None listed
Conditions
Brief summary
Everyone who reaches middle age will eventually need reading glasses due to an age-related eye condition known as presbyopia. Recently, Vuity eye drops (pilocarpine 1.25%) have emerged as an effective treatment for the blurry near vision that comes with presbyopia. However, the safety concerns that accompany this treatment have not yet been adequately addressed. This research aims to determine whether acute administration of Vuity eye drops can change choroidal thickness, choroidal blood flow, or retinal function. We will examine whether any physiological changes to the choroid or retina occur synergistically with uncorrected retinal defocus, resulting from pupil constriction or direct stimulation of the choroid and retina.
Interventions
This is an interventional study that will investigate Vuity eye drops' (pilocarpine 1.25%) mechanism of action on the choroid and retina, as the first step towards ensuring this treatment is safe for long-term use. The aim of this study is to understand whether acute pilocarpine administration can change choroidal thickness, choroidal blood flow, or retinal function. We hypothesise that this occurs via 3 mechanisms: 1/ by failing to correct retinal defocus, 2/ by constricting the pupil, or 3/ by
This is an interventional study that will investigate Vuity eye drops' (pilocarpine 1.25%) mechanism of action on the choroid and retina, as the first step towards ensuring this treatment is safe for long-term use. The aim of this study is to understand whether acute pilocarpine administration can change choroidal thickness, choroidal blood flow, or retinal function. We hypothesise that this occurs via 3 mechanisms: 1/ by failing to correct retinal defocus, 2/ by constricting the pupil, or 3/ by directly stimulating muscarinic receptors within the choroid and retina. Each participant will participate in 3 controlled experiments to understand whether acute administration of Vuity eye drops (pilocarpine 1.25%) can act directly or indirectly on the choroid and retina. Participants will receive 1 drop of Vuity in the experimental eye during each of the 3 study visits. - Experiment 1 will examine whether pilocarpine changes the physiology of the choroid and retina, independently from hyperopic defocus. In this experiment, participants will first undergo a 20-minute stabilisation period by watching a movie at a far viewing distance (6 m). After stabilisation, baseline measures of retinal and choroidal thickness and blood flow (using optical coherence tomography, OCT) and retinal function (using global flash multifocal electroretinography, gmfERG) will be acquired, with participants' eyes fully corrected for any hyperopic defocus. After baseline measures are completed, 1 drop of Vuity (pilocarpine 1.25%) is administered by a study researcher to the participants' experimental eye. Participants will then undergo 60-min stabilisation period by watching a movie at a far viewing distance (6 m) to allow pilocarpine to reach maximal effect in the eye, before measures of retinal and choroidal thickness and blood flow are repeated. - Experiment 2 will examine whether pilocarpine changes the physiology of the choroid and retina independently from both hyperopic defocus AND retinal illuminance (determined by pupil size). In this experiment, 1 drop of tropicamide (1%) will first be instilled by a study researcher to both eyes of the participant to control for pupil size and therefore retinal illuminance. Participants will then undergo a 20-minute stabilisation period by watching a movie at a far viewing distance (6 m). After stabilisation, baseline measures of retinal and choroidal thickness and blood flow (using optical coherence tomography, OCT) and retinal function (using global flash multifocal electroretinography, gmfERG) will be acquired, with participants' eyes fully corrected for any hyperopic defocus. After baseline measures are completed, 1 drop of Vuity (pilocarpine 1.25%) is administered by a study researcher to the participants' experimental eye. Participants will then undergo 60-min stabilisation period by watching a movie at a far viewing distance (6 m) to allow pilocarpine to reach maximal effect in the eye, before measures of retinal and choroidal thickness and blood flow are repeated. - Experiment 3 will examine whether pilocarpine changes the physiology of the choroid and retina by subjecting the eye to sustained periods of hyperopic retinal defocus, independently of retinal illuminance (determined by pupil size). In this experiment, 1 drop of tropicamide (1%) will first be instilled by a study researcher to both eyes of the participant to control for pupil size and therefore retinal illuminance. Participants will then undergo a 20-minute stabilisation period by watching a movie at a far viewing distance (6 m). After stabilisation, baseline measures of retinal and choroidal thickness and blood flow (using optical coherence tomography, OCT) and retinal function (using global flash multifocal electroretinography, gmfERG) will be acquired, with participants' eyes fully corrected for any hyperopic defocus. After baseline measures are completed, 1 drop of Vuity (pilocarpine 1.25%) is administered by a study researcher to the participants' experimental eye. Participants will then undergo 60-min stabilisation period by watching a movie at a near viewing distance (30 cm) to subject the eyes to hyperopic defocus while allowing pilocarpine to reach maximal effect in the eye, before measures of retinal and choroidal thickness and blood flow are repeated. Each experiment is anticipated to take 2 hours (total ~6 hours for the study). The 3 experiments will be conducted across 3 separate study visits, spaced at least 24 hours apart to ensure no carryover effects from the previous visit. Each experiment will be performed at the same time of day (±1 hour) to control for known diurnal variations in choroidal thickness. A random number generator will be used to randomise the experimental eye and the order of experiments for each participant.
Sponsors
The University of Auckland
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
40 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
Adults in good general and eye health who only wear optical correction (glasses and/or contact lenses) for presbyopia correction, and are willing and able to provide written informed consent for study participation.
Exclusion criteria
Medical conditions - Uncontrolled systemic disease or clinically significant disease state in any body system that, in the opinion of the investigator, could have affected the safety of the individual or interpretation of endpoint measures - History of ocular pathology or intraocular surgery that, in the opinion of the investigator, could have affected the safety of the individual or interpretation of endpoint measures Contraindications for Vuity eye drops - Known allergy or sensitivity to pilocarpine, other components in Vuity eye drops, or other cholinergic agonist medications - Narrow iridocorneal angles that are at risk of angle-closure and physiological anisocoria of >1 mm between pupils, as these conditions could affect the safety of the individual or interpretation of endpoint measures Prior/Concomitant therapy - Use of any topical prescription or over-the-counter ophthalmic medications that, in the opinion of the investigator, could have a substantial effect on visual function and affect interpretation of endpoint measures - Use of systemic medications with potential ocular side effects, including topiramate, hydroxychloroquine, ethambutol, phosphodiesterase 5 inhibitors (sildenafil, vardenafil, tadalafil), or tamoxifen, that could have a substantial effect on visual function and affect interpretation of endpoint measures - Use of systemic or intranasal anticholinergics and alpha-adrenergic receptor agonists with potential pupillary or accommodative effects, including oxymetazoline, tetrahydrozoline, phenylephrine, naphazoline, atropine, pilocarpine, beta-blockers, or antihistamines, that could have a substantial effect on visual function and affect interpretation of endpoint measures - Use of systemic maprotiline, tricyclic antidepressants, or monoamine oxidase inhibitors, that could have a substantial effect on visual function and affect interpretation of endpoint measures Diagnostic assessments - Astigmatic refractive error based on non-cycloplegic subjective refraction, defined as a magnitude of astigmatism of 1.00 Dioptres or higher. - Monocular unaided distance visual acuities poorer than 0.20 logMAR (Snellen 6/9.5) in both eyes, as this may be indicative of significant ametropia that may affect the interpretation of endpoint measures - Monocular best-corrected distance visual acuities poorer than 0.00 logMAR (Snellen 6/6) in both eyes, as this may be indicative of an underlying ocular condition or abnormality that may affect the safety of the individual or interpretation of endpoint measures Other - Females who are not pregnant or breastfeeding, and are not considering becoming pregnant or donating eggs during the study or for ~30 days after the last dose of study intervention, as safety of Vuity eye drops has not been established for use in pregnancy and lactation.
Outcome results
None listed