A 30-Year-Old Man with a Recent History of COVID-19 Requiring Treatment with Corticosteroids Who Developed Bilateral Central Serous Chorioretinopathy During 7-Month Follow-Up

Background

Central serous chorioretinopathy (CSCR) is a well-studied disease that was first described in 1866 by Von Graefe as “idiopathic detachment of the macula” [1].CSCR is characterized by localized serous detachment of the neurosensory retina due to retinal pigment epithelium (RPE) decompensation secondary to choroidal vascular changes [2].

Men are more commonly affected, with a male-female ratio of 6: 1, as found in a population-based study [3]. Type A personality, hypercortisolism, pregnancy, and Cushing syndrome are also considered as risk factors for developing CSCR [4]. Moreover, Carvalho-Recchia et al [5] reported that the use of corticosteroids, by any systemic route of administration, is associated with the acute onset of CSCR.

Possible symptoms of CSCR are blurred vision, micropsia, meta-morphopsia, relative scotoma, and color vision disturbances. The disease is primarily unilateral, but in up to 40% of cases, it presents as bilateral. CSCR is mainly confirmed by optical coherence tomography (OCT), with the characteristic neuro-sensory retinal detachment. Fundus fluorescein angiography (FFA), with 3 types of leakage – inkblot, smokestack, and diffuse – may also be used [2]. Indocyanine green angiography (ICGA) can also be performed to detect choroidal neovascularization in chronic CSCR. This entity often has a favorable natural course and spontaneous resolution is common in acute cases, so observation is recommended for 3–6 months.

Corona virus disease (COVID)-19, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus, is an infectious disease with a clinical picture ranging from asymptomatic to fatal. In severe cases, it can cause respiratory distress leading to hospitalization in the intensive care unit (ICU). The COVID-19 pandemic is a global medical emergency, with enormous impact on society and global health [6].

In 2020 alone, the SARS-CoV-2 pandemic is estimated to have infected about 70 000 000 people worldwide. About 1 500 000 deaths have been also attributed to coronavirus-19 disease (COVID-19) [6].

During the COVID-19 pandemic, several trials have suggested a suitable treatment for hospitalized patients. Empirical evidence, in some cases, has shown the potential benefit of intravenous corticosteroid treatment [7].

This report is of a 30-year-old man with a recent history of COVID-19 requiring treatment with corticosteroids who developed CSCR in both eyes.

Case Report

A 30-year-old male patient presented with symptoms of malaise and high fever (up to 41°C/106°F) for 7 days. The patient had tested positive for SARS-CoV-2, using real-time polymerase chain reaction (RT-PCR, Standard M10 SARS-CoV-2, SD Biosensor, Inc., Korea) for diagnosis confirmation, and was admitted to our hospital.

During his hospitalization, which lasted for 1 week, he received intravenous (IV) corticosteroids (6 mg dexamethasone once daily for 1 week) to reduce the COVID-19-induced systemic inflammatory response. Following his hospitalization, he received per os methylprednisolone 16 mg with gradual tapering (16 mg, once daily for 3 days, 8 mg once daily for 3 days, 4 mg once daily for 3 days, and 2 mg once daily for 3 days).

Upon discharge, he noticed bilateral visual deterioration, but he did not report this to his treating physicians.

One month after his discharge and the onset of his initial symptoms (April 2021), the patient presented for the first time to the Ophthalmology Clinic. Visual acuity (VA) was 20/100 in both eyes and slit lamp examination was normal. OCT demonstrated a small amount of subretinal fluid (SRF) in his right eye (Figure 1A) and SRF in his left eye (Figure 1B).

One month later (May 2021), he presented for his 1st follow-up visit, with a VA of 20/100 in the right eye and 20/20 in the left eye. In the right eye, OCT in the macular area revealed SRF and a small accumulation of subretinal material (Figure 1C). In the left eye, a disruption of the RPE was noted, with no visible SRF (Figure 1D). FFA revealed temporary leakage of the macula in the right eye (smoke stack-like) (Figure 1E, 1F). In the left eye, 2 small staining points in the macular area – 1 at the inferior macula and 1 superotemporal to the optic nerve – were found (Figure 1G, 1H).

One month later, in June 2021 (second follow-up visit), VA was 20/25 in the right eye and 20/20 in the left eye. In the right eye, OCT imaging revealed a small amount of SRF and a significant amount of subretinal fibrin-like material. Temporary folding of the inner retinal layers of the macula was also observed (Figure 2A, 2B). In the left eye, a disruption of the RPE was noted, with no visible SRF (Figure 2D, 2E). FFA demonstrated a single leakage temporally to the posterior pole (smokestack pattern) in the right eye (Figure 2C) the same leakage site observed in his first FFA. The presence or absence of macular neovascularization (MNV) in the right eye was not clear and the presence of MNV was not supported by the FFA images. In the left eye, FFA demonstrated 1 small staining point in the inferior macula (Figure 2F).

In July 2021 (at the third follow-up visit), VA was also 20/25 in the right eye and 20/20 in the left eye. An OCT scan of the right eye revealed a small amount of SRF and a reduction of the fibrin-like material. Folding of the inner retinal layers in the macula was also observed (Figure 3A, 3B), while OCT scans of the left eye revealed no changes (no SRF or disruption of the RPE, Figure 3C, 3D).

In August 2021, OCT scans showed resolution of neurosensory detachment in the macula, a small pigment epithelial detachment (PED), and absorption of most of the fibrin-like material, with residual material remaining temporally in the fovea (Figure 4A, 4B). In the left eye, there were RPE abnormalities, but no neurosensory retinal detachment was present (Figure 4C, 4D).

In September 2021, OCT scans of the right eye demonstrated a shallower PED and a small amount of the residual subretinal material temporally in the macula (Figure 5A, 5B), while an OCT scan of the left eye (Figure 5C, 5D) revealed the appearance of a new locus of SRF superonasally of the macula, surrounding the optic nerve head (ONH) (Figure 5E, 5F).

At the last follow-up visit, in October 2021, OCT images were the same as in September 2021 (Figure 5G–5L).

Visual acuity increased in the left eye after 1 month and in the right eye after 2 months and remained unchanged (20/25 in the right eye and 20/20 in the left eye) from June 2021 until October 2021.

Discussion

As more patients in various age groups are receiving corticosteroids for COVID-19, treating physicians should inform patients about the potential ocular adverse effects and advise them to seek immediate ophthalmic examination in the event of ocular disturbances.

CSCR is a well-studied disease, affecting the retina and the choroid. It can be triggered by various conditions like stress, anxiety, type A personality, and administration of corticosteroids, the latter being one of the most common.

During the COVID-19 pandemic, a significant number of patients of various ages have received corticosteroids, either orally or intravenously [8]. Use of corticosteroids for COVID-19 treatment is possibly related to CSCR development [9].

There have been reports of single cases who developed acute CSCR after hospitalization for COVID-19, treated with oral or IV administration of corticosteroids: 1 unilateral case by Sanjay et al [9], 1 bilateral case by Sharifi et al [10], 1 bilateral case by Mohd et al [11], and 1 unilateral case by Goyal et al [12]. The latter presented 1 mild unilateral CSCR case, who received corticosteroid treatment, in a series of 7 serious cases with ophthalmic complications following COVID-19 disease.

Amulya et al [13] were the first to report a unilateral CSCR case associated with COVID-19-related stress, without any administration of corticosteroids. Abrishami et al [8] also published a case series with 4 bilateral cases in total, with pachychoroid spectrum disorder findings following COVID-19 disease, with no corticosteroids administration. Bilateral localized serous retinal detachment was apparent in 3 out of 4 cases with pachychoroid spectrum disorder. The authors hypothesized that the underlying mechanism could be either the involvement of the choroid in the infection or the increase in cytokines that may ensue. They also concluded that the COVID-19 infection could be proposed as a new etiology for pachychoroid spectrum disorder. Most of the aforementioned cases were either observed or treated with eplerenone or nepafenac. Fibrin-like subretinal material was not observed in any of these cases.

Our patient had bilateral CSCR treated with IV and oral corticosteroids during and after hospitalization for COVID-19, with a follow-up time of 7 months. During the follow-up period, fibrin-like material was also noted subretinally in the right eye of our patient, most of which was absorbed. In the left eye, new loci of manifestation of CSCR were developed during the 7-month follow-up period.

The follow-up period in the aforementioned reports was a few weeks for Goyal et al, 2 months for Amulya et al, 1 month for Sanjay et al, 3 months for Mohd et al, 2 months for Sharifi et al, and 3–5 months for Abrishami et al. In our patient, there was a longer follow-up period (7 months).

Subretinal fibrin-like material in CSCR cases has been reported in the literature [14]. The composition of the subretinal hyper-reflective material (SRHM) is poorly understood. Classically, it has been described to be composed of fibrin in various studies [15,16]. Sahoo et al [17] stated that these deposits could be derived from the shed photoreceptor outer segments rather than fibrin. Eyes with SRHM in CSCR have a good visual prognosis, unless the external limiting membrane (ELM) is involved. The deposits disappear completely in most cases and treatment should be planned according to the severity of collections. Diffuse RPE damage at baseline may lead to persistence of SRHM, eventually predisposing to scar formation [17]. Cong et al [18] noticed that CSCR cases with subretinal hyper-reflective materials are more common in eyes with longer duration of disease. In our case, the fibrin-like material appeared in the right eye of the patient 2 months after the initial symptoms. The amount of the material increased for 2 months and then decreased, leaving a small amount temporally in the macula at the end of follow-up.

Visual acuity increased in the left eye after 1 month and in the right eye after 2 months and remained the same (20/25 in the right eye and 20/20 in the left eye) from June 2021 until October 2021 (the end of the follow-up time). It is unclear why the VA improvement in the right eye was observed for the first time in June 2021, when the amount of fibrin was the most pronounced. The patient’s systemic symptoms of COVID-19 were improved at that time. Concerning the steroid reduction, tapering had been concluded upon initial presentation (April 2021). We cannot attribute the improvement in visual acuity (June 2021) to steroid reduction, since it was observed 2 months after discontinuation of the corticosteroids. We cannot exclude the natural course of CSCR as a cause of improvement in this case. More recent publications used OCT imaging [19], or even histopathological methods [20] and molecular analyses, such as proteomics and metabolomics, to confirm the presence of fibrin or fibrin-like material. Rajesh et al [21] concluded that subretinal fibrin in CSCR seems to be associated with a RPE defect, allowing these large molecules to enter the subretinal space from the hyperpermeable choriocapillaris. In their publication, OCT imaging demonstrated that there may be a hypo-reflective vacuole adjacent to an RPE defect. It is postulated that this vacuole signifies leakage of fluid into the subretinal space, as this corresponded with the RPE leaks on FFA.

Mohan et al [22] pointed out that in cases of pathologies that need to be treated by corticosteroids, the patients must be informed and warned about the adverse effects of the treatment.

Conclusions

We have presented a case of post-COVID-19 development of simultaneous bilateral CSCR and subretinal fibrin-like material after treatment with corticosteroids. Physicians need to inform their patients about the possibility of COVID-19-related ophthalmic manifestations, especially when corticosteroids are administrated.

This report has highlighted the importance of timely ophthalmological examination in patients with sudden vision loss and identification of the association between corticosteroid use and CSCR as well as the importance of a longer follow-up period.