Neostigmine eyedrops may ease drooping of eyelids in MG patients
Study: Treatment has potential to be effective without bodywide effects
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- Neostigmine eyedrops (TNOS) show promise for treating myasthenia gravis-related drooping eyelids (ptosis).
- A 1.5 mg/mL dose safely reduced ptosis in most patients without systemic or ocular side effects.
- TNOS could offer a local, safer alternative for diagnosing and treating myasthenic ptosis.
An eyedrop formulation of neostigmine, an acetylcholinesterase inhibitor (AChEI) whose oral formulation was once a mainstay treatment for myasthenia gravis (MG), may safely reduce drooping eyelids in people with the neuromuscular disease.
That’s according to data from a small Phase 1 clinical trial (ACTRN12624000545561), which showed that one tested dose of the eyedrops, called topical neostigmine optical solution (TNOS), helped reduce the degree of drooping eyelids (ptosis) in most MG patients without reports of adverse events.
TNOS has the potential to diagnose and treat MG-related ptosis without systemic (whole-body) effects, such as those caused by oral or injectable AChEIs, researchers noted.
“The development of TNOS as a diagnostic tool or therapeutic agent in patients with myasthenic ptosis might offer distinct benefits over systemic AChEIs, including reduced systemic side effects and greater simplicity in preparation and administration,” researchers wrote.
The trial findings were described in the study “Phase 1 dose-finding study of topical neostigmine ophthalmic solution for alleviating myasthenic ptosis,” which was published in Scientific Reports.
Drooping eyelids a common symptom of both types of MG
Most MG cases are caused by self-reactive antibodies that mistakenly target proteins that help nerves and muscles communicate, most commonly the acetylcholine receptor (AChR) protein. This can cause muscle weakness around the eyes alone (ocular MG) or throughout the body (generalized MG). Ptosis is a common symptom of both types of MG.
AChEIs, currently available in oral and injectable formulations (systemic administration), are common MG treatments that aim to boost the effects of acetylcholine, the signaling molecule that binds and activates AChR proteins. This is expected to help alleviate the effects of the immune attacks and lessen muscle weakness.
Systemic neostigmine was once a mainstay treatment for MG, but its use has declined with the development of oral pyridostigmine (sold as Mestinon, with generics available), which is now the most commonly used symptomatic AChEI for MG.
AChEIs can also help doctors diagnose MG, particularly in ocular cases with subtle ptosis. If the eyelids become less droopy after injecting small amounts of an AChEI, this is often a sign of MG.
“However, the utilization of these medications is limited because the administration procedures are complicated, and the drugs potentially cause life-threatening adverse events,” the researchers wrote.
A local AChEI that only affects the eye area could help both diagnose and treat ptosis in MG.
“Despite frequent ocular symptoms, there is currently no available ophthalmic [eye] drop that directly alleviates myasthenic ptosis, which could be locally applied as a diagnostic tool or symptomatic treatment with fewer systemic side effects,” the researchers wrote.
5 of 6 participants in higher-dosage group met efficacy standard
In this study, a team of researchers in Thailand conducted a Phase 1 trial that evaluated the safety and efficacy of TNOS, a diluted form of neostigmine, as eyedrops in 12 adults (seven women and five men) with MG and ptosis. This is the first trial assessing the therapy’s effects as a local eye treatment.
Participants, with a median age of 61.5, could not receive other medications for MG, including oral pyridostigmine or immunosuppressive treatments, during the study. Six participants were treated with one eyedrop of 1 mg/mL TNOS and the remaining six were given a higher dose of 1.5 mg/mL.
The primary efficacy measure was the change in the distance between the upper and lower eyelids. Researchers considered the medication effective if the eyelid distance increased by at least 2 mm.
Five of six participants in the higher-dose group met this efficacy standard. The largest change was detected one hour after TNOS administration, with a mean widening of 3.3 mm. After about three hours, ptosis had largely returned to pretreatment levels.
The 1.5 mg/mL TNOS was considered the optimal … dose for alleviating myasthenic ptosis without adverse events.
All individuals in this group reported subjective improvement in ptosis, including the participant who didn’t meet the 2 mm efficacy cutoff. This patient started out with less severe ptosis, which may have affected their results, the researchers hypothesized.
“There might be a small residual [eyelid] height left that could be elevated by the effect of AChEIs,” they wrote.
Among the six participants who received the lower dose, two (33.3%) met efficacy criteria and reported ptosis lessening. The effect was smaller and slower than in the higher-dose group. It peaked after three hours, at a mean widening of 1.25 mm.
“All participants had no systemic or ocular adverse effects,” the researchers wrote.
Based on the safety and efficacy results, “the 1.5 mg/mL TNOS was considered the optimal … dose for alleviating myasthenic ptosis without adverse events,” the researchers concluded.
If additional clinical trials confirm their safety and efficacy, the eyedrops could have applications for both diagnosis and treatment as an alternative to pyridostigmine or other systemic AChEIs, they added.
Future studies with more patients that test multiple administrations and assess more outcomes, including more patient-reported metrics of symptom control, are needed to confirm TNOS’ therapeutic potential, the team noted.
Margie Jacobson
What about UPNEEQ eye drops ??
I have used them and they work
Jodi Enders
Hi Margie, thank you for sharing your experience. It may be something others can ask their MG specialist about to see whether it fits their individual situation. -Jodi, Patient Advocate