LIGHTSITE OFTALMOLOGIA RETINA SESSIONS.pptx

LIGHTSITE OFTALMOLOGIA RETINA SESSIONS

1. PHOTOBIOMODULATION IN DRY AMD FELLOW F2- MURILLO SALES

2. Age-related macular degeneration (AMD) is a retinal disease that results in irreversible, severe loss of vision, including legal blindness. Compromises in quality of life (QoL). The prevalence of AMD is projected to affect 196 million by the year 2020 with an expected growth rate to 288 million in 2040 .

3. The advanced late-stage dry form of AMD, which accounts for 80% to 90% of the cases, is characterized by retinal pigment epithelium (RPE) and outer retinal atrophy, whereas only 10% to 20% develop the exudative, wet late-stage form, with choroidal neovascularization (CNV) as a hallmark of respective disease.

4. The use of photobiomodulation (PBM) involves targeted use of selected wavelengths of visible light to near infrared (NIR) light (500–1,000 nm) produced by a laser or a noncoherent light source such as light-emitting diodes. The driving mechanism behind these benefits suggests that the mitochondrial enzyme cytochrome C oxidase is a key photoacceptor of light in the far red to NIR spectral range. The beneficial effects of PBM are linked to increases in mitochondrial energy generation through ATP, replication, density, and activity and increases in RNA and protein synthesis.

5. Purpose: The LIGHTSITE I study investigated the efficacy and safety of photobiomodulation (PBM) treatment in subjects with dry age-related macular degeneration.

6. Methods SUBJECT SELECTION AND SETTING Dry AMD (AREDS) categories 2 to 4 BCVA scores as determined by the (ETDRS) with a letter score between 50 and 85 (Snellen equivalent of 20/40 to 20/200) Excluded: previous/active wet AMD, with a history of epilepsy, with cognitive impairment, other significant retinal disease, or other significant disease Subjects could use AREDS vitamin supplementation

7. Methods SUBJECT SELECTION AND SETTING A total of 40 subjects were screened for the study, of which 30 subjects were randomized into the study. Both eyes were included if inclusion criteria were met in both eyes. Therefore, an adapted AREDS classification was used A total of 46 eyes were treated and analyzed. This study took place at a single site located in Toronto, ON, Canada.

8. Study Design

9. Evaluated Parameters BCVA using the ETDRS charts (Precision Vision) CS at 1.5, 3, 6, 12, and 18 cycles per degree (Levels A–E) (FACT, Stereo Vision Optec 6500) Quality of life was assessed using the visual function questionnaire-25 (VFQ-25) Retinal sensitivity was recorded using microperimetry C10-2 grid with 68 tested points (MAIA; Centervue )

10. Evaluated Parameters High-speed SD-OCT volume scans ( Spectralis OCT; Heidelberg Engineering, Heidelberg, Germany) Fundus autofluorescence (FAF) imaging with 488-nm wavelength ( Spectralis OCT; Heidelberg Engineering)

11. Evaluated Parameters SD-OCTS AND FAF WERE ANALYZED FOR FOLLOWING PARAMETERS: aligned mean central retinal thickness aligned mean retinal volume GA lesion área aligned drusen volume presence of reticular pseudodrusen refractile drusen incomplete and complete outer retinal atrophy incomplete and complete RPE and outer retinal atrophy ( iRORA and cRORA [ corresponds to GA]) evidence of a CNV ( pseudo ) vitelliform lesions and irregularity / disruption of the external limiting membrane ellipsoid zone, and interdigitation zone were assessed

12. Photobiomodulation Treatment

13. https://www.youtube.com/watch?v=lCETovOyEZA

14. Results 30 subjects for a total of 46 qualifying eyes The mean age was 76 years (±8.3) Women (60%) Men (40%) The median duration of dry AMD was 7.8 years (±7.6) since diagnosis.

15. Results

16. Best- Corrected Visual Acuity Assessment

17. Best- Corrected Visual Acuity Assessment

18. Best- Corrected Visual Acuity Assessment The Snellen population comparison suggests eyes that most significantly respond to PBM treatment are eyes with remaining good baseline vision at Snellen equivalents of 20/100 or better.

19. Contrast Sensitivity Assessment

20. 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.

21. Quality of Life Assessment (VFQ-25) The PBM-treated subjects demonstrated a statistically significant improvement in the QoL composite score at M3 (P = 0.003), M7 (P = 0.015), and M9 (P = 0.003) and select questions related to activities of daily living at M3, M7, and M9. The sham group did not demonstrate a statistically significant improvement (P > 0.05) in any assessment.

22. Anatomical Assessments

23. Safety Assessment

24. Discussion first double-masked, randomized, sham-controlled, parallel group study to evaluate PBM in subjects with dry AMD The results from the study illustrate positive benefits after PBM treatment in both clinical and anatomical outcomes in subjects with dry AMD The high number of subjects with advanced stage AMD contributed to the reduced overall benefits seen in BCVA letter score in the intent-to-treat group analysis. Any visual gain in this patient population, which has not experienced rapid profound vision loss due to CNV, should be considered clinically relevant.

25. Methods Subjects were eligible for trial if they were at least 50 years of age Had a diagnosis of non-exudative AMD Visual Acuity chart with a letter score between 50 and 80 (Snellen equivalent of 20/25 to 20/100). Excluded: current or a history of macular neovascularization, presence of center involving GA within the central ETDRS 500 μm diameter, a history of epilepsy, other significant retinal disease or other significant disease. Subjects could use AREDS vitamin supplementation. An adapted AREDS classification was used

26. Study Design

27. Study Design ETDRS BCVA Mars letter CS Radner reading chart and Visual Function Questionnaire-25 (VFQ-25) Heidelberg optical coherence tomography (OCT) Fundus autofluorescence (FAF) Imaging optional Optos UWF ( ultra-widefield ) color and UWF autofluorescence imaging of the retina The subRPE macular drusen volume was assessed within the whole 6 × 6-mm ETDRS grid, while the mean central subfield subRPE drusen thickness was analyzed within the central 1-mm ETDRS subfield.

28. Photobiomodulation Treatment with Valeda Light Delivery System

29. COVID-19 Interference In March 2020, all clinical sites were contacted to inform them that LumiThera had decided to suspend new patient enrollment into the LIGHTSITE II study. The study remained on hold for 11 + weeks The protocol continued to define the earliest time points subjects could be seen for the month 4, 8 and 10 visits, but did not provide a specific window for time points beyond the ideal visit date.

30. Results

31. Efficacy Assessments

32. Safety Assessments

33. Discussion Demonstrated positive PBM benefits on efficacy and safety outcomes in subjects with non-exudative AMD. Interference from the COVID-19 pandemic

34. Methods Same as Lightsite II Subjects were enrolled across 10 centers throughout the United States

35. Study Design

36. Evaluated Parameters BCVA ( change from baseline) low-luminance BCVA (LLBCVA) Mars letter contrast sensitivity Radner reading speed Farnsworth–Munsell D-15 dichotomous color vision testing Visual function questionnaire-25 (VFQ-25) SD -(OCT) volume scans , fundus autofluorescence (FAF), and fundus photography ( Spectralis optical coherence tomography , Heidelberg Engineering , Heidelberg, Germany )

37. Tratamento de fotobiomodulação com Valeda Light Delivery System Same as Lightsite II

38. Results

39. Efficacy Assessments

40. Efficacy Assessments Secondary and exploratory evaluation of LLBCVA, contrast sensitivity, Radner reading charts, and the VFQ-25 showed normal or near normal visual outcomes at baseline, which were stable through the 13-month time point in both groups

41. Anatomical Outcomes

42. Safety and Compliance Outcomes

43. Discussion The study met the predetermined primary efficacy endpoint with a statistically significant difference in BCVA between the PBM versus Sham treatment groups. A mean letter gain ≥ 5 letters was observed following PBM. Furthermore, 55.0% of PBM-treated eyes showed ≥ 5 letter gain, and 26.4% showed ≥ 10 letter gain. Earlier stage dry AMD patients with better vision are not capable of large magnitude gains as seen in later stage patients with worse BCVA.

44. Drusen GA

45. OBRIGADO