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Game Changer for Presbyopia?
Optimised pilocarpine drop shows promise for presbyopia. Cheryl Guttman Krader reports from ASCRS 2021 in Las Vegas, USA
AGN-190584, a topical optimised formulation of pilocarpine HCl 1.25%, is a safe, well-tolerated, and effective treatment for presbyopia, suggest the results of GEMINI 1, a phase 3 vehicle-controlled study.
As reported in a series of presentations at the conference, the findings showed AGN-190584 was associated with statistically significant and clinically meaningful improvements in near and intermediate vision in addition to high patient satisfaction. Moreover, it did not compromise distance vision.
“Marketing approval of AGN-190584 will be a milestone event, and its availability will be a big-time game changer for our patients,” George O Waring IV, MD said.
The GEMINI 1 study was a multicentre, double-masked trial that randomised 323 patients aged 40 to 55 years in a one-to-one ratio to AGN-190584 or vehicle administered once daily, bilaterally, for 30 days.
“Patients with severe dry eye were excluded, but those with a history of previous LASIK or PRK were encouraged to participate. Remarkably, 99% of patients in the AGN-190584 group and 96% of controls completed the study that involved marathonlength study visits,” William C Christie MD reported.
EFFICACY DATA The GEMINI 1 study met its primary endpoint. The percentage of participants with at least three lines of improvement or better in mesopic distance-corrected near visual acuity (DCNVA) at three hours post-administration on day 30 was significantly greater with AGN-190584 treatment compared to vehicle. A post-hoc analysis also showed no participants with less than a three-line improvement reported more than a five-letter loss in mesopic, corrected distance visual acuity (CDVA) on day 30, hour three. AGN-190584 also demonstrated statistical superiority to vehicle for the key secondary endpoint analysing the percentage of participants with at least three lines or better improvement in mesopic DCNVA at six hours post dosing.
Data for other efficacy endpoints showed statistically significant differences favouring AGN-190584 versus vehicle for increasing the percentage of participants achieving 20/40 or better in DCNVA. Researchers observed a significant difference in the two-line or greater gain in mesopic, high-contrast binocular DCNVA. Significant treatment benefits were also observed for improvements in measures of distance-corrected intermediate acuity (DCIVA).
PUPIL MEASUREMENTS Pupil measurement data showed the onset and duration of improvement in mesopic DCNVA corresponded with the onset and duration of change in pupil size. Change in pupil diameter mirrored improvement in DCNVA with onset at 15 minutes. Pupil diameter returned to baseline within 24 hours after the last drop.
The pupillary response to light after AGN-190584 treatment was maintained under mesopic and photopic conditions, and its response to AGN-190584 remained consistent from day 1 to day 30, David C Wirta MD reported.
“The latter finding is important for showing there was no tachyphylaxis to AGN-190584,” he said.
PATIENT-REPORTED OUTCOMES Questionnaires used to collect patient-reported outcomes included the Near Vision Presbyopia Task Questionnaire (NVPTQ) based on reading a book, newspaper, menu, and nutrition label. GEMINI 1 met the prespecified secondary endpoints evaluating mean change from baseline in mesopic NVPTQ performance and satisfaction at day 30, hour three. Additional analyses showed AGN-190584 significantly improved photopic NVPTQ performance and patient satisfaction.
Dr Wirta presented results from the Presbyopia Impact and Coping Questionnaire that showed AGN-190584 was associated with statistically significant reductions in presbyopia impact and frequency of compensatory coping behaviours, such as squinting or changing font size, compared to the vehicle group.
Results from the Presbyopia Patient Satisfaction Questionnaire showed that compared to controls, the AGN190584 patients were significantly more satisfied with aspects of their treatment.
SAFETY On average, “Loss of distance vision was not observed. In fact, there was a slight improvement in the mean distance vision in the AGN-190584 group relative to the control group at many of the timepoints during the study,” said Dr Waring, who attributed the finding to the optical effect of a small aperture.
Headache was the most common adverse event in both the AGN-190584 (14.1%) and control (9.4%) groups. Dr Waring observed patients were prompted to report headache because it is a potential concern with ophthalmic pilocarpine.
“There were no severe headaches or discontinuations for headache in the AGN-190584 group. Headaches were mostly mild, transient, and did not require treatment,” he reported.
George O Waring IV, MD, FACS is the founder and Medical Director of the Waring Vision Institute in Mt. Pleasant, South Carolina, USA. gwaring@waringvision.com
William C Christie MD practices in Cranberry Township, Pennsylvania, USA. info@scottandchristie.com
Enhancements After Refractive Surgery
Rates trending downward, but some determining factors remain under surgeon control. Cheryl Guttman Krader reports from the 39th Congress of the ESCRS in Amsterdam
Areview of the published literature shows that residual refractive error and poor optical quality are the main reasons for retreatments after corneal and lens-based refractive surgeries. Encouragingly, data also show that outcomes and patient satisfaction after the primary procedure have improved over time, reported Thomas Kohnen MD, PhD.
Recognising however, that the risk of residual refractive error or poor optical quality is affected by a variety of preoperative, intraoperative, and postoperative factors, he counselled his colleagues to focus on prevention and be judicious when considering retreatment.
“Avoid residual refractive error and optical disturbances by performing good surgery and for the correct indications. Second, only do retreatment for these issues if the patient is bothered and not because you think the outcome is not perfect. We have to consider our patients’ satisfaction, not just our own,” Prof Kohnen advised.
Prof Kohnen discussed his centre’s experience and reviewed selected studies reporting outcomes for laser corneal refractive procedures, phakic IOL implantation, and refractive lens exchange. While the incidence of retreatment after refractive surgery has changed over time because of the ongoing procedure evolution, he concluded the overall incidence ranges from 1% to 5% and depends on the procedure and the refractive correction magnitude.
Published data demonstrate how patient satisfaction after LASIK has increased over time. A 2009 article reviewing the world literature reported that 95% of patients were happy with their outcomes. In 2016, a paper that included data from 97 articles published between 2008 and 2015 encompassing approximately 68,000 eyes reported 99% of patients were satisfied, and the rate of loss of fewer than two lines of CDVA was only 0.61%. Another paper published in 2020 reviewing a consecutive series of approximately 70,000 eyes treated with LASIK or PRK reported only 0.37% of eyes lost fewer than two lines of CDVA.
Literature reports on phakic IOL procedures also show outcomes have improved over time in parallel with advances in technology. For example, a study of eyes implanted with an ICL (Staar Surgical) showed a better functional outcome using the newer iteration with the central hole versus the model without the hole. Prof Kohnen referenced results from a study his group submitted for publication that showed excellent refractive predictability was achieved in eyes implanted with the central hole model (ICL V4c).
“The need for retreatment after ICL implantation will decrease significantly with the availability of the toric version that allows us to correct astigmatism,” he predicted.
Two papers from his group analysed outcomes in patients undergoing refractive lens exchange with an implant of trifocal or quadrifocal presbyopia-correcting IOLs. Both papers showed high predictability of the refractive result and attainment of an outcome very close to emmetropia, which is the target in these cases, Dr Kohnen said.
“Of course, these results were achieved in clinical studies, and we have to look at real-world outcomes,” he cautioned.
Thomas Kohnen MD, PhD is Professor and Chair, Department of Ophthalmology, Goethe University, Frankfurt am Main, Germany. prof.dr.kohnen@gmail.com
