Chorioretinopathy Post COVID-19: A Systematic Review and Prevalence Assessment, Unveiling Insights into an Emerging Ocular Entity

ABSTRACT

Purpose

To investigate the occurrence of chorioretinopathy post-COVID-19, emphasizing demographic characteristics, medication history, clinical presentation, diagnostic evaluation, and treatment approaches, with a specific focus on the role of corticosteroid use.

Methods

Our protocol was registered prospectively on PROSPERO (CRD42023457712). A systematic search of databases (PubMed, Cochrane, WOS, Scopus) from November 2020 to August 2023 were performed to identify any original research reporting chorioretinopathy in COVID-19 patients. Data extraction included patient demographics, COVID-19 timeline, medication history, symptoms, diagnostic tests, and treatment outcomes. We used Joanna Briggs Institute (JBI) critical appraisal tool to assess the quality of our included studies.

Results

We identified seven case reports and two case series including 10 patients, six females and four males (mean age 36.5 years), who exhibited chorioretinopathy after COVID-19. Onset varied from 6 days to three months post-infection (average = 24.3 days). Seven patients (70%) had a history of corticosteroid use during COVID-19 treatment. Symptoms included visual loss, blurred vision, and deterioration. Diagnostic assessments revealed central serous chorioretinopathy in seven patients (70%) and punctate inner choroidopathy in two (20%). Treatment approaches varied, with corticosteroid discontinuation leading to symptom improvement, while two patients were treated with corticosteroids. Five patients who discontinued corticosteroids were reported to have improvement in visual acuity, two of them changed to 20/25 after being 20/40, two changed to 6/6, and one changed to 20/20, while the visual acuity in the sixth patient was not reported. Regarding the two patients who were treated with corticosteroids, visual acuity was reported in one case only and it improved to 20/20.

Conclusion

This systematic review states the prevalence and potential association between chorioretinopathy, and corticosteroid use in the context of COVID-19. This relation is still unclear because of the relief of symptoms in some cases after corticosteroid discontinuation, while two other cases were treated with corticosteroids and their symptoms improved.

KEYWORDS:

• Chorioretinopathy
• corticosteroids
• COVID-19
• ocular complications
• systematic review

INTRODUCTION

SARS-CoV-2, the virus that caused COVID-19, is a potentially fatal infectious disease that was discovered in the Chinese town of Wuhan in November 2019. After that, it began to spread quickly throughout the world, and in March 2020, the World Health Organization (WHO) officially designated it as a pandemic disease.¹

Acute SARS-CoV-2 infections can cause a great deal of harm, ranging from nearly asymptomatic to a systemic disease requiring intensive care and occasionally fatal. However, there is strong evidence that the clinical burden of COVID-19 may persist well beyond the acute infective period, with medium- and long-term consequences that could have a major impact on the quality of life of those affected and present a significant global health challenge.² A recent meta-analysis, encompassing a population of 5,717 COVID-19 patients, revealed ocular involvement in 8.8% of cases. The predominant ocular symptoms reported were conjunctival hyperemia, conjunctival discharge, epiphora, and a sensation of foreign bodies. Notably, there have been emerging reports of chorioretinopathy as one of the ocular manifestations.³

Chorioretinopathy is a condition that involves an accumulation of fluids under the retina resulting in neurosensory retinal detachment, serous pigment epithelium detachment (PED), and retinal pigment epithelium atrophy. Chorioretinopathy manifestations include color vision changes, central relative scotoma, metamorphopsia, central relative scotoma, and micropsia. Middle-aged males are the most common group affected with chorioretinopathy.^4,5

Prior research indicated that SARS-CoV-2 may bind to human cell receptors for the angiotensin-converting enzyme (ACE) 2. All major organs, including the heart, lungs, and vascular endothelium, contain ACE 2 receptors. Consequently, endotheliitis brought on by SARS-CoV-2 can result in endothelial dysfunction.⁶ The precise pathophysiology of chorioretinopathy is still unknown. Retinal pigment epithelium (RPE) pump dysfunction, endothelial dysfunction, and hyperpermeability of the Choriocapillaris are theoretical causes of the disease.⁴ Nevertheless, there is no proof that SARS-CoV-2 can directly cause chorioretinopathy.

Regardless of the drug’s dosage or mode of administration, chorioretinopathy is a recognized side effect of steroid use. It may happen a few days to several months after starting the medication.⁴ Also, chorioretinopathy is primarily attributed to elevated cortisol levels, which have been observed to surge in individuals with COVID-19. The surge in cortisol is often linked to the stress response triggered by the viral infection. Stress, recognized as a significant risk factor, is intricately connected with cortisol secretion. This association underscores the potential role of stress-induced cortisol elevation in contributing to chorioretinopathy as part of the ocular involvement seen in COVID-19 cases.^4,7

The management of COVID-19 patients frequently involves the use of steroids (intravenously, orally, or via an inhaler). All prior reports of chorioretinopathy following COVID-19 infection included a history of steroid use.^8–10 Thus, the use of steroids may be the most likely cause of the post-COVID-19 associated chorioretinopathy. The majority of these reports^8,9,11 described unilateral central serous chorioretinopathy (CSCR) that improved on its own initiative without the need for interventions.

In this systematic review of case reports and case series, we investigated the occurrence of chorioretinopathy following COVID-19. Our objective is to thoroughly analyze demographic data, past medication history, clinical presentation, diagnostic evaluation for chorioretinopathy, and treatment approaches that have demonstrated notable effectiveness to be able to find a possible cause and solution to chorioretinopathy following COVID-19.

METHODS

Data Source and Searches

This systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.¹² Our protocol was registered prospectively on PROSPERO (CRD42023457712). From November 2020 till August 2023, we searched the following databases (PubMed, Cochrane, WOS and Scopus) using this strategy: (((Chorioretinopathies OR Chorioretinopathy OR Chorioretinitis OR Retinochoroiditis OR Retinochoroiditides OR Retinochoroidopathy OR Retinopathy OR Retinochoroidopathies OR “retinal microvasculopathy” OR retinitis OR “retinal diseases”) OR ((ophthalmological OR ocular) AND (complication OR affection OR condition OR disorder OR disease OR complaint))) AND (“COVID 19” OR SARS-CoV-2 OR “SARS CoV 2” OR Coronavirus OR 2019-nCoV OR “2019 nCoV” OR COVID-19 OR “severe Acute Respiratory Syndrome” OR SARS OR COVID19)) for articles mentioning the occurrence of chorioretinopathy in COVID-19 patients or after COVID-19 infection. We included any original research reporting chorioretinopathy after or during COVID-19 infection. No restrictions on the language were made.

Screening and Data Extraction

Three authors (M.M.E, E.E.L, A.S) independently evaluated the eligibility of included articles. Three authors (M.M.E, M.E, S.G) extracted the following data from articles: age, sex, location, COVID-19 infection timeline, any previous medication, eye involved, symptoms, onset and duration of symptoms, investigations, treatment, and final outcome.

Quality Assessment

The methodological quality of case reports was assessed by two independent reviewers (M.E, M.M.E). We used Joanna Briggs Institute (JBI) critical appraisal tool to assess the quality of our included studies.¹³ We assessed the included studies as regard the clarity of the following items: patient’s demographics, patient’s history, current clinical condition, diagnostic tests and its results, the intervention(s) or treatment procedure(s), post-intervention clinical condition, adverse events and presence of takeaway lessons. The answers of items were graded as yes, no, unclear or not applicable. Each item had a score of one if its answer was yes and a score of zero if it was no, unclear or not applicable. The study was considered of low quality if met 1:3 out of 8 appraisal criteria for case reports, moderate if met 4:6 and high quality if met 7 or 8. The same applies for case series but the appraisal criteria is out of 10.

RESULTS

The present systematic review included seven case reports and two case series^{8,9,11,14–19} with a total of 10 patients who suffered chorioretinopathy after COVID-19 infection. (Figure 1) Among them, six were females and four were males with a mean (SD) age of 36.5 (8.11) years. The appearance of chorioretinopathy symptoms varied from 6 days post-COVID-19 in the case report by Miyata et al.¹⁸ infection to three months after the infection has occurred as reported by Sharifi et al.¹⁴ with an average of 24.3 days. Among the 10 included patients, seven (70%) of them were reported to have taken corticosteroids (mainly dexamethasone) during COVID-19 infection (Table 1). Four patients (40%) were reported to be treated with antibiotics such as ceftriaxone, cefoperazone plus sulbactam, azithromycin, and doxycycline. Three patients were reported to be treated with remdesivir and three patients were treated with heparin as a part of their management plan of COVID-19 infection. One patient was treated with vitamin supplements for COVID (Table 1).

Figure 1. PRISMA flowchart of included studies.

The presenting symptom was visual loss in three (30%) patients, blurred vision in three (30%) patients and deterioration of vision in four patients (40%). By examination of the patients using different parameters such as optical coherence tomography, visual acuity examination, anterior segment examinations, fundus examination, and biomicroscopy, eight (80%) patients were diagnosed with CSCR and two (20%) patients were diagnosed with punctate inner choroidopathy. Among the patients with CSCR, six (60%) were managed by discontinuation of corticosteroids, one with propranolol 20 mg and eplerenone 25 mg daily for one-month, topical non-steroidal anti-inflammatory eye drops (nepafenac), and one was managed by rest only then follow up. Regarding the two patients with punctate inner choroidopathy, one was treated with oral prednisolone 30 mg/day. The corticosteroid was changed to oral dexamethasone upon discharge, with a slow tapering dose as it was reduced to 15 mg/day for the next 14 days, to 10 mg/day for the next 14 days, and to 5 mg/day for the next 28 days and the other was treated with systemic methylprednisolone (1 mg/kg/day). (Table 2)

Improvement of symptoms took a time that ranged between 2 days in the case reported by Nicolai et al.¹⁵ to three months as reported by Mohd-Alif et al.¹⁶ and Fuganti et al.¹⁷ Five patients who discontinued corticosteroids were reported to have improvement in visual acuity, two of them changed to 20/25 after being 20/40,^11,17 two changed to 6/6,^8,16 and one changed to 20/20,¹⁷ while the visual acuity in the sixth patient was not reported but visual improvement was observed.⁹ Regarding the two patients who were treated with corticosteroids, visual acuity was reported in one case only and it improved to 20/20 and the other study reported visual improvement.¹⁸ Summary and baseline characteristics in addition to the treatments and outcomes of the patients are illustrated in Table 1 and 2.

Table 1. Baseline characteristics of the included studies.

Study ID	Study design	Location	Gender	Age	Onset and duration of symptoms	Any previous medication
Fuganti^Citation17	Case series	Brazil	Male	41	13 days after COVID-19 infection, improved after 3 months	8 mg of oral dexamethasone
		Brazil	Female	43	20 days after diagnosis of COVID-19 and 5 days after completion of treatment for pneumonia secondary to COVID-19. improved after 1 month	antibiotics and high doses of dexamethasone intravenously (10 mg/day) and orally (8 mg/day)
Goyal^Citation8	Case series	India	Female	27	2 weeks after recovery from COVID-19, had signs of visual deterioration for 10 days, improved after a few weeks	oral steroids for covid infection
Miyata^Citation18	Case report	Japan	Female	25	6 days after the symptoms of COVID-19 infection. duration of 12 days after the onset of symptoms	N/R
Mohd-Alif^Citation16	Case report	Malaysia	Male	38	3 weeks after COVID-19 infection. regained full visual recovery after three months	intravenous ceftriaxone 1 g daily and dexamethasone 4 mg three times daily over his nine-day stay at the hospital. The corticosteroid was changed to oral dexamethasone upon discharge, with a slow tapering dose for over two weeks.
Nicolai^Citation15	Case report	Italy	Female	29	3 weeks after COVID-19 infection and resolved after 2 days of treatment	Cyclosporine 3 mg/kg/day 6 months ago
Sanjay^Citation9	Case report	India	Female	42	12 Days after COVID-19 infection and improved after 1 month	I.V Cefoperazone+ Sulbactam, S.C Heparin, I.V Remdesivir, ORAL (Dexamethasone, Azithromycin, Doxycycline, Levocetirizine, Montelukast and Levocetirizine combination, Vitamin C, Pantoprazole, Ivermectin) Inhalation (OXYGEN, Formoterol fumarate dehydrate and budesonide 200 combination, Salbutamol rotacaps)
Sharifi^Citation14	Case report	Iran	Female	49	3 months after COVID-19 infection, symptoms improved after 2 months	During her five-day hospital admission, intravenous Remdesivir (200 mg as an initial dose, and then 100 mg daily) and Dexamethasone (4 mg daily) with subcutaneous low-molecular-weight heparin (50 mg twice daily) for prophylaxis of thrombosis had been administrated, and she had been discharged with prednisolone 10 mg twice daily for two weeks.
Amulya, and Thanuja^Citation19	Case report	India	Male	30	2 weeks after COVID-19 infection, duration 2 months	Vit C 500 mg BD, Vitamin supplements and he was on regular anti-hypertensive medication.
Sanjay^Citation12	Case report	India	Male	41	22 days after COVID-19 infection and a month later, he had improvement in his symptoms with no cells in both eyes with topical steroids with resolution of serous retinopathy.	intravenous dexamethasone, ceftriaxone, remdesivir 200 mg 1st day followed by 100 mg for next 4 days, and subcutaneous low-molecular-weight heparin 40 mg for prophylaxis and oral azithromycin 500 mg/oseltamivir 75 mg orally twice a day for 5 days and was discharged after a week with oral steroids 20 mg and apixaban 2.5 mg twice daily, intravenous dexamethasone, ceftriaxone, remdesivir 200 mg 1st day followed by 100 mg for next 4 days, and subcutaneous low-molecular-weight heparin 40 mg for prophylaxis and oral azithromycin 500 mg/oseltamivir 75 mg orally twice a day for 5 days and was discharged after a week with oral steroids 20 mg and apixaban 2.5 mg twice daily. Intravenous methylprednisolone was administered for a delayed cytokine storm in the second admission followed by oral tapering dose of 20 mg steroids and insulin for diabetes at discharge. Steroids gradually tapered over the next 4 weeks. He was a recently detected diabetic and was on 50 mg oral sitagliptin for the last 6 months and mild cutaneous psoriasis and not on any treatment for the past 5 years.

Table 2. Presentation and outcomes of chorioretinopathy following COVID-19.

Study ID	Laterality	Symptoms	Investigations	Treatment	Final outcome
Fuganti^Citation17	Left eye	unilateral acute visual loss	Biomicroscopy of the anterior segment, pupillary reaction, intraocular pressure, Fundus examination, Laboratory tests, complete blood count (CBC), chest and sinus X-rays, C-reactive protein.	corticosteroid discontinuation	By 3 months follow-up, the subretinal fluid spontaneously and completely resorbed, and the best-corrected visual acuity of the left eyes improved to 20/25.
	Right eye	visual loss	Biomicroscopy of the anterior segment, pupillary reactions, B-scan spectral-domain and intraocular pressure, fundus examination, Laboratory tests, CBC, and chest and sinus X-rays	corticosteroid discontinuation	At 1-month follow-up, the BCVA of the right eye improved to 20/20. best-corrected visual acuity of the right eye improved to 20/20
Goyal^Citation8	Left eye	central vision deterioration in the Left eye	Fundus examination, Optical coherence tomography	No treatment, corticosteroid was stopped before presentation at the hospital	symptoms resolved spontaneously a few weeks later
Miyata^Citation18	Right eye	blurred vision, fever	Color fundus photography, Fundus autofluorescence, fundus infrared image, Optical coherence tomography (OCT) angiography of the outer retina to the choriocapillaris layer, fluorescein fundus angiography, Indocyanine green fundus angiography	oral prednisolone 30 mg/day. corticosteroids was changed to oral dexamethasone upon discharge, with a slow tapering dose for over two weeksfor 14 days to manage Punctate inner choroidopathy. Fundus abnormality decreasedand ocular symptoms improved. Oral prednisolone reduced to 15 mg/day for thenext 14 days, to 10 mg/day for the next 14 days, and to5 mg/day for the next 28 days	visual improvement general side effects.
Mohd-Alif^Citation16	Both	central visual loss in both eyes, multiple blackish spots increasing in size over time, affecting his central vision	Visual acuity examination, anterior segment examinations, Fundus examination, and Spectral-domain optical coherence tomography (OCT) of the macula	The patient was treated with topical non-steroidal anti-inflammatory eye drops (nepafenac).	full recovery after 3 months
Nicolai^Citation15	Right eye	acute decrease of visual acuity in her right eye	Visual acuity (BCVA), intraocular pressure measured using Goldmann applanation tonometry, fundus examination, and enhanced depth imaging optical coherence tomography (EDI-OCT) were assessed.	High-dose corticosteroids: systemic methylprednisolone (1 mg/kg/day)	Two days later, after administration of systemic methylprednisolone (1 mg/kg/day), the visual acuity of the RE improved to 20/20.EDI-OCT of the RE showed complete regression of RPE elevation and a fainter hyperreflective signal under the RPE; the photoreceptor inner/outer segment junction discontinuities were less marked and the intraretinal fluid disappeared.
Sanjay^Citation9	Right eye	She experienced symptoms such as fever, chills, shortness of breath, and cough, accompanied by fatigue, and subsequently tested positive for COVID-19 through RT-PCR. Notably, unilateral blurring in the right eye developed 12 days after the onset of the COVID-19 infection.	Visual acuity, fundus examination, intraocular pressure measurement, SpectralisTM optical coherence tomography (SD-OCT) scan, complete blood count (CBC), erythrocyte sedimentation rate (ESR), random blood sugar (RBS), COVID-19 rapid antigen test, upper respiratory swab for COVID-19, WIDAL test, urine analysis, and chest X-ray	Inhalational and oral steroids were stopped.	One month later, there was an improvement in her vision to 20/25 in OD, OCT showed a reduction of the sub-retinal fluid and the hyper-reflective material and resolution of the pigment epithelial detachment.
Sharifi^Citation14	Both	gradual blurring of vision in both eyes	optical coherence tomography	propranolol 20 mg and eplerenone 25 mg daily for one month.	The symptoms were resolved about two months later, and the BCVA of both eyes improved to 20/25.
Amulya, and Thanuja^Citation19	right eye	sudden diminution of vision in his right eye for 3 days	A comprehensive ophthalmologic examination was performed, encompassing assessments such as visual acuity in the right eye (OD) and left eye (OS), color vision in both eyes, anterior segment examination of both eyes, fundus examination, and optical coherence tomography. Additionally, blood investigations included assessments of lactate dehydrogenase, C-reactive protein (CRP), D-dimer, and serum ferritin levels.	No treatment but rest and follow up after 2 months	the patient showed visual recovery within 2 months as his VA was 6/6 in both eyes.
Sanjay^Citation11	both	unilateral blurring, glare, and pain in the left eye	Ocular investigations: - Eye evaluation showed corrected distance visual acuity of 20/20 in both the eyes (BEs). - Anterior chamber showed inflammation in the LE, a day later in the right eye. − Fundus examination of the BE showed retinal pigment epithelial changes with serous elevation suggestive of multifocal serous chorioretinopathy. - A spectral-domain optical coherence tomography scan on the Spectralis™ (Heidelberg Engineering, Heidelberg, Germany) of the RE showed serous detachment temporal to the disc and in the LE showed posterior vitreous cells and serous detachment near the superior/inferior arcade. - An optical coherence tomography angiography done on the Optovue AngioVue ™(Optovue, Inc., Fremont, CA) did not show any pathological changes in retinal or choroid circulation. Non-ocular investigations: - The patient had a chest computed tomography (CT) scan which showed ground glass opacities in his lungs.	The patient was administered intravenous dexamethasone, ceftriaxone, remdesivir, subcutaneous low-molecular-weight heparin, oral azithromycin, and oseltamivir for COVID-19 treatment. He was discharged after a week with oral steroids and apixaban. Three days after discharge, he developed a fever and was readmitted. Intravenous methylprednisolone was administered for a delayed cytokine storm in the second admission followed by oral tapering dose of 20 mg steroids and insulin for diabetes at discharge. Steroids gradually tapered over the next 4 weeks. Topical steroids were also used for the patient’s ocular symptoms	a month later, he had improvement in his symptoms with no cells in both eyes with topical steroids with resolution of serous retinopathy. The patient was advised to continue follow-up with the ophthalmology department.

Quality Assessment

In assessing the included case reports, six out of seven demonstrated high quality, with scores ranging between 7 and 8. One case report received a moderate quality score of 6. Concerning the case series, one achieved high quality with a score of 9, indicating a robust study design. The second case series obtained a moderate quality score of 6. (Table 3 and 4)

Table 3. The quality assessment of the included case reports.

Study ID	1. Were patient’s demographic characteristics clearlydescribed?	2. Was the patient’s history clearly described and presented as a timeline?	3. Was the current clinical condition of the patient on presentation clearly described?	4.Were diagnostic tests or assessment methods and the results clearly described?	5. Was the intervention(s) or treatment procedure(s) clearlydescribed?	6. Was the post-intervention clinical condition clearly described?	7. Were adverse events (harms) or unanticipated events identified and described?	8. Does the case report provide takeaway lessons?	Quality
Sharifi^Citation14	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes	7/8, high
Sanjay^Citation9	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes	7/8, high
Nicolai^Citation15	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes	7/8, high
Mohd-Alif^Citation16	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes	7/8, high
Miyata^Citation18	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes	7/8, high
Sanjay^Citation11	Yes	No	Yes	Yes	Yes	Yes	No	Yes	6/8, moderate
Amulya, and Thanuja^Citation19	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	8/8, high

Table 4. The quality assessment of the included case series.

Study ID	1. Were there clear criteria for inclusion in the case series?	2. Was the condition measured in a standard, reliable way for all participants included in the case series?	3. Were valid methods used for identification of the condition for all participants included in the case series?	4.Did the case series have consecutive inclusion of participants?	5. Did the case series have complete inclusion of participants?	6. Was there clear reporting of the demographics of the participants in the study?	7. Was there clear reporting of clinical information of the participants?	8. Were the outcomes or follow up results of cases clearly reported?	9. Was there clear reporting of the presenting site(s)/clinic(s) demographic information?	10. Was statistical analysis appropriate?	Quality
Goyal^Citation8	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Unclear	9/10, high
Fuganti^Citation17	Yes	Yes	Yes	No	Unclear	Yes	Yes	Yes	Unclear	Unclear	6/10, moderate

DISCUSSION

The present study showed that the patients suffering from COVID-19 infection can present with chorioretinopathy (CSCR or punctate inner choroidopathy) whether during the infection period or after the resolution of infection. Regarding CSCR, the signs of visual loss or deterioration were improved after the discontinuation of corticosteroid therapy. This shows that corticosteroids are linked to the occurrence of chorioretinopathy. However, patients diagnosed with punctate inner choroidopathy were treated with corticosteroids and this treatment was associated with good outcomes.

Few case reports have also documented various forms of choroiditis and retinitis as a result of both the COVID-19 infection and the vaccine. A 71-year-old lady had acute macular neuroretinopathy 14 days after contracting COVID-19,²⁰ while a 27-year-old woman developed it two days after receiving the COVID-19 vaccine.²¹ Additionally, two months and 10 days after contracting COVID-19²² and three days after receiving the second dose of the COVID-19 vaccination,²³ a 17-year-old man and a 30-year-old woman both experienced numerous evanescent white dot syndrome. A 41-year-old lady developed serpiginous choroiditis after contracting COVID-19.²⁴ One week after receiving the second dose of the COVID-19 vaccine, a 34-year-old male was diagnosed with the previously stated multifocal choroiditis.²⁵ Therefore, autoimmune choroiditis or retinitis may occasionally be linked to both COVID-19 infection and immunization. The etiology is not known but may be due to sensitization of antigens within photoreceptors, retinal pigment epithelial cells, and choriocapillarisespecially by adjuvants based vaccines.²⁶

As one of the main groups of drugs used in the treatment of COVID-19, corticosteroids are known to reduce inflammation, which can cause lung harm. They have been shown to decrease mortality and shorten hospital stays in COVID-19-infected individuals.²⁷ A systemic corticosteroid was administered to the majority of the reported cases during COVID-19 infection. The development of CSCR in these cases may have been caused by or potentiated by this.

A prothrombotic impact, steroid-induced systemic hypertension, enhanced adrenergic receptor transcription or potentiation of vascular reactivity are some hypotheses for the mechanism of CSCR. Another possible mechanism is Bruch’s membrane-based inhibition of collagen synthesis. Ion and water transport issues could make the RPE barrier function less effective.²⁸

Regardless of the route of administration, corticosteroid use exacerbates CSCR, and this medication is regarded as a significant risk factor for the onset of illness. Possible contributing factors to the development of CSCR in patients on corticosteroid therapy include impaired vascular autoregulation caused by elevated adrenergic receptor transcription, systemic hypertension brought on by steroids, and a prothrombotic impact.^29–32 Congestion, hyperpermeability, and choroid thickness are characteristics of CSCR, which causes the RPE, which is in charge of maintaining the blood-retinal barrier, to malfunction. If its integrity is compromised, subretinal fluid will build up and cause a significant loss of central macular vision.³³ Rapid loss of central vision, neurosensory macular detachment with or without a PED, focal or multifocal RPE alterations, and increased choroid thickness and hyperpermeability are all signs of CSCR in its acute form.^33–35

CSCR is thought to be brought on by the use of steroids, regardless of the dosage or method of delivery. After the medicine is started, it may continue for a few days to months.⁴ Patients with COVID-19 are frequently managed with steroids (intravenously, orally, or via an inhaler), and all prior reports of post-COVID-19 linked CSCR had a history of steroid treatment.^8–11 Therefore, steroid use may be the most likely cause of the post-COVID-19 related CSCR. The majority of these publications^8,9,11 described unilateral CSCR with spontaneous improvement. There haven’t been many reports on the disease’s bilateral manifestation yet.¹⁰ Patients over 50 years old (our patient was 49 years old) are more likely to experience bilateral CSCR.³⁶

Age, race, corticosteroid use, mental stress, type-A behavior, Helicobacter pylori infection, sleep apnea, pregnancy, organ transplantation, and autoimmune illnesses are only a few of the risk variables that have been connected to CSCR.³⁷ A case with two of the aforementioned risk factors—psychological stress brought on by COVID infection and corticosteroid therapy—was reported by Mohd-Alif et al. .¹⁶ Significant psychological effects from the COVID-19 pandemic have been felt in day-to-day life. Increased levels of stress, anxiety, and depression are among these.³⁸ Risk factor reduction and careful monitoring are the conventional first-line treatments for CSCR. It has a very good prognosis and resolves naturally over time as visual function returns. In light of the numerous lesions and involvement of both eyes, Mohd-Alif et al.¹⁶ reported starting their patient on topical nepafenac. After three months, which is a somewhat longer period of time than other cases of CSCR after COVID-19 infection that have been reported,^8,11,19 he demonstrated full visual recovery and practically total remission of the condition.

The majority of patients with acute CSCR experience spontaneous neurosensory retinal reattachment and subretinal fluid absorption over the course of two to three months. subretinal fluid may persist for longer than six months in 15% of individuals, which is referred to as persistent CSCR. Interventions are required for patients with chronic or recurrent CSCR, such as the use of anti-steroid medications like eplerenone or spironolactone, anti-adrenergic medications like propranolol or metoprolol, or photodynamic treatment.³⁹ Due to the disease’s bilateral involvement, Sharifi et al.¹⁴ chose to treat the patient medically with eplerenone and propranolol. After around two months, her visual issues started to get better.

Our study included all the published case reports and case series investigating the risk of chorioretinopathy during or after COVID-19 infection. We tried to link the cause to the most common characteristic in the included patients and according to the known evidence and it was most probably due to corticosteroids. Visual disturbance whether by loss, or deterioration was the main presenting symptom that was resolved after corticosteroid discontinuation which shows that corticosteroids may play a main role. However, this study has many limitations such as the small number of included cases which make it difficult to produce strong evidence and may result in bias and prevent generalization of our findings. In addition, case reports aren’t able to provide a causative relationship. Moreover, many risk factors may be related to the occurrence of CSCR. Therefore, longitudinal studies with large sample sizes are required to be able to draw a causative relationship between corticosteroids and chorioretinopathy in COVID-19 patients. In addition, the main mechanism of occurrence needs further studies to be fully obvious.

CONCLUSION

This systematic review states the prevalence and potential association between chorioretinopathy, and corticosteroid use in the context of COVID-19. This relation is still unclear because of the relief of symptoms in some cases after corticosteroid discontinuation, while two other cases were treated with corticosteroids and their symptoms improved. Despite limitations, including a small sample size and the retrospective nature of case reports, the study prompts further investigation. Longitudinal studies with larger cohorts are essential to establish causative relationships and elucidate the underlying pathophysiology of chorioretinopathy in the post-COVID-19 period. However, since the pandemic has subsided, the longitudinal studies are difficult to be done. Therefore, there is a need for any retrospective studies with larger sample sizes to provide higher evidence than just case reports.

Authors’ contributions

Conceptualization: MME, MHEM, EEL; Data curation: MME, MHEM; Formal analysis: ME, AS, SG; Funding acquisition: HAS; Investigation: EEL, ME; Methodology: MME, MHEM, EEL; Project administration: SG, IMA; Resources: EEL, ME, AS; Software; IMA, HAS; Supervision: HAS; Validation: HAS; Visualization: MME, MHEM; Roles/Writing - original draft: IMA, MME, MHEM, EEL, ME, AS; Writing - review & editing: IMA, HAS. All authors read and approved the final manuscript.

Availability of data and material

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

Open Access funding provided by the Qatar National Library.