less significant.[15] The study participants (cases and controls) underwent ASOCT between 9 AM to 6 PM, and none of the cases were evaluated in early morning. Four patients in CSC group and six patients in control group were hypertensive. Studies evaluating the role of hypertension on scleral thickness are not available in the literature. One patient in CSC group was on oral steroids for ulcerative colitis. However, due to a small sample, the analysis of impact of these parameters on the results was not possible.

Conclusion

In this study, we noted that the anterior scleral thickness was similar in eyes with CSC and healthy eyes. There was no positive correlation between anterior scleral thickness and subfoveal choroidal thickness in eyes with CSC. As the study sample mainly included eyes with simple CSC, the findings indicate that the anterior scleral thickness may not be involved in the pathogenesis of simple CSC. However, studies with larger samples of complex CSC are required to establish whether the anterior scleral thickness has a role in complex CSC.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.