Lindstrom's Perspective

Potential presbyopia treatments exciting, but regulatory and adoption barriers may be an issue

Presbyopia is very common, estimated to affect 120 million Americans and just more than 2 billion people globally. After decades of being limited to spectacles and contact lenses to overcome the handicap of presbyopia, we and our patients now also have pharmacologic and surgical treatment options available or in development. In this commentary, I will share some personal thoughts on how we might evaluate these treatments in regard to efficacy, safety and patient acceptance. The opinions expressed are my own but are based on being an engaged participant in research and development in the field of optical, medical and surgical treatment of presbyopia for 35 years. I will disclose that I work widely in this field and consult for companies large and small, and that I own equity and have served as a paid consultant, a medical advisory board member and even on the board of directors of companies with the goal of treating presbyopia. I may ramble a bit, but in the end, I believe my comments will at a minimum catalyze your thinking.

Safety is easier. We all want a minimally invasive, reversible treatment with no side effects or vision-threatening complications. I have found the early-stage presbyope, especially the emmetropic presbyope who still has excellent distance and intermediate vision without correction, is very risk averse. For this reason, most opt for glasses — usually for the emmetropic presbyope, just readers. Some will choose intermittent contact lens wear utilizing either monovision or multifocal contact lenses. Now that we have daily disposable soft contact lenses with great comfort, high safety and reasonable cost, this is a viable option. Data suggest the most popular approach with contact lenses is monovision, followed by modified monovision in which a multifocal contact lens is worn in one eye only, and in last place, bilateral multifocal contact lenses. Bilateral multifocal lenses are the least popular because of the same issues we encounter with bilateral multifocal IOLs: reduced quality of vision and unwanted night vision symptoms, primarily halos.

The coming miotic drops for the temporary improvement of near vision also appear to be very safe and, of course, reversible. Low-concentration miotics have minimal side effects and have been used safely for decades in the glaucoma patient. Of interest, small-diameter aperture optics (pinhole effect) also masks mild hyperopia, myopia and astigmatism, improving distance vision as well as near and intermediate in the mild ametrope. This will be another indication for these drops in patients with 1 D or less of hyperopia, myopia and astigmatism. Making the pupil small is, of course, an issue in mesopic and scotopic environments, but the drops can be discontinued before dark, and with neuroadaptation, many patients do extremely well with small-diameter aperture optics even at night, as shown in the AcuFocus, now CorneaGen, Kamra inlay experience and AcuFocus IC-8 studies. Small-diameter aperture optics also improve vision in the patient with significant higher-order aberrations, potentially helping many patients with prior corneal refractive surgery, corneal scars or corneal dystrophies such as keratoconus.

We also have drops in development that appear capable in preliminary studies of increasing the elasticity of the normal lens, improving accommodative amplitude. This approach would be an actual treatment of the primary cause of presbyopia and would be synergistic with all other methods of treatment, optical, surgical or with miotics. For me, it is impossible to not be excited about this opportunity, but it will not be on the market in the U.S. for at least 5 to 6 years.

The market studies I have seen suggest that both ophthalmologists and optometrists as well as patients will be attracted to drop therapy for presbyopia. In my opinion, it will be important globally. There will be many off-label uses, and we will be prescribing these drops frequently as well as treating progressive myopia with drops such as low-dose atropine. The pharmacologic treatment of refractive error is in its infancy but will be an important part of the future practice of the younger eye doctor. Follow this closely and engage early.

Now, on to surgery. I have personally lived the emmetropic presbyope’s typical journey. My manifest and cycloplegic refractions were plano at age 45. I first needed readers at 48. I used half glasses until age 60, when my mild progressing hyperopia became an issue and then switched to progressive add glasses. I tried monovision and could adapt, but glasses were easier and worked well for me. I did not like the loss of quality of vision and optical side effects of multifocal contact lenses, so I am now a progressive add spectacle wearer at age 72 with a +1.25 D distance refraction and a +2.5 add in both eyes. I read 20/15 Snellen acuity at all distances with correction. I, of course, have some developing nuclear sclerosis, but my color perception and quality of vision remain excellent. Miotic drops improve my reading vision two to three lines depending on potency, from just less than 20/70 distance corrected to 20/50 or 20/40 with good lighting. For me, this level of near vision is not good enough to be useful, so I do not benefit from miotic drops.

I find from personal experience and working with presbyopes in and out of studies that every 0.5 D of accommodative loss reduces near vision one line. The reverse is also true; every 0.5 D of add improves vision one line at near. The minimum near vision improvement that is useful in my experience is two and preferably three lines, equivalent to about 1 D to 1.5 D of plus add spectacle correction. This is what miotic drops give to most patients. So, miotic drops will be most useful for the presbyope with 1 D to 1.5 D of presbyopia. This is the patient in their late 40s to middle 50s. I find the required level of uncorrected intermediate and near vision to generate high patient satisfaction is 20/25 using Snellen notation (J2 or logMAR 0.1). This level of vision improvement is my standard for “20/happy” at distance, intermediate and near. So, any optical, medical or surgical treatment has to allow vision of 20/25 or better at all distances to generate high patient satisfaction and, secondarily, adoption and willingness to pay privately for the treatment.

In addition, the treatment cannot have significant unwanted optical side effects, such as loss of visual quality or halo and glare at night. Unfortunately, this is a high standard. To me, it explains the relatively low adoption of multifocal contacts and IOLs globally. It also helps me evaluate data sets from potential treatments and set minimal standards for counseling patients. Any drug or device that generates less than 20/25 at all three distances will disappoint many patients and result in reduced patient satisfaction.

Of course, many patients will accept wearing glasses for intermediate with a diffractive bifocal IOL that is distance and near dominant or for near in an extended depth of focus IOL that is distance and intermediate dominant, but what they and I want is 20/25 or better at all distances. A few examples. Miotic drops will be popular up to age 55 or so but not so useful for the over age 60 phakic presbyope. Trifocal and EDOF IOLs, when capable of providing 20/25 or better at all three distances, will generate growth in the presbyopia-correcting IOL marketplace. For an accommodating IOL to be highly successful, it will need to generate at least 1 D and preferably 1.5 D of accommodative amplitude. Adding the 0.5 D to 1 D of pseudoaccommodation inherent in every monofocal IOL, it should then generate our goal of 20/25 or better at all distances in most patients with normal maculas, especially with bilateral implants. On the negative side, accommodating IOLs that provide less than 1 D of accommodation, allowing only say 20/40 (J5 or logMAR 0.3) near vision, will not be winners.

I believe the same is true for invasive surgical procedures designed to treat presbyopia. They must generate at least two and preferably three lines of improvement at intermediate and near and achieve 20/25 or better for the patient operated at every distance, or they will not be widely adopted. And, for the mild to moderate presbyope to choose a surgical correction, safety will have to be very high and invasiveness and postoperative morbidity low. So, while the barriers to achieve regulatory approval of a treatment for presbyopia are high, the barriers to gain broad market adoption and commercial success may be even higher.

Disclosure: Lindstrom reports relevant financial disclosures with Bausch Health, Johnson & Johnson Vision, Novartis, AcuFocus, CorneaGen, Encore, Orasis, Lentechs, ForeSight 6, Refractec, Imprimis and Harrow Health.

Presbyopia is very common, estimated to affect 120 million Americans and just more than 2 billion people globally. After decades of being limited to spectacles and contact lenses to overcome the handicap of presbyopia, we and our patients now also have pharmacologic and surgical treatment options available or in development. In this commentary, I will share some personal thoughts on how we might evaluate these treatments in regard to efficacy, safety and patient acceptance. The opinions expressed are my own but are based on being an engaged participant in research and development in the field of optical, medical and surgical treatment of presbyopia for 35 years. I will disclose that I work widely in this field and consult for companies large and small, and that I own equity and have served as a paid consultant, a medical advisory board member and even on the board of directors of companies with the goal of treating presbyopia. I may ramble a bit, but in the end, I believe my comments will at a minimum catalyze your thinking.

Safety is easier. We all want a minimally invasive, reversible treatment with no side effects or vision-threatening complications. I have found the early-stage presbyope, especially the emmetropic presbyope who still has excellent distance and intermediate vision without correction, is very risk averse. For this reason, most opt for glasses — usually for the emmetropic presbyope, just readers. Some will choose intermittent contact lens wear utilizing either monovision or multifocal contact lenses. Now that we have daily disposable soft contact lenses with great comfort, high safety and reasonable cost, this is a viable option. Data suggest the most popular approach with contact lenses is monovision, followed by modified monovision in which a multifocal contact lens is worn in one eye only, and in last place, bilateral multifocal contact lenses. Bilateral multifocal lenses are the least popular because of the same issues we encounter with bilateral multifocal IOLs: reduced quality of vision and unwanted night vision symptoms, primarily halos.

The coming miotic drops for the temporary improvement of near vision also appear to be very safe and, of course, reversible. Low-concentration miotics have minimal side effects and have been used safely for decades in the glaucoma patient. Of interest, small-diameter aperture optics (pinhole effect) also masks mild hyperopia, myopia and astigmatism, improving distance vision as well as near and intermediate in the mild ametrope. This will be another indication for these drops in patients with 1 D or less of hyperopia, myopia and astigmatism. Making the pupil small is, of course, an issue in mesopic and scotopic environments, but the drops can be discontinued before dark, and with neuroadaptation, many patients do extremely well with small-diameter aperture optics even at night, as shown in the AcuFocus, now CorneaGen, Kamra inlay experience and AcuFocus IC-8 studies. Small-diameter aperture optics also improve vision in the patient with significant higher-order aberrations, potentially helping many patients with prior corneal refractive surgery, corneal scars or corneal dystrophies such as keratoconus.

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We also have drops in development that appear capable in preliminary studies of increasing the elasticity of the normal lens, improving accommodative amplitude. This approach would be an actual treatment of the primary cause of presbyopia and would be synergistic with all other methods of treatment, optical, surgical or with miotics. For me, it is impossible to not be excited about this opportunity, but it will not be on the market in the U.S. for at least 5 to 6 years.

The market studies I have seen suggest that both ophthalmologists and optometrists as well as patients will be attracted to drop therapy for presbyopia. In my opinion, it will be important globally. There will be many off-label uses, and we will be prescribing these drops frequently as well as treating progressive myopia with drops such as low-dose atropine. The pharmacologic treatment of refractive error is in its infancy but will be an important part of the future practice of the younger eye doctor. Follow this closely and engage early.

Now, on to surgery. I have personally lived the emmetropic presbyope’s typical journey. My manifest and cycloplegic refractions were plano at age 45. I first needed readers at 48. I used half glasses until age 60, when my mild progressing hyperopia became an issue and then switched to progressive add glasses. I tried monovision and could adapt, but glasses were easier and worked well for me. I did not like the loss of quality of vision and optical side effects of multifocal contact lenses, so I am now a progressive add spectacle wearer at age 72 with a +1.25 D distance refraction and a +2.5 add in both eyes. I read 20/15 Snellen acuity at all distances with correction. I, of course, have some developing nuclear sclerosis, but my color perception and quality of vision remain excellent. Miotic drops improve my reading vision two to three lines depending on potency, from just less than 20/70 distance corrected to 20/50 or 20/40 with good lighting. For me, this level of near vision is not good enough to be useful, so I do not benefit from miotic drops.

I find from personal experience and working with presbyopes in and out of studies that every 0.5 D of accommodative loss reduces near vision one line. The reverse is also true; every 0.5 D of add improves vision one line at near. The minimum near vision improvement that is useful in my experience is two and preferably three lines, equivalent to about 1 D to 1.5 D of plus add spectacle correction. This is what miotic drops give to most patients. So, miotic drops will be most useful for the presbyope with 1 D to 1.5 D of presbyopia. This is the patient in their late 40s to middle 50s. I find the required level of uncorrected intermediate and near vision to generate high patient satisfaction is 20/25 using Snellen notation (J2 or logMAR 0.1). This level of vision improvement is my standard for “20/happy” at distance, intermediate and near. So, any optical, medical or surgical treatment has to allow vision of 20/25 or better at all distances to generate high patient satisfaction and, secondarily, adoption and willingness to pay privately for the treatment.

PAGE BREAK

In addition, the treatment cannot have significant unwanted optical side effects, such as loss of visual quality or halo and glare at night. Unfortunately, this is a high standard. To me, it explains the relatively low adoption of multifocal contacts and IOLs globally. It also helps me evaluate data sets from potential treatments and set minimal standards for counseling patients. Any drug or device that generates less than 20/25 at all three distances will disappoint many patients and result in reduced patient satisfaction.

Of course, many patients will accept wearing glasses for intermediate with a diffractive bifocal IOL that is distance and near dominant or for near in an extended depth of focus IOL that is distance and intermediate dominant, but what they and I want is 20/25 or better at all distances. A few examples. Miotic drops will be popular up to age 55 or so but not so useful for the over age 60 phakic presbyope. Trifocal and EDOF IOLs, when capable of providing 20/25 or better at all three distances, will generate growth in the presbyopia-correcting IOL marketplace. For an accommodating IOL to be highly successful, it will need to generate at least 1 D and preferably 1.5 D of accommodative amplitude. Adding the 0.5 D to 1 D of pseudoaccommodation inherent in every monofocal IOL, it should then generate our goal of 20/25 or better at all distances in most patients with normal maculas, especially with bilateral implants. On the negative side, accommodating IOLs that provide less than 1 D of accommodation, allowing only say 20/40 (J5 or logMAR 0.3) near vision, will not be winners.

I believe the same is true for invasive surgical procedures designed to treat presbyopia. They must generate at least two and preferably three lines of improvement at intermediate and near and achieve 20/25 or better for the patient operated at every distance, or they will not be widely adopted. And, for the mild to moderate presbyope to choose a surgical correction, safety will have to be very high and invasiveness and postoperative morbidity low. So, while the barriers to achieve regulatory approval of a treatment for presbyopia are high, the barriers to gain broad market adoption and commercial success may be even higher.

Disclosure: Lindstrom reports relevant financial disclosures with Bausch Health, Johnson & Johnson Vision, Novartis, AcuFocus, CorneaGen, Encore, Orasis, Lentechs, ForeSight 6, Refractec, Imprimis and Harrow Health.