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

Abstract

Purpose: The LIGHTSITE III study evaluated multiwavelength photobiomodulation (PBM) therapy in nonexudative (dry) age-related macular degeneration (AMD) using the LumiThera Valeda Light Delivery System.

Methods: LIGHTSITE III is a randomized, controlled trial to assess the safety and effectiveness of PBM in dry AMD. Subjects were given multiwavelength PBM (590, 660, and 850 nm) or Sham treatment delivered in a series of nine sessions over 3 to 5 weeks every four months over 24 months. Subjects were assessed for efficacy and safety outcomes. Data from the 13-month analysis are presented in this report.

Results: A total of 100 subjects (148 eyes) with dry AMD were randomized. LIGHTSITE III met the primary efficacy best-corrected visual acuity endpoint with a significant difference between PBM (n = 91 eyes) and Sham (n = 54 eyes) groups (Between group difference: 2.4 letters (SE 1.15), CI: -4.7 to -0.1, P = 0.02) (PBM alone: 5.4 letters (SE 0.96), CI: 3.5 to 7.3, P < 0.0001; Sham alone: 3.0 letters (SE 1.13), CI: 0.7-5.2, P < 0.0001). The PBM group showed a significant decrease in new onset geographic atrophy ( P = 0.024, Fisher exact test, odds ratio 9.4). A favorable safety profile was observed.

Conclusion: LIGHTSITE III provides a prospective, randomized, controlled trial showing improved clinical and anatomical outcomes in intermediate dry AMD following PBM therapy.

Fig. 1.

LIGHTSITE III study Design. Subjects were randomized in a 2:1 fashion (PBM:Sham treatment) and followed for 24 months. Data analyses were planned for Month 13 and Month 24. The PBM mode delivered 590, 660, and 850 nm multiwavelength treatment. The Sham mode delivered a 50x reduction of the 590 nm and a 100x reduction of the 660 nm wavelengths; the 850 nm was omitted. BL, baseline; M, month; R, randomized; Tx, treatment.

Fig. 2.

Diagram of LIGHTSITE III subject enrollment. A total of 100 subjects and 148 eyes were enrolled into the study.

Fig. 3.

Photobiomodulation improves BCVA in early/intermediate stage dry AMD. A. Subjects received PBM or Sham treatment at baseline, Month 4, Month 8 and Month 12 time points. Significant improvements in BCVA were observed through Month 13 following PBM treatment. B. At Month 13, nonstudy eyes showed a mean letter loss of 2.3 letters, Sham-treated eyes showed a mean letter gain of 3.0 letters, and PBM-treated eyes showed a mean letter gain of 5.4 letters. *Within-group (PBM) comparison, P < 0.005, ^PBM versus sham between-group comparison, P < 0.05. BL, baseline; M, month.

Fig. 4.

Distribution of BCVA letter gain and loss by treatment group at Month 13. A. Approximately 55.0% of PBM-treated eyes showed ≥5 letter gain (mean of 9.7 letters, SD 3.7) compared with 40.8% of Sham, 26.4% of PBM-treated eyes showed ≥ 10 letter gain (mean of 12.8 letters, SD 2.7) compared with 14.9% of Sham, and 5.5% of PBM-treated eyes showed ≥ 15 letter gain compared with 1.9% of Sham. B. A higher number of Sham-treated and nonstudy eyes showed BCVA letter losses compared with PBM as noted in the −11 to −15, −6 to −10, and −1 to −5 letter loss groups. A higher number of PBM-treated eyes showed BCVA letter gains in the 5 to 9, 10 to 14, 15 to 19, and ≥ 20 letter gain groups. * Patient had vision loss because of worsening of posterior capsule opacity. BL, baseline.

Fig. 5.

Impact of photobiomodulation on anatomical outcomes. A. A numerical increase in macular drusen volume was observed in Sham-treated eyes, ns, P > 0.05. B. Macular drusen volume increased 0.049 mm³ in Sham-treated eyes and 0.006 mm³ in PBM-treated eyes. The occurrence of new GA was observed in 5 of 51 (9.8%) Sham-treated eyes and one of 88 (1.1%) PBM-treated eyes. C. The occurrence of new GA was significantly higher in the Sham group than in the PBM group (P = 0.025, Fisher exact test, odds ratio 9.3). BL, baseline; M, month.

Fig. 6.

Representative imaging of macular drusen reduction following photobiomodulation treatment. A significant reduction in macular drusen volume was observed following four series of PBM treatment without the loss of photoreceptor or retinal pigment epithelium visible. A 4-letter increase in BCVA was observed from 75 letters to 79 letters at Month 13.

Fig. 7.

Representative imaging of macular drusen increase following Sham treatment. A significant increase in macular drusen volume was observed following four series of sham treatment with confluent drusen that further developed into large RPE detachments. A 3-letter decrease in BCVA was observed from 72 letters to 69 letters at Month 13. The subject subsequently converted to nAMD.