Bilateral ciliochoroidal detachment: Drug- or COVID-19-related? A case report and literature review

Abstract

Background

This report describes a case of bilateral transient myopia with a shallow anterior chamber and ciliochoroidal detachment following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and indapamide intake.

Case presentation

A 37-year-old man with coronavirus disease 2019 (COVID-19) was referred to our department due to bilateral blurred vision. The patient had been treated with ibuprofen for fever and indapamide for uncontrolled blood pressure. After four days of indapamide intake, the patient complained of bilateral visual blurring. On ocular examination, his uncorrected visual acuity was 20/400 in both eyes. Slit-lamp examination revealed shallow anterior chambers. The following day, the patient experienced pain and redness in both eyes, which began the previous night. Ocular examination revealed a significant decrease in intraocular pressure (IOP) compared to the previous day: 11 mmHg and 12 mmHg in the right eye (OD) and left eye (OS), respectively. Slit-lamp examination revealed conjunctival injection and the presence of inflammatory cells (2+) in the shallow anterior chambers of both eyes. Ultrasound biomicroscopy revealed ciliary body detachment and B-scan ultrasonography showed peripheral shallow choroidal detachment in both eyes. Discontinuing indapamide and initiating treatment with oral prednisolone, topical tobramycin dexamethasone and tropicamide phenylephrine eye drops resulted in the rapid recovery of signs and symptoms after three days.

Discussion and conclusions

Indapamide intake may contribute to bilateral ciliochoroidal detachment, with SARS-CoV-2 infection possibly increasing susceptibility to drug-induced side effects. Timely drug withdrawal and symptomatic treatment can result in a good prognosis.

1. Introduction

Ciliochoroidal detachment can arise from several pathological conditions and can be triggered by many factors such as trauma, intraocular surgery, inflammation, drugs, or neoplasms [1,2]. Some drugs can induce ciliochoroidal effusion with transient myopia, including sulpha drugs (such as topiramate, hydrochlorothiazide, acetazolamide, and indapamide), anti-Parkinsonian drugs, mefenamic acid, latanoprost, etc. The Coronavirus disease 2019 (COVID-19) global pandemic has raised concerns about dysregulated immune and inflammatory responses, potentially leading to complications across multiple organs. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can increase susceptibility to autoimmune disorders and trigger retinal and choroidal manifestations, such as acute macular neuroretinopathy, retinal vein occlusions, episcleritis, anterior uveitis and reactivation of previously quiescent uveitis [[3], [4], [5], [6], [7], [8]].

This case report presents a rare occurrence of bilateral ciliochoroidal detachment accompanied by a transient myopic shift in a patient following SARS-CoV-2 infection, coinciding with the administration of indapamide.

2. CASE/CASE series presentation

A 37-year-old man with COVID-19 was referred to our department with bilateral blurred vision. He tested positive for COVID-19 by RT-PCR and was treated with ibuprofen for fever, which was relieved after three days and ibuprofen was discontinued. He had no history of uveitis but had hypertension. Three days later, he started taking indapamide due to uncontrolled hypertension, which he had never taken before, to control the blood pressure in addition to his usual valsartan amlodipine tablets. After indapamide intake for four days, the patient experienced bilateral visual blurring. Ocular examination revealed an uncorrected visual acuity of 20/400 in both eyes. Funduscopic examination showed no obvious abnormalities [Fig. 1(A-B)]. No abnormal fundus autofluorescence (FAF) was observed, except for focal hyperautofluorescent spots in the macula of the left eye (OS) [Fig. 1(C-D)]. Fluorescein angiography excluded retinal vasculitis, chorioretinitis [Fig. 2(A-B)]. Optical coherence tomography (OCT) B-scan showed no significant abnormalities in the retinal and choroidal structures, with subfoveal choroidal thickness (SFCT) of 383μm OD and 353μm OS [Fig. 2(C-D)]. Best-corrected visual acuity was 20/20 with a correction of −3.00 DS, −3.25 DC × 145 in OD, and 20/20 with a correction of −3.00 DS, −3.00 DC × 135 in OS. Intraocular pressure (IOP) was 21 mmHg in both eyes, and slit-lamp examination revealed a shallow anterior chamber with no inflammation. Axial length (AL), aqueous depth (AD), central corneal thickness (CCT), and lens thickness (LT) were measured by ocular biometry. AL was 24.66 OD and 24.74 mm OS; AD was 1.7 mm OD and 1.74 mm OS; CCT was 579 μm OD and 583 μm OS; and LT was 4.03 mm OD and 4.22 mm OS.

Fig. 1.

Wide-angle fundus imaging and fundus autofluorescence (FAF). A and B. No obvious abnormality was found in fundus of both eyes. C and D. No abnormal FAF was observed other than focal hyperautofluorescence spots in the macula of OS.

Fig. 2.

Fluorescein angiography (FA) and OCT imaging. A and B. Late phase in OD and in OS of FA revealed no obvious vasculitis. B. Focal window defect in the macula of OS. C and D. B-scan showed no obvious abnormalities in the retinal and choroidal structures and revealed a subfoveal choroidal thickness (SFCT) of 383μm OD and 353μm OS.

The following day, the patient experienced pain and redness in both eyes, which started the previous night. Ocular examination revealed a significant decrease in IOP compared to the previous day: 11 mmHg and 12 mmHg in the OD and OS, respectively. Slit-lamp examination revealed conjunctival injection and inflammatory cells (2+) in the shallow anterior chambers of both eyes. Ultrasound biomicroscopy (UBM) revealed ciliary body detachment in all four quadrants, anterior rotation and oedema of the ciliary body, and anterior movement of the iris and lens in both eyes [Fig. 3(B–D)]. B-scan ultrasound showed peripheral shallow choroidal detachment in both eyes [Fig. 3(A–C)].

Fig. 3.

B-scan ultrasound and UBM. B-scan ultrasound showed peripheral shallow choroidal detachment in OD (A) and in OS (C). UBM revealed anterior rotation and oedema of the ciliary body, anterior movement of the iris and lens and ciliary body detachment in OD (B) and in OS (D).

Laboratory values were as follows: neutrophil count, 8.92 × 10⁹/L; lymphocyte count, 1.06 × 10⁹/L; haemoglobin level, 166 g/L; platelet count, 307 × 10⁹/L; ferritin, 570.4 ng/ml; fibrinogen, 3.2 g/L; ASO, 218IU/ml; ESR, 3 mm/h; fasting blood-glucose, 6.6 mmol/L; serum creatinine, 129 umol/L; glutamic-pyruvic transaminase, 59IU/L; glutamic oxalacetic transaminase, 29IU/L. Tests for anti-dsDNA antibody, anticardiolipin antibody (ACA) IgM/IgG, antinuclear antibodies (ANA), anti-extractable nuclear antigens (ENA) antibodies (anti-Sm/RNP antibodies, anti-Sm antibodies, anti-SSA antibodies, anti-SSB antibodies, anti-RNP antibodies, anti-Scl-70 antibodies, anti-Ro-52 antibodies, anti-Jo-1 autoantibodies), antilipoprotein lipase antibody, HLA-B27, rapid plasma reagin (RPR), Treponema pallidum particle agglutination (TPPA), and human immunodeficiency virus (HIV) antigens and antibodies were all negative.

The patient was administered oral prednisolone 40 mg/day, topical tobramycin dexamethasone eye drops four times a day, tropicamide phenylephrine eye drops three times a day, and oral indapamide was discontinued immediately.

After 3 days of treatment, slit-lamp examination showed no inflammation and anterior chamber depth recovery. UBM and B-scan ultrasound confirmed the disappearance of ciliary body detachment and choroidal detachment in both eyes. The best-corrected visual acuity improved to 20/20 with −0.50 DS, −1.25 DC × 135 correction in the OD and 20/20 with −0.75 DS, −1.00 DC × 125 correction in the OS. After treatment with oral prednisolone, topical tobramycin dexamethasone, and tropicamide phenylephrine eye drops for 7 days, all medications were discontinued, and no recurrence of ocular symptoms was found during the subsequent eight weeks of follow-up.

3. Literature review

Four cases (two males and two females; age range, 33–60 years) of indapamide-induced transient myopia with uveal effusion following indapamide-containing drug intake have been reported previously. Table 1 shows their clinical characteristics [[9], [10], [11], [12]]. The inflammation of the anterior segment was not reported in one case and was not mentioned in the other three cases. IOP increased in six eyes of three patients, and UBM/B-ultrasonography/OCT of the anterior segment manifestation revealed bilateral ciliochoroidal effusion with anterior rotation and oedema of the ciliary body in these three patients (patients 1, 2, and 4). The patient with normal IOP (patient 3) presented with diffuse choroidal thickening on B-ultrasonography and retinal striae on fundus photography. Two patients discontinued indapamide-containing drugs without additional treatment, while two patients used topical antihypertensive drugs in addition to discontinuing indapamide intake, and one patient was additionally treated with 0.5 % tropicamide/0.5 % phenylephrine hydrochloride drops (patient 4). The symptoms resolved completely without sequelae in all four patients at the last visit.

Table 1.

Clinical characteristics and treatments of patients with indapamide-induced and COVID-19 related supraciliary effusion.

patients	age, years	sex	ACD (OD/OS), mm	UBM/B-ultrasonography/OCT of the anterior segment manifestation	AL	inflammation of the anterior segment	intraocular pressure(mmHg)	treatment	author
P1	37	male	not mentioned	bilateral ciliochoroidal effusion with anterior rotation of the ciliary body and iridocorneal angle narrowing(UBM)	N.A.	not mentioned	36 in OD and 34 in OS	brimonidine and timolol, topical treatment; stop taking indapamide	Pedrosa et al.
P2	39	female	2.32/2.49	bilateral detached ciliary body, forward rotated ciliary processes		not mentioned	25 in OD and 24 in OS	stop taking indapamide	Végh et al.
P3	33	male	3.6/3.6	diffuse choroidal thickening(B-ultrasonography)		not mentioned	14.6 in OU	stop taking a triple drug combination (triplixam)	Jaruseviciene et al.
P4	60	female	1.34/1.276	forward displacement of the lens and the edematous ciliary body; choroidal effusion		no inflammation	26 in OD and 29 in OS	0.5 % tropicamide/0.5 % phenylephrine hydrochloride drops and 1 % betamethasone topical treatment; stop taking indapamide	Takahashi et al.
P5	28	female	not mentioned	shallow AC; cystic choroidal effusion		no inflammation	26 in OD and 24 in OS	0.5 % timolol maleate eye drops; intravenous methylprednisolone	Deori et al.

ACD: anterior chamber depth; UBM: Ultrasound biomicroscopy; OCT: optical coherence tomography; AC: anterior chamber.

One patient with transient myopia due to choroidal effusion without inflammation of the anterior segment after SARS-CoV-2 infection has been reported (Patient 5; Table 1) [13]. This patient experienced a slight increase in IOP. UBM revealed a shallow anterior chamber (AC) due to anterior displacement of the iris. B-ultrasonography revealed shallow choroidal effusion in both eyes (OU). The patient was treated with 0.5 % timolol maleate eye drops and intravenous methylprednisolone. After five days, complete resolution of clinical manifestations was observed.

4. Discussion

In this case report, the patient initially presented with a transient myopic shift in both eyes, accompanied by a shallow anterior chamber due to ciliochoroidal detachment. Notably, these signs and symptoms appeared ten days after confirmation of COVID-19 positivity. The patient provided crucial information regarding drug use, revealing he had been prescribed indapamide to treat uncontrolled hypertension, which he had never previously used. In this case, there seemed to be multiple suspected etiological factors, including SARS-CoV-2 infection and the drug-induced side effects of indapamide or ibuprofen. Any of these factors, independently or in combination, could have led to the patient's clinical presentation.

Indapamide, a sulphonamide-containing thiazide-like diuretic, is used to treat hypertension and can induce acute transient myopia and choroidal effusion [[9], [10], [11], [12]]. Previously reported cases involving indapamide presented with transient myopia and supraciliary effusion, similar to our case. This condition develops in rare susceptible patients and is probably mediated by stimulating the synthesis of prostaglandins (PGs) through the inhibition of anti-inflammatory cyclooxygenase-2. Prostaglandins can increase vasodilation and permeability as the mediators of inflammation, leading to ciliary body oedema, exudation, and detachment. These pathological changes cause anterolateral rotation, relaxation of the zonules, and anterior movement of the iris and lens [[9], [10], [11], [12],[14], [15], [16]]. In this case, bilateral ciliochoroidal effusion with anterior rotation and oedema of the ciliary body were observed. Therefore, based on the pathological mechanism and the time correlation, indapamide was likely related to this patient's morbidity.

Furthermore, inflammation of the anterior segment was observed on the day of the next visit in this study, which has not been reported in previous indapamide-induced cases [[9], [10], [11], [12], [13]]. Systemic sulphonamides have also been reported to cause bilateral anterior uveitis [17]; while previous reports of indapamide-induced acute transient myopia with choroidal effusion did not include anterior chamber inflammation, making our case unique. In this case, inflammation of the anterior chamber was not observed on the first visit but was observed the next day. This may be due to the different disease stages observed by the authors, individual differences, or other pathogenic mechanisms.

Unlike previously reported cases of indapamide, our patient also had a history of COVID-19 infection. Reports indicate that SARS-CoV-2 could enhance concentrations of prostaglandin E2 (PGE2), prostaglandin F2α (PGF2α), and Thromboxane A2(TxA2)in biological samples of patients with COVID-19 [18]. The first causative hypothesis is that SARS-CoV-2 infection and indapamide can both enhance the release of PGs and have a synergistic effect on the occurrence of ciliochoroidal detachment with transient myopia. The second hypothesis posits that ocular condition was solely caused by SARS-CoV-2 infection, although this possibility was relatively low in our case. A previous study reported that a patient presented with transient myopia with choroidal effusion as a novel complication of COVID-19 [13]. And SARS-CoV-2 infection was reported as a possible trigger for intraocular inflammation in serpiginous choroiditis [19,20]. Raised titres of auto-antibodies and disrupted balance of pro-inflammatory and anti-inflammatory cytokines could be found in patients with COVID-19 in previous studies [6], while no elevation in the titres of the autoantibodies tested was found in this patient, undermining the possibility that SARS-CoV-2 stimulates uveal effusion through activating autoimmunity by raising the titres of autoantibodies. Moreover, uveal effusion has been observed after other viral infections, although its pathogenesis remains unclear [21,22]. Furthermore, several studies have provided evidence of Angiotensin Converting Enzyme-2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) receptor expression within ocular tissues, thereby rendering them vulnerable to infection by coronaviruses [23]. However, the patient was not treated with antiviral therapy, but with local and systemic corticosteroid therapy as well as discontinuing indapamide, the signs and symptoms were resolved, which does not support the possibility of direct infection of the virus induced. More evidence is needed in the future to explore the causal relationship and possible mechanisms between viral infection and this condition.

Another suspected drug, ibuprofen, has been reported to induce aseptic meningitis and iridocyclitis in one case, and a hypersensitivity reaction to nonsteroidal anti-inflammatory drugs (NSAIDs) was considered; nevertheless, ciliary body detachment did not develop in that case [24]. Among NSAIDs, aspirin have been identified as causes of transient myopia with a shallowing of the anterior chamber and an increase in the anteroposterior diameter of the lens [25]. Mefenamic acid has also been reported to induce bilateral transient myopia, secondary angle closure glaucoma, and choroidal detachment [16,26]. However, no similar drug-related reactions were observed with ibuprofen. In addition, the patient did not exhibit ocular abnormalities until 7 days after discontinuing ibuprofen. Given the temporal correlation, the association of ibuprofen appears to be less significant.

This study has some limitations. One of its shortcomings is the inability to definitively differentiate between drug effects and infection outcomes, because this study included only one case and did not include controls. However, this may provide insights into the possible interplay between the COVID-19 pandemic and ongoing drug treatments. Another limitation is the lack of biological samples from the patient, such as intraocular fluid, to confirm the speculated pathogenesis. Future research should include further case observations, cohort studies, and the collection of relevant biological samples to elucidate the pathogenesis.

5. Conclusion

We presented a case of bilateral transient myopic shift with a shallow anterior chamber and ciliochoroidal detachment in both eyes of a patient with indapamide intake and SARS-CoV-2 infection. This condition is presumably due to indapamide intake, and to some extent, SARS-CoV-2 infection may have had a synergistic effect on the pathology in this patient, but the exact physiopathological mechanism remains uncertain. The potential coexistence of dual pathogenic factors should be considered in diagnosing and treating such clinical presentations. Timely drug withdrawal and symptomatic treatment can result in a good prognosis.

Ethics statement

That individual has been given the explicit written and fully informed consent, and signed informed consent for publication.

Data availability statement

All the relevant data of this study are available from the corresponding author upon request.

CRediT authorship contribution statement

Huiping Yao: Writing – original draft, Data curation, Conceptualization. Ting Shen: Writing – review & editing, Data curation. Yanwei Chen: Writing – review & editing, Conceptualization. Yufeng Zhou: Data curation, Conceptualization. Xiaoqing Liu: Writing – original draft, Data curation. Xi Shen: Writing – review & editing, Conceptualization.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.