Analysis of retinal sensitivity between acute and recurrent central serous chorioretinopathy assessed by microperimetry

Abstract

Background

Central serous chorioretinopathy (CSC) is a common chorioretinal disease of unresolved etiology that is characterized by localized and limited serous retinal detachments (SRD) often associated with one or more areas of leakage from the choroid through a defect in the retinal pigment epithelium (RPE) on fluorescein angiography (FA)[1, 2]. CSC used to be classified in acute and chronic forms. Acute CSC ,a self-limiting disease lasting more than 4 or 6 months, manifests as a dome-shaped area of retinal sensory detachment and usually has a self-limiting process in the majority of cases with few recognized visual sequelae, so observation during the first four months is the most widely used strategy[1, 3].Chronic CSC, lasting more, can be a sight-threatening disease leading to legal blindness, for the persistence of SRD that may develop progressive photoreceptor damagement and widespread RPE changes, resulting in permanent loss of visual acuity, so timely effective treatment should be given to stop this progression and improve vision [2, 4]. Nevertheless, the classification relying only on temporal criteria seems too simplistic.

A clear concept of the clinical subtypes of CSC and their exact limits is critical for treatment since it determines the appropriate timing for intervention. But the classical forms of acute and chronic CSC, depending on the duration of symptom and on the presence of non-resolving SRD or RPE changes, are somewhat ambiguous. Daruich et al[5] suggested a newer classification: acute CSC as self-resolving SRD within 4 months from the onset; persistent CSC as acute CSC with duration of SRD longer than 4 months after onset of symptoms, often associated with elongated photoreceptor outer segments on SD-OCT; recurrent CSC as episode of acute CSC following a previous episode with complete SRD resolution; Chronic CSC as chronic chorioretinopathy with widespread RPE decompensation with or without SRD, associated or not with active leakage sites; Inactive CSC as patients with history of acute CSC but without SRD at the time of evaluation. The key point of terminology is the distinction between acute and recurrent CSC. As a matter of fact, the duration of symptoms reported from patients is always subjectivity and randomness. For some patients self-describe their disease duration as lasting only a few days, whereas fundus imaging may reveal evidence of prolonged disease, so patient-reported disease duration may therefore be considered unreliable[6]. Beyond the subjective visual acuity examination, retinal sensitivity in macular region can be assessed through microperimetry. Microperimetry, also called ‘Fundus-controlled perimetry’, is an essential method of examination to assess retinal sensitivity while directly observing the fundus in macular disorders[7-9].The information of microperimetry can help physicians to provide an early treatment if necessary, reducing the chance of permanent vision impairment and CSC chronicity[9]. The purpose of this study was to investigate the difference of macular retinal sensitivity between acute and recurrent CSC using microperimetry, and further to help to select the appropriate management strategy for CSC.

Methods

This was a retrospective observational case series study conducted at Eye Hospital of Wenzhou Medical University at Hangzhou in China. The procedures used in this research adhered to the tenets of the Declaration of Helsinki, and Institutional Review Board approval for this study was obtained from the local Ethics Committee. Informed consent was obtained from all subjects and all data were anonymized.

Acute CSC was defined as self-resolving subretinal detachment (SRD) within 4months from the first onset of symptoms, and recurrent CSC as an episode of acute CSC following a previous episode with complete SRD resolution[5].All subjects underwent a comprehensive ophthalmic examination including best-corrected visual acuity (BCVA), slit-lamp biomicroscopic examination, indirect ophthalmoscopy, color fundus photography (CR-2, Canon, Tokyo, Japan), fluorescein and Indocyanine green angiography (HRA Spectralis, Heidelberg Engineering, Heidelberg, Germany), spectral domain OCT(SD-OCT) (OCT Spectralis, Heidelberg Engineering, Heidelberg, Germany) and microperimetry (microperimeter MP-3,NIDEK, Aichi, Japan).

The central retinal thickness (CRT) at the center of the fovea, including the subretinal fluid if present, was evaluated by SD-OCT. Microperimetry assessment was conducted in a dark room with the fellow eye patched and the examination was operated by the same experienced operator. The following testing parameters were used for MP-3：a 64-stimuli grid overlying the central 20°; Goldmann III stimulus with a duration of 200 ms; 4–2 full-threshold staircase strategy; 1° diameter red circle fixation target. The mean retinal sensitivity values for the macula, global macular sensitivity (GMS) from 64 loci in the 20° central macular area and local macular sensitivity (LMS) from test locations in affected region of SRD, were obtained on the basis of the projected stimuli mean value (Figure 1).

The results obtained were expressed as mean±SD (range). Statistical analyses were performed using Kolmogorov–Smirnov normality test and a t test. P<0.05 was considered statistically significant, and analysis was performed with statistics software (IBM SPSS, version 23; IBM Corp., Armonk, NY, USA).

Results

Twenty-five eyes of 25 subjects who were diagnosed as either acute (Group A) or recurrent (Group R) CSC without any previous treatment were included in this study. Group A included 3 females and 9 males, with a mean age of 40.3±9.3 years (range: 26-55), and the clinical characteristics were shown in Table 1. Group R included 2 females and 11 males, with a mean age of 41.7±7.4 years (range: 28-55), and the clinical characteristics were shown in Table 2. The comparison of clinical parameters between Group A and Group R were shown in Table 3. The clinical parameters, including age, duration, mean LogMAR BCVA and CRT, were not statistically significant between Group A and Group R. GMS and LMS were both significantly different between the two groups. The mean GMS was significantly (p=0.018) lower for Group R (23.0±2.0 dB) compared with Group A (24.9±1.6 dB). In addition, the mean LMS was also significantly (p=0.044) lower with Group R (19.9±2.3 dB) compared with Group A (21.8±2.1 dB).

Table 1 Clinical characteristics of cases of acute CSC

Table 2 Clinical characteristics of cases of recurrent CSC

Table 3 Comparison of clinical parameters between Group A and Group R

F, female; M, male; BCVA, best-corrected visual acuity; CRT, central retinal thickness; GMS, global macular sensitivity; LMS, local macular sensitivity.

Discussion

Microperimetry can allow for accurate spatial characterization of visual function providing insightful information about disease severity and progression not reflected by BCVA in a large range of disorders both in clinical practice as well as research[10]. The usefulness of microperimetry in evaluating retinal sensitivity of macular region is well known in CSC. Ojima et al[11] examined macular sensitivity with resolved CSC using Microperimeter-1 (MP-1) and found that eyes of resolved CSC with reduced retinal function at focal affected areas, which were consistent with irregularity of the RPE or with defects of the outer retinal layers. Roisman and colleagues [9] investigated the relationship between retinal sensitivity and persistence of subretinal fluid in acute CSC by MAIA microperimetry and suggested microperimetry with a cutoff of 20 dB may be a useful test to predict the persistence of subretinal fluid. A study by Parodi et al[12] compared retinal sensitivity obtained with MP1 and MAIA microperimeters in patients affected by retinal dystrophies and in healthy subjects, and the results showed the MAIA microperimeter was more suited to precisely characterizing scotomatous areas with low sensitivity for it had a broader range of retinal light thresholds to be detected than the MP-1. The MP-3 device, which is the successor to the MP-1, is the latest generation of microperimetry and features faster tracking, increased automation and a better structure-function relationship[13]. Interestingly, Balasubramanian et al[8] compared and correlated the retinal sensitivity measurements obtained with MP-3 and MAIA microperimeters among healthy subjects, and as a result, the retinal sensitivity measures higher, but luminance and contrast sensitivity measure lower for MAIA-generated values compared with the MP-3, however, the relationships appeared fairly consistent and application of a standard correction factor allowed the data to be inter-related. To date, there is still a lack of standardization for testing (test-pattern, staircase strategy, adaptation, pupil dilatation), criteria for test repetition as well as reporting standards[10].

In this current study, MP-3 measurement was carried out using 4–2 full-threshold staircase strategy with the standard Goldmann III stimulus size, similar to previous studies[13, 14], and we found that macular sensitivities were significantly lower in recurrent CSC than in acute disease. Although acute episodes are usually self-resolving,15% to 50% of affected eyes may later present recurrence in follow-up varied from 2 to 13 years[5]. The initial BCVA did not differ between recurrent and nonrecurrent cases, but the final BCVA was near-significantly worse in recurrent than nonrecurrent cases[15]. It is plausible that the number of recurrent episodes correlates with visual outcomes in CSC, for repeated episodes and prolonged serous detachment lead to irreversible photoreceptor/RPE damage, and vision loss[2, 16]. Male sex, age, and sleep disorders are risk factors for recurrent or persistent CSC in the natural history[17]. The subfoveal choroidal thickness, nonintense fluorescein leakage at baseline, and history of shift work are independent predictors of CSC recurrence[15]. Microperimetry may be a useful test to predict the persistence of subretinal fluid, allowing the ophthalmologist to use treatment tools earlier, preventing extracellular damage and visual impairment[9]. Although acute CSC usually resolves spontaneously without no long-term subjective symptoms in most cases, some visual sequelae may persist after the resolution of SRD, such as decreased retinal sensitivity[18]. With the automatic tracking system for the retina, the MP-3 microperimeter can project target lights to the retina directly, so even when there is an eye movement, they still stimulate an intended identical retinal location. Recently, Fujita et al[14] demonstrated retinal sensitivity measured using the MP-3 microperimeter was significantly correlated to the integrity of ellipsoid zone in resolved CSC. The information of microperimetry may contribute to identify CSC patients at higher risk of recurrence, who could benefit from the most suitable treatment at optimal timing for intervention.

This current study has several limitations. Firstly, the study design was retrospective. Secondly, the sample size was small. Thirdly, the longitudinal follow-up was absent. Finally, there was not the correlation with microperimetry alterations and angiography findings. However, our findings do suggest that recurrent CSC often show worse retinal function in focal affected macular areas than acute disease. This microperimetry information can help doctors to provide an early treatment if necessary to reduce the chance of permanent vision impairment and disease chronicity. Due to the continuous progress in the field of microperimetry, it is believed that the robust tool has great potential for prediction, early detection and treatment-monitoring of macular diseases.

Declarations

Conflicts of Interest

The authors declare that they have no conflicts of interest.

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