LIGHTSITE II Randomized Multicenter Trial: Evaluation of Multiwavelength Photobiomodulation in Non-exudative Age-Related Macular Degeneration
NCT03878420 | LIGHTSITE II | Burton et al. (2023)
Burton B, Battaglia Parodi M, Jürgens I, Zanlonghi X, et al. LIGHTSITE II Randomized Multicenter Trial: Evaluation of Multiwavelength Photobiomodulation in Non-exudative Age-Related Macular Degeneration. Ophthalmology Therapy, 2023; 12:953–968.
Locations
Seven centers across Europe (UK, France, Spain, Germany, Italy)
Study Period
Not reported
Study Design
Randomized, double-masked, multicenter, parallel-group, sham-controlled trial
Study Population
Experimental Group
Control Group
Follow-up Time: 9 months
Outcomes
Durability
Not reported.
Vision
Best-Corrected Visual Acuity (BCVA)
The mean change over 9 months (Primary Outcome):
• PBM: +2.3 letters (SD 5.23)
• Sham: +2.04 letters (SD 3.34)
• Comparison: p-value= 0.85.
Vision Maintaining
Patients with vision loss (losing <15 letters) from baseline to Month 9:
• PBM: 3 patients (2.8%)
• Sham: Not reported
Patients with vision gain (gaining ≥15 letters) from baseline to Month 9:
• PBM: 6 (35.3%)
• Sham: 2 (16.6%)
Patients with ≥5-letter improvement from baseline to Month 9:
• PBM: 35.3%
• Sham: 16.6%.
Contrast Sensitivity (CS)
CS at 40 cm at Month 9:
• PBM: -0.003 (SD 0.12)
• Sham: 0.11 (SD 0.15)
• Comparison: p-value= 0.10
Other
Efficacy: Progression Outcomes
Geographic atrophy (GA)
• GA area size at baseline: PBM: 4.86 mm² (SD 6.32) vs. Sham: 6.65 mm² (SD 8.91)
• Change at Month 9: PBM: +0.73 mm² vs. Sham: +1.29 mm²
• 19.4% less GA growth in the PBM group.
Converted to Wet AMD
Throughout the course of the study, three eyes converted to wet AMD. One eye was in the sham treatment group, one eye was in the PBM treatment group, and one eye was a non-study eye that did not receive either treatment.
Quality of Life (QoL)
VFQ-25 Composite Scores
• The overall mean VFQ-25 composite scores in the PBM group were numerically higher than in the sham group at each time point but did not reach statistical significance.
• No statistically significant differences in change from baseline were observed between groups in VFQ-25-specific category subscales (p>0.05).
Reading Acuity (logRAD)
• No statistically significant effects were observed between PBM and sham groups on logRAD score, maximum reading speed, or critical print size at month 9 (p>0.05).
Immunognicity
Not reported.
Pharmokinetics
Not reported.
Anatomic
Macular Drusen Volume
The mean change from baseline to Month 9:
• PBM: 0.0003 (SD 0.04) mm³
• Sham: 0.03 (SD 0.14) mm³
Central Subfield Drusen Thickness
The mean change from baseline to Month 9:
• PBM: -0.71 (SD 13.24) µm
• Sham: 4.07(SD 14.36) µm
Safety
AEs
A total of 49 AEs were reported in addition to the SAEs
The most common AEs:
• Infections and infestations (n = 12, 24.5%)
• Nervous system disorders (n = 8, 16.3%)
• Respiratory, thoracic and mediastinal disorders (n = 8, 16.3%)
Ocular-related AEs
• PBM: 12 subjects
• Sham: 7 subjects.
Serious AEs
• A total of seven serious adverse events (SAEs) were reported during the study
• No SAEs were considered related to the Valeda device.
Death
One subject died prior to study completion. His passing was determined unrelated to the treatment.
Conclusion
PBM treatment improved BCVA and prevented drusen volume increase over 9 months. The study supports PBM as a novel non-invasive treatment for intermediate non-exudative AMD, warranting further research.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Low risk
Note: “An independent statistician not associated with the study generated the randomization tables and the codes…” No information on whether the two groups are balanced on baseline.
Missing Outcome Data
Low risk
Note: The evidence that the result was not biased by missing outcome data (sensitivity analysis): “Secondary analysis of sham-treated (n = 19) vs. PBM-treated (n = 32) eyes on BCVA change from baseline at month 9 showed…”
Selection of the Reported Results
Low risk Note: Registration with the protocol.
Deviations from Intended Observations
Low risk Note: This is a double-masked study. mITT principle was applied to the primary outcome analysis.
Measurement of the Outcome
Some concerns Note: This is a double-masked study, including the assessors. However, as a multiple-site study, the measurement of primary outcome may be inconsistent.
Overall
Some concerns
Categories: Dry AMD