Safety and Efficacy of Subretinally Administered Palucorcel for Geographic Atrophy of Age-Related Macular Degeneration: Phase 2b Study.

PURPOSE: To evaluate safety and successful use of a novel subretinal delivery system and suprachoroidal surgical approach and safety and activity of human umbilical tissue-derived cells (palucorcel) via a novel delivery system in patients with geographic atrophy (GA). DESIGN: Multicenter, open-label phase 2b study. PARTICIPANTS: Participants were 55 to 90 years with GA secondary to age-related macular degeneration (AMD) and best-corrected visual acuity (BCVA) of 20/80 to 20/800. Exclusion criteria included neovascular AMD in the intervention eye, glaucoma with intraocular pressure of 25 mmHg or more, or other significant ophthalmologic conditions. METHODS: Participants received a subretinal injection of palucorcel, 3.0 × 105 cells in 50 µl, using the custom-designed delivery system and surgical procedure. MAIN OUTCOME MEASURES: Safety assessments included treatment-emergent adverse events (AEs), immunologic assessments, and ophthalmologic evaluations. Efficacy was evaluated as change in mean number of BCVA letters from baseline, proportion of participants gaining 15 BCVA letters or more, and growth rate of GA lesions at 12 months. RESULTS: Surgery and palucorcel administration were performed in 21 participants at 8 sites by 8 different surgeons. At baseline, median total area of GA was 13.4 mm2 and median BCVA was 43 letters in the intervention eye. Eye-related AEs occurred in 76% of participants (16/21), including conjunctival hemorrhage (n = 5), retinal hemorrhage (n = 4), and vitreous floaters (n = 4). Most AEs were mild and resolved within 1 month. No serious AEs, no retinal detachment or perforation, and no significant changes in intraocular pressure occurred. At month 12, mean change in BCVA from baseline was -5.9 letters correct (standard deviation, 13.0 letters correct) in the intervention eye and -3.7 letters correct (standard deviation, 9.0 letters correct) in the fellow eye. No participants showed improvement of 15 letters or more in the intervention eye, and 3 participants lost more than 15 letters by month 1. No apparent effect of treatment was observed. CONCLUSIONS: Palucorcel was delivered successfully to the targeted subretinal site using a novel delivery system and suprachoroidal approach for most participants; however, improvement in GA area, retardation of growth, or visual acuity were not demonstrated.

Patient-Reported Wearing Experience From Hydrogel Daily Disposable Wearers Older Than 40 Years From the TEMPO Registry.

OBJECTIVES: To describe the patient-reported wearing experience over time among wearers of hydrogel daily disposable (HydDD) contact lenses (CLs) in the TruEye and Moist Performance Overview (TEMPO) Registry (NCT01467557). METHODS: Registered wearers older than 40 years who were recently fit with 1-DAY ACUVUE MOIST HydDDs completed self-administered questionnaires four times during a year-long Registry. Overall opinion of CLs, replacement schedules, Contact Lens Dry Eye Questionnaire (CLDEQ-8), and compliance were queried. Data were analyzed with analysis of variance and signed rank tests. RESULTS: A total of 86 subjects (24% men, age 50.2±7.1 years) completed the Registry. Approximately 76% were new to daily disposable lenses, and 8% were neophytes. Overall opinion of CLs improved significantly after refitting with HydDDs (baseline 57% excellent/very good vs. 69%-79% at follow-ups, P<0.05 all vs. baseline). Changing to HydDDs maintained average and comfortable wear time (P>0.05), and it did significantly improve CLDEQ-8 scores at all follow-ups (baseline, 11.2±7.3 vs. 2 weeks, 7.8±5.8, P<0.0001; 4 months, 8.6±6.5, P=0.0006; 12 months, 9.3±6.5, P=0.01). Self-assessment of compliance was excellent/very good for 80% at baseline, and improved to 92% to 98% at follow-ups (P<0.0001). More than 90% never slept in their HydDDs, although compliance to daily replacement diminished from 2-week to 4-month surveys (93% vs. 84%, P=0.007). CONCLUSIONS: After refitting with HydDDs, older wearers reported significantly higher overall opinions of their lenses, better CLDEQ-8 symptom scores, and most were compliant with proper daily disposable lens use. Diminishing daily replacement rates from 2 weeks to 4 months indicate a need to reinforce that recommendation. Wearers of HydDD CLs older than 40 years experienced many benefits from refitting with these daily disposable lenses.

Lid Wiper Epitheliopathy in Soft Contact Lens Wearers.

PURPOSE: To evaluate lid wiper epitheliopathy (LWE) in soft contact lens (SCL) wearers on initial presentation and after using various SCL and solution combinations. METHODS: LWE was assessed in 253 habitual SCL wearers who attended a screening visit at one of three study sites. LWE was assessed using lissamine green and sodium fluorescein dyes (Korb scale); a final LWE grade was calculated as the averaged LWE grade of the two dyes. Eligible habitual wearers continued into the four study periods, during which they wore one of three SCL types (etafilcon A, galyfilcon A, or senofilcon A) while using each of four care solutions for 10 to 14 days in randomized order. Statistical analyses were performed using linear mixed models, testing for differences in LWE for subject characteristics and between three multipurpose (MPS) test solutions (BioTrue, OPTI-FREE PureMoist, RevitaLens OcuTec) compared to a hydrogen peroxide (Clear Care) control solution. RESULTS: LWE was present in 85% of habitual SCL wearers. LWE was not different for age (p = 0.28), sex (p = 0.99), race (p = 0.34), and comfort (p = 0.38) and not correlated with refractive error (r = 0.07). LWE was lower in habitual senofilcon A wearers (least-squares (LS) mean ± SE = 0.82 ± 0.19) compared to wearers of lotrafilcon B (1.34 ± 0.20; p < 0.02), comfilcon A (1.41 ± 0.21; p < 0.01), and other (1.18 ± 0.16; p < 0.03). Two hundred three participants completed all four study solutions with their assigned lens type; LWE was not different between the MPSs compared to the peroxide control solution across lens materials, except for less LWE for BioTrue (0.88 ± 0.17) versus Clear Care for participants wearing galyfilcon A (1.11 ± 0.18; p < 0.01). CONCLUSIONS: On initial presentation, LWE was present in 85% of habitual wearers and found to be independent of age, sex, race, comfort, and refractive error but dependent on habitual SCL type. There were no clinically meaningful differences in LWE between the MPSs and hydrogen peroxide solution for the three lens types studied.

Eyelid Margin and Meibomian Gland Characteristics and Symptoms in Lens Wearers.

PURPOSE: To describe the lid margin characteristics of contact lens wearers and relate them to comfort during lens wear. METHODS: Three study sites enrolled habitual contact lens wearers. Subjects completed the Comfort domain of the Contact Lens User Experience (CLUE) questionnaire, and each eye was graded for the presence of mucocutaneous junction (MCJ) displacement, lid margin irregularity, and lid margin vascularity. Examiners counted the number of meibomian gland (MG) orifices in the central centimeter of the lower eyelid and the number of those that showed pouting/plugging and vascular invasion. MG expressibility was graded according to the Shimazaki schema. Subjects were grouped based on presence/absence of each characteristic, total number of orifices (≥5 vs. <5), and expressibility (grade 0 vs. >0). Descriptive statistics are reported. A linear model was used to assess the fixed effect of each characteristic on combined CLUE score and each CLUE statement, if the effect on combined CLUE score showed p < 0.10. RESULTS: The study included 203 subjects (67.5% female) with mean age (±SD) of 30.3 ± 9.6 years. The most commonly observed characteristics were orifice pouting/plugging, compromised MG expressibility, and lid margin vascularity (35.0, 30.3, and 20.4%, respectively). MCJ displacement and MG expressibility had an effect on the combined CLUE score such that individual CLUE statements were analyzed (p = 0.01 and p = 0.06, respectively). MCJ displacement had an effect on comfort upon insertion (p = 0.01), comfort after 5 minutes (p = 0.03), end-of-day comfort (p = 0.01), and ability to maintain ocular moisture (p = 0.030). MG expressibility had a significant effect on general comfort (p = 0.01), comfort throughout the day (p = 0.02), and the ability to maintain ocular moisture (p = 0.02). CONCLUSIONS: MCJ displacement and MG expressibility have an effect on contact lens comfort.

Subjective Comfort and Physiology with Modern Contact Lens Care Products.

PURPOSE: To compare subjective comfort and ocular physiology with three multipurpose solutions (MPSs) to that of a peroxide-based system with three different soft contact lens materials. METHODS: Habitual soft contact lens wearers (n = 236) were enrolled at three sites and completed a washout period with no contact lens solution for ≥4 days. Subjects were randomly assigned to one of three lens types: etafilcon A, galyfilcon A, or senofilcon A. A new lens of the assigned type was worn for 10 to 14 days each while using one of four care solutions, in random order (A-polyaminopropyl biguanide + polyquaternium, B-POLYQUAD + Aldox, C-alexidine + polyquaternium-1, and D-hydrogen peroxide) with a washout period (≥4 days) between each solution. After each care solution, biomicroscopy was performed and subjective comfort was assessed using the Contact Lens User Experience (CLUE) questionnaire and other instruments including comfortable wear time (CWT). Linear mixed models were used for analysis. Comfort and biomicroscopy signs with each MPS were compared to that of the peroxide solution. RESULTS: Subjective CLUE Comfort score across all lens types with each MPS was not significantly different than with the peroxide solution (p = 0.98). There were no differences in CWT between each MPS and the peroxide solution for any lens type (range of differences: -0.8 to 0.8 h; all p ≥ 0.13). Six MPS/material combinations had no clinically meaningful change in corneal staining versus peroxide (<0.5 units); three combinations could increase staining by up to 0.57 units. Staining was

Cutoff score and responsiveness of the 8-item Contact Lens Dry Eye Questionnaire (CLDEQ-8) in a Large daily disposable contact lens registry.

PURPOSE: To report (1) results of the 8-item Contact Lens Dry Eye Questionnaire (CLDEQ-8) among a large sample of SCL wearers before and during 1 year after fitting with one of 2 daily disposable (DD) lenses (etafilcon A or narafilcon B) in the TEMPO Registry, (2) the cut-off score to identify highly symptomatic SCL wearers and (3) the clinically important difference (CID) in the CLDEQ-8 score. METHODS: Demographics, CL history and patterns of SCL use were documented. Construct validity of the CLDEQ-8 was tested versus overall opinion (OO) of habitual SCLs, eye dryness and eye sensitivity at baseline. Responsiveness to change in OO was tested. Cutoff score, CID, and predictive accuracy were analyzed with general linear mixed models, adjusting for clustering by site with Bonferoni correction for multiple comparisons. RESULTS: Baseline CLDEQ-8 data from 977 habitual SCL wearers showed significant association with OO, eye dryness and sensitivity (p<0.0001, all). CLDEQ-8 scores improved significantly after refitting and reflected change in OO over time (p<0.0001). Diagnostic cutoff of≥12 and CID of 3 points performed best. CONCLUSIONS: The CLDEQ-8 score of ≥12 points is proposed to identify SCL wearers who could benefit from clinical management of their CL-related symptoms. The clinically important difference was ±3 points. Refitting to these DD lenses in the TEMPO Registry provided significant and stable reduction in SCL-related symptoms across the year of follow-up. Use of the CLDEQ-8 in clinical practice and clinical research will help quantify and standardize symptom measures in SCL wearers.

Rates of adverse events with hydrogel and silicone hydrogel daily disposable lenses in a large postmarket surveillance registry: the TEMPO Registry.

PURPOSE: To report annualized adverse events (AEs) including corneal infiltrative events (CIEs) with use of silicone hydrogel (SiHyDD) and hydrogel daily disposable (HydDD) soft contact lenses (SCLs) in the 1•DAY ACUVUE TruEye or 1•DAY ACUVUE MOIST Performance Overview (TEMPO) Registry (NCT01467557). METHODS: Annualized incidence of symptomatic daily disposable (DD)-related AEs was calculated from 3064 surveys from 1171 subjects (601 SiHyDD and 570 HydDD, 31.8 ± 13.5 years, 68% female) during 1 year. Three independent experts adjudicated potential AE cases. Demographics were compared between wearers with and without AEs. RESULTS: The registry tracked 960.3 years of lens wear: SiHyDD 489.4 years and HydDD 470.9 years. In that period, the 601 SiHyDD wearers reported eight AEs with office visits (1.6%/y; 2 CIEs, 0.4%/y), eight (1.6%/y) without office visits, and four AEs unrelated to SCLs (0.8%/y) (SiHyDD wearers with AEs; 44.8 ± 12.5 years; 75% female). The 570 HyDD wearers reported three AEs with office visits (0.6%/y; no CIEs), five without office visits (1.1%/y), and one non-SCL-related AE (0.2%/y) (HydDD wearers with AEs; 26.3 ± 8.0 years; 100% female). These CIE rates are significantly lower than the lowest estimate of 3.3% from prior studies. Wearers with SiHyDD-related AEs were significantly older than unaffected wearers (P = 0.02), but not for HydDD-related AEs. CONCLUSIONS: The CIE rates of 0.4% and 0% with these DD lenses are significantly lower than rates reported with reusable SCLs (3%-4%/y), indicating improved safety outcomes with these DD lenses. Compared to unaffected wearers, SiHyDD lens wearers with AEs requiring clinical visits were significantly older. (ClinicalTrials.gov number, NCT01467557.).

Contact Lens Dry Eye Questionnaire-8 (CLDEQ-8) and opinion of contact lens performance.

PURPOSE: To report on the development and validation of a short form of the Contact Lens Dry Eye Questionnaire (the CLDEQ-8) to enable it to reflect status of and change in overall opinion ("opinion") of soft contact lenses (SCLs). METHODS: Item reduction for the CLDEQ was achieved by correlation with overall opinion of SCLs at follow-up visits in a sample of 38 SCL wearers at one academic clinical site. The CLDEQ-8 score (frequency plus late day intensity of dryness, discomfort, and "blurry vision"; frequency of "closing eyes to rest them" and "removing CLs to relieve discomfort") was then tested in 379 SCL wearers in a multicenter study with analysis stratified by opinion ratings at baseline and 2 weeks postrandomization to new silicone hydrogel SCLs. The sum of CLDEQ-8 scores (maximum 37) was correlated with opinion by Spearman's rank correlation coefficient and analyzed for change in opinion by analysis of variance (ANOVA). RESULTS: The CLDEQ-8 scores in the validation sample were highly correlated with habitual baseline opinion (-0.44, p < 0.0001) and responsive to change in opinion postrandomization (-0.58, p < 0.0001). Baseline CLDEQ-8 scores by opinion status were as follows: Fair: 17.4 ± 8.7, Good 13.7 ± 6.4, Very Good 9.1 ± 4.7, and Excellent 6.4 ± 3.7 (ANOVA, F = 291.1, p < 0.0001). After 2 weeks, change in CLDEQ-8 scores by improvement status was as follows: Much Improved: -16.7 ± 10.0, Unchanged: -2.3 ± 5.0, to Much Worse +8.5 ± 5.8 (ANOVA, F = 16.5, p < 0.001). CONCLUSIONS: The CLDEQ-8 score significantly reflected baseline status and change in overall opinion after refitting with two types of silicone hydrogels. The CLDEQ-8 score is a valid outcome measure in SCL clinical trials to reflect opinion of SCLs.