Secondary angle closure induced by hydrochlorothiazide in a patient on oral steroids and immunosuppressants: A case report

Dear Editor,

Bilateral acute angle-closure glaucoma has been associated with the use of sulphonamide-derived medications, including acetazolamide, topiramate, sulphasalazine, and hydrochlorthiazide.[1] Drug-induced angle closure has been attributed to anterior uveal effusions and anterior rotation of the ciliary body, with consequent forward displacement of the iris-lens diaphragm.[2] Topical and/or systemic corticosteroids are recommended for the management of drug-induced angle closure, as uveal effusions are presumed to be secondary to inflammation.[3] To the best of our knowledge, drug-induced angle closure has not been reported in individuals on systemic corticosteroid therapy.

A 43-year-old female presented with complaints of painless, progressive defective vision in both eyes (OU) for 10 days. She was referred as a case of primary angle-closure glaucoma. The patient had a history of rheumatoid arthritis diagnosed 4 years ago, managed with methylprednisolone (4mg once daily), tofacitinib (5 mg twice daily), and methotrexate (5 mg weekly). Recently, systemic hypertension had been diagnosed, and a combination of telmisartan (40 mg), amlodipine (5 mg), and hydrochlorothiazide (12.5 mg) was initiated 10 days prior to this visit.

On examination, her uncorrected visual acuity (UCVA) was 20/120 in OU, improving to 20/30 with correction. Refraction revealed −4.25 D of spherical power OU, while her previous glass prescription was −2.5 spherical for the right eye (OD) and −3.25 spherical for the left eye (OS). Intraocular pressure (IOP), measured by applanation tonometry, was 30 mmHg in OD and 31 mmHg in OS. Slit-lamp examination revealed shallow anterior chambers graded 0 by Van Herrick system. Gonioscopy showed occludable angles OU, graded 0 by Shaffer system. Fundus examination was normal with undilated pupils. Ultrasound biomicroscopy (UBM) OU revealed irido-corneal apposition with the presence of suprachoroidal fluid. [Fig. 1]. B-scan ultrasound demonstrated a thickened choroid with retino-choroidal-scleral thickness measuring 2.0 mm in OD and 1.8 mm in OS [Fig. 2]. Blood investigations revealed normal serum electrolyte levels. Given the clinical findings and medication history, secondary angle closure (SAC) induced by hydrochlorothiazide was suspected. The patient was advised to discontinue hydrochlorothiazide while continuing telmisartan and amlodipine.

Figure 1.

UBM (OU) shows irido-corneal apposition in the presence of suprachoroidal fluid (white arrows), leading to anterior rotation of the ciliary processes and angle closure (white arrowhead)

Figure 2.

Initial presentation: Slit-lamp image (OD) showing shallow anterior chamber depth in periphery and centre. Ultrasound biomicroscopy (OU) shows a shallow anterior chamber with peripheral irido-corneal opposition. B-scan ultrasound demonstrated a thickened choroid with retino-choroidal-scleral thickness measuring 2.0 mm in OD and 1.8 mm in OS, with minimal uveal effusion in OU. (white arrow head)

At the one-week follow-up, her UCVA was 20/120 OU but improved to 20/20 with her previous glass prescription (OD −2.5, OS −3.25). The IOP had decreased to 21 mmHg OD and 19 mmHg OS. Slit-lamp examination revealed a normal anterior chamber depth, graded 4 by Van Herrick system, and gonioscopy showed wide-open angles graded 4 by Shaffer system. Fundus examination was normal. UBM OU confirmed wide-open angles, and B-scan ultrasound demonstrated normalization of the retino-choroidal-scleral thickness to 1.64 mm in OD and 1.52 mm in OS [Fig. 3].

Figure 3.

After discontinuing hydrochlorthiazide: Slit-lamp image showing normal anterior chamber depth in the periphery and centre. Ultrasound biomicroscopy (OU) shows wide-open angles. B-scan shows normalized retino-choroidal-scleral thickness measuring 1.64 mm in OD and 1.52 mm in OS

Discussion

Hydrochlorothiazide is a commonly prescribed antihypertensive agent. Medications like hydrochlorothiazide have been associated with precipitating angle closure, typically through idiosyncratic drug reactions leading to ciliary body edema, forward rotation of the ciliary body, choroidal effusion, and anterior displacement of the lens-iris diaphragm.[2]

Chen et al.[3] reported that hyponatremia induced by hydrochlorothiazide could contribute to secondary angle-closure glaucoma. However, in this case, the patient’s serum sodium levels were within normal limits, highlighting that angle closure can occur even in the absence of electrolyte disturbances.

Several studies highlight the role of steroids in managing drug-induced SAC. Mehta et al.[2] reported a rare case of multiple glaucoma medication-induced SAC, where only topical steroids and cycloplegics were used to treat the disease. Mishra et al.[4] used both topical and systemic steroids to effectively treat choroidal effusions. Gopalakrishna et al.[5] reported the use of systemic steroids to manage ocular inflammation in one of six patients presenting with topiramate-induced choroidal effusion. Topical and/or systemic steroids are used in these cases due to the inflammatory component of uveal effusions.[6,7] Chen et al.[3] also emphasized the utility of topical corticosteroids in resolving drug-induced angle closure. Rhee et al.,[8] recommend the use of systemic steroids and hyperosmolar agents for the rapid recovery of topiramate-induced angle-closure glaucoma.

The above literature supports a definitive role for steroids in managing drug-induced SAC. However, this case is unique, as the patient was already on oral steroids and immunosuppressants for rheumatoid arthritis at the time of hydrochlorothiazide initiation. Despite these medications, the patient developed SAC, suggesting an idiosyncratic immune-mediated reaction that may not be impacted by prior systemic steroid therapy.

Management of drug-induced SAC requires a thorough medication history, including discontinuation of the offending drug.[5] In early presentations with high IOP, angle closure, myopic shift, and minimal effusion, discontinuing the drug alone is sufficient, with resolution within 7–10 days.[9] Late presentations or significant effusion require topical steroids and glaucoma medications. Systemic steroids accelerate recovery in slow responders.[6,7,8,9] Gopalakrishna et al.[5] avoided using oral acetazolamide since carbonic anhydrase inhibitors could also precipitate SAC. Intravenous mannitol aids in rapid recovery.[8,9] Cycloplegics help by retracting the ciliary processes and reversing forward lens-iris diaphragm displacement.[10] YAG peripheral iridotomy is ineffective, as pupillary block is not the underlying mechanism.[11] Early diagnosis ensures a good prognosis, while delayed treatment increases the risk of permanent glaucomatous damage.

Conclusion

This case emphasizes that while steroids are commonly used to manage moderate to severe cases of drug-induced SAC, they do not prevent its development. The most critical step in treatment is identifying and discontinuing the offending agent. All other therapeutic measures are secondary, as SAC will not respond effectively unless the primary causative agent is removed. To our knowledge, this is the first reported case of hydrochlorothiazide-induced SAC occurring in a patient on systemic steroids and immunosuppressants, thus contributing a novel insight to the literature.

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Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.