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

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.

Corneal Surface Ablation Laser Refractive Surgery for the Correction of Myopia: A Network Meta-analysis.

PURPOSE: To systematically compare the efficacy, predictability, safety, postoperative haze, pain scores, and epithelial healing time of four corneal surface ablation procedures. METHODS: PubMed, Embase, Cochrane Library, and the U.S. trial registry were searched up to June 2018. Randomized controlled trials were selected. Efficacy (uncorrected distance visual acuity of 20/20 or better), predictability (refractive spherical equivalent within ±0.50 diopters [D] of the target), and safety (loss of two or more lines of spectacle corrected distance visual acuity) were set as primary outcome measures. Haze, pain scores, and epithelial healing time were set as secondary outcome measures. RESULTS: Eighteen studies involving 1,423 eyes were included. According to the Grading of Recommendations Assessment, Development, and Evaluation, the quality of outcomes were moderate to high (70.6%). There were no differences in efficacy, predictability, safety, haze, day 1 pain, and epithelial healing time between treatments. Epithelial laser in situ keratomileusis (epi-LASIK) had statistically significantly higher pain scores on day 3 compared to photorefractive keratectomy (PRK) (weighted mean differences [WMD] = 2.2, 95% credible intervals [CrI] = 0.19 to 4.01) and transepithelial PRK (T-PRK) (WMD = 2.7, 95% CrI = 0.51 to 4.84). The surface under the cumulative ranking curve ranking results (best to worst) showed laser epithelial keratomileusis (LASEK) ranked highest for efficacy, predictability, safety, and day 1 pain scores. Epi-LASIK ranked best for grade 1 haze scores. T-PRK ranked best for haze of 0.5 or higher, haze scores day 3 pain scores, and epithelial healing time. CONCLUSIONS: Surface laser refractive surgeries are comparable in terms of efficacy, predictability, safety, and postoperative haze except for day 3 pain scores, with epi-LASIK being more painful compared to PRK and T-PRK. [J Refract Surg. 2018;34(11):726-735.].

Web-based versus paper administration of common ophthalmic questionnaires: comparison of subscale scores.

OBJECTIVE: To compare participants' responses to Web-based and paper-and-pencil versions of an ophthalmic, patient-reported outcome (PRO) questionnaire. DESIGN: Questionnaire development. PARTICIPANTS: Matched subjects with ocular surface disease (OSD) (n = 68) and without OSD (controls, n = 50). METHODS: Subjects completed a standard, paper-and-pencil and a Web-based version of the same questionnaire in randomized order. The administered questionnaire included several ophthalmic PRO subscales: the National Eye Institute's (NEI's) Refractive Error Quality of Life Instrument's Clarity of Vision, Near Vision, Far Vision, Glare, Symptoms, Worry, and Satisfaction with Correction subscales; the Ocular Surface Disease Index's (OSDI's) Symptoms subscale; and the NEI's Visual Function Questionnaire's Driving subscale. Possible scores for each subscale ranged from 0 (no difficulty) to 100 (most difficulty). Agreement of subscale scores between modes of administration was assessed using the Bland-Altman approach and multivariable logistic regression. MAIN OUTCOME MEASURES: Subscale scores and an unweighted average total score for each mode of administration. RESULTS: Mean differences in scores between modes of administration ranged from -2.1 to +2.3 units. Although no differences were found to be statistically significant, the Worry and Satisfaction with Correction subscales approached statistical significance (P = 0.07 and 0.08, respectively). Although most subscale mean differences in score did not differ significantly by gender, age (≥40 vs. <40 years), disease status (OSD vs. control), order of administration, or time between completion of the questionnaires, women had slightly greater score differences than men for the Driving (P = 0.04) and Clarity of Vision (P = 0.03) subscales; those with OSD had greater score differences for Clarity of Vision than did controls (P = 0.0006); and those aged ≥40 years had slightly greater differences in OSDI Symptoms subscale than those aged <40 years (P = 0.04). CONCLUSIONS: To our knowledge, this Food and Drug Administration and NEI collaboration is the first study to evaluate the equivalence of Web-based and paper versions of ophthalmic PRO questionnaires. We found no evidence of clinically significant differences between scores obtained by the 2 modes for any of the examined subscales. A Web-based instrument should yield scores equivalent to those obtained by standard methods, providing a useful tool that may facilitate ophthalmic innovation. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.