PCON Reports

Drug-eluting contacts years away from market, researchers say

Drug-eluting contact lenses have been discussed as a potential treatment modality for decades but have yet to reach patients. To those researching and developing this novel drug delivery method, the lenses continue to represent a possibility of more efficient treatment for a multitude of ocular issues.

Alex Hui, OD, a PhD candidate at the Centre for Contact Lens Research, University of Waterloo, told Primary Care Optometry News that nearly every type of ocular drug has been evaluated for contact lens delivery.

“In addition to studies of antibiotics and glaucoma, drugs for dry eye or ocular surface disease (cyclosporine A), anti-inflammatory drugs (dexamethasone, prednisolone), nonsteroidal anti-inflammatory drugs (ketorolac) and anti-allergy drugs (ketotifen) have all been investigated,” he said.

Establishing a need

While the current gold standard for ocular drug delivery – topical eye drops – has been well adopted by ophthalmic practitioners, it also suffers from critical shortcomings that can limit its therapeutic efficacy. Utilization of contact lenses as a delivery method could fill a need that currently exists in treating ocular disease with topical pharmaceuticals.

“At present, topical eye drops remain the most common method for treating ocular disease, accounting for 90% of ophthalmic formulations, and they are readily accepted by patients due to their convenience and cost effectiveness,” Phan and colleagues wrote in a Clinical & Experimental Pharmacology report. “However, the ocular anatomy presents several barriers that prevent the effective and efficient delivery of medication from eye drops, including continuous tear dilution, dispersion and drainage during blinking and tear flow, nonspecific absorption and variable drug penetration. This results in only 1% to 7% of the medication within an eye drop reaching the target tissue and exerting a therapeutic effect.”

Lyndon Jones, BSc, PhD, FCOptom, DipCLP, DipOrth, FAAO, FIACLE, professor at the University of Waterloo and director of the Centre for Contact Lens Research, echoed this sentiment and lauded the use of contact lenses as a potentially superior delivery system.

“Data shows that less than 5% of the active drug in an eye drop actually reaches its target, due to poor administration techniques, tear clearance and poor adsorption,” he told PCON. “Contact lenses will be able to deliver therapeutic agents from periods ranging from days to several weeks, and the delivery to the target tissue will be much more effective.”

Improving efficacy

“With a contact lens, the contacts are placed right on the cornea, so the drug in the contact lens has to go to the cornea because it has nowhere else to go,” Anuj Chauhan, PhD, professor and researcher at the University of Florida, said in an interview. “There’s a significant increase in bioavailability when you deliver drugs by contact lenses.”

Phan and colleagues noted in their study that using contact lenses could translate to an efficiency 35 times greater than that of conventional eye drops.

“Over 50% of the drugs released from a contact lens can diffuse into the cornea,” they reported. “This increase in efficiency permits substantially reduced concentrations to be used, decreasing the potential for side effects, as less drug is absorbed systemically.”

Many researchers such as Chauhan, Daniel S. Kohane, MD, PhD, professor at Harvard Medical School and director of the Laboratory for Biomaterials Drug Delivery at Boston’s Children Hospital, and Joseph B. Ciolino, MD, assistant professor of ophthalmology at Harvard Medical School and a clinician scientist at Massachusetts Eye and Ear, have focused on treating glaucoma with drug-eluting contacts.

Hui and colleagues are studying molecular imprinting to extend drug release from contact lenses. These lenses are embedded with ciprofloxacin, causing a yellow tinge.

Hui and colleagues are studying molecular imprinting to extend drug release from contact
lenses. These lenses are embedded with ciprofloxacin, causing a yellow tinge.

Image: Muntz A

“We looked at the clinical need, and glaucoma has a large patient population that suffers from a potentially blinding condition with a notoriously poor adherence rate,” Ciolino told PCON. “We believe that there are certainly glaucoma patients who would benefit from a drug-releasing contact lens.”

A 2009 Ophthalmology study designed to measure compliance rates in glaucoma patients recorded that many patients were not using their medication as prescribed, providing quantitative support for Ciolino’s claim.

“Nearly 45% of patients using an electronic monitoring device who knew they were being monitored and were provided free medication used their drops less than 75% of the time,” Okeke and colleagues reported. “Patients reported far higher medication use than their actual behavior. The ability of the physician to identify which persons are poorly adherent from their self-report or from other subjective clues is poor.”

Hui explained that combining a patient’s medication with their corrective lenses may address the issue of adherence.

“It is well established that patient compliance with medications is low, even with severe diseases where blindness or death may be a real consequence of treatment nonadherence,” he said. “The one advantage to a contact lens system in this context is that they can also concurrently correct for refractive error, which generally provides immediate benefits for usage of the device.

Alex Hui, OD

Alex Hui

“The thinking is that by coupling a behavior that the patient can readily ignore (taking their medication/using their eye drops) with correction of a condition that provides immediate benefit (correction of refractive error with the contact lens),” Hui said, “compliance with the treatment regimen can be improved. Whether this would be shown when these lenses are actually used is unknown.”

Challenges remain

Although the researchers and clinicians interviewed for this article believe that contact lenses as a form of drug delivery may revolutionize treatment, they also acknowledged that there are still hurdles to climb before the devices reach the market.

“Drug delivery itself is a fairly young field and it hasn’t been applied in these various contexts that long, so knowing exactly what to shoot for is sometimes a bit of a challenge,” Kohane acknowledged.

“Researchers are facing many challenges in developing drug-eluting contact lenses,” Jones said. “These include issues relating to developing materials that can be appropriately loaded with a certain drug, appropriate control so the drug is delivered at a therapeutic concentration for a suitable period of time, manufacturing issues relating to sterilization and packing of the lens and drug combination so it is active upon opening, developing methods to ensure that the drug has not eluted into the packing solution, shelf-life concerns, regulatory issues and many others.”

Ciolino noted in an interview that custom tuning of the drug delivery profile from contact lenses can now be achieved to ensure sustained therapeutic efficacy.

“The historical challenge with contact lens drug delivery has been the ability to control the release of the medication from the contact lens,” he said. “That’s a challenge that we have, for the most part, overcome, but it is still something we continue to optimize.”

In the 2014 Biomaterials study that he referred to, Ciolino, Kohane and colleagues reported success in delivering latanoprost via contact lenses for a month in rabbits.

“We have developed a latanoprost-eluting contact lens that can deliver a therapeutic amount of drug into the eye for at least 1 month,” the researchers said in the study. “Eluted latanoprost did not appear to be altered by the production and release processes. The contact lens appeared safe in both cell culture and animal studies. This contact lens design may offer an alternative to the current treatment of glaucoma and may serve as an ocular drug delivery platform capable of treating other eye diseases.”

Another challenge that researchers will eventually face is receiving approval from the U.S. Food and Drug Administration.

Kohane explained that the process has not yet been considered thoroughly.

Hui also acknowledged that many factors could affect the approval process.

“The Food and Drug Administration approval process will depend on the nature of the drug and material being used,” he said. “A contact lens that is already on the market that is modified in some way, used to deliver a drug that is already FDA-approved for use in the eye would conceivably have an easier regulatory approval process than one that uses a brand new type of material that has never been used in humans. The designation as to whether the combination contact lens-drug delivery system should be classified as a drug or a treatment device will also complicate regulatory approval.”

“Another major challenge is that we need support from big contact lens companies who are willing to take it all the way through the FDA,” Chauhan said. “It’s very expensive to go through the FDA, and we need to target a disease that has a big enough market so that big contact lens companies will be interested.”

Patient, practitioner approval

Lyndon Jones, BSc, PhD, FCOptom, DipCLP, DipOrth, FAAO, FIACLE

Lyndon Jones

Researchers also admitted that FDA approval was not the only acceptance they would need to launch a successful product.

“There will be issues with both practitioner and patient acceptance,” Jones said. “Patients may not want to wear such devices and struggle to insert and remove them. Practitioners will need convincing that they are better than the current option of drops, and regulatory issues may limit the number of lenses fitted, and by whom.”

In a 2004 Eye & Contact Lens study, Karlgard and colleagues sent surveys to 2,000 ophthalmic practitioners in the U.S. and Canada.

Of those that responded, 93% indicated that they would be interested in a contact lens that was capable of delivering a topical pharmaceutical drug.

Chauhan reported that he personally encounters clinicians who are similarly intrigued by this system and interested in using it in their own practices.

“Practitioners are the ones who are really asking for it,” he said. “Every conference that I go to and give a talk, every doctor gets up and says, ‘How do we get this to patients?’

“There will be certain issues that need to be addressed,” Chauhan admitted. “How are these people going to get the lenses? Normally, contact lenses are given by the practitioner, but the practitioner cannot actually give you the drugs because the pharmacy gives you the drugs. Will these contact lens-eluting drugs be sold by the practitioners, in which case we will need some changes in policy, or will they be sold by the pharmacy, with the practitioner simply writing the prescriptions? There are some issues to work on, but, in general, practitioners have very much bought into the idea.”

Getting the device into patients

Due to the time and resources required to optimize this delivery system, demonstrate its efficacy and successfully navigate the FDA approval process, it will still be years before drug-eluting contact lenses are on the market, our sources say.

“We are hoping to be going into humans within the year in clinical testing,” Kohane told PCON. “How long it will take to get onto the market thereafter we don’t know at this point.”

Nonetheless, many of the researchers speculated that it could be in the range of 5 to 10 years.

“I was asked this question about 5 years back and I answered about 5 to 10 years,” Chauhan said. “It’s very difficult to anticipate. If I have to give a number, I would say hopefully in under 5 years you will see some kind of product in patients.” – by Chelsea Frajerman

References:
Ciolino JB, et al. Biomaterials. 2014;35(1):432-429.
Karlgard CC, et al. Eye Contact Lens. 2004;30(1):25-30.
Okeke CO, et al. Ophthalmology. 2009;116(2):191-199.
Phan CM, et al. Clin Exp Pharmacol. 2014;3:145.
For more information:
Anuj Chauhan, PhD, is a professor and researcher at the University of Florida. He can be reached at (352) 392-2592; chauhan@che.ufl.edu.
Joseph B. Ciolino, MD, is an assistant professor of ophthalmology at Harvard Medical School and a clinician scientist. He can be reached at mary_leach@MEEI.Harvard.edu.
Alex Hui, OD, is a PhD candidate at the Centre for Contact Lens Research, University of Waterloo. He can be reached at alex.hui@uwaterloo.ca.
Lyndon Jones, BSc, PhD, FCOptom, DipCLP, DipOrth, FAAO, FIACLE, is a professor at the University of Waterloo and director of the Centre for Contact Lens Research. He can be reached at lwjones@uwaterloo.ca.
Daniel S. Kohane, MD, PhD, is a professor at Harvard Medical School and director of the Laboratory for Biomaterials Drug Delivery at Boston’s Children Hospital. He can be reached at daniel.kohane@childrens.harvard.edu.
Disclosures: Chauhan has several issued and pending patents covering methods of designing lenses for extended drug delivery. Ciolino and Kohane are listed as authors on a patent. Hui has been a consultant and speaker for Alcon, Bausch + Lomb and Innova. Jones is a consultant for and has received honoraria from Alcon, CIBA Vision and Johnson & Johnson Vision Care and has received honoraria from CooperVision. His research group has received support from AMO, Advanced Vision Research, Alcon, AgliPharma, Allergan, Bausch + Lomb, CIBA, CooperVision, Essilor, J&J Vision Care, Oculus, TearScience and Visioneering Technologies.

Drug-eluting contact lenses have been discussed as a potential treatment modality for decades but have yet to reach patients. To those researching and developing this novel drug delivery method, the lenses continue to represent a possibility of more efficient treatment for a multitude of ocular issues.

Alex Hui, OD, a PhD candidate at the Centre for Contact Lens Research, University of Waterloo, told Primary Care Optometry News that nearly every type of ocular drug has been evaluated for contact lens delivery.

“In addition to studies of antibiotics and glaucoma, drugs for dry eye or ocular surface disease (cyclosporine A), anti-inflammatory drugs (dexamethasone, prednisolone), nonsteroidal anti-inflammatory drugs (ketorolac) and anti-allergy drugs (ketotifen) have all been investigated,” he said.

Establishing a need

While the current gold standard for ocular drug delivery – topical eye drops – has been well adopted by ophthalmic practitioners, it also suffers from critical shortcomings that can limit its therapeutic efficacy. Utilization of contact lenses as a delivery method could fill a need that currently exists in treating ocular disease with topical pharmaceuticals.

“At present, topical eye drops remain the most common method for treating ocular disease, accounting for 90% of ophthalmic formulations, and they are readily accepted by patients due to their convenience and cost effectiveness,” Phan and colleagues wrote in a Clinical & Experimental Pharmacology report. “However, the ocular anatomy presents several barriers that prevent the effective and efficient delivery of medication from eye drops, including continuous tear dilution, dispersion and drainage during blinking and tear flow, nonspecific absorption and variable drug penetration. This results in only 1% to 7% of the medication within an eye drop reaching the target tissue and exerting a therapeutic effect.”

Lyndon Jones, BSc, PhD, FCOptom, DipCLP, DipOrth, FAAO, FIACLE, professor at the University of Waterloo and director of the Centre for Contact Lens Research, echoed this sentiment and lauded the use of contact lenses as a potentially superior delivery system.

“Data shows that less than 5% of the active drug in an eye drop actually reaches its target, due to poor administration techniques, tear clearance and poor adsorption,” he told PCON. “Contact lenses will be able to deliver therapeutic agents from periods ranging from days to several weeks, and the delivery to the target tissue will be much more effective.”

Improving efficacy

“With a contact lens, the contacts are placed right on the cornea, so the drug in the contact lens has to go to the cornea because it has nowhere else to go,” Anuj Chauhan, PhD, professor and researcher at the University of Florida, said in an interview. “There’s a significant increase in bioavailability when you deliver drugs by contact lenses.”

Phan and colleagues noted in their study that using contact lenses could translate to an efficiency 35 times greater than that of conventional eye drops.

“Over 50% of the drugs released from a contact lens can diffuse into the cornea,” they reported. “This increase in efficiency permits substantially reduced concentrations to be used, decreasing the potential for side effects, as less drug is absorbed systemically.”

Many researchers such as Chauhan, Daniel S. Kohane, MD, PhD, professor at Harvard Medical School and director of the Laboratory for Biomaterials Drug Delivery at Boston’s Children Hospital, and Joseph B. Ciolino, MD, assistant professor of ophthalmology at Harvard Medical School and a clinician scientist at Massachusetts Eye and Ear, have focused on treating glaucoma with drug-eluting contacts.

Hui and colleagues are studying molecular imprinting to extend drug release from contact lenses. These lenses are embedded with ciprofloxacin, causing a yellow tinge.

Hui and colleagues are studying molecular imprinting to extend drug release from contact
lenses. These lenses are embedded with ciprofloxacin, causing a yellow tinge.

Image: Muntz A

PAGE BREAK

“We looked at the clinical need, and glaucoma has a large patient population that suffers from a potentially blinding condition with a notoriously poor adherence rate,” Ciolino told PCON. “We believe that there are certainly glaucoma patients who would benefit from a drug-releasing contact lens.”

A 2009 Ophthalmology study designed to measure compliance rates in glaucoma patients recorded that many patients were not using their medication as prescribed, providing quantitative support for Ciolino’s claim.

“Nearly 45% of patients using an electronic monitoring device who knew they were being monitored and were provided free medication used their drops less than 75% of the time,” Okeke and colleagues reported. “Patients reported far higher medication use than their actual behavior. The ability of the physician to identify which persons are poorly adherent from their self-report or from other subjective clues is poor.”

Hui explained that combining a patient’s medication with their corrective lenses may address the issue of adherence.

“It is well established that patient compliance with medications is low, even with severe diseases where blindness or death may be a real consequence of treatment nonadherence,” he said. “The one advantage to a contact lens system in this context is that they can also concurrently correct for refractive error, which generally provides immediate benefits for usage of the device.

Alex Hui, OD

Alex Hui

“The thinking is that by coupling a behavior that the patient can readily ignore (taking their medication/using their eye drops) with correction of a condition that provides immediate benefit (correction of refractive error with the contact lens),” Hui said, “compliance with the treatment regimen can be improved. Whether this would be shown when these lenses are actually used is unknown.”

Challenges remain

Although the researchers and clinicians interviewed for this article believe that contact lenses as a form of drug delivery may revolutionize treatment, they also acknowledged that there are still hurdles to climb before the devices reach the market.

“Drug delivery itself is a fairly young field and it hasn’t been applied in these various contexts that long, so knowing exactly what to shoot for is sometimes a bit of a challenge,” Kohane acknowledged.

“Researchers are facing many challenges in developing drug-eluting contact lenses,” Jones said. “These include issues relating to developing materials that can be appropriately loaded with a certain drug, appropriate control so the drug is delivered at a therapeutic concentration for a suitable period of time, manufacturing issues relating to sterilization and packing of the lens and drug combination so it is active upon opening, developing methods to ensure that the drug has not eluted into the packing solution, shelf-life concerns, regulatory issues and many others.”

Ciolino noted in an interview that custom tuning of the drug delivery profile from contact lenses can now be achieved to ensure sustained therapeutic efficacy.

“The historical challenge with contact lens drug delivery has been the ability to control the release of the medication from the contact lens,” he said. “That’s a challenge that we have, for the most part, overcome, but it is still something we continue to optimize.”

In the 2014 Biomaterials study that he referred to, Ciolino, Kohane and colleagues reported success in delivering latanoprost via contact lenses for a month in rabbits.

“We have developed a latanoprost-eluting contact lens that can deliver a therapeutic amount of drug into the eye for at least 1 month,” the researchers said in the study. “Eluted latanoprost did not appear to be altered by the production and release processes. The contact lens appeared safe in both cell culture and animal studies. This contact lens design may offer an alternative to the current treatment of glaucoma and may serve as an ocular drug delivery platform capable of treating other eye diseases.”

PAGE BREAK

Another challenge that researchers will eventually face is receiving approval from the U.S. Food and Drug Administration.

Kohane explained that the process has not yet been considered thoroughly.

Hui also acknowledged that many factors could affect the approval process.

“The Food and Drug Administration approval process will depend on the nature of the drug and material being used,” he said. “A contact lens that is already on the market that is modified in some way, used to deliver a drug that is already FDA-approved for use in the eye would conceivably have an easier regulatory approval process than one that uses a brand new type of material that has never been used in humans. The designation as to whether the combination contact lens-drug delivery system should be classified as a drug or a treatment device will also complicate regulatory approval.”

“Another major challenge is that we need support from big contact lens companies who are willing to take it all the way through the FDA,” Chauhan said. “It’s very expensive to go through the FDA, and we need to target a disease that has a big enough market so that big contact lens companies will be interested.”

Patient, practitioner approval

Lyndon Jones, BSc, PhD, FCOptom, DipCLP, DipOrth, FAAO, FIACLE

Lyndon Jones

Researchers also admitted that FDA approval was not the only acceptance they would need to launch a successful product.

“There will be issues with both practitioner and patient acceptance,” Jones said. “Patients may not want to wear such devices and struggle to insert and remove them. Practitioners will need convincing that they are better than the current option of drops, and regulatory issues may limit the number of lenses fitted, and by whom.”

In a 2004 Eye & Contact Lens study, Karlgard and colleagues sent surveys to 2,000 ophthalmic practitioners in the U.S. and Canada.

Of those that responded, 93% indicated that they would be interested in a contact lens that was capable of delivering a topical pharmaceutical drug.

Chauhan reported that he personally encounters clinicians who are similarly intrigued by this system and interested in using it in their own practices.

“Practitioners are the ones who are really asking for it,” he said. “Every conference that I go to and give a talk, every doctor gets up and says, ‘How do we get this to patients?’

“There will be certain issues that need to be addressed,” Chauhan admitted. “How are these people going to get the lenses? Normally, contact lenses are given by the practitioner, but the practitioner cannot actually give you the drugs because the pharmacy gives you the drugs. Will these contact lens-eluting drugs be sold by the practitioners, in which case we will need some changes in policy, or will they be sold by the pharmacy, with the practitioner simply writing the prescriptions? There are some issues to work on, but, in general, practitioners have very much bought into the idea.”

Getting the device into patients

Due to the time and resources required to optimize this delivery system, demonstrate its efficacy and successfully navigate the FDA approval process, it will still be years before drug-eluting contact lenses are on the market, our sources say.

“We are hoping to be going into humans within the year in clinical testing,” Kohane told PCON. “How long it will take to get onto the market thereafter we don’t know at this point.”

Nonetheless, many of the researchers speculated that it could be in the range of 5 to 10 years.

“I was asked this question about 5 years back and I answered about 5 to 10 years,” Chauhan said. “It’s very difficult to anticipate. If I have to give a number, I would say hopefully in under 5 years you will see some kind of product in patients.” – by Chelsea Frajerman

References:
Ciolino JB, et al. Biomaterials. 2014;35(1):432-429.
Karlgard CC, et al. Eye Contact Lens. 2004;30(1):25-30.
Okeke CO, et al. Ophthalmology. 2009;116(2):191-199.
Phan CM, et al. Clin Exp Pharmacol. 2014;3:145.
For more information:
Anuj Chauhan, PhD, is a professor and researcher at the University of Florida. He can be reached at (352) 392-2592; chauhan@che.ufl.edu.
Joseph B. Ciolino, MD, is an assistant professor of ophthalmology at Harvard Medical School and a clinician scientist. He can be reached at mary_leach@MEEI.Harvard.edu.
Alex Hui, OD, is a PhD candidate at the Centre for Contact Lens Research, University of Waterloo. He can be reached at alex.hui@uwaterloo.ca.
Lyndon Jones, BSc, PhD, FCOptom, DipCLP, DipOrth, FAAO, FIACLE, is a professor at the University of Waterloo and director of the Centre for Contact Lens Research. He can be reached at lwjones@uwaterloo.ca.
Daniel S. Kohane, MD, PhD, is a professor at Harvard Medical School and director of the Laboratory for Biomaterials Drug Delivery at Boston’s Children Hospital. He can be reached at daniel.kohane@childrens.harvard.edu.
Disclosures: Chauhan has several issued and pending patents covering methods of designing lenses for extended drug delivery. Ciolino and Kohane are listed as authors on a patent. Hui has been a consultant and speaker for Alcon, Bausch + Lomb and Innova. Jones is a consultant for and has received honoraria from Alcon, CIBA Vision and Johnson & Johnson Vision Care and has received honoraria from CooperVision. His research group has received support from AMO, Advanced Vision Research, Alcon, AgliPharma, Allergan, Bausch + Lomb, CIBA, CooperVision, Essilor, J&J Vision Care, Oculus, TearScience and Visioneering Technologies.