Systemic Medication Associations with Presumed Advanced or Uncontrolled Primary Open-Angle Glaucoma

Design

Database study

N= 36,780

Objective

Study Groups

POAG cases (n= 6,130)

Control (n= 30,650)

Inclusion Criteria

Exclusion Criteria

Methods

The POAG cases were defined by the patient's prescription codes during the 5-year period before the procedure. The control group consisted of patients undergoing cataract surgery during the identification period, with the assumption that pre and postoperative ophthalmic assessment would have detected glaucoma if presented. This is based on epidemiological studies of glaucoma prevalence that indicated developed countries have approximately 50% of patients with undiagnosed glaucoma. Five-time as many controls were included versus POAG cases to increase the study's power.

Duration

Data inclusion period of January 1, 2007 to December 31, 2014 which also included:

Identification period: 2-year period for identification of cases and controls from January 1, 2012, to December 31, 2013

Look-back period: 5-year looking back for examination of prescription drug use

Look-forward period: 1-year period ahead to exclude delayed glaucoma diagnosis in controls

Outcome Measures

Baseline Characteristics

POAG cases (n= 6,130)

Age, years

Male

Results

Endpoint

Odds ratio (95% Confidence Interval [CI])

Citalopram association with primary open-angle glaucoma

Drug class association with primary open-angle glaucoma

Selective serotonin reuptake inhibitor

Beta-blockers

Calcium channel blockers

Sexual function disorder medications

Serotonin-norepinephrine reuptake inhibitor

Fibric acid derivatives

Angiotensin II antagonists

0.70 (0.64 to 0.76)

0.77 (0.72 to 0.83)

1.26 (1.18 to 1.35)

1.39 (1.22 to 1.58)

0.71 (0.61 to 0.82)

0.74 (0.65 to 0.84)

1.19 (1.10 to 1.28)

Other generic drugs association with primary open-angle glaucoma

Amlodipine

Esomeprazole

Tamsulosin

1.27 (1.18 to 1.37)

0.81 (0.73 to 0.89)

1.29 (1.15 to 1.44)

Adverse Events

Study Author Conclusions

InpharmD Researcher Critique

The data presented is strictly exploratory. The association between results and treatment or confounders is unknown and the reason for protective results of citalopram to primary open-angle glaucoma cannot be adequately described with the current information.

The control group was based on an assumption of missed glaucoma cases. It is unknown whether they truly had glaucoma for side-by-side comparison. The majority of baseline characteristics were regarding the region of residence, plan type, and employment status. 

Bilateral symptomatic angle closure associated with a regular dose of citalopram, an SSRI antidepressant

Design

Case presentation

A 55-year-old caucasian female presented with sudden onset of bilateral blurred vision which lasted for a few hours and left the patient with a mild headache. The patient had a history of depression and received radioactive iodine for thyrotoxicosis in the past. Her antidepression medication was switched from imipramine to citalopram 20 mg/day approximately 5 months from admission and thyroxine approximately 3 months from admission. While the patient had stable vision and corneas looked clear, intraocular pressure (IOP) was measured to be 56 mmHg in the right eye and 34 mmHg in the left eye. The patient was diagnosed with bilateral symptomatic angle closure and was treated with IV acetazolamide 500 mg, G pilocarpine 2%, plus G apraclonidine and G levobunolol in both eyes. While the left eye pressure lowered, the right eye required laser iridoplasty. The patient was eventually discharged with controlled IOP in both eyes along with pilocarpine 2% and G prednisolone 1% for use in both eyes four times a day along with stopping citalopram tablets.

The follow-up visits up to 3 months later revealed IOP ranging from 15 to 16 mmHg but developed symptoms related to chronic anxiety disorder and leading to restart of imipramine 25 mg/day. This led to signs of increased IOP once more and the patient received pilocarpine 1% therapy while continuing imipramine until switching to mirtazapine. The last known follow-up, the patient had normalized IOP and angles but continued topical treatment.

Study Author Conclusions

From the current literature, the risk of angle closure related with the use of SSRIs appears small but can lead to significant morbidity. More laboratory‐based studies are needed to further elucidate the long‐term effects of SSRIs on the iris, angle and IOP.

Topiramate-associated acute glaucoma in a migraine patient receiving concomitant citalopram therapy: a case-report

Design

Case presentation

A 34-year old man with a diagnosis of migraine with and without aura complained of blurred vision and ocular pain as an intense compression after seven days of treatment with topiramate and admitted to a clinic where a pressure of 40 mmHg in both eyes was found, compatible with diagnosis of acute glaucoma. The opthalmologist also confirmed severe acute myopia due to reduction of depth of the anterior chamber, hyperemia of the sclera and light corneal edema. Upon investigation, it was revealed that he had also been taking citalopram 20 mg daily for two months to treat anxious-depressive syndrome.

Topiramate was discontinued and the patient received acetazolamide 250 mg tablet BID, latanoprost, timolol 0.5% (one drop TID) and pilocarpine 2% (one drop for TID) in eyewash. After two days, ocular pressure was reduced to 14 mmHg in the right eye and to 17 mmHg in the left eye at the ophthalmological checkup. Finally, symptoms completely resolved following eight days of stopping topiramate and initiation of new antiglaucoma therapy.

Study Author Conclusions

The authors concluded that topiramate and citalopram were both associated with the increase of intraocular pressure and the development of glaucoma. Despite there is no evidence showing that a contemporary assumption of both these drugs within therapeutic doses can increase the risk of acute glaucoma, the authors suggested that citalopram may increase ocular pressure (in a dose-dependent manner) through an intraocular accumulation of serotonin, leading to increasing the risk of topiramate-induced glaucoma in a patient with a predisposed genetic substratum.

Citalopram associated with acute angle-closure glaucoma: case report

Design

Case presentation

A 54-year-old caucasian female with a history of depression and suicidal ideation but non-smoker was admitted for an episode of overdose with citalopram and alcohol. The actual ingestion rate is unclear but the patient may have received up to 14 to 30 tablets of 20 mg citalopram along with 2 bottles of red wine. Soon after admission, the patient complained of painful left eye with blurred vision which was found to have an intraocular pressure of 23 mmHg in the right eye and 60 mmHg of mercury in the left eye with left corneal edema and fixed dilated pupils. The patient was diagnosed with left angle-closure glaucoma and therapy was initiated to reduce elevated intraocular pressure. Pulse rate and blood pressure were normal.

Eye examinations 48 hours later revealed subhyaloid and retinal hemorrhages. The patient's intraocular pressure was eventually controlled 72 hours later and she was discharged to the local psychiatric unit due to continued expression of suicidal thoughts and low mood. After 14 days of treatment with timolol, pilocarpine, and dexamethasone eye drops for eyes along with chlordiazepoxide for alcohol dependence, the patient improved but with stable ocular pressure but still displayed retinal hemorrhages in the left eye.

Study Author Conclusions

The pathophysiological basis for acute angle-closure glaucoma in relation to antidepressant medications remains unclear. The authors suggest citalopram may have a direct action on the iris or ciliary body muscle through serotonergic or anti-cholinergic mechanisms or both. This case highlights the importance of the awareness of the underlying risks, which may predispose an individual to develop acute angle-closure glaucoma, and reminds clinicians of the significance of history taking and examination of the eye before and after starting anti-depressants. This area needs to be further researched.