Nightly phentolamine drops improved dim-light vision in a placebo-controlled phase 3 trial

Design

Phase 3, multicentre, double-masked, randomised, placebo-controlled

Population

145 adults with dim light disturbances, mesopic pupil 5 mm or more and mesopic low-contrast acuity 30 ETDRS letters or worse

Primary outcome

Mesopic low-contrast best-corrected distance visual acuity over 14 nights

Effect

Improvement at day 8 (13 vs 3 per cent placebo, P < 0.05) and day 15 (21 vs 3 per cent, P < 0.01), with reduced glare, halos and starburst (P < 0.01)

One hundred and forty-five people with self-reported dim light disturbances, a mesopic pupil of 5 mm or more and mesopic low-contrast best-corrected distance acuity of 30 ETDRS letters or worse were randomised 1:1 to 0.75 per cent phentolamine ophthalmic solution or placebo, one drop in each eye nightly for 14 days, double-masked. Twenty-five had had keratorefractive surgery.

Mesopic low-contrast acuity improved in the treated arm at day 8 (13 per cent against 3 per cent on placebo, P < 0.05) and day 15 (21 per cent against 3 per cent, P < 0.01). Note that the abstract does not define what those percentages count - almost certainly a responder threshold rather than a mean change - so quote the direction and the placebo contrast rather than the figure itself. Patient-reported overall severity of dim light disturbance and the photic symptoms of glare, halos and starburst all improved at both time points (P < 0.01). Conjunctival hyperaemia did not differ between arms, and adverse events were described as mostly mild and transient.

This is a genuine randomised, double-masked, placebo-controlled phase 3 result on a symptom that has had no pharmacological answer, and the mechanism - alpha-adrenergic blockade reducing pupil diameter - is plausible for it. Two caveats limit how far it travels: fourteen nights is short for a chronic complaint, and the post-keratorefractive analysis was post hoc in 25 people. Availability in India is not addressed by the trial.

• Measure and record mesopic pupil diameter before attributing night-vision complaints to anything else.
• Separate glare and halo symptoms from reduced acuity when taking the history; they responded as distinct outcomes here.
• Treat the post-keratorefractive finding as hypothesis-generating - it was a post-hoc subgroup of 25.
• Ask about duration before offering a 14-night regimen as an answer to a years-old symptom.
• Check availability and licensing before discussing this with a patient in India; the trial says nothing about either.

The statistics, in plain English

A placebo arm that moved 3 per cent while the treated arm moved 13 then 21 per cent is the shape you want, but without the definition of the responder threshold the absolute size cannot be judged - which is why the direction is quotable and the number is not. With 145 subjects the trial is powered for its primary outcome and not for safety, so mild and transient adverse events at 14 days say little about a drug used nightly for years. The post-keratorefractive result is a post-hoc subgroup and carries the usual discount.

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