Latanoprost with high precision, piezo-print microdose delivery for IOP lowering: clinical results of the PG21 study of 0.4 µg daily microdose

Louis R Pasquale,1 Shan Lin,2 Robert N Weinreb,3 James C Tsai,4 Robert L Kramm,5 Tsontcho Ianchulev5,6 1Department of Ophthalmology, Harvard Medical School, Cambridge, MA, USA; 2Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USA; 3Department of Ophthalmology, University of California San Diego, San Diego, CA, USA; 4Department of Ophthalmology, Mount Sinai School of Medicine, New York, NY, USA; 5Eyenovia Incorporated, New York, NY, USA; 6Department of Ophthalmology, New York Eye and Ear Infirmary, Mount Sinai Medical School, New York, NY, USA Background: Topical high-precision piezo-print delivery of microdoses of latanoprost achieved significant IOP reduction consistent with the eyedropper effect but with a 75% reduced exposure to drugs and preservatives. Prostaglandin analogs are a mainstay glaucoma therapy. However, conventional eyedroppers deliver 30–50 μL drops that greatly exceed the physiologic 7-μL ocular tear film capacity. Eyedropper overdosing floods the eye with excess drug compounds and preservatives, resulting in ocular surface toxicity, periorbitopathy, and other well-characterized ocular side effects. Piezoelectric high-precision microdosing provides targeted delivery that can reduce exposure to both drug and preservatives compared to conventional eyedropper delivery, with the potential to deliver similar biologic effect. Methods: Both eyes (N=60) of 30 healthy volunteers received single 8-μL microdoses of 0.005% latanoprost (0.4 μg; μRx-latanoprost) on the morning of Days 1 and 2 using a high-precision, piezo-print horizontal delivery system. Diurnal IOP was measured before and 2 days after microdosing. Main efficacy outcomes were diurnal IOP change after μRx-latanoprost microdosing and accurate microdosing success rates, and the primary safety outcome was adverse event (AE) incidence. Results: μRx-latanoprost reduced baseline IOP by 26% and 30% at 1 and 2 days postadministration, respectively. Successful topical dosing was achieved in 100% of technician-assisted deliveries. All patients successfully self-administered microdoses after receiving training. Microdose administration was well tolerated and did not result in any AEs. Conclusion: Microdosing of 0.4 μg of μRx-latanoprost achieved significant IOP reduction. Lower ocular exposure with topical prostaglandin analog microdosing can enable new therapeutic opportunities for optimizing glaucoma treatment. Microdosing may also be beneficial in reducing ocular side effects associated with excessive drug product and preservatives often used to treat chronic ocular diseases such as glaucoma. Keywords: microdosing, piezo-ejection system, latanoprost, IOP, IOP lowering, glaucoma, ocular drug delivery, Optejet, self-administration, usabilit

Comparison of Peristat Online Perimetry with the Humphrey Perimetry in a Clinic-Based Setting

Purpose We determined the receiver operating characteristic (ROC) curves for Peristat online perimetry at detecting varying degrees of glaucoma and the correlation between Peristat online perimetry and Humphrey visual field. Methods: A prospective, comparative study of Peristat online perimetry (an achromatic static computer threshold testing program) and Humphrey visual field (HVF) 24-2 SITA standard testing was performed by 63 glaucoma patients and 30 healthy controls in random order. The number of total adjacent abnormal test points were identified for each test, and compared with Spearman correlation. Receive operating characteristic curves were generated for Peristat online perimetry detection of mild and moderate-severe glaucoma patients using contrast sensitivity thresholds of −16.7, −21.7, and −26.7 dB. Results: The area under the ROC curve for glaucoma detection ranged from 0.77 to 0.81 for mild disease (mean deviation [MD], >−6 dB on HVF) and 0.85 to 0.87 for moderate to severe disease (MD, <−6 dB on HVF) depending on contrast threshold. Peristat online perimetry and Humphrey visual field abnormal points were highly correlated with Spearman rank correlations ranging from 0.55 to 0.77 (all P < 0.001). Conclusions: Peristat online perimetry exhibits a reasonable ROC curve without specialized equipment and exhibited significant correlation with the conventional 24° Humphrey visual field test. Translational Relevance Low cost widely available internet-based visual fields may complement traditional office-based visual field testing