• In this original research trial, the safety and efficacy of a lipoic acid choline ester eye drop for the treatment of presbyopia was evaluated. Overall, bilateral near visual acuity was improved by –0.189 LogMAR in the study group compared with –0.089 in the placebo group (P = .021). This improvement maintained significance even after subgroup analysis that removed patients with 20/40 or better pre-trial near visual (–0.198 vs –0.099, P = .004). Drug-related adverse events were found in 22% of treated eyes, but nearly all were classified as mild or moderate, with no significant change in distance visual acuity, intraocular pressure, or clinical examination findings.
  • The lipoid acid choline ester eye drop, UNR844, shows promise as a safe and effective topical treatment for presbyopia.

This study is sure to attract attention because of the interest that recently FDA-approved Vuity (1.25% pilocarpine) has attracted in aiding near acuity in presbyopia.  The mechanism by which the topical lipoic acid (LA) choline ester eye drop used in this study improves near visual acuity in presbyopia is uncertain.  The authors speculate that because loss of accommodation is linked to loss of elasticity in the lens with age, LA as an antioxidant shown to chemically reduce lens disulfide bonds between crystalline lens proteins might restore lens elasticity and dynamic refractive power during accommodation.  However, restoring lens elasticity once lost might be a greater challenge than preserving intact ability.  In that regard, this drug has the potential to become popular as a way of keeping presbyopia at bay directly rather than through the miotic effects of pilocarpine employed by Vuity.  And if it can mitigate cataracts, then we have the closest thing to an ocular fountain of youth drug.  Of course this is all very preliminary and more studies need to be done with many more subjects over a longer period of time, and in masked fashion, but the results of this early phase placebo controlled trial are intriguing.

The purpose of this paper was to determine, “… the safety of topical lipoic acid choline ester (UNR844, 1.5%) ophthalmic solution and its efficacy in improving distance-corrected near visual acuity (DCNVA) in subjects with presbyopia.” The there were 75 subjects who were randomized 2:1 to UNR844 or placebo in this prospective, double-masked, and multicenter clinical trial. The authors state that the experimental drug, “…produced no safety concerns and was well-tolerated, with no clinically-relevant changes in best-corrected distance visual acuity, pupil size, intraocular pressure, or discontinuations due to adverse events.” They found that, “Bilateral DCNVA improved, with 53.1% UNR844 vs. 21.7% placebo subjects gaining ≥10 letters.” Clearly, the placebo effect was strong in this study. Similarly, “…82.0% of subjects completed the study with better than 20/40 (bilateral) vision when treated with UNR844, compared with 48.0% treated with placebo. The authors also report that, “Improvements in DCNVA were sustained at 5 and 7 months after UNR844 dosing ceased.” Relative to the mechanism of action, the authors state that, “Lipoic acid (LA) is an antioxidant shown to chemically reduce lens disulfide bonds.” In this way, the medication increases lens elasticity.  Significantly, in contrast to pilocarpine, it actually modifies the mechanism of presbyopia.  It is interesting to note that, “The majority of subjects were emmetropic (51 subjects; 68%), compared with 15 (20%) myopes and 9 (12%) hyperopic subjects.” It would have been interesting to know if there had been a differential effect on any specific refractive group.  Moreover, the authors state that, “No clinically meaningful differences were observed in manifest refraction, a measurement of distance vision, from baseline or last dose.” If the medication changes the lens elasticity it seems somewhat surprising that it does not impact lens shape and, therefore, refractive error. The authors discuss this point. The authors also discuss the lack of effect on pupil size. Obviously, this feature of the medication would be a major advantage over pilocarpine as the authors note.  It will be very interesting to see if the medication’s effects on disulfide bonds can help prevent the development of cataracts. If this study can be confirmed in larger studies for a longer duration, it is potential game changer.

OBJECTIVES

This study evaluated the safety of topical lipoic acid choline ester (UNR844, 1.5%) ophthalmic solution and its efficacy in improving distance-corrected near visual acuity (DCNVA) in subjects with presbyopia.

SUBJECTS AND METHODS

This was a prospective, randomized, double-masked, and multicentre clinical trial. Subjects with a diagnosis of presbyopia (n = 75) were randomized 2:1 to UNR844 or placebo. On days 1-7, all subjects were dosed unilaterally (twice a day, b.i.d.) in their non-dominant eye to ensure safety and tolerability prior to days 8-91 when dosing was changed to bilateral (b.i.d.). Clinical assessments, including DCNVA and adverse events (AEs), were recorded at each study visit. Patients who completed the study were recruited into a non-interventional follow-up study that monitored them until 7 months after their final UNR844 exposure. The primary endpoints were safety and the mean change in DCNVA from baseline in the study eye.

RESULTS

UNR844 administration (n = 50) produced no safety concerns and was well-tolerated, with no clinically-relevant changes in best-corrected distance visual acuity, pupil size, intraocular pressure, or discontinuations due to adverse events. DCNVA improved in the study eye in the UNR844 group compared to placebo during the 91 days of treatment [UNR844 vs. placebo, mean change in LogMAR (SD); -0.159 (0.120) vs. -0.079 (0.116)]. Bilateral DCNVA improved, with 53.1% UNR844 vs. 21.7% placebo subjects gaining ≥10 letters. Improvements in DCNVA were sustained at 5 and 7 months after UNR844 dosing ceased.

CONCLUSIONS

These results support further development of UNR844 ophthalmic solution for the treatment of presbyopia.

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