Double-Masked, Randomized, Sham-Controlled, Single-Center Study with Photobiomodulation for the Treatment of Dry Age-Related Macular Degeneration
Not reported | LIGHTSITE I Trial | Markowitz SN et al. (2020)
Markowitz SN, Devenyi RG, Munk MR, et al. A Double-Masked, Randomized, Sham-Controlled, Single-Center Study with Photobiomodulation for the Treatment of Dry Age-Related Macular Degeneration. Retina, 2020; 40(8):1471-1482.
Locations
Single-center study in Toronto, Canada
Study Period
Not reported
Study Design
Randomized, double-masked, sham-controlled, parallel-group study
Study Population
Experimental Group
Control Group
Follow-up Time: 1 year
Outcomes
Durability
Not reported
Vision
Best-Corrected Visual Acuity (BCVA) Baseline BCVA (mean ± SD) ETDRS letters:
• PBM: 73.8 ± 1.9
• Sham: 71.9 ± 2.5 The mean change (SD) in BCVA (ETDRS letters) from baseline to Month 1 → Month 2→ Month 3 → Month 6 → Month 7 → Month 9→ Month 12 (primary outcome):
• PMB: 3.8 (5.1)→2.6 (5.6) →4.1 (5.4 ) →2.4 (5.5) →4.3 (6.2)→ 1.2 (7.4)→ 0.5 (8.4)
• Sham: 1.2 (5.4)→2.7 (6.5)→1.4 (6.0)→0.4 (5.4)→1.7( 6.0) →2.0 (6.9)→ 0.6 (5.5) Vision Maintaining The proportion of eyes gaining ≥5 ETDRS letters at Month 1:
• PBM: 50%
• Sham: 13.6% Contrast Sensitivity Mean change in contrast sensitivity at Month 12 (Level E, 18 cycles/degree):
• PBM: +0.35±0.1 LogCS (Wilcoxon signed-rank test, P < 0.05) Mean change in contrast sensitivity over the first 6 months (Level D, 12 cycles/degree):
• PBM: a positive trend in benefits (Wilcoxon signed-rank test, P =0.45) Mean change in contrast sensitivity (Level B, 3 cycles/degree):
• Significant at 12 months between the PBM-treated and sham groups (P = 0.026)
• Not significant at any other time point Mean change in contrast sensitivity (Level A, 1.5 cycles/degree and Level C, 6 cycles/degree ):
• PBM versus Sham: not statistically significant (Wilcoxon signed-rank test, P> 0.05) The mean change in microperimetry assessment:
• No statistically significant reduction in bicurve ellipse area measure fixation stability (FS) was observed between PBM- or sham-treated subjects, LME model analysis (P > 0.05) at M1 or M12
Other
Quality of Life (QoL) General QoL The VFQ-25 QoL composite score improvement from baseline:
• PBM: M3 (P = 0.003), M7 (P = 0.015), and M9 (P = 0.003) (Wilcoxon signed-rank test)
• Sham: Did not demonstrate a statistically significant improvement (Wilcoxon signed-rank test, P >0.05)
Immunognicity
Not reported
Pharmokinetics
Not reported
Anatomic
Geographic Atrophy (GA) No difference in terms of GA lesion growth in the PBM-treated subjects compared with the sham-treated subjects after treatment at 12 months was recorded (Linear mixed-effects (LME) analyses, P> 0.05). Central Retinal Thickness (CRT) and Retinal Volume No statistically significant change in retinal volume or central retinal thickness was observed in the PBM- and sham-treated groups. Drusen Mean change in drusen volume at Month 12:
• PBM: 70% of eyes showed reduction
• Sham: 100% of eyes showed an increase
• LME: p = 0.05
• Mean change in central 1-mm drusen thickness:
• PBM vs. Sham: Statistically significant difference in M7 (LME, p=0.03)
• PBM vs. Sham: No statistically significant difference in M12 (LME, p=0.18)
Safety
AEs Patients with AEs:
• PBM: 4 with 16 events
• Sham: 7 with 5 events. Serious ocular AEs One case of neovascular AMD conversion in PBM group (4.2%). Non-ocular AEs Comparable between groups.
Conclusion
PBM improved BCVA and contrast sensitivity at multiple time points, with anatomical benefits in drusen volume. However, effects diminished over time, requiring repeated treatments. No major safety concerns were noted.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Some concerns
Note: No information on the randomization or allocation concealment method. In addition, no information on whether there is a baseline imbalance between the two groups.
Missing Outcome Data
Low risk
Note: The evidence of the primary outcome analysis was not biased by the missingness (adjustment): “Linear mixed-effects models were used to allow for the possibility of missing values at particular time points in ITT analyses.”
Selection of the Reported Results
Some concerns Note: The protocol was not available publicly.
Deviations from Intended Observations
Low risk Note: This is a double-masked study. “Analyses used the Intent to Treat (ITT) population…”
Measurement of the Outcome
Low risk Note: “Subjects and study staff were masked to the treatment.” “Subjects were assessed for BCVA using the ETDRS charts (Precision Vision).” This is a single-site study, the BCVA measurement should be consistent.
Overall
Some concerns
Categories: Dry AMD