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. 2023 Apr;12(2):953-968.
doi: 10.1007/s40123-022-00640-6. Epub 2023 Jan 2.

LIGHTSITE II Randomized Multicenter Trial: Evaluation of Multiwavelength Photobiomodulation in Non-exudative Age-Related Macular Degeneration

Ben Burton  1 , Maurizio Battaglia Parodi  2 , Ignasi Jürgens  3 , Xavier Zanlonghi  4 , Dan Hornan  5 , Johann Roider  6 , Katrin Lorenz  7 , Marion R Munk  8 , Cindy L Croissant  9 , Stephanie E Tedford  10 , Michael Walker  9 , Rene Ruckert  9 , Clark E Tedford  9
Affiliations

LIGHTSITE II Randomized Multicenter Trial: Evaluation of Multiwavelength Photobiomodulation in Non-exudative Age-Related Macular Degeneration

Ben Burton et al. Ophthalmol Ther. 2023 Apr.

Abstract

Introduction: Photobiomodulation (PBM) represents a potential treatment for non-exudative age-related macular degeneration (AMD). PBM uses wavelengths of light to target components of the mitochondrial respiratory chain to improve cellular bioenergetic outputs. The aim of this study was to further investigate the effects of PBM on clinical, quality of life (QoL) and anatomical outcomes in subjects with intermediate stage non-exudative AMD.

Methods: The multicenter LIGHTSITE II study was a randomized clinical trial evaluating safety and efficacy of PBM in intermediate non-exudative AMD. The LumiThera Valeda® Light Delivery System delivered multiwavelength PBM (590, 660 and 850 nm) or sham treatment 3 × per week over 3-4 weeks (9 treatments per series) with repeated treatments at baseline (BL), 4 and 8 months. Subjects were enrolled with 20/32 to 20/100 best-corrected visual acuity (BCVA) and no central geographic atrophy (GA) within the central fovea (500 μm).

Results: LIGHTSITE II enrolled 44 non-exudative AMD subjects (53 eyes). PBM-treated eyes showed statistically significant improvement in BCVA at 9 months (n = 32 eyes, p = 0.02) with a 4-letter gain in the PBM-treated group versus a 0.5-letter gain in the sham-treated group (ns, p < 0.1) for patients that received all 27 PBM treatments (n = 29 eyes). Approximately 35.3% of PBM-treated eyes showed ≥ 5-letter improvement at 9 months. Macular drusen volume was not increased over time in the PBM-treated group but did show increases in the sham-treated group. While PBM and sham groups both showed GA lesion growth in the trial period, there was 20% less growth in the PBM group over 10 months, suggesting potential disease-modifying effects. No safety concerns or signs of phototoxicity were observed.

Conclusion: These results confirm previous clinical testing of multiwavelength PBM and support treatment with Valeda as a novel therapy with a unique mechanism of action as a potential treatment for non-exudative AMD.

Trial registration: Clinicaltrial.Gov Registration Identifier: NCT03878420.

Keywords: Age related macular degeneration; Mitochondria; Multiwavelength; Ocular disease; Photobiomodulation; Vision.

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Conflict of interest statement

Ben Burton, Maurizio Battaglia Parodi, Ignasi Jürgens, Xavier Zanlonghi, Dan Hornan, Johann Roider and Katrin Lorenz were PIs in the LIGHTSITE II trial and received support from LumiThera for their efforts. Ben Burton received support from LumiThera for his efforts including honoraria fees, funding/hospitality to support attendance at conferences and support for commercially funded research for LumiThera and uses the LumiThera Valeda in his private practice. Maurizio Battaglia Parodi is a consultant for Novartis. Ignasi Jürgens was a PI in the LT2 trial and received support from LumiThera for his efforts. Dan Hornan is a consultant for Reneo Pharmaceuticals; Eye Department at Peterborough Hospital was lent an Optos imaging device by the Sponsor. Michael Walker is a statistics consultant for LumiThera. Marion R. Munk is a consultant for LumiThera, Ocuterra, RetinAI, Isarna Therapeutics, Bayer, Novartis, Roche, Abbvie, Gensight Therapeutics, Kubota, Helbling and Zeiss. Stephanie Tedford, Cindy L. Croissant, Clark E. Tedford and Rene Ruckert are all employees of LumiThera.

Figures

Fig. 1
Fig. 1
LIGHTSITE II study design. The study employed a prospective, randomized, double-masked clinical trial design to evaluate the safety and efficacy of PBM in intermediate non-exudative AMD subjects. Data were collected during 31 visits over the course of the 10-month study. AMD age-related macular degeneration, BCVA best-corrected visual acuity, BL baseline, M month, PBM photobiomodulation, Tx treatment
Fig. 2
Fig. 2
LIGHTSITE II subject disposition. Data from one subject was dropped because of an eligibility violation and one subject discontinued due to personal reasons. The full protocol sub-stratification analysis included all subjects that completed all treatment visits. PBM photobiomodulation
Fig. 3
Fig. 3
PBM effect on visual and anatomical outcomes. A A statistically significant improvement in BCVA at M9 was seen within PBM-treated subjects (MITT, n = 32 eyes), p = 0.02. B A ~ 4-letter BCVA improvement was seen in PBM-treated subjects vs. 0.5 letters in sham subjects that completed the full protocol (n = 29 eyes). C A numerical increase in macular drusen growth was observed in sham subjects over time. No macular drusen growth was observed in PBM-treated subjects (ns, p > 0.05; n = 36 eyes). Data presented include least squared means plus standard error means. BCVA best-corrected visual acuity, BL baseline, M month, PBM photobiomodulation, Tx treatment
Fig. 4
Fig. 4
Representative OCT B-scans of macular drusen volume changes in PBM (A,B) and sham (C,D) subjects that completed all study treatments. A PBM subject with overall ETDRS drusen volume of 0.61 mm3 at baseline. B At end of study (month 10), the PBM subject showed a reduction in macular drusen volume to 0.56 mm3. C Sham subject with overall ETDRS drusen volume of 1.07 mm3 at baseline. D At end of study (month 10), the sham subject showed an increase in macular drusen volume to 1.10 mm3. Segmentation of Bruch’s membrane (red line) and the RPE (blue line). ETDRS early treatment diabetic retinopathy study, PBM photobiomodulation
Fig. 5
Fig. 5
Representative FAF scans of geographic lesion growth in PBM and sham subjects that completed all study treatments. The hypoFAF lesions, corresponding to the GA lesions, were semiautomatically assessed using the Heidelberg region finder and marked in blue. A PBM subject showing overall lesions of 0.58 mm2 at baseline. B At end of study (month 10), the lesions had grown to 0.78 mm2. Following PBM treatment, the difference in lesion area was 0.16 mm2. C Sham subject showing overall lesions of 20.53 mm2 at baseline. D At the end of study (month 10), the lesion exceeded the image. The measured area was 25.6 mm2. Following sham treatment, the difference in lesion area was 5.07 mm2. FAF fundus autofluorescence
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