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Phentolamine Mesylate Treatment of Severe Night-Vision Complaints

ASCRS 2011, San DiegoASCRS 2011, San Diego

Marguerite McDonald, MD, FACSMarguerite McDonald, MD, FACSClinical Professor of OphthalmologyClinical Professor of Ophthalmology

NYU Langone Medical CenterNYU Langone Medical CenterNew York, New YorkNew York, New York

Adjunct Clinical Professor of OphthalmologyAdjunct Clinical Professor of OphthalmologyTulane University Health Sciences CenterTulane University Health Sciences Center

New Orleans, LouisianaNew Orleans, Louisiana

Ophthalmic Consultants of Long IslandOphthalmic Consultants of Long IslandLynbrook, New YorkLynbrook, New York

Relevant disclosures: The author is a consultant and received grant support from Ocularis PharmaRelevant disclosures: The author is a consultant and received grant support from Ocularis Pharma

2Pupil Management Therapies Can Help our Pupil Management Therapies Can Help our Unhappy Patients with Severe Night Vision Unhappy Patients with Severe Night Vision

ComplaintsComplaints• Post-multifocal IOL patients with Yags;Post-multifocal IOL patients with Yags;

• LASIK patients who need a topo-guided LASIK patients who need a topo-guided enhancement;enhancement;

• Corneal ectasia patients (post-LASIK or Corneal ectasia patients (post-LASIK or keratoconus);keratoconus);

• Post-RK patients;Post-RK patients;

• Post-PKP, DSAEK, DMEK , or DMAEK Post-PKP, DSAEK, DMEK , or DMAEK patients;patients;

• Post-corneal infection, now with a central or Post-corneal infection, now with a central or paracentral scar (glare, distortion, paracentral scar (glare, distortion, ↓ ↓ VA, etc)VA, etc)

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BackgroundBackground• Night vision problemsNight vision problems—including glare, halos, and —including glare, halos, and

starbursts—can represent a serious impairment to starbursts—can represent a serious impairment to affected individuals and are often associated with affected individuals and are often associated with reduced contrast sensitivity.reduced contrast sensitivity.

• Approaches to improving night vision have included Approaches to improving night vision have included topical treatment with the topical treatment with the miotic agents pilocarpine and miotic agents pilocarpine and brimonidinebrimonidine. Pilocarpine is a muscarinic agonist and . Pilocarpine is a muscarinic agonist and brimonidine is an αbrimonidine is an α22-adrenergic antagonist. Both have -adrenergic antagonist. Both have the effect of reducing pupil size and preventing light the effect of reducing pupil size and preventing light traveling through aberrated areas of the peripheral traveling through aberrated areas of the peripheral cornea to reach the retina. Eliminating aberrated light cornea to reach the retina. Eliminating aberrated light has the potential to enhance image quality and reduce has the potential to enhance image quality and reduce glare, halos, and starbursts caused by peripheral glare, halos, and starbursts caused by peripheral aberrations. aberrations.

1. Chalita MR, Krueger RR. Ophthalmol Clin N Am. 2004; 17: 135-142.1. Chalita MR, Krueger RR. Ophthalmol Clin N Am. 2004; 17: 135-142...

3. Robin AL. Trans Am Ophthalmol Soc. 1996; 94: 89-101.3. Robin AL. Trans Am Ophthalmol Soc. 1996; 94: 89-101.4. Brown SM, et al. Am J Ophthalmol. 2004; 138: 149-151.4. Brown SM, et al. Am J Ophthalmol. 2004; 138: 149-151.

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BackgroundBackground• Side effects Side effects associated with available miotic associated with available miotic

drops have limited their widespread clinical use drops have limited their widespread clinical use as a means of reducing night vision symptoms. as a means of reducing night vision symptoms. Pilocarpine causes a myopic shift in patients’ Pilocarpine causes a myopic shift in patients’ vision and frequently causes headaches, while vision and frequently causes headaches, while repeated use of brimonidine can lead to repeated use of brimonidine can lead to tachyphylaxis and rebound mydriasis*. tachyphylaxis and rebound mydriasis*.

• Phentolamine mesylate (PM) is an Phentolamine mesylate (PM) is an αα11-adrenergic -adrenergic antagonist antagonist that has also been shown to produce that has also been shown to produce pupillary miosis and may offer pupillary miosis and may offer a safer and more a safer and more effective topical alternative effective topical alternative to treat night vision to treat night vision problems. problems.

1. Chalita MR, Krueger RR. Ophthalmol Clin N Am. 2004; 17: 135-142.1. Chalita MR, Krueger RR. Ophthalmol Clin N Am. 2004; 17: 135-142.22*Brown et al. Arch Ophathalmol. 1976; 94: 1716-1719.*Brown et al. Arch Ophathalmol. 1976; 94: 1716-1719.

3. Robin AL. Trans Am Ophthalmol Soc. 1996; 94: 89-101.3. Robin AL. Trans Am Ophthalmol Soc. 1996; 94: 89-101.4. Brown SM, et al. Am J Ophthalmol. 2004; 138: 149-151.4. Brown SM, et al. Am J Ophthalmol. 2004; 138: 149-151.

5Pupil Management Therapies Can Pupil Management Therapies Can Help our Unhappy PatientsHelp our Unhappy Patients

• Pearl: patients will accept pharmacologic Pearl: patients will accept pharmacologic manipulation of their pupil size if they think it is manipulation of their pupil size if they think it is temporarytemporary

– Reassure patients that “Father Time” will make Reassure patients that “Father Time” will make their pupils smaller (as well as long term use of a their pupils smaller (as well as long term use of a topical miotic) topical miotic)

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1% Phentolamine Formulations BID in RabbitsDifference in Pupil Size: Control vs Active

2 Hours after Second Daily Dose

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Days

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* p<< 0.05 that Day 9 pupil size delta is different from Day 1 pupil size delta.

* * Formulations

Rabbit Study: 4 rabbits, i.e., 8 eyes, in each groupRabbit Study: 4 rabbits, i.e., 8 eyes, in each group

*P ˂˂ 0.05: Day 9 pupil size ▲ is different from Day 0 pupil size ▲, and Days 1 & 9 are statistically the same*P ˂˂ 0.05: Day 9 pupil size ▲ is different from Day 0 pupil size ▲, and Days 1 & 9 are statistically the same

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Human study: Purpose & Inclusion CriteriaHuman study: Purpose & Inclusion Criteria• PurposePurpose

– To determine if reducing pupil size with a single To determine if reducing pupil size with a single topical dose of PM improves mesopic visual topical dose of PM improves mesopic visual function as measured by visual acuity, contrast function as measured by visual acuity, contrast sensitivity, and wavefront aberrometry.sensitivity, and wavefront aberrometry.

• Inclusion criteriaInclusion criteria– ≥ ≥ 18 years of age18 years of age– good general healthgood general health– reports of severe night vision problemsreports of severe night vision problems

– score of at least 2 lines or better improvement on score of at least 2 lines or better improvement on mesopic low contrast visual acuity testing mesopic low contrast visual acuity testing (Precision Vision) during contralateral illumination (Precision Vision) during contralateral illumination by flashlightby flashlight..

8Exclusion CriteriaExclusion Criteria• Patients with:Patients with:

– contact lens wearcontact lens wear

– untreated cataractsuntreated cataracts

– refractive surgery (LASIK or PRK) or IOL insertion < refractive surgery (LASIK or PRK) or IOL insertion < 5 weeks5 weeks

– low blood pressure or heart rate abnormalitieslow blood pressure or heart rate abnormalities

– investigational drug use within past 30 daysinvestigational drug use within past 30 days

– use of pharmacologic eye drops within past 7 daysuse of pharmacologic eye drops within past 7 days

– use of systemic a-adrenergic antagonists, or use of systemic a-adrenergic antagonists, or hypersensitivity to adrenergic antagonistshypersensitivity to adrenergic antagonists

– pregnancy and lactationpregnancy and lactation

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Treatment and MeasuresTreatment and Measures• TreatmentsTreatments

– Active (N = 16): 1 drop per eye 1% PM in Tears Naturale II Active (N = 16): 1 drop per eye 1% PM in Tears Naturale II (Alcon)(Alcon)

– Placebo (N = 8) 1 drop per eye of Tears Naturale II (Alcon)Placebo (N = 8) 1 drop per eye of Tears Naturale II (Alcon)

• Measures (baseline and 2-3 hours post treatment)Measures (baseline and 2-3 hours post treatment)

– heart rate, blood pressure, pupil diametersheart rate, blood pressure, pupil diameters

– mesopic and photopic distance high-contrast visual acuity mesopic and photopic distance high-contrast visual acuity (Optec 6500)(Optec 6500)

– mesopic and photopic low-contrast visual acuity (Precision mesopic and photopic low-contrast visual acuity (Precision Vision with 5% translucent 5% low contrast chart)Vision with 5% translucent 5% low contrast chart)

– mesopic contrast sensitivity at spatial frequencies from 1.5 to 18 mesopic contrast sensitivity at spatial frequencies from 1.5 to 18 cycles (Optec 6500, “far” distance and “night” settings)cycles (Optec 6500, “far” distance and “night” settings)

– wavefront aberrometry (Wavescan, AMO)wavefront aberrometry (Wavescan, AMO)

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Treatment and MeasuresTreatment and Measures

• Post-Treatment Safety MeasuresPost-Treatment Safety Measures

– pupil roundness and reactivity pupil roundness and reactivity

– direct ophthalmoscopic exam on direct ophthalmoscopic exam on dilated pupilsdilated pupils

– grading of eye rednessgrading of eye redness

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Study PopulationStudy Population

12Results: Pupil diameter, wavefront, Results: Pupil diameter, wavefront, visual acuity, slit lampvisual acuity, slit lamp

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Results: contrast sensitivityResults: contrast sensitivity

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ConclusionsConclusions

• Phentolamine mesylate (PM) was safe and Phentolamine mesylate (PM) was safe and well-tolerated, and did not increase either well-tolerated, and did not increase either heart rate or blood pressureheart rate or blood pressure

• PM significantly decreased mean pupil size, PM significantly decreased mean pupil size, decreased mean RMS error, and improved decreased mean RMS error, and improved visual acuity in a significant number of visual acuity in a significant number of subjectssubjects

• PM was associated with a significant PM was associated with a significant increase in eye redness as assessed by slit increase in eye redness as assessed by slit lamp examinationlamp examination

• PM significantly improved contrast sensitivity PM significantly improved contrast sensitivity in both the presence and absence of glare in both the presence and absence of glare

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DiscussionDiscussion• Phentolamine mesylate (PM) Phentolamine mesylate (PM) has the potential to has the potential to

improve functional vision in a large number of improve functional vision in a large number of patients with aberrated and/or scarred corneas, patients with aberrated and/or scarred corneas, including patients with night myopia, multifocal including patients with night myopia, multifocal IOLs, early PRK or LASIK, as well as several IOLs, early PRK or LASIK, as well as several other conditions such as keratoconus, post-LASIK other conditions such as keratoconus, post-LASIK ectasia, corneal trauma and corneal ulcers. Even ectasia, corneal trauma and corneal ulcers. Even some types of early cataract patients may find PM some types of early cataract patients may find PM useful. useful.

• Mild to moderate hyperemia, a pharmacologic Mild to moderate hyperemia, a pharmacologic effect of PM, was seen in some patients. effect of PM, was seen in some patients. This This effect, although generally regarded as cosmetic, effect, although generally regarded as cosmetic, may concern some patients. One time use of over may concern some patients. One time use of over the counter vasoconstrictors has been shown to the counter vasoconstrictors has been shown to minimize this effect (unpublished data) after minimize this effect (unpublished data) after dosing with PM.dosing with PM.

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DiscussionDiscussion

• PM can be made up by a compounding PM can be made up by a compounding pharmacist (such as Chuck Leiter in LA)pharmacist (such as Chuck Leiter in LA)

• Hopefully will be available commercially Hopefully will be available commercially soonsoon

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In Summary:In Summary:Pupil Management Therapies Pupil Management Therapies

Can Help our Unhappy Patients Can Help our Unhappy Patients with Suboptimal Optics and with Suboptimal Optics and

Severe Night Vision ComplaintsSevere Night Vision Complaints

• Pharmacological Pharmacological miotic agents such as miotic agents such as phenolamine mesylate can give long phenolamine mesylate can give long lasting improvement in the quantity and lasting improvement in the quantity and quality of vision:quality of vision: ↑ VA, ↑ VA, ↑ ↑ CS, and CS, and ↓ ↓ HOAs;HOAs;

• There are There are viable non-surgical options viable non-surgical options for for our unhappy and/or demanding patientsour unhappy and/or demanding patients