Table 2.
Clinical Studies of PG-HPG Nanoemulsion Lubricant Eye Drops in the Management of DED
| Study Treatment | Outcome Parameters | Results |
|---|---|---|
| Silverstein et al, 2020;38 A phase IV, multicenter, open-label, single arm interventional study in adult patients with DED (N=134) of aqueous-deficient (n=41), evaporative (n=44), and mixed (n=49) subtypes | ||
| PG-HPG nanoemulsion (SystaneTM Complete) | Dry eye symptoms: VAS score, 0 (no symptoms) to 10 (worst imaginable symptoms) | Change in VAS score at 0 h; 4h; and 8 h (median, 95% CI) Overall cohort: −1.0 (−3.0, −1.0); −2.0 (−3.0, −2.0); and −2.0 (−2.0, −1.0), respectively ADDE: −1 (−3.0, −1.0); −2.5 (−4.0, −2.0); and −2 (−3.0, −1.0), respectively EDE: −2 (−3.0, −1.0); −2 (−3.0, −1.0); and −2 (−3.0, −1.0), respectively Mixed DED: −1 (−3.0, −1.0); −2 (−3.0, −1.0); and −1 (−3.0, −1.0), respectively |
| Soothing sensation: VAS score, 0 (eyes feeling good) to 10 (no soothing feeling at all) | VAS score at 0 h; 4 h; and 8h (median [range]) Overall cohort: 3 (0–10); 3 (0–10); and 3.5 (0–10), respectively ADDE: 3 (0–9); 2 (0–8); and 3 (0–8), respectively EDE: 3 (0–10); 3 (0–10); and 4 (0–9), respectively Mixed DED: 3 (0–10); 3 (0–10); and 3 (0–10), respectively |
|
| Tolerability assessment: VAS score, 0–5 (no symptoms to mild symptoms); 6–10 (moderate to severe symptoms) | Patient (%) with tolerability assessment score range 0–5 for burning, stinging, blur, and foreign body sensation Overall: 97.0%, 96.3%, 92.5%, and 94.8%, respectively ADDE: 97.6%, 97.6%, 90.2%, and 100%, respectively EDE: 95.5%, 95.5%, 93.2%, and 93.2%, respectively Mixed DED: 98.0%, 95.9%, 93.9%, and 91.8%, respectively |
|
| Yeu et al, 2020;50 A phase IV, multicenter, open-label, single arm interventional study in adult patients with DED (N=134) of aqueous-deficient (n=41), evaporative (n=44), and mixed (n=49) subtypes | ||
| PG-HPG nanoemulsion (SystaneTM Complete) | Tear film stability: TFBUT | TFBUT at baseline (mean±SD): 2.6±1.01 seconds Change in TFBUT from baseline to Day 14 (mean±SD): Overall cohort: 1.5±2.8 seconds ADDE: 1.1±2.41 seconds EDE: 2.4±3.17 seconds Mixed: 1.2±2.63 seconds Change in TFBUT from baseline to Day 28 (mean±SD): Overall cohort: 1.4±2.8 seconds ADDE: 0.6±1.47 seconds EDE: 2.5±3.94 seconds Mixed: 1.1±2.08 seconds |
| Ocular discomfort: VAS score (0-100) | VAS score at baseline (mean±SD): 45.9±24.33 Change in VAS score from baseline to Day 14 (mean±SD): Overall cohort: −17.3±24.80 ADDE: −22.0±21.73 EDE: −17.6±24.17 Mixed: −13±27.49 |
|
| Ocular surface characteristics: corneal staining | Patient (%) with corneal staining absent/minimal and mild/moderate/marked at Day 28 Overall cohort: 104 (77.6%); and 26 (19.4%), respectively ADDE: 33 (80.5%); and 8 (19.5%), respectively EDE: 35 (79.5%); and 8 (18.2%), respectively Mixed: 36 (73.5%); and 10 (20.4%), respectively |
|
| Safety: AEs/SAEs | Treatment-emergent AEs: 19 in 9 (6.7%) patients Patients (%) with ocular AEs: 6 (4.5%); one AE of blurred vision that was mild, transient, and not related to product Patients (%) with non-ocular AEs: 8 (6%) No severe ocular or non-ocular AEs reported Treatment discontinuation due to AEs: n=2; eye pruritis: 1 (0.7%); and viral conjunctivitis: 1 (0.7%) |
|
| Weisenberger et al, 2020;52 Part 1, crossover study comparing nanoemulsion vs non-emollient eye drops followed by part 2, a 1-month observational study of nanoemulsion eye drops in patients with dry eye symptoms (N=20) | ||
| Part 1, PG-HPG nanoemulsion (SystaneTM Complete) vs non-emollient (SystaneTM Ultra) eye drops; Part 2, 1-month follow-up of patients treated with PG-HPG nanoemulsion (SystaneTM Complete) | Lipid layer thickness | LLT at baseline (mean±SD): 45.15±12.42 nm Change in LLT (nm) from baseline to 15 min after instillation (mean±SD), p-value vs baseline All patients (N=20): Overall: 4.89±15.57, p>0.05 vs −1.03±7.92, p>0.05 Superior: 3.69±14.34, p>0.05 vs −0.69±6.38, p>0.05 Middle: 4.86±18.20, p>0.05 vs −0.99±8.48, p>0.05 Inferior: 6.08±16.39, p>0.05 vs −1.97±9.98, p>0.05 Patients with baseline LLT <50 nm (n=15) Overall: 8.51±13.95, p<0.05 vs −1.34±5.35, p>0.05 Superior: 6.13±13.41, p>0.05 vs −1.05±3.95, p>0.05 Middle: 9.33±16.84, p>0.05 vs −1.19±5.01, p>0.05 Inferior: 9.15±14.60, p<0.05 vs −1.79±7.32, p>0.05 Patients with baseline LLT ≥50 nm (n=5) Overall: −5.97±16.53, p>0.05 vs −0.09±13.75, p>0.05 Superior: −3.62±16.08, p>0.05 vs 0.39±11.53, p>0.05 Middle: −8.55±16.77, p>0.05 vs −0.38±15.70, p>0.05 Inferior: −3.14±19.71, p>0.05 vs −2.51±16.48, p>0.05 |
| Ocular symptoms for dryness | Change in VAS score from baseline to time points (mean±SD), p value vs baseline All patients (N=20): 15 min: −12.6±19.4, p<0.05 vs −15.3±17.3, p<0.05 1 h: −14.1±19.1, p<0.05 vs −11.2±20.5, p<0.05 2 h: −14.9±18.9, p<0.05 vs −14.3±21.0, p<0.05 4 h: −12.2±16.3, p<0.05 vs −16.0±21.9, p<0.05 6 h: −8.6±16.7, p<0.05 vs −9.8±19.9, p<0.05 1 month of QID use of nanoemulsion: −10.2±21.2, p=0.045 Patients with baseline LLT <50 nm (n=15): 15 min: −9.8±17.4, p<0.05 vs −17.2±17.1, p<0.05 1 h: −12.1±16.8, p<0.05 vs −11.0±20.5, p>0.05 2 h: −13.0±17.3, p<0.05 vs −15.5±21.6, p<0.05 4 h: −9.5±13.8, p<0.05 vs −17.7±22.7, p<0.05 6 h: −5.3±13.6, p>0.05 vs −10.8±19.9, p>0.05 1 month of QID use of nanoemulsion: −7.1±14.6, p>0.05 Patients with baseline LLT ≥50 nm (n=5): 15 min: −21.0±24.6, p>0.05 vs −9.4±18.6, p>0.05 1 h: −20.2±26.2, p>0.05 vs −11.6±22.9, p>0.05 2 h: −20.4±24.6, p>0.05 vs −10.6±21.1, p>0.05 4 h: −20.4±21.9, p>0.05 vs −10.6±20.9, p>0.05 6 h: −18.2±22.8, p>0.05 vs −6.8±21.7, p>0.05 1 month of QID use of nanoemulsion: −19.2±35.3, p>0.05 |
|
| Muntz et al, 2020;51 A prospective, double-masked, contralateral, randomized crossover trial in participants with DED (N=28) | ||
| Lipid-based artificial tear: PG-HPG nanoemulsion lubricant eye drop (SystaneTM Complete) vs non-lipid-based artificial tear: PEG/PG-HPG lubricant eye drop (SystaneTM Ultra) | Dry eye symptomatology | SANDE score (out of 100) (mean±SD): Baseline: 44±24 vs 45±23, p>0.99 Post instillation: 19±16 vs 24±17, p=0.17 Post exposure to adverse environment: 22±16 vs 33±16, p=0.006 |
| Tear film quality: NITBUT, tear film layer grade | NITBUT (mean±SD): Baseline: 8.3±3.8 vs 8.2±4.1, p=0.99 Post instillation: 11.1±4.5 vs 10.2±5.4, p=0.51 Post exposure to adverse environment: 10.4±5.6 vs 8.3±4.7, p=0.02 Tear film grade (median [IQR]): Baseline: 2 (1–3) vs 2 (1–3), p=0.98 Post instillation: 3 (2–4) vs 2 (1–3), p=0.003 Post exposure to adverse environment: 3 (2–3) vs 2 (0–2), p<0.001 |
|
| Safety: AEs | No AEs reported during the study period | |
| Craig et al, 2021;49 Prospective, multicenter, randomized, double-masked, parallel group, six-month efficacy trial at clinical academic sites in Australia, Canada, New Zealand and the UK in participants fulfilling the TFOS DEWS II diagnostic criteria for DED (N=99) | ||
| Lipid-aqueous eye drop (SystaneTM Complete), and aqueous-based eye drop (SystaneTM Ultra) | Ocular symptoms: OSDI, DEQ-5, and SANDE scores | Consistent reductions in OSDI, DEQ-5, and SANDE scores from Day 30 onwards in both treatment groups (all p≤0.01, multiplicity-adjusted post-hoc analysis) |
| Tear film stability: NITBUT | Consistent improvement from Day 120 onwards in both treatment groups (all p<0.05, multiplicity-adjusted post-hoc analysis) | |
| Tear film lipid layer quality | Improvements in tear film lipid layer quality from Day 90 onwards only with the lipid-based tear drops (all p<0.05, multiplicity-adjusted post-hoc analysis), with measurements being greater compared to non-lipid containing eye drop (all p<0.05) Subgroup analysis showed that significant change in tear film lipid layer grade during the study period was limited to participants with a baseline grade ≤3 (median change of +1 versus 0 grades, p=0.01). |
|
| Ocular surface characteristics: lid wiper epitheliopathy grade, and sodium fluorescein and lissamine green staining scores | Superior lid wiper epitheliopathy grade significantly decreased in both treatment groups from Day 60 onwards (all p≤0.01, multiplicity-adjusted post-hoc analysis) Sodium fluorescein and lissamine green staining scores improved from Day 120 onwards in both groups (all p<0.05, multiplicity-adjusted post-hoc analysis) |
|
| Safety: AEs | Non-significant AE related to drops: 1 (itching and irritation following application); non-significant AE unrelated to drops: 2 (conjunctivitis); all AEs resolved within 3–7 days after onset | |
Abbreviations: ADDE, aqueous deficient dry eye; AEs, adverse events; CI, confidence interval; DED, dry eye disease; DEQ-5, dry eye questionnaire-5; EDE, evaporative dry eye; HPG, hydroxypropyl guar; LLT, lipid layer thickness; NITBUT, non-invasive tear break-up time; OSDI, ocular surface disease index; PG, propylene glycol; QID, quarter in a day; SAEs, serious adverse events; SANDE, Symptom Assessment Questionnaire iN Dry Eye; SD, standard deviation; TFBUT, tear film break-up time; TFOS DEWS II, Tear Film and Ocular Surface Society Dry Eye WorkShop II; UK, United Kingdom; VAS, visual analog scale.