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.

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.

Ocular Therapeutics and Molecular Delivery Strategies for Neovascular Age-Related Macular Degeneration (nAMD).

Age-related macular degeneration (AMD) is the leading cause of vision loss in geriatric population. Intravitreal (IVT) injections are popular clinical option. Biologics and small molecules offer efficacy but relatively shorter half-life after intravitreal injections. To address these challenges, numerous technologies and therapies are under development. Most of these strategies aim to reduce the frequency of injections, thereby increasing patient compliance and reducing patient-associated burden. Unlike IVT frequent injections, molecular therapies such as cell therapy and gene therapy offer restoration ability hence gained a lot of traction. The recent approval of ocular gene therapy for inherited disease offers new hope in this direction. However, until such breakthrough therapies are available to the majority of patients, antibody therapeutics will be on the shelf, continuing to provide therapeutic benefits. The present review aims to highlight the status of pre-clinical and clinical studies of neovascular AMD treatment modalities including Anti-VEGF therapy, upcoming bispecific antibodies, small molecules, port delivery systems, photodynamic therapy, radiation therapy, gene therapy, cell therapy, and combination therapies.

Photobiomodulation therapy in age-related macular degeneration.

PURPOSE OF REVIEW: To review the available data supporting the use of photobiomodulation therapy (PBT) in the treatment of age-related macular degeneration (AMD). RECENT FINDINGS: PBT might be used in treating nonexudative AMD. Limited evidence suggests that exudative AMD may also benefit from PBT. SUMMARY: The optimal device would deliver doses of 60 J/cm2 or more with a multiwavelength composition through the pupil over short treatment intervals. Safe upper limits have not been established. More studies are needed to evaluate the efficacy of PBT in treating exudative and nonexudative AMD.

A DOUBLE-MASKED, RANDOMIZED, SHAM-CONTROLLED, SINGLE-CENTER STUDY WITH PHOTOBIOMODULATION FOR THE TREATMENT OF DRY AGE-RELATED MACULAR DEGENERATION.

PURPOSE: The LIGHTSITE I study investigated the efficacy and safety of photobiomodulation (PBM) treatment in subjects with dry age-related macular degeneration. METHODS: Thirty subjects (46 eyes) were treated with the Valeda Light Delivery System, wherein subjects underwent two series of treatments (3× per week for 3-4 weeks) over 1 year. Outcome measures included best-corrected visual acuity, contrast sensitivity, microperimetry, central drusen volume and drusen thickness, and quality of life assessments. RESULTS: Photobiomodulation-treated subjects showed a best-corrected visual acuity mean letter score gain of 4 letters immediately after each treatment series at Month 1 (M1) and Month 7 (M7). Approximately 50% of PBM-treated subjects showed improvement of ≥5 letters versus 13.6% in sham-treated subjects at M1. High responding subjects (≥5-letter improvement) in the PBM-treated group showed a gain of 8 letters after initial treatment (P < 0.01) and exhibited earlier stages of age-related macular degeneration disease. Statistically significant improvements in contrast sensitivity, central drusen volume, central drusen thickness, and quality of life were observed (P < 0.05). No device-related adverse events were reported. CONCLUSION: Photobiomodulation treatment statistically improved clinical and anatomical outcomes with more robust benefits observed in subjects with earlier stages of dry age-related macular degeneration. Repeated PBM treatments are necessary to maintain benefits. These pilot findings support previous reports and suggest the utility of PBM as a safe and effective therapy in subjects with dry age-related macular degeneration.