Dorzolamide

What it is

Dorzolamide is a synthetic sulfonamide designed to inhibit human carbonic anhydrase II, supplied as a 2% eye drop (20 mg per mL) for use three times a day. It was the first carbonic anhydrase inhibitor that could be given as a drop rather than a tablet, which is the point of it: the older oral drugs in this family worked but caused systemic side effects. It is still absorbed into the body through the eye, where it builds up in red blood cells by binding the carbonic anhydrase there, and washes out slowly with a terminal half-life of about four months. It is also sold combined with timolol in a fixed-combination drop.

What the research says

Dorzolamide reliably lowers eye pressure, and the question the literature actually answers is by how much and whether that translates into saved sight. In a network meta-analysis of 114 randomised trials it reduced intraocular pressure by 2.49 mmHg at three months - near the bottom of the first-line drug ranking, about half the effect of bimatoprost. Over a year it cut pressure by roughly 23% at peak, comparable to betaxolol and a little less than timolol. But the one large placebo-controlled trial of dorzolamide for preventing glaucoma in people with ocular hypertension, the European Glaucoma Prevention Study, found no significant difference in conversion to glaucoma at five years (13.4% versus 14.1%), largely because the placebo vehicle itself lowered pressure. The characteristic problems are local: burning or stinging in about a third of people, a bitter taste in about a quarter, superficial punctate keratitis in 10 to 15%, and - the signal that matters most - irreversible corneal swelling in people whose corneal endothelium is already damaged.

Evidence grade: Well established.

How it works

Drug class: Topical carbonic anhydrase inhibitor (sulfonamide), ocular hypotensive

Carbonic anhydrase is an enzyme that speeds up the conversion of carbon dioxide and water into bicarbonate. In the ciliary processes inside the eye, that reaction drives the secretion of aqueous humour, the fluid that fills the front of the eye. Dorzolamide blocks carbonic anhydrase II there, so less bicarbonate is formed, less sodium and fluid are pumped across, less aqueous humour is made, and the pressure inside the eye falls. It does not act on the drainage side of the system at all. (Source 1)

What it is used for

• Pressure-lowering is well established: 2.49 mmHg at three months in a network meta-analysis of 114 trials, and about 23% at peak and 17% at trough over a year in the pivotal comparison against timolol and betaxolol. It is one of the weaker first-line agents, and the evidence that it specifically preserves the visual field is absent - the Cochrane review states the dorzolamide-versus-placebo comparison failed to show a protective effect. Evidence: established. (Source 2)
• The European Glaucoma Prevention Study randomised 1,081 people with ocular hypertension to dorzolamide or its vehicle and found conversion rates of 13.4% versus 14.1% at five years (hazard ratio 0.86, 95% CI 0.58-1.26, P = 0.45). Dorzolamide did lower pressure by 15 to 22%, but the placebo vehicle also lowered it by 9 to 19%, which the authors identified as the reason no difference emerged. Evidence: not-supported. (Source 3)
• Topical dorzolamide is used off-label to reduce retinal fluid, on the theory that carbonic anhydrase inhibition improves fluid transport across the retinal pigment epithelium. The published work is small and mostly uncontrolled: a prospective non-randomised open study of 93 eyes with diabetic cystoid macular oedema reported mean central macular thickness falling from 535.27±97.4 µm at baseline to 376.23±114.5 µm at 3 months (P<0.001) with improved acuity, and the rest of the literature consists of case reports and case series. There was no control group and no randomisation, so the change cannot be attributed to the drug with confidence. Evidence: limited. (Source 4)
• The label states dorzolamide may be used with other topical pressure-lowering drops, five minutes apart, and a fixed dorzolamide/timolol combination is marketed. The combination carries the beta-blocker's systemic risks as well as dorzolamide's, and case reports of corneal decompensation after endothelial surgery involve the fixed combination. Evidence: established. (Source 2)

Interactions

• High-dose aspirin and other salicylates (label): Oral carbonic anhydrase inhibitors can disturb acid-base and electrolyte balance, which has caused salicylate toxicity. Those disturbances were not seen in the dorzolamide drop trials, but because the drop is absorbed systemically the label says the possibility should still be considered. (Source 5)
• Oral carbonic anhydrase inhibitors (acetazolamide, methazolamide) (pharmacokinetic study): Dorzolamide is absorbed into the body and inhibits the same enzyme, so adding it to an oral carbonic anhydrase inhibitor stacks the same mechanism without adding eye-pressure benefit. Dorzolamide builds up in red blood cells by binding carbonic anhydrase II there and washes out with a terminal half-life of about four months, so the systemic exposure persists long after the drops stop. (Source 6)
• Other eye drops, including beta-blocker drops such as timolol (label): Dorzolamide may be used with other pressure-lowering drops, but they should be given at least five minutes apart so one does not wash the other out. If the other drop is a beta blocker, its systemic effects add to any oral beta blocker the person is taking - relevant to anyone also on bisoprolol. (Source 2)
• Sulfonamide antibiotics (co-trimoxazole, sulfamethoxazole) and a reported 'sulfa allergy' (case reports): A past reaction to a sulfonamide antibiotic was associated with about a 2.8 times higher chance of reacting to a non-antibiotic sulfonamide like dorzolamide - but the same people were at even higher risk from penicillins, so the cohort study concluded this reflects a general tendency to drug allergy rather than true sulfonamide cross-reactivity. (Source 7)
• Food, alcohol and dietary supplements (pharmacokinetic study): No food, alcohol or supplement interaction is documented for dorzolamide, and there is a mechanistic reason: it is given as a drop, plasma concentrations are generally below the limit of detection, and what is absorbed is excreted largely unchanged in the urine rather than being metabolised by the liver enzymes that food and supplement interactions usually act on. The only interaction section in the label concerns high-dose salicylates. (Source 6)
• Contaminated multi-dose dropper bottles (case reports): Not a chemical interaction but a documented hazard of the delivery form: bacterial keratitis has been reported with multi-dose topical eye-drop containers that patients inadvertently contaminated, most often where there was already corneal disease or a break in the eye's surface. (Source 8)

Stopping it

• There is no withdrawal syndrome, dependence or rebound described for dorzolamide, and the published literature on stopping it is about safety rather than hazard: when corneal swelling or allergic conjunctivitis appears, stopping the drug is the treatment, and the label instructs that it be discontinued and the patient assessed before any restart. (Source 9)
• Stopping does not clear the drug quickly from the body. Dorzolamide leaves red blood cells non-linearly, with a fast initial fall and then a slow phase with a half-life of about four months, so systemic carbonic anhydrase inhibition can persist for months after the last drop. The eye-pressure effect, by contrast, is lost within days. (Source 6)
• The important caveat on stopping is that in the corneal decompensation case series the damage did not reverse: nine eyes developed overt corneal decompensation that persisted after the drug was withdrawn, and seven of the nine went on to need a corneal transplant. Withdrawal is therefore not a guaranteed remedy once endothelial failure has occurred. (Source 10)
• In the only placebo-controlled prevention trial, the vehicle arm shows what happens without the active drug: eye pressure in the placebo group still fell by 9% at six months and 19% at five years, and conversion to glaucoma was 14.1% against 13.4% on dorzolamide - so for someone with ocular hypertension at moderate risk, the measurable consequence of not taking it was not detectable in that trial. (Source 3)

What goes wrong

About one in three people get ocular burning or stinging and one in four a bitter taste, with superficial punctate keratitis in 10 to 15% and allergic-type ocular reactions in about 10%. (Source 11)

• Randomized trial, Moderate certainty.
• Size: Pooled controlled clinical trials in the registration programme.
• Who: Adults with ocular hypertension or open-angle glaucoma using dorzolamide 2% three times daily.
• How long: Up to one year in the controlled trials.
• Result: The most frequent adverse reactions associated with Dorzolamide Hydrochloride Ophthalmic Solution were ocular burning, stinging, or discomfort immediately following ocular administration (approximately one-third of patients). Approximately one-quarter of patients noted a bitter taste following administration. Superficial punctate keratitis occurred in 10 to 15% of patients and signs and symptoms of ocular allergic reaction in approximately 10%. Reactions occurring in approximately 1 to 5% of patients were conjunctivitis and lid reactions [see Warnings and Precautions ( 5.4 )] , blurred vision, eye redness, tearing, dryness, and photophobia.
• Funding: Manufacturer-conducted registration trials reported in the FDA label; the label notes rates from different drugs' trials cannot be directly compared.

Superficial punctate keratitis occurred in 10 to 15% of patients and signs and symptoms of ocular allergic reaction in approximately 10%. Reactions occurring in approximately 1 to 5% of patients were conjunctivitis and lid reactions [see Warnings and Precautions ( 5.4 )] , blurred vision, eye redness, tearing, dryness, and photophobia. Other ocular reactions and systemic reactions were reported infrequently, including headache, nausea, asthenia/fatigue; and, rarely, skin rashes, urolithiasis, and iridocyclitis.

Nine eyes developed corneal decompensation after starting dorzolamide that did NOT reverse when the drug was stopped; all nine had prior intraocular surgery or endothelial disease, and seven needed a corneal transplant. (Source 10)

• Case series, Very low certainty.
• Size: 9 eyes of 9 patients, multicentre chart review.
• Who: Glaucoma patients with histories consistent with corneal endothelial compromise - prior cataract surgery, anterior chamber lenses, previous penetrating keratoplasty with rejection episodes, or asymptomatic Fuchs endothelial dystrophy.
• How long: Onset 3 to 20 weeks after starting dorzolamide (mean 7.8 weeks)
• Result: Nine eyes of nine patients developed overt corneal decompensation after starting topical dorzolamide, a condition that did not resolve with drug cessation. This occurred after 3 to 20 weeks (mean, 7.8) of therapy. All nine patients had undergone intraocular surgery. Eight patients had undergone cataract surgery; three were aphakic and three had posterior chamber intraocular lenses. Two patients had anterior chamber intraocular lenses and also had undergone trabeculectomies. Four patients had undergone penetrating keratoplasties, each case complicated by episodes of corneal allograft rejection that were successfully treated. Two patients had asymptomatic Fuchs endothelial dystrophy. Seven patients have since undergone successful penetrating keratoplasties.
• Funding: Multicentre chart review in the American Journal of Ophthalmology; funding not stated.

The reports suggest that dorzolamide can cause irreversible corneal edema in a subset of glaucoma patients with endothelial compromise. The findings suggest a rationale for research into the long-term effects of dorzolamide on the corneal endothelium.

Acute corneal swelling developed the same day a dorzolamide/timolol drop was started two weeks after endothelial keratoplasty, and resolved only when the drop was stopped. (Source 12)

• Case report, Very low certainty.
• Size: 1 patient.
• Who: A 75-year-old woman two weeks after Descemet stripping automated endothelial keratoplasty, prescribed the fixed combination for raised pressure.
• How long: Deterioration on day 1, severe corneal oedema at 5 days, gradual recovery after stopping.
• Result: Single reversible case; corneal thickness fell again after the drop was withdrawn.
• Funding: Case report in Cornea; funding not stated.

Topical DTFC should be used with caution after corneal endothelial transplantation because of the possibility of iatrogenic corneal endothelial dysfunction.

Although given as a drop, dorzolamide is absorbed systemically and carries the sulfonamide class risks, including rare fatal reactions such as Stevens-Johnson syndrome, aplastic anaemia and other blood dyscrasias. (Source 8)

• Official position, Certainty not rated.
• Size: No rates given; cumulative label safety data.
• Who: Anyone using dorzolamide eye drops, including people with a known sulfonamide sensitivity.
• How long: Not stated; sensitisation can recur on re-exposure by any route.
• Result: No frequencies given. The label lists Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anaemia and other blood dyscrasias as rare but fatal possibilities.
• Funding: US FDA-approved prescribing information (a regulatory position with its publication date, not a trial)

Fatalities have occurred, although rarely, due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Sensitization may recur when a sulfonamide is readministered irrespective of the route of administration.

Carbonic anhydrase is present in the corneal endothelium, which is why people with low endothelial cell counts are at greater risk of corneal swelling on dorzolamide. (Source 9)

• Official position, Certainty not rated.
• Size: No numbers given.
• Who: People with low corneal endothelial cell counts - after cataract or corneal surgery, or with Fuchs dystrophy.
• How long: Not stated.
• Result: No rates given; the label advises caution in this group rather than contraindicating the drug.
• Funding: US FDA-approved prescribing information.

Carbonic anhydrase activity has been observed in both the cytoplasm and around the plasma membranes of the corneal endothelium. There is an increased potential for developing corneal edema in patients with low endothelial cell counts. Caution should be used when prescribing Dorzolamide Hydrochloride Ophthalmic Solution to this group of patients.

Chronic use produces allergic-type conjunctivitis and lid reactions that resolve when the drug is stopped. (Source 9)

• Randomized trial, Moderate certainty.
• Size: Clinical studies in the registration programme; rates of approximately 10% for allergic-type ocular reactions.
• Who: People using dorzolamide long-term.
• How long: Chronic administration.
• Result: Signs and symptoms of ocular allergic reaction in approximately 10% of patients; conjunctivitis and lid reactions in approximately 1 to 5%.
• Funding: Manufacturer registration studies reported in the FDA label.

In clinical studies, local ocular adverse effects, primarily conjunctivitis and lid reactions, were reported with chronic administration of Dorzolamide Hydrochloride Ophthalmic Solution. Many of these reactions had the clinical appearance and course of an allergic-type reaction that resolved upon discontinuation of drug therapy.

What the evidence supports

Across 114 randomised trials, dorzolamide lowered intraocular pressure by 2.49 mmHg at three months, placing it near the bottom of the first-line drug ranking. (Source 13)

• Meta-analysis, Moderate certainty.
• Size: 114 randomised controlled trials, 20,275 participants.
• Who: People with primary open-angle glaucoma or ocular hypertension.
• How long: Intraocular pressure at 3 months.
• Result: The mean reductions (95% credible intervals) in IOP in millimeters of mercury at 3 months ordered from the most to least effective drugs were as follows: bimatoprost 5.61 (4.94; 6.29), latanoprost 4.85 (4.24; 5.46), travoprost 4.83 (4.12; 5.54), levobunolol 4.51 (3.85; 5.24), tafluprost 4.37 (2.94; 5.83), timolol 3.70 (3.16; 4.24), brimonidine 3.59 (2.89; 4.29), carteolol 3.44 (2.42; 4.46), levobetaxolol 2.56 (1.52; 3.62), apraclonidine 2.52 (0.94; 4.11), dorzolamide 2.49 (1.85; 3.13), brinzolamide 2.42 (1.62; 3.23), betaxolol 2.24 (1.59; 2.88), and unoprostone 1.91 (1.15; 2.67).
• Funding: Bayesian network meta-analysis published in Ophthalmology; the authors note the overall risk of bias of included trials is mixed.

dorzolamide 2.49 (1.85; 3.13), brinzolamide 2.42 (1.62; 3.23), betaxolol 2.24 (1.59; 2.88), and unoprostone 1.91 (1.15; 2.67). Conclusions: All active first-line drugs are effective compared with placebo in reducing IOP at 3 months.

Over one year, dorzolamide 2% three times daily lowered eye pressure by about 23% at peak and 17% at trough, comparable with betaxolol and slightly less than timolol. (Source 14)

• Randomized trial, Moderate certainty.
• Size: 523 patients at 34 international sites.
• Who: People aged 17 to 85 with open-angle glaucoma or ocular hypertension, after washout of previous drops.
• How long: Up to 1 year, double-masked.
• Result: At 1 year, the mean percent reduction in intraocular pressure at peak of 2% dorzolamide, 0.5% timolol, and 0.5% betaxolol was approximately 23%, 25%, and 21%, respectively. At afternoon trough, the mean percent reduction in intraocular pressure was 17%, 20%, and 15% for dorzolamide, timolol, and betaxolol, respectively.
• Funding: Conducted by the International Dorzolamide Study Group with the manufacturer (Merck); the comparator drugs named are Merck and Alcon products.

The ocular hypotensive efficacy of 2.0% dorzolamide, given three times a day, is comparable with that of 0.5% betaxolol, given twice daily, for up to 1 year. In addition, long-term use of dorzolamide was not associated with clinically meaningful electrolyte disturbances or systemic side effects commonly observed with the use of oral carbonic anhydrase inhibitors.

Lowering eye pressure with drops as a class reduces the onset of visual field defects in ocular hypertension, with an odds ratio of 0.62. (Source 15)

• Systematic review, Moderate certainty.
• Size: 26 trials randomising 4,979 participants; 10 trials in the main meta-analysis.
• Who: People with primary open-angle glaucoma or ocular hypertension.
• How long: Trials of at least one year.
• Result: Meta-analysis of 10 trials clearly demonstrated reduction of onset of VF defects in treated OHT (OR 0.62, 95% CI 0.47 to 0.81). No single drug showed a significant VF protection compared to placebo or untreated controls. We did identify some border line evidence for a positive influence of treatment on VF prognosis (OR 0.67, 95% CI 0.45 to 1.00) for the beta-blockers.
• Funding: Cochrane review; no industry funding stated.

The results of this review support the current practice of IOP lowering treatment of OHT. A visual field protective effect has been clearly demonstrated for medical IOP lowering treatment.

What the evidence does not support

In the only large placebo-controlled trial, dorzolamide did not reduce conversion from ocular hypertension to open-angle glaucoma over five years: 13.4% versus 14.1%. (Source 3)

• Randomized trial, High certainty.
• Size: 1,081 patients enrolled by 18 European centres.
• Who: Adults aged 30 and over with intraocular pressure 22 to 29 mmHg, two normal reliable visual fields and a normal optic disc.
• How long: 5 years, randomised and double-masked.
• Result: At 60 months, the cumulative probability of converting to an efficacy end point was 13.4% in the dorzolamide group and 14.1% in the placebo group (hazard ratio, 0.86; 95% confidence interval [CI], 0.58-1.26; P = 0.45). The cumulative probability of developing an efficacy or a safety end point was 13.7% in the dorzolamide group and 16.4% in the placebo group (hazard ratio, 0.73; 95% CI, 0.51-1.06; P = 0.1).
• Funding: Multicentre European trial; dorzolamide and its vehicle were the study drugs, with manufacturer involvement in supply.

the EGPS failed to detect a statistically significant difference between medical therapy and placebo in reducing the incidence of POAG among a large population of OHT patients at moderate risk for developing POAG, because placebo also significantly and consistently lowered IOP.

The Cochrane review states explicitly that the dorzolamide-versus-placebo comparison failed to demonstrate a visual field protective effect, while cautioning that absence of data is not proof of absence of effect. (Source 15)

• Systematic review, Moderate certainty.
• Size: 26 trials, 4,979 participants.
• Who: People with primary open-angle glaucoma or ocular hypertension.
• How long: Trials of at least one year.
• Result: No single drug showed significant visual field protection versus placebo or untreated controls; only beta blockers showed borderline evidence (OR 0.67, 95% CI 0.45 to 1.00)
• Funding: Cochrane review; no industry funding stated.

the comparison of dorzolamide to placebo failed to demonstrate a protective effect. However, absence of data or failure to prove effectiveness should not be interpreted as proof of absence of any effect.

Over a year, dorzolamide did not reduce corneal endothelial cell counts or increase corneal thickness more than betaxolol or timolol in people with normal corneas. (Source 16)

• Randomized trial, Moderate certainty.
• Size: A one-year comparison within the registration programme (three treatment groups)
• Who: People with glaucoma or ocular hypertension and presumably normal corneal endothelium.
• How long: 1 year.
• Result: There were no statistically significant differences between groups in corneal endothelial cell counts or in corneal thickness measurements. There was a mean loss of approximately 4% in the endothelial cell counts for each group over the one year period.
• Funding: Manufacturer registration study reported in the FDA label.

There were no statistically significant differences between groups in corneal endothelial cell counts or in corneal thickness measurements. There was a mean loss of approximately 4% in the endothelial cell counts for each group over the one year period.

Having reacted allergically to a sulfonamide antibiotic predicts allergic reactions to non-antibiotic sulfonamides such as dorzolamide, but the pattern points to a general allergic predisposition rather than true cross-reactivity. (Source 7)

• Cohort study, Moderate certainty.
• Size: 969 patients with a prior sulfonamide antibiotic reaction and 19,257 without.
• Who: UK General Practice Research Database patients subsequently prescribed a sulfonamide non-antibiotic.
• How long: Allergic reactions within 30 days of the prescription.
• Result: Of 969 patients with an allergic reaction after a sulfonamide antibiotic, 96 (9.9 percent) had an allergic reaction after subsequently receiving a sulfonamide nonantibiotic. Of 19,257 who had no allergic reaction after a sulfonamide antibiotic, 315 (1.6 percent) had an allergic reaction after receiving a sulfonamide nonantibiotic (adjusted odds ratio, 2.8; 95 percent confidence interval, 2.1 to 3.7). However, the risk of allergic reactions was even greater after the receipt of a penicillin among patients with a prior hypersensitivity reaction to a sulfonamide antibiotic, as compared with patients with no such history (adjusted odds ratio, 3.9; 95 percent confidence interval, 3.5 to 4.3).
• Funding: Retrospective cohort study published in the New England Journal of Medicine; funding not stated in the abstract.

There is an association between hypersensitivity after the receipt of sulfonamide antibiotics and a subsequent allergic reaction after the receipt of a sulfonamide nonantibiotic, but this association appears to be due to a predisposition to allergic reactions rather than to cross-reactivity with sulfonamide-based drugs.

Where the research disagrees

Whether dorzolamide protects sight, as opposed to simply lowering a number

• The Cochrane review authors (Vass and colleagues), Systematic review of 26 randomised trials (4,979 participants) with at least one year of treatment: No single drug showed a significant VF protection compared to placebo or untreated controls. We did identify some border line evidence for a positive influence of treatment on VF prognosis (OR 0.67, 95% CI 0.45 to 1.00) for the beta-blockers (Source 15)
• The European Glaucoma Prevention Study investigators, on why their own trial was null, Randomised double-masked placebo-controlled trial of 1,081 people over five years: Dorzolamide reduced IOP by 15% to 22% throughout the 5 years of the trial. However, the EGPS failed to detect a statistically significant difference between medical therapy and placebo in reducing the incidence of POAG among a large population of OHT patients at moderate risk for developing POAG, because placebo also significantly and consistently lowered IOP. (Source 3)

How much

• Reference intake: There is no reference intake for a prescription eye drop; the regimen is set by the prescriber. As a position, the US prescribing information states the dose is one drop in the affected eye or eyes three times daily, of a 2% solution containing 20 mg per mL. (Source 2)
• Upper limit: No upper limit is specified beyond the labelled regimen. As a position, the label gives three times daily as the dose and 2% (20 mg per mL) as the only strength, with no higher strength or more frequent schedule approved. (Source 2)
• Studied: The one-year double-masked comparison gave dorzolamide 2% three times daily against timolol 0.5% twice daily and betaxolol 0.5% twice daily in 523 patients. (Source 14)
• Studied: The European Glaucoma Prevention Study randomised 1,081 people with ocular hypertension to dorzolamide or to the vehicle of dorzolamide as placebo, over five years. (Source 3)
• Studied: The off-label macular oedema study gave topical dorzolamide 2% three times daily for one month to 93 eyes with diabetic cystoid macular oedema, with follow-up to 3 months. (Source 4)

A common belief, and what the research shows

The belief: If you have a 'sulfa allergy' you cannot use dorzolamide drops; and eye drops stay in the eye, so they cannot affect the rest of the body.

What the research shows: Both halves are wrong in opposite directions. On sulfa allergy: a cohort study of 969 people with a documented reaction to a sulfonamide antibiotic found 9.9% reacted to a later non-antibiotic sulfonamide, versus 1.6% of those with no such history - a real association, but the same people reacted even more often to penicillins, and the authors concluded the pattern was 'due to a predisposition to allergic reactions rather than to cross-reactivity with sulfonamide-based drugs'. A sulfa antibiotic reaction is a reason for care, not an automatic bar. On the drops staying local: the label is explicit that dorzolamide 'although administered topically, it is absorbed systemically', it accumulates in red blood cells, and it washes out with a terminal half-life of about four months - which is why the sulfonamide class warnings apply to a drop at all.

Questions and answers

What is it?

Dorzolamide is a synthetic sulfonamide eye drop, not a nutrient and not anything that occurs in the body or in food. It is supplied as a 2% solution, 20 mg of dorzolamide per mL, used one drop three times a day in the affected eye. It is the first drug in its family that worked well enough as a drop to replace the tablets that preceded it. It is also sold combined with the beta blocker timolol in a single bottle. (Source 2)

What does it do in the body?

It blocks carbonic anhydrase II in the ciliary processes of the eye. That enzyme normally helps make bicarbonate, which drives the secretion of the fluid that fills the front of the eye, so blocking it means less fluid is made and the pressure inside the eye drops. The effect is modest: 2.49 mmHg at three months in the network meta-analysis, roughly half what bimatoprost achieves. (Source 1)

Is it good or bad for you?

It is useful but weak, and it is a problem for one specific group. Lowering eye pressure with drops as a class does protect the visual field (odds ratio 0.62 in the Cochrane meta-analysis), and dorzolamide does lower pressure. But it is among the least potent first-line options, its own placebo-controlled prevention trial was null, and in people whose corneal endothelium is already compromised - after cataract or corneal surgery, or with Fuchs dystrophy - it has caused corneal swelling that did not reverse when the drug was stopped. (Source 10)

How do you get more of it?

Dorzolamide is prescription-only and there is no food, supplement or behaviour that increases it. The labelled regimen is one drop three times daily, and the label notes it can be combined with other pressure-lowering drops given at least five minutes apart, or taken as a fixed combination with timolol. Any change to the regimen is a prescriber's decision; nothing here is a dose for a reader. (Source 2)

If it is harmful, what reduces it?

Stopping the drops is what the label advises when corneal swelling or an allergic lid or conjunctival reaction develops, and those allergic reactions resolve on withdrawal. But dorzolamide does not leave the body quickly: it washes out of red blood cells with a slow phase whose half-life is about four months. And in the published case series of corneal decompensation, stopping the drug did not reverse the damage. (Source 6)

Why might someone be low in it or missing it?

Being 'low' in dorzolamide does not apply - it is a manufactured drug, not something the body makes or absorbs from food. The enzyme it acts on, carbonic anhydrase, IS endogenous: humans have about fifteen isoforms, each in different tissues, and it is a zinc-containing enzyme. Genuine deficiency of a carbonic anhydrase isoform is a rare inherited condition rather than anything to do with this drug. (Source 17)

Which whole foods contain it or feed it?

No whole food contains dorzolamide or feeds it. The related biology is that its target enzyme family needs zinc - carbonic anhydrases are zinc metalloenzymes - but eating more zinc does not alter what the drug does, and no food or supplement interaction with dorzolamide is documented. The one interaction the label records is with high-dose salicylates, not with food. (Source 17)

What happens if you do not have it?

Nothing happens from lacking dorzolamide itself; what matters is whether eye pressure is left untreated. For established glaucoma or ocular hypertension, treating pressure with drops as a class reduced the onset of visual field defects with an odds ratio of 0.62 in the Cochrane meta-analysis. For dorzolamide specifically in moderate-risk ocular hypertension, the placebo arm of the European Glaucoma Prevention Study converted to glaucoma at 14.1% over five years against 13.4% on the drug - no detectable difference. (Source 3)

How can you test for it?

There is no blood test used to monitor dorzolamide, and there would be little point: plasma concentrations are usually below the assay's limit of detection even during chronic dosing. What gets measured instead is the thing the drug is for - intraocular pressure by tonometry, plus visual fields and optic disc assessment, which were the endpoints in the prevention trial. Corneal endothelial cell counts and corneal thickness are the relevant tests for the main safety concern. (Source 6)

References

1. DailyMed / US FDA label. DORZOLAMIDE HYDROCHLORIDE SOLUTION/DROPS - prescribing information (Sagent Pharmaceuticals). 2026. Read the source
2. DailyMed / US FDA label. DORZOLAMIDE HYDROCHLORIDE SOLUTION/DROPS - prescribing information (Sagent Pharmaceuticals). 2026. Read the source
3. Ophthalmology. Results of the European Glaucoma Prevention Study. 2005. PMID 15745761, DOI 10.1016/j.ophtha.2004.11.030. Read the source
4. International journal of ophthalmology. Efficacy of topical dorzolamide 2% in diabetic cystoid macular edema. 2021. PMID 34540619, DOI 10.18240/ijo.2021.09.18. Read the source
5. DailyMed / US FDA label. DORZOLAMIDE HYDROCHLORIDE SOLUTION/DROPS - prescribing information (Sagent Pharmaceuticals). 2026. Read the source
6. DailyMed / US FDA label. DORZOLAMIDE HYDROCHLORIDE SOLUTION/DROPS - prescribing information (Sagent Pharmaceuticals). 2026. Read the source
7. The New England journal of medicine. Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics. 2003. PMID 14573734, DOI 10.1056/nejmoa022963. Read the source
8. DailyMed / US FDA label. DORZOLAMIDE HYDROCHLORIDE SOLUTION/DROPS - prescribing information (Sagent Pharmaceuticals). 2026. Read the source
9. DailyMed / US FDA label. DORZOLAMIDE HYDROCHLORIDE SOLUTION/DROPS - prescribing information (Sagent Pharmaceuticals). 2026. Read the source
10. American journal of ophthalmology. Irreversible corneal decompensation in patients treated with topical dorzolamide. 1999. PMID 10218692, DOI 10.1016/s0002-9394(98)00438-3. Read the source
11. DailyMed / US FDA label. DORZOLAMIDE HYDROCHLORIDE SOLUTION/DROPS - prescribing information (Sagent Pharmaceuticals). 2026. Read the source
12. Cornea. Reversible Corneal Decompensation Caused by a Topical Dorzolamide/Timolol Fixed Combination After Descemet Stripping Automated Endothelial Keratoplasty. 2022. PMID 35942545, DOI 10.1097/ico.0000000000002894. Read the source
13. Ophthalmology. Comparative Effectiveness of First-Line Medications for Primary Open-Angle Glaucoma: A Systematic Review and Network Meta-analysis. 2016. PMID 26526633, DOI 10.1016/j.ophtha.2015.09.005. Read the source
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