Functional and morphological retinal impairment following resolved chronic central serous chorioretinopathy

Purpose Central serous chorioretinopathy is a complex ocular entity that, in its chronic form, can lead to serious visual impairment and morphological damage to the retina. The aim of the current retrospective study was to evaluate the damage present after long-standing but resolved central serous chorioretinopathy. Correlations between measurable factors—for example, duration of the disease, baseline retinal morphological parameters, or patient age and/or their degree of impairment—were also assessed. Materials and methods Thirty-two eyes with chronic central serous chorioretinopathy in which complete resolution of subretinal fluid was achieved after subthreshold micropulse laser treatment were analyzed according to final best-corrected visual acuity and retinal morphological parameters as measured by spectral optical coherence tomography with angiography option (OCTA). Results were compared with the outcomes of a control group. Statistical analysis included regarding correlation between final visual acuity and final central retinal thickness and retinal and functional parameters prior to treatment. Results Final best-corrected visual acuity after chronic central serous chorioretinopathy was 0.23 logMAR (0.6 Snellen) and central retinal thickness was 39.32 µm smaller than in controls. No correlation was found between final visual acuity and retinal thickness and duration of the disease, patient age, and baseline morphological retinal parameters. OCTA scans revealed impaired choroidal perfusion even following resolution of the disease. Conclusion Chronic central serous chorioretinopathy is a potentially damaging clinical entity that results in serious visual impairment, retinal thinning, and choroidal flow defects. No significant correlation between duration of central serous chorioretinopathy and amount of visual deficit has been found, therefore it is possible that the biggest damage occurs within the first months of active chorioretinopathy.


Introduction
Central serous chorioretinopathy (CSCR) is a well-known ophthalmological entity; however, its pathogenesis remains still unclear. The disease affects mainly young and active people aged between 20 years and 50 years, with strong dominance of males. [1] It has also been recognized as accompanying systemic diseases or treatments [2,3,4] Risk factors listed most often include stress, type A personality, high testosterone serum levels in men, hyperopia and systemic vascular diseases such as hypertension or high heart rate. [5,6,7,8,9] At present, most authors agree that the pathology is localized in the choroid rather than in the retinal pigment epithelium (RPE). [10,11,12] Alterations of the RPE are thought to be secondary to choroidal defects or dysfunctions. [13,14] CSCR occurs in two basic forms: acute and chronic. The acute form morphologically presents predominantly as a serous fluid under the neurosensory retina. The chronic form, on the other hand, may present in a few different ways-specifically, either as subretinal fluid (SRF) similarly to in the acute form, as a RPE detachment, or as a mixture of both.
Acute CSCR usually recedes spontaneously within a period of one month to three months without any significant visual impairment. Conversely, the chronic type (chronic CSCR; CCSCR) lasts longer, even for a few years. Chronic accumulation of SRF, if central, leads to retinal thinning and the loss of photoreceptors. Patients usually end up with some degree of visual impairment, which in some cases can be significant. As the disease affects mainly young and active people, it has important socioeconomic impact. Patients have problems with such everyday activities as driving or working on a computer. Difficulties are often escalated due to the personality type A presented by the patients. For years, different therapies for CCSCR have been tested. One of the recent advances in treating CSCR is subthreshold micropulse laser therapy (SMPLT), which is effective in terms of resolution of SRF; however, in CCSCR, this treatment elicits only a moderate improvement of visual acuity. [15,16,17,18,19] Furthermore, the complete resolution of SRF after many months or years of active disease does not necessary mean a restoration of normal vision or normal retinal morphology will occur. To our knowledge, this damage has not yet been precisely assessed in the medical literature; thus, our study sought to evaluate functional and morphological impairments in the retina in long-standing but resolved CCSCR following SMPLT. We also considered measurable factors that could influence the amount of the damage, such as the duration of the disease, baseline retinal morphological parameters, or the age of the patient.

Materials And Methods
All procedures performed in this retrospective study were done in accordance with the ethical standards of the institutional research committee and with the principles of the 1964 Declaration of Helsinki. The material for the study consisted of 32 eyes with CCSCR that responded well to SMPLT. SMPLT treatment was performed with Supra 577 multispot yellow laser (Quantel Medical 2013). In 28 cases just one session of SMPLT treatment was needed to achieve a complete resolution of SRF. Remaining 4 cases needed 2 sessions separated by 3 months interval to achieve that goal. The study included symptomatic patients that had been under observation for a period of time longer than 4 months. This meets the criteria of clinical chronicity of CSCR, which are accepted in medical literature.
The average duration of symptoms in our study group was close to 19 months.
Demographics and characteristics of the study group are presented in Table 1. In this cases not only CRT parameter but also CRTA and CV could be affected.
SRF was present under the foveola in all cases; in some eyes however, its maximum accumulation was not exactly at the center of the macula. Therefore, maximum SRF height was measured and used as an additional parameter for determining the change in retinal morphology after SMPLT.
The schedule for BCVA and SOCT measurements was prior to treatment and at two months after each instance of SMPLT. If residual SRF was still present at two months after the first SMPLT, another laser session was scheduled for one month later (hence, a three-month interval occurred between the SMPLT sessions in these cases). At two months after the second SMPLT session, BCVA and SOCT measurements were then taken once again.
Analysis of the measurements obtained from the study group was performed after a maximum of two laser sessions. SMPLT procedure was carried out basing on the SOCT retinal maps. The whole area of the SRF presence was covered with confluent foci of micropulse yellow laser (577 nm). The following laser parameters were used: focus diameter -160 μm, the power -fixed level of 250 mW, the time of exposure -0.2 s, and the duty cycle -5%.
In 18 cases with resolved fluid, OCT angiography (OCTA) was performed. An analysis was completed at the level of the choriocapillaries, as follows: scan: 6 mm × 6 mm; slice: 175; and reference and offset: top RPE is +29 µm and bottom RPE is +49 µm.
The results of the study group were compared with OCT and BCVA parameters measured in the control group, which consisted of 40 eyes of healthy individuals with no present or previous ophthalmic disorders and who presented with full BCVA (0.0 logMAR). In all cases in the control group, OCTA was performed.
There was no statistically significant difference between age and gender between the study group and the control group (chi-squared test was used for gender, Mann-Whitney U test was used for age).
The characteristics of the control group are presented in Table 2. There was no significant difference in age and gender between control group and the study group. Additionally, we aimed to find a correlation between final BCVA and final CRT and certain Additionally, we aimed to find a correlation between final BCVA and final CRT and certain 8 parameters such as patient age, duration of disease, and baseline morphological parameters of the retina. Statistical methods for this evaluation are described in the following section.

Statistical analysis
The statistical significance of the results of SMPLT treatment (change in functional and morphological parameters) was assessed by use of the Wilcoxon matched-pairs test.
The measure of the functional impairment after long-standing disease was the difference in BCVA between the study group and the control group. Morphological impairment was measured by the difference in retinal parameters (i.e., CRT, CRTA, and CV) between the study group and the control group.
For the difference in BCVA between the study and control group, the Mann-Whitney U nonparametric test was used. The difference in morphological parameters (i.e., CRT, CRTA, and CV) was assessed by use of a t-test for independent variables.
Correlation between final BCVA and baseline patient characteristics (e.g., age, duration of CCSCR, CRT, CRTA, CV, and SRF height) was evaluated using the Spearman rank correlation coefficient. The same test was also used to assess the correlation between final CRT and baseline patient characteristics.

Results
The results of SMPLT treatment are presented in Table 3. The improvement of BCVA and the reduction of retinal morphological parameters were statistically significant (Table 4).
BCVA changed from 0.34 logMAR to 0.23 logMAR, which is equivalent to approximately a one-line improvement on the Snellen chart. In the study group, the retina was distinctly thinner in its central part : CRT was significantly lower in patients after CSCR as compared with in the control group. However, such a difference was not noted in the two other parameters of CV and average CRT (Table 5).  There was also a lack of correlation between final CRT and patient age, duration of the disease, and baseline visual acuity. Table 7. CRT and the height of SRF before SMPLT treatment did not correlate with final CRT either. However, a correlation was found between baseline CV and baseline average CRT and final CRT. Notably, patients with higher CV and CRTA parameters prior to SMPLT also had higher CRT values after the therapy. It must be recalled, however, that CV and CRTA parameters measure the retina according to large areas and volumes, not just the foveal part, the integrity of which is crucial for preserving visual acuity.  In all cases of the study group, a variable number of spots of hyporeflectance were noted. Image reveals areas of hyporeflectance that refer to impaired perfusion. SOCT scan (B) shows retinal thinning in the central part.
In some cases, especially when the retina was significantly thinner, hyporeflectant spots were accompanied by areas of hyperreflectance. (Fig.3 There are small hyporeflectannt spots in the center that refer to the areas of hypoperfusion. Area of PED on the right is visible as larger area of hyporeflectance on the OCTA scan Areas or spots of hyporeflectance represent areas of disturbed perfusion at the level of the chioriocapillaries. The effect of hyperreflectance are probably attributed to the "window defect" and represent better visualization of the choroidal vessels due to retinal atrophy but not due to increased blood flow.

Discussion
Our study sought to reveal the amount of functional and morphological damage present after long-standing CSCR. Thus far, the medical literature on the subject concentrates predominantly on discussing the effects of treatment of CSCR. [15,16,17,18,19]  The exclusion of a large group of patients with completely resorbed SRF after CCSCR might be a problem. This disease has a long course with remissions and recurrences, so it is difficult to find a point at which reliable measurements can be performed. In our study, we chose a group that responded well to SMPLT. As patients were followed up with every two months, it was possible to identify any points of remission and to obtain BCVA and OCT measurements.
Other studies that have employed SMPLT in the treatment of CSR usually have concentrated on an improvement in BCVA and the reduction of CRT. [15,17,18,19,20,21,22] Final BCVA is usually given as an average value of the whole cohort of patients, which is composed of both responders and nonresponders. We found that the central retina in the study group measured 225.19 ± 33.8 µm in the foveal part, which was on average 39.32 µm thinner than the same areas in the controls. However, these authors did not present final CRT values. [24] Interestingly, in our study, parts of the central retina outside the fovea were not that The present study did not find any correlation between patient age, duration of symptoms, or baseline retinal morphology and final visual acuity after remission of symptoms. Also, final central retinal thickness, a morphological parameter that was significantly affected by the disease (retinal thinning), did not correlate with the duration of the disease.
These findings are in agreement with those of our previous study. [30]

Declarations
The study was approved by our internal ethics committee of Dobry Wzrok ophthalmological clinic. This was a retrospective study and included analysis of the results of routine treatment conducted in our clinic. Each patient has signed a consent form for 18 the procedures that were carried out in the clinic.

Consent for publication
Not applicable Availability of data and material The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Competing Interests: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. Image reveals areas of hyporeflectance that refer to impaired perfusion. SOCT scan (B) shows retinal thinning in the central part.