Data for 125 eyes (N = 65 patients) treated with LBN 0.024% were reviewed across nine clinical sites. Among the charts, the earliest baseline IOP evaluation was conducted in December 2017, whereas the latest was conducted in March 2019. The mean (standard deviation [SD]) age of patients was 59 (14) years, 22 (33.8%) were White, and most (53.8%) were female (Table 1). The majority, or 70.8%, of patients were diagnosed with primary OAG (ICD-10 code H40.11), 13.8% were diagnosed with OAG with borderline findings (H40.01), 7.7% with low-tension glaucoma (H40.12), 3.1% as glaucoma suspect (H40.00), 1.5% with both primary OAG and low-tension glaucoma, and 1.5% with OHT (H40.05). No diagnostic code was recorded for 1.5% of patients (Table 1). All but five patients had glaucoma/OHT bilaterally and were treated with LBN bilaterally. Some patients were prescribed additional non-IOP lowering ocular medications (n = 2 lifitegrast, n = 3 loteprednol etabonate 0.5%, n = 1 loteprednol etabonate 0.2%, n = 3 cyclosporine, n = 1 olopatadine); with few exceptions these were utilized for the management of concurrent dry eye disease. Medical comorbidities specified in patient charts were systemic hypertension (n = 25, 38.5%), diabetes (n = 17, 26.2%), and cardiovascular disease (n = 5, 7.7%). Systemic medications included atorvastatin (n = 13, 20.0%), amlodipine (n = 10, 15.4%), aspirin (n = 7; 10.8%), losartan (n = 7, 10.8%), metformin (n = 7, 10.8%), and lisinopril (n = 6; 9.2%).
The study eye, defined as the eye with the higher IOP at baseline, was the right eye in 34 patients (52.3%) and the left eye in the remaining 31 patients (47.7%). The majority of sites used applanation tonometry to measure IOP, with a Tono-Pen used at a single site, and the method of IOP measurement used for each patient was consistent across visits. No IOP was recorded at follow-up visit 1 for two patients; these patients were included in all outcome analyses with the exception of IOP outcomes at visit 1. Mean (SD) IOP at baseline was 21.7 (5.9) mmHg in the study eye and 19.7 (5.5) mmHg in the treated fellow eye. Baseline CDR was recorded for 53 patients (81.5%), with the method noted for two (spectral domain ocular coherence tomography). Mean CDR was 0.6 (min = 0.15, max = 0.9) in the study eye and 0.6 (min = 0.2, max = 0.9) in the treated fellow eye. Central corneal thickness was recorded at baseline for approximately half of patients, while visual fields (all showing mild field loss) were recorded for only six patients.
All patients were prescribed LBN 0.024% therapy once a day to be administered in the evening following their baseline visit. Medical records from six patients included notations that they were not adherent to the LBN dosing regimen (i.e., regularly missing dosages). The mean time (SD) between the baseline visit and the first and second follow-up visit was 43 (41) and 141 (76) days, respectively. The timing of IOP measurement at each visit varied, with an overall mean difference of 2 h 35 min between the patients’ earliest IOP measurement and latest IOP measurement.
IOP Lowering at Each Visit
Treatment with LBN 0.024% resulted in a mean (SD) IOP of 14.7 (4.1) mmHg (n = 63) at follow-up visit 1 and 14.4 (3.2) mmHg (n = 65) at follow-up visit 2 in the study eye. The mean (SD) reduction in IOP from baseline was 7.1 (4.7) and 7.3 (5.1) mmHg at the first and second follow-up visit, respectively (P < 0.0001 for both; Fig. 1). Corresponding mean (SD) percent reductions were 30.8 (17.2) % at the first and 30.8 (17.1) % at the second follow-up visit. The degree of IOP lowering in patients whose IOP was measured with a Tono-Pen (n = 13) was consistent with that for the overall data set.
Mean (SD) IOP in the subset of patients with higher IOP (> 21 mmHg; n = 30) was 26.7 (4.6) mmHg at baseline and 16.7 (4.5) mmHg and 15.6 (3.6) mmHg at follow-up visits 1 and 2, respectively. Mean (SD) reductions in IOP within this subset of patients were 10.0 (4.5) and 11.1 (4.6) mmHg at the first and second follow-up visit, respectively (P < 0.0001 for both vs. baseline) with corresponding mean (SD) percent reductions of 37.1 (13.8) % and 40.9 (13.4) % at the two follow-up visits.
Mean (SD) IOP for the subset of patients with lower IOP (≤ 21 mmHg; n = 35) at baseline was 17.4 (2.8) mmHg at baseline and 12.9 (2.8) mmHg and 13.4 (2.4) mmHg at visits 1 and 2, respectively. Among these patients, mean (SD) IOP reductions were 4.7 (3.2) and 4.0 (2.6) mmHg at the first and second follow-up visit, respectively (P < 0.0001 for both vs. baseline), which corresponded to mean (SD) percent reductions of 25.4 (18.1) % and 22.1 (15.2) %.
A total of 13 patients had data recorded in their charts for a third follow-up visit. The mean (SD) days to visit 3 in these patients was 230 (120). Among these patients, IOP lowering with LBN was sustained through visit 3. The mean (SD) IOP was 21.8 (4.8) mmHg at baseline, decreasing to 14.5 (3.3) mmHg at follow-up visit 1, 14.2 (3.2) at visit 2, and 15.0 (3.2) mmHg at visit 3. Corresponding mean (SD) reductions from baseline were 7.3 (2.5) mmHg at visit 1, 7.5 (4.8) mmHg at visit 2, and 6.8 (3.4) mmHg at visit 3 (P ≤ 0.0001 for all).
Analyses of IOP lowering in patients’ treated fellow eyes (n = 60) were supportive of findings in patients’ study eyes, with significant reductions from baseline at follow-up visits in the full data set of fellow treated eyes, as well as in the subset of fellow treated eyes with higher IOP at baseline (n = 19) and subset of fellow treated eyes with lower IOP at baseline (P < 0.0001 vs. baseline for all, both visits).
Overall, 50 (79.4%) and 51 (78.5%) patients had at least a 20% reduction from baseline in the study eye IOP at follow-up visits 1 and 2, respectively (Fig. 2). More than half of patients had at least a 30% reduction from baseline at follow-up visit 1 (n = 34, 54.0%) and follow-up visit 2 (n = 33, 50.8%). More than a quarter of patients had at least a 40% reduction from baseline at follow-up visit 1 (n = 17, 27.0%) and follow-up visit 2 (n = 18, 28.1%).
At follow-up visit 1, 27 (93.1%) patients with higher baseline IOP (> 21 mg Hg) had at least a 20% reduction from baseline in IOP (Fig. 2). In addition, more than half (n = 16, 53.3%) attained an IOP lowering of at least 40% at follow-up visit 2. Among the patients with lower baseline IOP (≤ 21 mmHg), 23 (67.6%) achieved an IOP reduction in the study eye of at least 20% relative to baseline at follow-up visit 1.
Non-responders were defined as having < 10% reduction in study eye IOP from baseline. Six patients appeared to be non-responders at follow-up visit 1, but all but one were responders (≥ 10% reduction in IOP) at follow-up visit 2. Another two patients appeared to be non-responders at follow-up visit 2; of these, one was a responder at follow-up visit 1, while the other had missing IOP data at follow-up visit 1.
For the overall data set, the only variable statistically related to the change in IOP in the study eye from baseline to follow-up visit 1 was baseline IOP, with a coefficient of −0.567 (R2 = 0.5131; P < 0.0001), indicating that each added mmHg in baseline IOP was associated with a decrease of 0.567 mmHg in IOP at follow-up visit 1. Variables statistically related to the change in IOP in the study eye from baseline to follow-up visit 2 were baseline IOP (coefficient, −0.867; P < 0.0001) and follow-up visit 1 IOP (coefficient, 0.339; P = 0.0008). The R2 for the second linear regression model was 0.7679.
Results of regression analysis of data for treated fellow eyes were supportive of results obtained for study eyes data (data not shown).
There were no systemic AEs recorded in the charts. Overall, 33 patient charts (50.7%) included notations of at least one ocular AE (Table 2). Common ocular AEs noted in the charts included blurred vision (n = 10, 12 events), dryness (n = 8, 11 events), itching (n = 5, 6 events), irritation (n = 5, 6 events), and light sensitivity (n = 5, 5 events). Ocular redness was recorded for only one patient, treated unilaterally and only for the study eye. There were no discontinuations recorded due to an AE, nor were there notations as to potential relationship of any AE to treatment(s).
Visual acuity was measured using the same method (typically Snellen) at baseline and follow-up visit 1 for 55 study eyes and at baseline and follow-up visit 2 for 46 study eyes. There were no meaningful changes in VA in the study eye or in the treated fellow eye from baseline to either follow-up visit. Mean VA was 20/39.5 (n = 60) at baseline, 20/39.6 (n = 55) at the first visit and 20/37.8 (n = 46) at the second visit for the study eye and 20/29.2 (n = 55) at baseline, 20/27.5 (n = 51) at the first visit and 20/25.6 (n = 44) at the second on treatment visit for the treated fellow eye. One treated fellow eye had a loss of three lines (from 20/20 to 20/40 at both follow-up visits), while no study eyes had a loss of > 2 lines at either follow-up visit.
Cup-to-disk ratio measurements were available at both baseline and follow-up visit 1 for 38 patients and at both baseline and follow-up visit 2 for 35 patients. Study eye mean (standard error) change in CDR ratio from baseline to follow-up visit 1 (−0.00842 [0.0104]) and to follow-up visit 2 (−0.00486 [0.0109]) was not statistically significant for either comparison (P = 0.4227 and P = 0.6584, respectively).
Adjunctive IOP-Lowering Medications and IOP-Lowering Medication Switches
Adjunctive medication use and medication switches are presented in Fig. 3. At their first follow-up visit, two patients at one site were prescribed an additional IOP-lowering medication (netarsudil ophthalmic solution 0.02% [Rhopressa®]) as an adjunct to treatment with LBN. In one patient study eye IOP decreased from 38 mmHg at baseline to 16 mmHg at visit 1, and subsequently decreased another 2 mmHg to 14 mmHg with the addition of netarsudil; in the second patient, study eye IOP decreased from 18 mmHg to 15 mmHg at visit 1 and subsequently decreased another 4 mmHg to 11 mmHg with the addition of netarsudil. Two more patients were prescribed an adjunctive IOP-lowering medication after their second follow-up visit (dorzolamide hydrochloride-timolol maleate ophthalmic solution [Cosopt®] for 1 patient, bimatoprost ophthalmic solution 0.01% [Lumigan®] for the other). However, no further follow-up information was available for these patients at the time of their chart reviews. Seven patients were switched from LBN to another IOP-lowering medication after the second follow-up visit: five to bimatoprost ophthalmic solution 0.01% (two due to cost/insurance coverage, three reason not reported), one to netarsudil plus latanoprost ophthalmic solution 0.005% (reason not reported), and one to travoprost ophthalmic solution 0.004% (due to insurance coverage). One additional patient, noted as being non-adherent to treatment, discontinued LBN at visit 2 and was started on travoprost 4 months later.