LIGHTSITE III: 13-Month Efficacy and Safety Evaluation of Multiwavelength Photobiomodulation in Nonexudative (Dry) Age-Related Macular Degeneration Using the Lumithera Valeda Light Delivery System
NCT04065490 | LIGHTSITE III | Boyer D et al. (2024)
Boyer, D., Hu, A., Warrow, D., Xavier, S., Gonzalez, V., Lad, E., Rosen, R. B., Do, D., Schneiderman, T., Ho, A., Munk, M. R., Jaffe, G., Tedford, S. E., Croissant, C. L., Walker, M., Rückert, R., Tedford, C. LIGHTSITE III: 13-Month Efficacy and Safety Evaluation of Multiwavelength Photobiomodulation in Nonexudative (Dry) Age-Related Macular Degeneration Using the Lumithera Valeda Light Delivery System. Retina, 2024; 44:487–497.
Locations
10 centers in the United States
Study Period
Not reported
Study Design
Randomized, double-masked, sham-controlled trial
Study Population
Experimental Group
Control Group
Follow-up Time: 13 months
Outcomes
Durability
Not reported
Vision
Best-Corrected Visual Acuity (BCVA)
Mean BCVA change at 13 months (Primary Outcome):
• PBM = +5.4 ± 9.2 letters
• Sham = +3.0 ± 8.3 letters
• Difference = +2.4 letters (95% CI: 0.1 to 4.7, p = 0.02).
Proportion of Eyes Gaining ≥5 Letters
At 13 months:
• PBM: 54.9%
• Sham: 40.7%
• Difference = +14.2% (95% CI: 2.5 to 25.9, p = 0.018).
Proportion of Eyes Gaining ≥10 Letters
At 13 months:
• PBM: 25.8%
• Sham: 15.1%
• Difference = +10.7% (95% CI: 1.9 to 19.5, p = 0.021).
Proportion of Eyes Gaining ≥15 Letters
At 13 months:
• PBM: 4.4%
• Sham: 1.9%
• Difference = +2.5% (95% CI: -1.2 to 6.2, p = 0.19).
Other
Efficacy: Progression
New-Onset Geographic Atrophy At 13 months
• PBM: 1.1%
• Sham: 10.0%
• Difference = -8.9% (95% CI: -16.1 to -1.7, p = 0.024, odds ratio: 9.4).
Others
At 13 months:
• A total of one Sham eye (1.8%), five PBM-treated eyes (5.4%), and three nonstudy eyes (8.3%) converted to nAMD
• A numerical trend showed an increase in GA lesion area in Sham (1.48, SE 0.94; SD 1.62) compared with PBM-treated eyes (1.16, SE 0.66; SD 1.32, p = 0.75)
Immunognicity
Not reported
Pharmokinetics
Not reported
Anatomic
Drusen Volume
• No change in subRPE macular drusen volume was seen in PBMtreated eyes (0.006 mm3); however, an increase was seen in the Sham group (0.049 mm3).
• At Month 13, a statistically significant correlation was observed for measured macular drusen volume in PBM-treated eyes.
• Subjects with higher BCVA scores showed lower values for macular drusen volume in the PBM group (p =0.004).
Safety
Device-related AEs
• Only one ocular-specific SAE was reported and was not considered related to the treatment
• Four ocular-specific AEs were considered related to the treatment
Ocular AEs
Study eyes:
• PBM: 21/93, 22.6%
• Sham: 21/55, 21.8%
Conclusion
LIGHTSITE III demonstrated a significant improvement in BCVA and reduced risk of new-onset GA with PBM treatment in intermediate AMD. PBM was well-tolerated with a favorable safety profile.
Risk of Bias Assessment for Primary Outcome
Randomization Process
High risk
Note: No information on how to perform the randomization and allocation concealment. In addition, the basic characteristics of the two groups looks not balanced for some variables (Table 1).
Missing Outcome Data
Low risk
Note: There is evidence that the result was not biased by missing outcome data “… with the analysis of measured values considered to be a sensitivity analysis.”
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 and “modified intent-to-treat (mITT) analyses were conducted across outcomes.”
Measurement of the Outcome
Low risk Note: This is a double-masked study and “An independent, masked, imaging center reviewed and graded all images.”
Overall
High risk
Categories: Dry AMD Geographic Atrophy