Acute Myopic Shift after a Single Dose of Acetazolamide: A Case Report and Review of the Literature

Keywords

acetazolamide - uveal effusion - angle closure - myopic shift - idiosyncratic drug reaction - UBM

Schlüsselwörter

Ultraschallbiomikroskopie (UBM) - Myopisierung - Acetazolamid - Uvealeffusion

Introduction

Acetazolamide-induced anterior displacement of the iris-lens diaphragm is a rare idiosyncratic reaction and was first described by Back in 1956 [1]. We report the case of a young patient presenting with an acute myopic shift due to a uveal effusion following a single administration of 250 mg acetazolamide. We also reviewed the literature in order to systematize the clinical presentation and treatment options of this adverse reaction.

History and Signs

A 32-year-old phakic, nearly emmetropic (+ 0.25D OU), male patient, with no relevant medical history, was referred because of recurrent episodes of vertical diplopia associated with a cerebellar oculomotor syndrome, and a positive family history. After an extensive workup, transient episodic ataxia, a rare autosomal dominant inherited disorder, was suspected and the patient was initiated oral acetazolamide 250 mg bid, the usual treatment for most forms of episodic ataxia [2]. A few hours after the first dose, his vision became blurred, with increasing near-sightedness. Upon examination 12 hours after the drug intake, a bilateral myopic shift of − 4.5D OU was observed, while best-corrected visual acuity was still 20/20 OU. Both anterior chambers were shallow, with some rare cells and flare.

Therapy and Outcome

An anterior ciliary body rotation with displacement of the iris-lens diaphragm, an extremely rare complication of acetazolamide, was suspected and the patient was admitted for monitoring because of the risk of angle closure. Twelve hours later, his myopia had progressed to − 5.5 D with angle closure while intraocular pressure (IOP) remained normal at 12 mmHg (RE) and 13 mmHg (LE). A bilateral circumferential anterior uveal detachment was revealed on ultrasound biomicroscopy ([Fig. 1]). In order to reverse the anterior ciliary body rotation, cycloplegia was initiated with atropine 0.5% bid associated with topical dexamethasone 0.1% qid. The evolution was favorable, with a progressive deepening of the anterior chambers, reopening of the iridocorneal angle ([Fig. 2]), and complete resolution of the myopic shift after 5 days. Best-corrected visual acuity remained 20/20 OU throughout this follow-up.

Fig. 1 Circumferential ultrasound biomicroscopy (48 MHz): anterior uveal effusion associated with iridocorneal angle narrowing/closure (RE).

Fig. 2 a Slit lamp and gonioscopy photo at presentation. Shallow anterior chamber due to anterior iris-lens displacement. b Anterior segment OCT B-scan. Favorable evolution of anterior chamber depth, angle closure and reopening, and the associated refraction following drug withdrawal, cycloplegia, and topical steroids to reverse acetazolamide-induced anterior uveal effusion (RE).

Discussion

Sulfonamideʼs derivatives, such as topiramate, hydrochlorothiazide, and acetazolamide, have been rarely reported to induce ciliochoroidal effusion [3], [4]. Acetazolamide administration, specifically, has been associated with a transient myopic shift, iridocorneal angle closure with or without ocular hypertension, and a ciliochoroidal detachment [1], [5] – [23]. To our knowledge, this rare adverse reaction has only been reported in 23 patients since 1956, including our patient ([Table 1]). In summary, after the administration of a median dose of 500 mg (125 – 1000) acetazolamide, all cases presented a myopic shift after a median 24 hours (3 – 24), complicated in about a third of patients by angle closure ocular hypertension. A uveal effusion was observed in about half of the patients. When acetazolamide was stopped, all cases recovered completely after a median of 5 days (2 – 14), with the aid of additional cycloplegia, anti-glaucomatous agents, and/or steroid treatment in about a quarter, a third, and more than half of the patients, respectively [1], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23].

Table 1 Overview of case reports on acetazolamide-induced myopic shift, summarizing drug dosage, time till onset of presentation, clinical characteristics, management, and time to recovery.

First author (et al.), year	Dose of acetazolamide (mg)	Time till onset of symptoms (hours)	Clinical presentation (1 = mentioned in paper)			Treatment (1 = mentioned in paper)				Time to recovery (days)
			Myopic shift	Angle-closure glaucoma	Uveal effusion	Stop acetazolamide	Cycloplegia	Anti-glaucomatous treatment Topical = a Systemic = b	Corticosteroids Topical = a Systemic = b
*When the time till onset of symptoms or time to recovery was reported as a “few” hours or days, we arbitrarily used the number 4 to allow calculations
Back 1956 [1]	250	24	1	–	–	1	–	–	–	2
Kronning 1957 [5]	750	24	1	–	–	1	–	–	–	5
	250	24	1	–	–	1	–	–	–	3
Binder et al. 1957 [6]	250	24	1	–	–	1	–	–	–	14
Muirhead et al. 1959 [7]	250	24	1	–	1	1	–	–	–	7
Halpern et al. 1959 [8]	250	24	1	–	–	1	–	–	–	3
Galin et al. 1962 [9]	500	24	1	–	–	1	–	–	–	7
	500	24	1	–	–	1	–	–	–	4*
Garland et al. 1962 [10]	750	24	1	–	1	1	–	–	–	5
Fan et al. 1993 [11]	500	24	1	1	1	1	–	1a	1a	7
Parthasarathi et al. 2007 [12]	250	4*	1	1	1	1	–	1b	1b	5
Bayer and Moroi 2010 [13]	250	4*	1	1	1	1	1	1a	1a	4
Malagola et al. 2013 [14]	500	3	1	1	1	1	–	1b	–	3
de Rojas et al. 2013 [15]	500	24	1	1	1	1	–	1a	1a, 1b	5
Man et al. 2016 [16]	500	4*	1	1	1	1	1	1a	1a	14
Llovet-Raussel et al. 2016 [17]	750	24	1	1	1	1	1	1a	1a	14
Hill 2016 [18]	1000	12	1	–	–	1	–	–	1b	7
Grigera and Grigera 2017 [19]	500	24	1	–	1	1	1	–	1a, 1b	2
Kalina and Kalina 2020 [20]	500	4*	1	–	–	1	–	–	1a	4
Anwar et al. 2021 [21]	250	6	1	1	1	1	–	1b	1b	8
Rothwell and Anderson 2021 [22]	125	4*	1	–	1	1	–	–	1a	7
Musetti et al. 2022 [23]	250	4*	1	–	1	1	1	–	1a	7
This case	250	4	1	–	1	1	1	–	1a	5
Median (range)	500 (125 – 1000)	24 (3 – 24)	–	–	–	–	–	–	–	5 (2 – 14)
% of cases	–	–	100%	34.7%	52%	100%	26%	21.7% a 13% b	43.5% a 17.4% b	–

Because of its rarity, no etiopathogenic study was conducted to date. An attempt was made in 1962 by Galin et al., who reported no changes in anterior chamber depth in 30 eyes of normal individuals following the administration of acetazolamide (500 mg iv or 5 mg/kg qid po) [9]. Several pathogenetic theories have been proposed [9], [10], [13]. A hypersensitivity reaction is considered less likely, as the reaction occurs upon a first-time administration [13], [17], [18], [19], as in our case. While remaining uncertain, pathophysiology is attributed to an idiosyncratic uveal reaction provoking an anterior displacement of the iris-lens diaphragm. The effect seems to be dose independent, starting from a single dose of 125 mg [22], and, as said, independent of prior drug exposure [1], [10], [16]. Also, the severity of the reaction does not appear to be correlated with the dose, though drug continuation does exacerbate the condition [12]. In addition, the presence of the lens seems to be irrelevant, as cases have been reported after cataract surgery [12], [21], [23] as well as in phakic individuals [5], [16], [22].

Therapeutic strategies vary in the literature ([Table 1]). Following drug withdrawal, they include simple observation, cycloplegia, topical aqueous-humor suppressors, and/or intravenous mannitol in case of ocular hypertension, as well as topical, periocular, and/or systemic (po or iv) corticosteroids. The efficacy of systemic corticosteroids does not seem to be superior to drops and may have serious side effects.

Ophthalmologists and internists should be aware of this rare side effect of acetazolamide, a drug often used for the treatment of intraocular hypertension amongst other indications, and maintain a high level of suspicion if a patient reports bilateral near-sightedness following drug administration. Differential diagnosis with primary angle-closure glaucoma may prove challenging, and drug withdrawal should be the first step. Aqueous misdirection syndrome, presenting with a similar mechanism and characteristics, is distinguished by its exclusive presence in a single eye, in contrast to our condition, which consistently affects both eyes. In cases where patients with a history of acetazolamide treatment for angle-closure glaucoma exhibit bilateralization of angle closure after drug administration, drug-induced choroidal effusion should be considered. When diagnostic uncertainty arises, ultrasound biomicroscopy (UBM) can help differentiate between the two conditions. Rare attempts to reproduce the effect with repeat acetazolamide administration have been met with a relapse or no effect at all [1]. It is advised though to avoid prescribing acetazolamide to individuals presenting this idiosyncratic reaction because of the risk of acute angle closure.

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