{"paper_id":"276323b5-3df4-4ec9-94bb-3ac8e4abd2f8","body_text":"Prospective Study of Safety and Biomarkers Using Multimodal Analysis with Swept-Source Oct and Oct-Angiography in Patients with Dry Age Related Macular Degeneration Treated with Photobiomodulation. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prospective Study of Safety and Biomarkers Using Multimodal Analysis with Swept-Source Oct and Oct-Angiography in Patients with Dry Age Related Macular Degeneration Treated with Photobiomodulation. Marcussi Palata Rezende, Fernanda Atoui Faria, Julia Polido, Rubens Belfort Jr, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5424107/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: The Photobiomodulation-Valeda device is an innovative approach for treating dry age-related macular degeneration (AMD). The main objective of this study was to conduct a multimodal imaging analysis using swept-source technology in OCT (SS-OCT) and OCT-Angiography (SS-OCTA) in patients with dry AMD treated with Photobiomodulation (PBM), focusing primarily on safety and biomarkers. Materials and Methods: A prospective interventional study was conducted involving 19 patients (25 eyes) diagnosed with dry AMD. The treatment consisted of nine sessions of PBM using the Valeda Light Delivery System. Various biomarkers were assessed before and one week after the treatment, including Best Corrected Visual Acuity (BCVA) for logMAR, central macular thickness (CMT), subfoveal choroidal thickness (SCT), capillary density (CD), and avascular areas of the superficial (AASP) and deep plexus (AADP). Results: The study included 25 eyes, predominantly in AREDS category II. Significant improvements were observed in BCVA (p = 0.001). No significant changes were observed in CMT, SCT, CD, AASP, and AADP (p > 0,05). The treatment was well tolerated, with few mild side effects, and no patient developed wet AMD. Conclusion: PBM-Valeda therapy shows promise as a treatment strategy for dry AMD, resulting in improved visual acuity (as previously demonstrated in Lightsite I, II, and III). It is important to emphasize the safety of the treatment, as none of the biomarkers (CMT, SCT, CD, AASP, and AADP) exhibited harmful changes. Side effects were minimal, there were no signs of retinotoxicity, and no patient developed exudative AMD, after 1 cycle: 9 sessions of PBM treatment. photobiomodulation multiwavelength dry age-related macular degeneration swept-source optical coherence tomography OCT OCT-A OCT angiography ocular disease vision retina Figures Figure 1 INTRODUCTION Age-related macular degeneration (AMD) is a leading cause of vision impairment in people over the age of 50 in Western countries, often resulting in irreversible vision loss. As the population continues to age, the number of AMD cases in the USA is projected to increase from 2.7 million in 1970 to 7.5 million by 2030. In Brazil, although there are no population-based studies to determine the exact impact of AMD, it is estimated that 3 million elderly individuals are affected by the disease at various stages. AMD is categorized into two types: dry and neovascular. Neovascular AMD is characterized by choroidal neovascularization (CNV), where abnormal blood vessels grow between the retinal pigment epithelium (RPE) and Bruch's membrane, or between the sensory retina and the RPE. While neovascular AMD represents only about 10% of all AMD cases, it accounts for approximately 80% of legal blindness caused by the disease. 1 , 5 The Age-Related Eye Disease Study (AREDS) classified AMD into categories based on the presence of drusen, atrophy, and neovascularization. Drusen were classified as small (< 63 µm in diameter), intermediate (63–124 µm), or large (> 125 µm). AREDS categories of AMD were defined as: 1) No AMD: if there were fewer than five small drusen; 2 ) Early or Mild AMD: based on the identification of multiple small drusen or at least one intermediate-sized drusen; 3) Intermediate AMD: classified by extensive intermediate-sized drusen, more than one large drusen, or non-central geographic atrophy (GA); and 4) Advanced AMD: determined by central GA or CNV causing vision loss, defined as visual acuity (VA) worse than 20/32 in one eye. Treatment for wet AMD involves periodic intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) compounds. However, the more common dry form of AMD has fewer treatment options, with lifestyle changes and vitamin supplements being the main recommendations. This underscores the urgent clinical need for the development of new treatment strategies as the number of affected individuals continues to rise. 5 , 6 , 7 In the US, there were no approved treatments for the early or intermediate stages of dry AMD, other than antioxidant supplementation, which only slows disease progression in 20–25% of cases, 8 , 9 but recently (November 2024) the FDA approved PBM-Valeda for the treatment of patients with dry AMD. In contrast, in the European Union and Brazil, the management of dry AMD with Multiwavelength Photobiomodulation – VALEDA (PBM-VALEDA) has already been approved by drug regulatory agencies (similar to the FDA in the USA). PBM-VALEDA is a well-established biotechnology that utilizes light from the visible spectrum to near-infrared (NIR) (500-1,000 nm) to target specific tissues, producing beneficial cellular effects. The mechanism of PBM involves stimulating components of the mitochondrial respiratory chain, which helps stabilize metabolic functions and activates signaling pathways that promote cell proliferation and protection. Cytochrome C oxidase is recognized as the main photoacceptor of light within the far-red to NIR range. Its activation enhances the efficiency of the electron transport chain, leading to increased ATP production, the primary energy source for cells. 6 , 8 , 9 LumiThera developed the first multiwavelength PBM device to treat dry AMD. Valeda is designed to emit 590 nm, 660 nm, and 850 nm wavelengths using specific light-emitting diodes (LEDs). The use of 590 nm was selected based on its ability to inhibit vascular endothelial growth factor (VEGF) expression in retinal cell cultures following exposure to PBM at various wavelengths. 10 , 11 The 660 nm and 850 nm wavelengths were selected based on their direct interaction with cytochrome c oxidase (CcO). CcO is an enzyme located in the inner mitochondrial membrane and is part of complex IV of the electron transport chain, serving as a target chromophore for both wavelengths. 11 , 12 Near-infrared (850 nm) is known to be absorbed by copper CuA moieties within CcO, which are important for supporting electron flow from cytochrome C into the CcO complex. Red (660 nm) wavelengths are known to be absorbed by copper CuB moieties within CcO and have been demonstrated to enhance O₂ binding at the active site. 11 , 13 Both wavelengths have independent stimulatory effects on CcO enzyme activity, thereby restoring mitochondrial membrane potential and leading to enhanced ATP production. 11 Multiple studies across different conditions have consistently shown improvements in both clinical and anatomical results after PBM therapy. Recent ophthalmological clinical trials, including LIGHTSITE I, II, and III, examined the effects of multiwavelength PBM using the Valeda light therapy system, reporting enhancements in clinical vision outcomes and anatomical indicators of the disease. In conclusion, these three major studies—LIGHTSITE I, II, and III—indicate that PBM-VALEDA treatment enhances visual acuity, reduces central drusen volume, and improves contrast sensitivity. 6 , 8 , 9 Swept-source Optical Coherence Tomography (SS-OCT) is a novel modality with higher resolution and speed than spectral-domain OCT (SD-OCT) for retina imaging. This device (SS-OCT) operates at a speed of 100,000 A-scans per second and provides an 8 µm axial resolution in tissue with a 1050 nm wavelength. In addition, the automatic measurement and three-dimensional (3D) reconstruction of regional imaging result in more reproducible and reliable measurements of choroidal thickness. The dispersion caused by the retinal pigmented epithelium (RPE) is reduced by using a longer laser wavelength (1050 nm) in SS-OCT scans, which provides a clearer boundary of the choroid-scleral interface. 14 , 15 Therefore, swept-source technology is the best option for studying choroidal thickness (one of the objectives of this study) because its longer wavelength allows for deeper tissue penetration, providing a better analysis of these structures. 14 , 15 The main objective of this research was conducted to a multimodal image evaluation using swept-source technology in SS-OCT and SS-OCT-Angiography (SS-OCT-A) exams in patients with dry age-related macular degeneration (AMD) treated with PBM-VALEDA. We analyzed side effects, possible progression to exudative AMD, and key biomarkers before and after treatment, which are as follows: best corrected visual acuity (VA LogMAR), central macular thickness (CMT), capillary density (CD), subfoveal choroidal thickness (SFCT), avascular area of the superficial plexus (AASP), and avascular area of the deep plexus (AADP). Methods A prospective interventional case series was conducted with a sample of 18 patients (22 eyes) diagnosed with AMD who had not previously received any treatment, aside from vitamin supplementation. The participants were recruited originating from the Retina Department at the Instituto de Oftalmologia de Presidente Prudente, SP, Brazil. A) Inclusion Criteria : Participants were considered eligible for the study if they fulfilled the following requirements: They were aged 50 or older, had a diagnosis of dry AMD characterized by the presence of drusen, and were taking mineral and antioxidant supplements as recommended by AREDS-2. They had nonfoveal center geographic atrophy (GA). Their best corrected visual acuity (BCVA), assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) and the Snellen Chart, ranged between 20/25 and 20/200. They had complete medical records, which included information such as sex, age, current medications, pre- and postoperative intraocular pressure (IOP), BCVA before and after the procedure, as well as SS-OCT and SS-OCTA scan results. They provided signed informed consent forms, which were documented in their medical records. B) Exclusion Criteria : Participants were excluded from the study if: They had a background of choroidal neovascularization (CNV). They had center-involving geographic atrophy (GA). They had other major retinal conditions such as diabetic retinopathy, epiretinal membrane, macular hole, or retinal dystrophies. They had other ophthalmological conditions, such as glaucoma. They had undergone previous eye surgeries, such as for retinal detachment or glaucoma. They discontinued treatmen Ethical Committee: The study was carried out in accordance with the guidelines outlined in Resolution 196/96 of the National Health Council of the Ministry of Health. The research protocol was submitted for analysis and received approval (28 September 2023) from the Ethics Committee of the Universidade do Oeste Paulista – UNOESTE – Presidente Prudente, SP (CAAE—70635623.5.0000.5515). Study Design: The participants underwent treatment with the Multiwavelength Valeda Light Delivery System (LumiThera, Inc., Poulsbo, WA), undergoing a total of nine sessions over a three-week period. Ophthalmological examinations, BCVA, IOP, biomicroscopy, retinal mapping, red-free, fundus autofluorescence (FAF), AREDS classification (Categories I to IV), SS-OCT, and SS-OCT-A were performed on the day PBM treatment began (baseline). These examinations were repeated one week after the end of the PBM treatment. Since the treatment lasted 3 weeks (21 days), the first assessment was carried out on day 1, immediately before starting treatment (baseline or pre-treatment), and the post-treatment assessment on day 28. The BCVA assessment involved a comprehensive refraction protocol and visual sharpness assessment, conducted using certified equipment and within standardized examination rooms. The SS-OCT and SS-OCT-Angiography (DRI-OCT Triton; Topcon – Tokyo, Japan) instrument was used to obtain high-definition images of the retina and choroid. The resulting images were analyzed by the automated layer segmentation software built into the SS-OCT system. In the SS-OCT examination, 7x7 mm scans were used, and in the SS-OCT-A, 4.5x4.5 mm scans were used. All OCT scans were conducted by the same experienced technician, who was blind to the study protocol. Retinal thickness was defined as the distance between the vitreoretinal interface and the RPE. Choroidal thickness was measured as the distance between the outer border of the RPE and the chorio-scleral border. Automated built-in calibration software determined the distance between these two lines. After the choroidal thickness map was obtained, the ETDRS grid was applied to the map. Using the averaged OCT images, we also measured central retinal thickness and choroidal thickness at the center of the fovea. Two investigators reviewed each line of the vitreoretinal interface, RPE, and chorio-scleral border in all images to confirm correct segmentation, with manual adjustments made if necessary. The avascular areas of the superficial and deep plexus, obtained by SS-OCTA, were manually assessed by an ophthalmologist and retinologist, confirmed by another professional. In case of discrepancies, a new expert was consulted. Capillary density was automatically provided by the device's software. Photobiomodulation Treatment with the Valeda Light Delivery System: Participants received treatment with the Valeda system using three specific wavelengths: yellow (590 nm; 4 mW/cm²; 2 x 35 seconds), red (660 nm; 65 mW/cm²; 2 x 90 seconds), and near-infrared (850 nm; 0.6 mW/cm²; 2 x 35 seconds). A total of nine treatment sessions were administered over a 3-week period. Data analysis: Statistical analysis was performed using Stata, version 17 (StataCorp LLC), and SPSS, version 20 (IBM Corp). The data were expressed as mean ± SD, median (interquartile range), or frequencies, depending on the nature of the characteristic evaluated. The means of measurements between two time points were evaluated using random effects models to account for possible dependence between eyes of the same patient. The normality of the distribution was assessed using the Kolmogorov-Smirnov test. The tests were two-sided, and P values of < 0.05 were considered significant. RESULTS The study included 25 eyes of 19 patients. According to Table 1, it is observed that 9 patients were female (47.4%) and 10 patients were male (52.6%). The mean age was 72.6 years (SD = 11.2 years), with a minimum age of 56 years and a maximum of 94 years. Of the 19 patients treated, 6 patients had both eyes treated (31.6%) and 13 were treated in just one eye (68.4%). Of the 13 patients whose contralateral eye was not treated, 6 (46.15%) had exudative AMD (treated with intravitreal injection of aflibercept 40 mg/ml), and 7 (53.85%) were diagnosed with dry AMD. These untreated eyes did not meet the inclusion criteria or were within the criteria for exclusion of this study. It is also noted that 48% of the treated eyes (12 eyes) were on the right side and 52% (13 eyes) were on the left side. According to the AREDS classification of the 25 eyes (Table 2): 16 eyes (64%) were in Category II, 9 eyes (36%) were in Category III, and no eyes fell into Categories I and IV. Table 3 shows all the biomarkers evaluated. We can see that AV LogMAR presented a baseline average of 0.38 (20/48 on the Snellen table), and post-treatment it was 0.32 (20/42), with statistical significance of p = 0.001 (Graph 1). On the other hand, CMT, SCT, CD, AASP, and AADP did not show statistical significance (Graphs 2 to 6). The mean CMT varied from 234.56 microns (µm) at baseline to 236.08 µm post-treatment (p = 0.198). The mean SCT varied from 163.00 µm at baseline to 161.8 µm post-treatment (p = 0.546). CD varied from 15.08 to 15.62 (p = 0.567), AASP from 187,644.80 µm² to 177,198.24 µm² (p = 0.466), and AADP from 268,296.72 µm² to 270,879.44 µm² (p = 0.865). In Table 4, we find all the biomarkers studied with their respective characteristics and summary measurements. In Figure 1, we observe the multimodal study with SS-OCT and SS-OCTA of the left eye of a 60-year-old patient included in this study, diagnosed with dry AMD. This image details the measurements between pre- and post-treatment of CMT and SCT in µm. CD, AASP, and AADP are measured in µm². No patient discontinued treatment due to side effects. The main side effect was dry eye, reported by 3 of the 19 patients, and the second was pruritus in 2 patients. These symptoms improved with the use of lubricating eye drops. There were no serious side effects, and no patient progressed to the exudative form of AMD. An important subjective observation in the study was that 15 of the 19 patients treated reported an improvement in visual acuity and a better subjective perception of color/contrast sensitivity. The remaining 4 patients reported stable AV. No patient complained of a worsening in VA after treatment with PB-VALEDA. IOP also did not show a notable difference, with a value of 12.68 ± 1.30 pre-treatment and 12.79 ± 1.44 post-treatment (p = 0.641). DISCUSSION The present study provides valuable information regarding the security and biomarkers associated with the use of swept-source technology in OCT and OCT-A examinations for patients affected by dry AMD treated with PBM-Valeda. We observed a significant improvement in VA-LogMAR with PBM-Valeda, a result consistent with findings already reported in the literature, such as in the LIGHTSITE I, II, and III studies, among others. In summary, PBM therapy in patients affected by dry AMD demonstrates: improved visual acuity (VA), enhanced contrast sensitivity, reduced central drusen volume, improved quality of life, and decreased progression of geographic degeneration. 6 , 8 , 9 , 19 The significant improvement in VA-LogMAR was measured in the study by Merry GF et al 18 immediately after the end of treatment (3 weeks) and at 3 months. In our study, it was measured 1 week after the end of treatment with PBM (1 month after baseline), showing improvement in VA-LogMAR. Similarly, LIGHTSITE I 6 also showed improvement in VA 1 month after baseline. According to the AREDS classification of the 25 eyes (Table 2 ): 16 eyes (64%) were in Category II, 9 eyes (36%) were in Category III, and no eyes fell into Categories I or IV. Regarding the AREDS classification, in our study, we had the distribution of patients in Categories II and III, with a predominance in Category II. Out of a total of 25 eyes, 16 eyes (64%) were in Category II, and 9 eyes (36%) were in Category III, with no eyes in Categories I or IV. In contrast, the main group observed in the following studies was in Category III: LIGHTSITE III (86.9%) and LIGHTSITE II (64.70%). In LIGHTSITE I, the majority of patients were in Category IV (67.4%) and Category III (30.4%). The CMT in normal patients is around 230 µm. The average CMT in patients affected by dry AMD, as measured in our study, was 234.56 µm, which is consistent with findings in the literature. 20 Affected by dry AMD, studies show that macular retinal thickness tends to become thinner as the disease progresses and approaches geographic atrophy. As Giani et al. demonstrated in their study, the average CMT in patients affected by dry AMD was 220 µm. 9 , 20 In our study, all patients were using vitamin supplementation according to the AREDS 2 study. Antioxidant and mineral supplementation can slow the advancement of nonexudative AMD to exudative AMD. For many years, the only proven supplement for nonexudative AMD was based on the findings of the Age-Related Eye Disease Study (AREDS) formulation, consisting of vitamin C, vitamin E, beta-carotene, zinc, and copper, which demonstrated a 25% reduced risk of severe vision loss in subjects with intermediate-sized drusen, at least one large druse, noncentral GA, or advanced AMD over 5 years. Subsequent supplementation trials included the AREDS 2 formula, which modified the compound by replacing beta-carotene with lutein and zeaxanthin. 21 The key finding of our study is the lack of significant change in biomarkers (CMT, SCT, CD, AASP, AADP) between pre- and post-treatment, confirming PBM's safety as shown in LIGHTSITE studies. The study focused on evaluating biomarker changes affected by dry AMD patients treated with PBM-Valeda, without using a control group. In this study, PBM-Valeda treatment was well tolerated, with a low occurrence of side effects, all of which were mild. This aligns with previous research that also demonstrated a favorable risk-benefit profile, a low occurrence of side effects, and no evidence of retinal toxicity, reinforcing that it is a highly safe and well-tolerated therapy. 6 , 8 , 9 , 22 CONCLUSION Based on our study, we conclude that PBM-VALEDA therapy could present a novel therapy option with a distinct mechanism and approach for patients with nonexudative AMD. Improvement in visual acuity, few non-serious side effects, absence of retinotoxicity, absence of progression to wet AMD during the study period, and no significant variation in biomarkers (CMT, SCT, CD, AASP, and AADP) as analyzed by SS-OCT and SS-OCTA after therapy using PBM (1 cycle: 9 sessions) all support the conclusion that this treatment is safe for dry AMD. Abbreviations AADP avascular area of the deep plexus AASP avascular area of the superficial plexus AMD Age-related macular degeneration Anti-VEGF anti-vascular endothelial growth factor AREDS Age-Related Eye Disease Study BCVA Best corrected visual acuity CcO Cytochrome c oxidase CD capillary density CMT central macular thickness CNV choroidal neovascularization ETDRS Early Treatment Diabetic Retinopathy Study FAF fundus autofluorescence GA geographic atrophy IOP intraocular pressure Micra µm NIR near infrared (NIR) PBM Photobiomodulation PBM-VALEDA Multiwavelength Photobiomodulation – VALEDA Post-treatment post Pre-treatment pre RPE retinal pigmented epithelium SD-OCT Spectro domain OCT SCT subfoveal choroidal thickness SS-OCT Swept Source Optical Coherence Tomography SS-OCTA SS-OCT-Angiography VA visual acuity VA Logmar Best corrected visual acuity for logmar Declarations Ethical Committee Approval: The study was carried out in accordance with the guidelines outlined in Resolution 196/96 of the National Health Council of the Ministry of Health. The research protocol was submitted for analysis and received approval (28 September 2023) from the Ethics Committee of the Universidade do Oeste Paulista – UNOESTE – Presidente Prudente, SP (CAAE—70635623.5.0000.5515). Competing Interest: The authors declare no competing interests. Funding: The authors have no funding to report. Authors’ contributions: The study design was a collaborative effort involving MPR, RB, and TC, who collectively contributed to the idea and initial design of the study. MPR leads the project, shapes the research question, and takes the lead in writing the paper, primarily drafting the document, while also conducting pre- and post-treatment ophthalmological exams and administering the treatment with PBM-Valeda. FAF collected medical records and exam data from SS-OCT and SS-OCTA devices, and also contributed to the design and planning of the study. JP collaborated on the literature review, examining existing research in the field. RB conducted comprehensive research and provided a critical review. TC contributed during the review phase. MPR oversaw the analysis and interpretation and submitted the manuscript to a journal, with all authors collectively addressing reviewers' comments. MPR the corresponding author. Ultimately, all authors are credited for the publication of the study. All authors read and approved the final manuscript. Acknowledgements: Not applicable. References Spaide RF, Jaffe GJ, Sarraf D, Freund KB, Sadda SR, Staurenghi G, Waheed NK, Chakravarthy U, Rosenfeld PJ, Holz FG, Souied EH, Cohen SY, Querques G, Ohno-Matsui K, Boyer D, Gaudric A, Blodi B, Baumal CR, Li X, Coscas GJ, Brucker A, Singerman L, Luthert P, Schmitz-Valckenberg S, Schmidt-Erfurth U, Grossniklaus HE, Wilson DJ, Guymer R, Yannuzzi LA, Chew EY, Csaky K, Monés JM, Pauleikhoff D, Tadayoni R, Fujimoto J. 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Choroidal Thickness in Diabetes and Diabetic Retinopathy: A Swept Source OCT Study. Invest Ophthalmol Vis Sci. 2020 Apr 9;61(4):29. doi: 10.1167/iovs.61.4.29. PMID: 32324858; PMCID: PMC7401852. Benlahbib M, Cohen SY, Torrell N, Colantuono D, Crincoli E, Amoroso F, Semoun O, Jung C, Souied EH. PHOTOBIOMODULATION THERAPY FOR LARGE SOFT DRUSEN AND DRUSENOID PIGMENT EPITHELIAL DETACHMENT IN AGE-RELATED MACULAR DEGENERATION: A Single-Center Prospective Pilot Study. Retina. 2023 Aug 1;43(8):1246-1254. doi: 10.1097/IAE.0000000000003805. PMID: 37027819. Siqueira RC, Belíssimo LM, Pinho TS, Dourado LFN, Alves AP, de Paiva MRB, Ajero U, Cunha ADS. Short-Term Results of Photobiomodulation Using Light-Emitting Diode Light of 670 nm in Eyes with Age-Related Macular Degeneration. Photobiomodul Photomed Laser Surg. 2021 Sep;39(9):581-586. doi: 10.1089/photob.2021.0005. PMID: 34546108. Merry GF, Munk MR, Dotson RS, Walker MG, Devenyi RG. Photobiomodulation reduces drusen volume and improves visual acuity and contrast sensitivity in dry age-related macular degeneration. Acta Ophthalmol. 2017 Jun;95(4):e270-e277. doi: 10.1111/aos.13354. Epub 2016 Dec 18. PMID: 27989012; PMCID: PMC5484346. Henein C, Steel DH. Photobiomodulation for non-exudative age-related macular degeneration. Cochrane Database Syst Rev. 2021 May 6;5(5):CD013029. doi: 10.1002/14651858.CD013029.pub2. PMID: 34097768; PMCID: PMC8273038. Giani A, Cigada M, Choudhry N, Deiro AP, Oldani M, Pellegrini M, Invernizzi A, Duca P, Miller JW, Staurenghi G. Reproducibility of retinal thickness measurements on normal and pathologic eyes by different optical coherence tomography instruments. Am J Ophthalmol. 2010 Dec;150(6):815-24. doi: 10.1016/j.ajo.2010.06.025. Epub 2010 Oct Erratum in: Am J Ophthalmol. 2011 Apr;151(4):737. PMID: 20965494. Samanta A, Aziz AA, Jhingan M, Singh SR, Khanani AM, Chhablani J. Emerging Therapies in Nonexudative Age-Related Macular Degeneration in 2020. Asia Pac J Ophthalmol (Phila). 2021 Jan 28;10(4):408-416. doi: 10.1097/APO.0000000000000355. PMID: 33512911. Kim JE, Glassman AR, Josic K, Melia M, Aiello LP, Baker C, Eells JT, Jampol LM, Kern TS, Marcus D, Salehi-Had H, Shah SN, Martin DF, Stockdale CR, Sun JK; DRCR Retina Network. A Randomized Trial of Photobiomodulation Therapy for Center-Involved Diabetic Macular Edema with Good Visual Acuity (Protocol AE). Ophthalmol Retina. 2022 Apr;6(4):298-307. doi: 10.1016/j.oret.2021.10.003. Epub 2021 Oct 8. PMID: 34628066; PMCID: PMC9011341. Tables Table 1 – Demographic and Ocular Characteristics Patients (N=19) Sex Female: 9 (47,4%) Male 10 (52,6%) Laterality Bilateral 6 (31,6%) Unilateral 13 (68,4%) Age (years) Mean ± SD 72,6 ± 11,2 Median (Min to Max): 72,0 (56,0 a 94,0) Eyes (N=25) Side Right Eye (OD): 12 (48,0%) Left Eye (OS): 13 (52,0%) Note : OD: right eye; OS: left eye. Table 2 – AREDS Classification. Category AREDS Number of Eyes Percentage 1 0 0 % 2 16 64 % 3 9 36 % 4 0 0 % Table 3 – Summary Measurements of VA LogMAR and Anatomical Characteristics Pre Post D (Post – Pre) p AV LogMAR 0,38 ± 0,20 0,32 ± 0,20 -0,06 ± 0,05 0,001 CMT 234,56 ± 28,94 236,08 ± 30,28 1,52 ± 6,02 0,198 SCT 163,00 ± 103,68 161,80 ± 102,85 -1,20 ± 10,14 0,546 CD 15,08 ± 4,18 15,62 ± 4,63 0,54 ± 4,79 0,567 AASP 187.644,80 ± 109.506,53 177.198,24 ± 120.992,85 -10.446,56 ± 73.135,47 0,466 AADP 268.296,72 ± 171.163,09 270.879,44 ± 196.084,36 2.582,72 ± 77.550,21 0,865 Number of patients – N = 19. Number of eyes – N = 25. p – descriptive level of the linear model with random effects. VA LogMAR : Visual Acuity in LogMAR; CMT : Central Macular Thickness; SCT : Subfoveal Choroidal Thickness; AASP : Avascular Area of the Superficial Plexus; AADP : Avascular Area of the Deep Plexus; CD : Capillary Density. Table 4 – Summary Measures of Characteristics Mean Standard Deviation Minimum Maximum 1st Quartile Median 3rd Quartile N Age (years) 72,6 11,2 56,0 94,0 64,0 72,0 82,0 19 VA Logmar Pre 0,38 0,20 0,18 1,00 0,24 0,30 0,48 25 Post 0,32 0,20 0,10 1,00 0,18 0,30 0,40 25 CMT Pre 234,56 28,94 194,00 290,00 210,50 226,00 256,50 25 Post 236,08 30,28 194,00 292,00 213,00 229,00 259,50 25 SCT Pre 163,00 103,68 49,00 355,00 62,50 128,00 242,00 25 Post 161,80 102,85 49,00 365,00 62,50 128,00 242,00 25 CD Pre 15,08 4,18 8,64 22,66 12,09 13,59 18,33 25 Post 15,62 4,63 6,36 23,77 11,82 15,44 18,89 25 AASP Pre 187.644,80 109.506,53 36.189,00 421.018,00 94.823,00 166.113,00 264.990,50 25 Post 177.198,24 120.992,85 69,02 499.922,00 86.814,00 146.338,00 253.817,50 25 AADP Pre 268.296,72 171.163,09 70.994,00 897.012,00 152.963,00 242.249,00 333.709,50 25 Post 270.879,44 196.084,36 81.277,00 1.087.646,00 168.091,00 220.891,00 330.743,50 25 Post – Pre Variation AV LogMar -0,06 0,05 -0,14 0,00 -0,10 -0,08 0,00 25 CMT 1,52 6,02 -16,00 11,00 0,00 2,00 4,00 25 SCT -1,20 10,14 -23,00 26,00 -8,00 -1,00 5,00 25 CD 0,54 4,79 -8,76 10,87 -2,25 -0,01 3,69 25 AASP -10.446,56 73.135,47 -262.222,00 141.394,00 -25.807,00 -5.735,00 13.843,00 25 AADP 2.582,72 77.550,21 -198.150,00 190.634,00 -24.817,50 3.164,00 26.400,00 25 VA LogMAR : Visual Acuity in LogMAR; CMT : Central Macular Thickness; SCT : Subfoveal Choroidal Thickness; AASP : Avascular Area of the Superficial Plexus; AADP : Avascular Area of the Deep Plexus; CD : Capillary Density. Pre: pre-treatment. Post: post-treatment. Graphs Graphs 1 to 6 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Graphs.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-5424107\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":384673369,\"identity\":\"329c8498-56fc-431f-858f-165feb7af7a6\",\"order_by\":0,\"name\":\"Marcussi Palata Rezende\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3klEQVRIiWNgGAWjYBADHgYG5mNgFhs78VrY0hgYEoAUMwkWmYG1MBDSott+9uFnnj91MubSZ749+PhjmzwfMwPjh485uLWYnUk3luZtO8xj2Ze73XBGwm3DNmYGZsmZ2/BoOZDGxszbcIDH4AzvNmmehNuMQC1AEXxazj9jYwY6DKiF5xlIiz1hLTeAtvAAEVALG0hLIhFanjFLzgX5pYfNTHJG2u3kNmbGZvx+OZ/G+OHNnzp7cx7mZxIfbG7bzm9vPvjhIx4tcGCAYDI2EKEeVcsoGAWjYBSMAlQAAHExRjlpJyivAAAAAElFTkSuQmCC\",\"orcid\":\"\",\"institution\":\"Federal University of São Paulo (UNIFESP)\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Marcussi\",\"middleName\":\"Palata\",\"lastName\":\"Rezende\",\"suffix\":\"\"},{\"id\":384673372,\"identity\":\"d9a4eff3-a8f7-4326-b5b7-adf0dba4508d\",\"order_by\":1,\"name\":\"Fernanda Atoui Faria\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Instituto de Oftalmologia de Presidente Prudente -SP\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Fernanda\",\"middleName\":\"Atoui\",\"lastName\":\"Faria\",\"suffix\":\"\"},{\"id\":384673373,\"identity\":\"ecf8412a-21d3-4e17-957f-72c330e2d4da\",\"order_by\":2,\"name\":\"Julia Polido\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"EBSERH/HUCAM, CCS-UFES-Federal University of Espírito Santo (UFES)\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Julia\",\"middleName\":\"\",\"lastName\":\"Polido\",\"suffix\":\"\"},{\"id\":384673374,\"identity\":\"f10999f8-064e-4ad5-93b7-a71623aadbcb\",\"order_by\":3,\"name\":\"Rubens Belfort Jr\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Federal University of São Paulo (UNIFESP)\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Rubens\",\"middleName\":\"\",\"lastName\":\"Belfort\",\"suffix\":\"Jr\"},{\"id\":384673375,\"identity\":\"1e684d97-1fa9-4481-ade9-8a80f4886635\",\"order_by\":4,\"name\":\"Thiago Cabral\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Federal University of São Paulo (UNIFESP)\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Thiago\",\"middleName\":\"\",\"lastName\":\"Cabral\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2024-11-10 03:38:08\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-5424107/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-5424107/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":71610486,\"identity\":\"0cf38607-d465-4e53-8c6d-184fda3e9842\",\"added_by\":\"auto\",\"created_at\":\"2024-12-17 06:46:23\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":3519686,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eMultimodal Images using SS-OCT and SS-OCT Angiography of a 60-year-old female patient included in the study with dry age-related macular degeneration, treated with nine sessions of PBM-Valeda. Retinography (1A: pre-treatment and 1B: post-treatment) shows yellowish-white dots corresponding to hard drusen in the macular area. SS-OCT B-Scan: Pre (2A) and post (2B) images with macular thickness delineation. The macular thickness map (ETDRS) images are shown in 3A (pre: CMT: 284 µm) and 3B (post: CMT: 288 µm). Images 4A (pre) and 4B (post) are SS-OCT B-scans with choroidal thickness delineation, and 5A (pre: SCT: 282 µm) and 5B (post: SCT: 258 µm) are choroidal thickness maps. Images 6A (pre) and 6B (post) correspond to Red-free imaging, while 7A and 7B correspond to Auto-Fluorescence imaging, pre- and post-treatment, where hyperautofluorescent lesions corresponding to hard drusen are observed. Image 8A shows a retinography with drusen and the scan delimitation of the 4.5x4.5 mm SS-OCT Angiography (green central square), and 8B shows the post-treatment scan. Images 9A (pre) and 9B (post) display the AASP (9A = 63.083 µm² and 9B = 69.016 µm²). Images 10A (pre) and 10B (post) show the Avascular Area of the Deep Plexus (10A = 70.994 µm² and 10B = 81.277 µm²). Images 11A (pre) and 11B (post) represent the Capillary Density map, showing values of 11A = 22.64 and 11B = 14.93 in the central foveolar region. Images 12A (pre) and 12B (post) are B-scans, with red areas corresponding to blood flow, as analyzed by the device's software. All biomarker analyses presented in this figure showed p \\u0026gt; 0.05.\\u003c/p\\u003e\\n\\u003cp\\u003eCMT: Central Macular Thickness; SCT: Subfoveal Choroidal Thickness; AASP: Avascular Area of the Superficial Plexus; AADP: Avascular Area of the Deep Plexus; CD: Capillary Density.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Picture1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5424107/v1/4a4b30c242df93a5c4d2703c.png\"},{\"id\":71612584,\"identity\":\"4b311d2d-4268-40a1-b66e-1c2d687a4bc1\",\"added_by\":\"auto\",\"created_at\":\"2024-12-17 07:02:27\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":3934589,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5424107/v1/b6eebf6c-488b-4d4e-9202-857b4f5b1d14.pdf\"},{\"id\":71610485,\"identity\":\"b08eb683-a7ad-4cea-8736-eb8e35a6e91c\",\"added_by\":\"auto\",\"created_at\":\"2024-12-17 06:46:23\",\"extension\":\"docx\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":28456,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"Graphs.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5424107/v1/0af2af57de67a7dfc7aeee3b.docx\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"\\u003cp\\u003eProspective Study of Safety and Biomarkers Using Multimodal Analysis with Swept-Source Oct and Oct-Angiography in Patients with Dry Age Related Macular Degeneration Treated with Photobiomodulation.\\u003c/p\\u003e\",\"fulltext\":[{\"header\":\"INTRODUCTION\",\"content\":\"\\u003cp\\u003eAge-related macular degeneration (AMD) is a leading cause of vision impairment in people over the age of 50 in Western countries, often resulting in irreversible vision loss. As the population continues to age, the number of AMD cases in the USA is projected to increase from 2.7\\u0026nbsp;million in 1970 to 7.5\\u0026nbsp;million by 2030. In Brazil, although there are no population-based studies to determine the exact impact of AMD, it is estimated that 3\\u0026nbsp;million elderly individuals are affected by the disease at various stages. AMD is categorized into two types: dry and neovascular. Neovascular AMD is characterized by choroidal neovascularization (CNV), where abnormal blood vessels grow between the retinal pigment epithelium (RPE) and Bruch's membrane, or between the sensory retina and the RPE. While neovascular AMD represents only about 10% of all AMD cases, it accounts for approximately 80% of legal blindness caused by the disease.\\u003csup\\u003e\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e\\u003c/sup\\u003e The Age-Related Eye Disease Study (AREDS) classified AMD into categories based on the presence of drusen, atrophy, and neovascularization. Drusen were classified as small (\\u0026lt;\\u0026thinsp;63 \\u0026micro;m in diameter), intermediate (63\\u0026ndash;124 \\u0026micro;m), or large (\\u0026gt;\\u0026thinsp;125 \\u0026micro;m). AREDS categories of AMD were defined as: 1) No AMD: if there were fewer than five small drusen; 2\\u003cb\\u003e)\\u003c/b\\u003e Early or Mild AMD: based on the identification of multiple small drusen or at least one intermediate-sized drusen; 3) Intermediate AMD: classified by extensive intermediate-sized drusen, more than one large drusen, or non-central geographic atrophy (GA); and 4) Advanced AMD: determined by central GA or CNV causing vision loss, defined as visual acuity (VA) worse than 20/32 in one eye. Treatment for wet AMD involves periodic intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) compounds. However, the more common dry form of AMD has fewer treatment options, with lifestyle changes and vitamin supplements being the main recommendations. This underscores the urgent clinical need for the development of new treatment strategies as the number of affected individuals continues to rise.\\u003csup\\u003e\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e\\u003c/sup\\u003e In the US, there were no approved treatments for the early or intermediate stages of dry AMD, other than antioxidant supplementation, which only slows disease progression in 20\\u0026ndash;25% of cases, \\u003csup\\u003e\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e\\u003c/sup\\u003e but recently (November 2024) the FDA approved PBM-Valeda for the treatment of patients with dry AMD. In contrast, in the European Union and Brazil, the management of dry AMD with Multiwavelength Photobiomodulation \\u0026ndash; VALEDA (PBM-VALEDA) has already been approved by drug regulatory agencies (similar to the FDA in the USA).\\u003c/p\\u003e \\u003cp\\u003ePBM-VALEDA is a well-established biotechnology that utilizes light from the visible spectrum to near-infrared (NIR) (500-1,000 nm) to target specific tissues, producing beneficial cellular effects. The mechanism of PBM involves stimulating components of the mitochondrial respiratory chain, which helps stabilize metabolic functions and activates signaling pathways that promote cell proliferation and protection. Cytochrome C oxidase is recognized as the main photoacceptor of light within the far-red to NIR range. Its activation enhances the efficiency of the electron transport chain, leading to increased ATP production, the primary energy source for cells.\\u003csup\\u003e\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e\\u003c/sup\\u003e LumiThera developed the first multiwavelength PBM device to treat dry AMD. Valeda is designed to emit 590 nm, 660 nm, and 850 nm wavelengths using specific light-emitting diodes (LEDs). The use of 590 nm was selected based on its ability to inhibit vascular endothelial growth factor (VEGF) expression in retinal cell cultures following exposure to PBM at various wavelengths.\\u003csup\\u003e\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e\\u003c/sup\\u003e The 660 nm and 850 nm wavelengths were selected based on their direct interaction with cytochrome c oxidase (CcO). CcO is an enzyme located in the inner mitochondrial membrane and is part of complex IV of the electron transport chain, serving as a target chromophore for both wavelengths.\\u003csup\\u003e\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e\\u003c/sup\\u003e Near-infrared (850 nm) is known to be absorbed by copper CuA moieties within CcO, which are important for supporting electron flow from cytochrome C into the CcO complex. Red (660 nm) wavelengths are known to be absorbed by copper CuB moieties within CcO and have been demonstrated to enhance O₂ binding at the active site.\\u003csup\\u003e\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e\\u003c/sup\\u003e Both wavelengths have independent stimulatory effects on CcO enzyme activity, thereby restoring mitochondrial membrane potential and leading to enhanced ATP production.\\u003csup\\u003e\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e \\u003cp\\u003eMultiple studies across different conditions have consistently shown improvements in both clinical and anatomical results after PBM therapy. Recent ophthalmological clinical trials, including LIGHTSITE I, II, and III, examined the effects of multiwavelength PBM using the Valeda light therapy system, reporting enhancements in clinical vision outcomes and anatomical indicators of the disease. In conclusion, these three major studies\\u0026mdash;LIGHTSITE I, II, and III\\u0026mdash;indicate that PBM-VALEDA treatment enhances visual acuity, reduces central drusen volume, and improves contrast sensitivity.\\u003csup\\u003e\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e \\u003cp\\u003eSwept-source Optical Coherence Tomography (SS-OCT) is a novel modality with higher resolution and speed than spectral-domain OCT (SD-OCT) for retina imaging. This device (SS-OCT) operates at a speed of 100,000 A-scans per second and provides an 8 \\u0026micro;m axial resolution in tissue with a 1050 nm wavelength. In addition, the automatic measurement and three-dimensional (3D) reconstruction of regional imaging result in more reproducible and reliable measurements of choroidal thickness. The dispersion caused by the retinal pigmented epithelium (RPE) is reduced by using a longer laser wavelength (1050 nm) in SS-OCT scans, which provides a clearer boundary of the choroid-scleral interface.\\u003csup\\u003e\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e\\u003c/sup\\u003e Therefore, swept-source technology is the best option for studying choroidal thickness (one of the objectives of this study) because its longer wavelength allows for deeper tissue penetration, providing a better analysis of these structures.\\u003csup\\u003e\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e \\u003cp\\u003eThe main objective of this research was conducted to a multimodal image evaluation using swept-source technology in SS-OCT and SS-OCT-Angiography (SS-OCT-A) exams in patients with dry age-related macular degeneration (AMD) treated with PBM-VALEDA. We analyzed side effects, possible progression to exudative AMD, and key biomarkers before and after treatment, which are as follows: best corrected visual acuity (VA LogMAR), central macular thickness (CMT), capillary density (CD), subfoveal choroidal thickness (SFCT), avascular area of the superficial plexus (AASP), and avascular area of the deep plexus (AADP).\\u003c/p\\u003e\"},{\"header\":\"Methods\",\"content\":\"\\u003cp\\u003eA prospective interventional case series was conducted with a sample of 18 patients (22 eyes) diagnosed with AMD who had not previously received any treatment, aside from vitamin supplementation. The participants were recruited originating from the Retina Department at the Instituto de Oftalmologia de Presidente Prudente, SP, Brazil.\\u003c/p\\u003e \\u003cp\\u003e \\u003cb\\u003eA) Inclusion Criteria\\u003c/b\\u003e: Participants were considered eligible for the study if they fulfilled the following requirements:\\u003c/p\\u003e \\u003cp\\u003e\\u003col\\u003e\\u003cspan\\u003e\\u003cli\\u003e\\u003cp\\u003eThey were aged 50 or older, had a diagnosis of dry AMD characterized by the presence of drusen, and were taking mineral and antioxidant supplements as recommended by AREDS-2.\\u003c/p\\u003e\\u003c/li\\u003e\\u003c/span\\u003e\\u003cspan\\u003e\\u003cli\\u003e\\u003cp\\u003eThey had nonfoveal center geographic atrophy (GA).\\u003c/p\\u003e\\u003c/li\\u003e\\u003c/span\\u003e\\u003cspan\\u003e\\u003cli\\u003e\\u003cp\\u003eTheir best corrected visual acuity (BCVA), assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) and the Snellen Chart, ranged between 20/25 and 20/200.\\u003c/p\\u003e\\u003c/li\\u003e\\u003c/span\\u003e\\u003cspan\\u003e\\u003cli\\u003e\\u003cp\\u003eThey had complete medical records, which included information such as sex, age, current medications, pre- and postoperative intraocular pressure (IOP), BCVA before and after the procedure, as well as SS-OCT and SS-OCTA scan results.\\u003c/p\\u003e\\u003c/li\\u003e\\u003c/span\\u003e\\u003cspan\\u003e\\u003cli\\u003e\\u003cp\\u003e They provided signed informed consent forms, which were documented in their medical records.\\u003c/p\\u003e\\u003c/li\\u003e\\u003c/span\\u003e\\u003c/ol\\u003e\\u003c/p\\u003e \\u003cp\\u003e \\u003cb\\u003eB) Exclusion Criteria\\u003c/b\\u003e: Participants were excluded from the study if:\\u003c/p\\u003e \\u003cp\\u003e \\u003col\\u003e \\u003cspan\\u003e \\u003cli\\u003e \\u003cp\\u003eThey had a background of choroidal neovascularization (CNV).\\u003c/p\\u003e \\u003c/li\\u003e \\u003c/span\\u003e \\u003cspan\\u003e \\u003cli\\u003e \\u003cp\\u003eThey had center-involving geographic atrophy (GA).\\u003c/p\\u003e \\u003c/li\\u003e \\u003c/span\\u003e \\u003cspan\\u003e \\u003cli\\u003e \\u003cp\\u003eThey had other major retinal conditions such as diabetic retinopathy, epiretinal membrane, macular hole, or retinal dystrophies.\\u003c/p\\u003e \\u003c/li\\u003e \\u003c/span\\u003e \\u003cspan\\u003e \\u003cli\\u003e \\u003cp\\u003eThey had other ophthalmological conditions, such as glaucoma.\\u003c/p\\u003e \\u003c/li\\u003e \\u003c/span\\u003e \\u003cspan\\u003e \\u003cli\\u003e \\u003cp\\u003eThey had undergone previous eye surgeries, such as for retinal detachment or glaucoma.\\u003c/p\\u003e \\u003c/li\\u003e \\u003c/span\\u003e \\u003cspan\\u003e \\u003cli\\u003e \\u003cp\\u003eThey discontinued treatmen\\u003c/p\\u003e \\u003c/li\\u003e \\u003c/span\\u003e \\u003c/ol\\u003e \\u003c/p\\u003e \\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eEthical Committee:\\u003c/h2\\u003e \\u003cp\\u003e The study was carried out in accordance with the guidelines outlined in Resolution 196/96 of the National Health Council of the Ministry of Health. The research protocol was submitted for analysis and received approval (28 September 2023) from the Ethics Committee of the Universidade do Oeste Paulista \\u0026ndash; UNOESTE \\u0026ndash; Presidente Prudente, SP (CAAE\\u0026mdash;70635623.5.0000.5515).\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec4\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStudy Design:\\u003c/h2\\u003e \\u003cp\\u003eThe participants underwent treatment with the Multiwavelength Valeda Light Delivery System (LumiThera, Inc., Poulsbo, WA), undergoing a total of nine sessions over a three-week period. Ophthalmological examinations, BCVA, IOP, biomicroscopy, retinal mapping, red-free, fundus autofluorescence (FAF), AREDS classification (Categories I to IV), SS-OCT, and SS-OCT-A were performed on the day PBM treatment began (baseline). These examinations were repeated one week after the end of the PBM treatment. Since the treatment lasted 3 weeks (21 days), the first assessment was carried out on day 1, immediately before starting treatment (baseline or pre-treatment), and the post-treatment assessment on day 28. The BCVA assessment involved a comprehensive refraction protocol and visual sharpness assessment, conducted using certified equipment and within standardized examination rooms. The SS-OCT and SS-OCT-Angiography (DRI-OCT Triton; Topcon \\u0026ndash; Tokyo, Japan) instrument was used to obtain high-definition images of the retina and choroid. The resulting images were analyzed by the automated layer segmentation software built into the SS-OCT system. In the SS-OCT examination, 7x7 mm scans were used, and in the SS-OCT-A, 4.5x4.5 mm scans were used. All OCT scans were conducted by the same experienced technician, who was blind to the study protocol. Retinal thickness was defined as the distance between the vitreoretinal interface and the RPE. Choroidal thickness was measured as the distance between the outer border of the RPE and the chorio-scleral border. Automated built-in calibration software determined the distance between these two lines. After the choroidal thickness map was obtained, the ETDRS grid was applied to the map. Using the averaged OCT images, we also measured central retinal thickness and choroidal thickness at the center of the fovea.\\u003c/p\\u003e \\u003cp\\u003eTwo investigators reviewed each line of the vitreoretinal interface, RPE, and chorio-scleral border in all images to confirm correct segmentation, with manual adjustments made if necessary. The avascular areas of the superficial and deep plexus, obtained by SS-OCTA, were manually assessed by an ophthalmologist and retinologist, confirmed by another professional. In case of discrepancies, a new expert was consulted. Capillary density was automatically provided by the device's software.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec5\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003ePhotobiomodulation Treatment with the Valeda Light Delivery System:\\u003c/h2\\u003e \\u003cp\\u003eParticipants received treatment with the Valeda system using three specific wavelengths: yellow (590 nm; 4 mW/cm\\u0026sup2;; 2 x 35 seconds), red (660 nm; 65 mW/cm\\u0026sup2;; 2 x 90 seconds), and near-infrared (850 nm; 0.6 mW/cm\\u0026sup2;; 2 x 35 seconds). A total of nine treatment sessions were administered over a 3-week period.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec6\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eData analysis:\\u003c/h2\\u003e \\u003cp\\u003eStatistical analysis was performed using Stata, version 17 (StataCorp LLC), and SPSS, version 20 (IBM Corp). The data were expressed as mean\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;SD, median (interquartile range), or frequencies, depending on the nature of the characteristic evaluated. The means of measurements between two time points were evaluated using random effects models to account for possible dependence between eyes of the same patient. The normality of the distribution was assessed using the Kolmogorov-Smirnov test. The tests were two-sided, and P values of \\u0026lt;\\u0026thinsp;0.05 were considered significant.\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"RESULTS\",\"content\":\"\\u003cp\\u003eThe study included 25 eyes of 19 patients. According to Table 1, it is observed that 9 patients were female (47.4%) and 10 patients were male (52.6%). The mean age was 72.6 years (SD = 11.2 years), with a minimum age of 56 years and a maximum of 94 years. Of the 19 patients treated, 6 patients had both eyes treated (31.6%) and 13 were treated in just one eye (68.4%). Of the 13 patients whose contralateral eye was not treated, 6 (46.15%) had exudative AMD (treated with intravitreal injection of aflibercept 40 mg/ml), and 7 (53.85%) were diagnosed with dry AMD. These untreated eyes did not meet the inclusion criteria or were within the criteria for exclusion of this study. It is also noted that 48% of the treated eyes (12 eyes) were on the right side and 52% (13 eyes) were on the left side.\\u003cbr\\u003e\\u0026nbsp;According to the AREDS classification of the 25 eyes (Table 2): 16 eyes (64%) were in Category II, 9 eyes (36%) were in Category III, and no eyes fell into Categories I and IV.\\u003c/p\\u003e\\n\\u003cp\\u003eTable 3 shows all the biomarkers evaluated. We can see that AV LogMAR presented a baseline average of 0.38 (20/48 on the Snellen table), and post-treatment it was 0.32 (20/42), with statistical significance of p = 0.001 (Graph 1). On the other hand, CMT, SCT, CD, AASP, and AADP did not show statistical significance (Graphs 2 to 6). The mean CMT varied from 234.56 microns (\\u0026micro;m) at baseline to 236.08 \\u0026micro;m post-treatment (p = 0.198). The mean SCT varied from 163.00 \\u0026micro;m at baseline to 161.8 \\u0026micro;m post-treatment (p = 0.546). CD varied from 15.08 to 15.62 (p = 0.567), AASP from 187,644.80 \\u0026micro;m\\u0026sup2; to 177,198.24 \\u0026micro;m\\u0026sup2; (p = 0.466), and AADP from 268,296.72 \\u0026micro;m\\u0026sup2; to 270,879.44 \\u0026micro;m\\u0026sup2; (p = 0.865). In Table 4, we find all the biomarkers studied with their respective characteristics and summary measurements. In Figure 1, we observe the multimodal study with SS-OCT and SS-OCTA of the left eye of a 60-year-old patient included in this study, diagnosed with dry AMD. This image details the measurements between pre- and post-treatment of CMT and SCT in \\u0026micro;m. CD, AASP, and AADP are measured in \\u0026micro;m\\u0026sup2;.\\u003cbr\\u003e\\u0026nbsp;No patient discontinued treatment due to side effects. The main side effect was dry eye, reported by 3 of the 19 patients, and the second was pruritus in 2 patients. These symptoms improved with the use of lubricating eye drops. There were no serious side effects, and no patient progressed to the exudative form of AMD. An important subjective observation in the study was that 15 of the 19 patients treated reported an improvement in visual acuity and a better subjective perception of color/contrast sensitivity. The remaining 4 patients reported stable AV. No patient complained of a worsening in VA after treatment with PB-VALEDA. IOP also did not show a notable difference, with a value of 12.68 \\u0026plusmn; 1.30 pre-treatment and 12.79 \\u0026plusmn; 1.44 post-treatment (p = 0.641).\\u003c/p\\u003e\"},{\"header\":\"DISCUSSION\",\"content\":\"\\u003cp\\u003eThe present study provides valuable information regarding the security and biomarkers associated with the use of swept-source technology in OCT and OCT-A examinations for patients affected by dry AMD treated with PBM-Valeda. We observed a significant improvement in VA-LogMAR with PBM-Valeda, a result consistent with findings already reported in the literature, such as in the LIGHTSITE I, II, and III studies, among others. In summary, PBM therapy in patients affected by dry AMD demonstrates: improved visual acuity (VA), enhanced contrast sensitivity, reduced central drusen volume, improved quality of life, and decreased progression of geographic degeneration.\\u003csup\\u003e\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e\\u003c/sup\\u003e The significant improvement in VA-LogMAR was measured in the study by Merry GF et al\\u003csup\\u003e\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e\\u003c/sup\\u003e immediately after the end of treatment (3 weeks) and at 3 months. In our study, it was measured 1 week after the end of treatment with PBM (1 month after baseline), showing improvement in VA-LogMAR. Similarly, LIGHTSITE I\\u003csup\\u003e\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e\\u003c/sup\\u003e also showed improvement in VA 1 month after baseline. According to the AREDS classification of the 25 eyes (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e): 16 eyes (64%) were in Category II, 9 eyes (36%) were in Category III, and no eyes fell into Categories I or IV.\\u003c/p\\u003e \\u003cp\\u003eRegarding the AREDS classification, in our study, we had the distribution of patients in Categories II and III, with a predominance in Category II. Out of a total of 25 eyes, 16 eyes (64%) were in Category II, and 9 eyes (36%) were in Category III, with no eyes in Categories I or IV. In contrast, the main group observed in the following studies was in Category III: LIGHTSITE III (86.9%) and LIGHTSITE II (64.70%). In LIGHTSITE I, the majority of patients were in Category IV (67.4%) and Category III (30.4%).\\u003c/p\\u003e \\u003cp\\u003eThe CMT in normal patients is around 230 \\u0026micro;m. The average CMT in patients affected by dry AMD, as measured in our study, was 234.56 \\u0026micro;m, which is consistent with findings in the literature.\\u003csup\\u003e\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e\\u003c/sup\\u003e Affected by dry AMD, studies show that macular retinal thickness tends to become thinner as the disease progresses and approaches geographic atrophy. As Giani et al. demonstrated in their study, the average CMT in patients affected by dry AMD was 220 \\u0026micro;m.\\u003csup\\u003e\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e \\u003cp\\u003eIn our study, all patients were using vitamin supplementation according to the AREDS 2 study. Antioxidant and mineral supplementation can slow the advancement of nonexudative AMD to exudative AMD. For many years, the only proven supplement for nonexudative AMD was based on the findings of the Age-Related Eye Disease Study (AREDS) formulation, consisting of vitamin C, vitamin E, beta-carotene, zinc, and copper, which demonstrated a 25% reduced risk of severe vision loss in subjects with intermediate-sized drusen, at least one large druse, noncentral GA, or advanced AMD over 5 years. Subsequent supplementation trials included the AREDS 2 formula, which modified the compound by replacing beta-carotene with lutein and zeaxanthin.\\u003csup\\u003e\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e \\u003cp\\u003eThe key finding of our study is the lack of significant change in biomarkers (CMT, SCT, CD, AASP, AADP) between pre- and post-treatment, confirming PBM's safety as shown in LIGHTSITE studies. The study focused on evaluating biomarker changes affected by dry AMD patients treated with PBM-Valeda, without using a control group.\\u003c/p\\u003e \\u003cp\\u003eIn this study, PBM-Valeda treatment was well tolerated, with a low occurrence of side effects, all of which were mild. This aligns with previous research that also demonstrated a favorable risk-benefit profile, a low occurrence of side effects, and no evidence of retinal toxicity, reinforcing that it is a highly safe and well-tolerated therapy.\\u003csup\\u003e\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\"},{\"header\":\"CONCLUSION\",\"content\":\"\\u003cp\\u003eBased on our study, we conclude that PBM-VALEDA therapy could present a novel therapy option with a distinct mechanism and approach for patients with nonexudative AMD. Improvement in visual acuity, few non-serious side effects, absence of retinotoxicity, absence of progression to wet AMD during the study period, and no significant variation in biomarkers (CMT, SCT, CD, AASP, and AADP) as analyzed by SS-OCT and SS-OCTA after therapy using PBM (1 cycle: 9 sessions) all support the conclusion that this treatment is safe for dry AMD.\\u003c/p\\u003e\"},{\"header\":\"Abbreviations\",\"content\":\"\\u003cdiv class=\\\"DefinitionList\\\"\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eAADP\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eavascular area of the deep plexus\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eAASP\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eavascular area of the superficial plexus\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eAMD\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eAge-related macular degeneration\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eAnti-VEGF\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eanti-vascular endothelial growth factor\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eAREDS\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eAge-Related Eye Disease Study\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eBCVA\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eBest corrected visual acuity\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eCcO\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eCytochrome c oxidase\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eCD\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003ecapillary density\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eCMT\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003ecentral macular thickness\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eCNV\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003echoroidal neovascularization\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eETDRS\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eEarly Treatment Diabetic Retinopathy Study\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eFAF\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003efundus autofluorescence\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eGA\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003egeographic atrophy\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eIOP\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eintraocular pressure\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eMicra\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003e\\u0026micro;m\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eNIR\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003enear infrared (NIR)\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003ePBM\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003ePhotobiomodulation\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003ePBM-VALEDA\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eMultiwavelength Photobiomodulation \\u0026ndash; VALEDA\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003ePost-treatment\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003epost\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003ePre-treatment\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003epre\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eRPE\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eretinal pigmented epithelium\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eSD-OCT\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eSpectro domain OCT\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eSCT\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003esubfoveal choroidal thickness\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eSS-OCT\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eSwept Source Optical Coherence Tomography\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eSS-OCTA\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eSS-OCT-Angiography\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eVA\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003evisual acuity\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eVA Logmar\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eBest corrected visual acuity for logmar\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003c/div\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eEthical Committee Approval:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe study was carried out in accordance with the guidelines outlined in Resolution 196/96 of the National Health Council of the Ministry of Health. The research protocol was submitted for analysis and received approval (28 September 2023) from the Ethics Committee of the Universidade do Oeste Paulista \\u0026ndash; UNOESTE \\u0026ndash; Presidente Prudente, SP (CAAE\\u0026mdash;70635623.5.0000.5515).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCompeting Interest:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors declare no competing interests.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors have no funding to report.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthors\\u0026rsquo; contributions:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe study design was a collaborative effort involving MPR, RB, and TC, who collectively contributed to the idea and initial design of the study. MPR leads the project, shapes the research question, and takes the lead in writing the paper, primarily drafting the document, while also conducting pre- and post-treatment ophthalmological exams and administering the treatment with PBM-Valeda. FAF collected medical records and exam data from SS-OCT and SS-OCTA devices, and also contributed to the design and planning of the study. JP collaborated on the literature review, examining existing research in the field. RB conducted comprehensive research and provided a critical review. TC contributed during the review phase. MPR oversaw the analysis and interpretation and submitted the manuscript to a journal, with all authors collectively addressing reviewers\\u0026apos; comments. MPR the corresponding author. Ultimately, all authors are credited for the publication of the study. All authors read and approved the final manuscript.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgements:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNot applicable.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eSpaide RF, Jaffe GJ, Sarraf D, Freund KB, Sadda SR, Staurenghi G, Waheed NK, Chakravarthy U, Rosenfeld PJ, Holz FG, Souied EH, Cohen SY, Querques G, Ohno-Matsui K, Boyer D, Gaudric A, Blodi B, Baumal CR, Li X, Coscas GJ, Brucker A, Singerman L, Luthert P, Schmitz-Valckenberg S, Schmidt-Erfurth U, Grossniklaus HE, Wilson DJ, Guymer R, Yannuzzi LA, Chew EY, Csaky K, Mon\\u0026eacute;s JM, Pauleikhoff D, Tadayoni R, Fujimoto J. Consensus Nomenclature for Reporting Neovascular Age-Related Macular Degeneration Data: Consensus on Neovascular Age-Related Macular Degeneration Nomenclature Study Group. Ophthalmology. 2020 May;127(5):616-636. doi: 10.1016/j.ophtha.2019.11.004. Epub 2019 Nov 14. Erratum in: Ophthalmology. 2020 Oct;127(10):1434-1435. doi: 10.1016/j.ophtha.2020.07.019. PMID: 31864668.\\u003c/li\\u003e\\n\\u003cli\\u003eBeraldo DP, Rezende MP, Alexander JG, Polido J, Belfort R Jr, Cabral T. Correlations between subfoveal choroidal thickness, macular thickness, and visual outcome in neovascular age-related macular degeneration using swept source OCT: insights from intravitreal aflibercept treatment. Int J Retina Vitreous. 2023 Nov 15;9(1):70. doi: 10.1186/s40942-023-00506-4. PMID: 37968771; PMCID: PMC10652476.\\u003c/li\\u003e\\n\\u003cli\\u003eCabral T, Lima LH, Polido J, Duong J, Okuda E, Oshima A, Serracarbassa P, Regatieri CV, Belfort R Jr. Aqueous vascular endothelial growth factor and clinical outcomes correlation after single intravitreal injection of bevacizumab in patients with neovascular age-related macular degeneration. Int J Retina Vitreous. 2017;1(3):6. https:// doi. org/ 10. 1186/s40942- 017- 0066-y.\\u003c/li\\u003e\\n\\u003cli\\u003eCabral T, Mello LGM, Lima LH, Polido J, Regatieri CV, Belfort R Jr, Mahajan VB. Retinal and choroidal angiogenesis: a review of new targets. Int J Retina Vitreous. 2017;21(3):31. https:// doi. org/ 10. 1186/ s40942- 017- 0084-9.\\u003c/li\\u003e\\n\\u003cli\\u003eCabral T, Lima LH, Mello LGM, Polido J, Correa EP, Oshima A, Duong J, Serracarbassa P, Regatieri CV, Mahajan VB, Belfort R Jr. Bevacizumab injection in patients with neovascular age-related macular degeneration increases angiogenic biomarkers. Ophthalmol Retina. 2018;2(1):31\\u0026ndash;7. https:// doi.org/ 10. 1016/j. oret. 2017. 04. 004.\\u003c/li\\u003e\\n\\u003cli\\u003eMarkowitz SN, Devenyi RG, Munk MR, Croissant CL, Tedford SE, R\\u0026uuml;ckert R, Walker MG, Patino BE, Chen L, Nido M, Tedford CE. A DOUBLE-MASKED, RANDOMIZED, SHAM-CONTROLLED, SINGLE-CENTER STUDY WITH PHOTOBIOMODULATION FOR THE TREATMENT OF DRY AGE-RELATED MACULAR DEGENERATION. Retina. 2020 Aug;40(8):1471-1482. doi: 10.1097/IAE.0000000000002632. PMID: 31404033; PMCID: PMC7392581.\\u003c/li\\u003e\\n\\u003cli\\u003eChew EY, Chew EY, Clemons TE, et al. Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report No. 3. JAMA Ophthalmol 2014;132:142\\u0026ndash;149.\\u003c/li\\u003e\\n\\u003cli\\u003eBurton B, Parodi MB, J\\u0026uuml;rgens I, Zanlonghi X, Hornan D, Roider J, Lorenz K, Munk MR, Croissant CL, Tedford SE, Walker M, Ruckert R, Tedford CE. LIGHTSITE II Randomized Multicenter Trial: Evaluation of Multiwavelength Photobiomodulation in Non-exudative Age-Related Macular Degeneration. Ophthalmol Ther. 2023 Apr;12(2):953-968. doi: 10.1007/s40123-022-00640-6. Epub 2023 Jan 2. PMID: 36588113; PMCID: PMC9805913.\\u003c/li\\u003e\\n\\u003cli\\u003eBoyer D, Hu A, Warrow D, Xavier S, Gonzalez V, Lad E, Rosen RB, Do D, Schneiderman T, Ho A, Munk MR, Jaffe G, Tedford SE, Croissant CL, Walker M, R\\u0026uuml;ckert R, Tedford CE. 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. Retina. 2024 Mar 1;44(3):487-497. doi: 10.1097/IAE.0000000000003980. PMID: 37972955; PMCID: PMC10885856.\\u003c/li\\u003e\\n\\u003cli\\u003eSzymanska J, Goralczyk K, Klawe JJ, et al. Phototherapy with low-level laser influences the proliferation of endothelial cells and vascular endothelial growth factor and transforming growth factor-beta secretion. \\u003cem\\u003eJ Physiol Pharmacol. \\u003c/em\\u003e2013;64(3):387-391.\\u003c/li\\u003e\\n\\u003cli\\u003eMunk MR, Valter k. Photobiomodulation as anInnovative and Promising Treatment for Retinal Disease. Evidence supports its use in ocular disease. Retinal Physician. Vol 19, page(s)36-39, april 2022. https://retinalphysician.com/issues/2022/april/photobiomodulation-as-an-innovative-and-promising-treatment-for-retinal-disease/\\u003c/li\\u003e\\n\\u003cli\\u003eWong-Riley MT, Liang HL, Eells JT, et al. Photobiomodulation directly benefits primary neurons functionally inactivated by toxins: role of cytochrome c oxidase. \\u003cem\\u003eJ Biol Chem. \\u003c/em\\u003e2005;280(6):4761-4771. doi: 10.1074/jbc.M409650200\\u003c/li\\u003e\\n\\u003cli\\u003eKaru T. Mitochondrial mechanisms of photobiomodulation in context of new data about multiple roles of ATP. Photomed Laser Surg. 2010;28(2):159-160. doi: 10.1089/pho.2010.2789\\u003c/li\\u003e\\n\\u003cli\\u003eLa\\u0026iacute;ns I, Wang JC, Cui Y, Katz R, Vingopoulos F, Staurenghi G, Vavvas DG, Miller JW, Miller JB. Retinal applications of swept source optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). Prog Retin Eye Res. 2021 Sep;84:100951. doi: 10.1016/j.preteyeres.2021.100951. Epub 2021 Jan 28. PMID: 33516833.\\u003c/li\\u003e\\n\\u003cli\\u003eWang W, Liu S, Qiu Z, He M, Wang L, Li Y, Huang W. Choroidal Thickness in Diabetes and Diabetic Retinopathy: A Swept Source OCT Study. Invest Ophthalmol Vis Sci. 2020 Apr 9;61(4):29. doi: 10.1167/iovs.61.4.29. PMID: 32324858; PMCID: PMC7401852.\\u003c/li\\u003e\\n\\u003cli\\u003eBenlahbib M, Cohen SY, Torrell N, Colantuono D, Crincoli E, Amoroso F, Semoun O, Jung C, Souied EH. PHOTOBIOMODULATION THERAPY FOR LARGE SOFT DRUSEN AND DRUSENOID PIGMENT EPITHELIAL DETACHMENT IN AGE-RELATED MACULAR DEGENERATION: A Single-Center Prospective Pilot Study. Retina. 2023 Aug 1;43(8):1246-1254. doi: 10.1097/IAE.0000000000003805. PMID: 37027819.\\u003c/li\\u003e\\n\\u003cli\\u003eSiqueira RC, Bel\\u0026iacute;ssimo LM, Pinho TS, Dourado LFN, Alves AP, de Paiva MRB, Ajero U, Cunha ADS. Short-Term Results of Photobiomodulation Using Light-Emitting Diode Light of 670\\u0026thinsp;nm in Eyes with Age-Related Macular Degeneration. Photobiomodul Photomed Laser Surg. 2021 Sep;39(9):581-586. doi: 10.1089/photob.2021.0005. PMID: 34546108.\\u003c/li\\u003e\\n\\u003cli\\u003eMerry GF, Munk MR, Dotson RS, Walker MG, Devenyi RG. Photobiomodulation reduces drusen volume and improves visual acuity and contrast sensitivity in dry age-related macular degeneration. Acta Ophthalmol. 2017 Jun;95(4):e270-e277. doi: 10.1111/aos.13354. Epub 2016 Dec 18. PMID: 27989012; PMCID: PMC5484346.\\u003c/li\\u003e\\n\\u003cli\\u003eHenein C, Steel DH. Photobiomodulation for non-exudative age-related macular degeneration. Cochrane Database Syst Rev. 2021 May 6;5(5):CD013029. doi: 10.1002/14651858.CD013029.pub2. PMID: 34097768; PMCID: PMC8273038.\\u003c/li\\u003e\\n\\u003cli\\u003eGiani A, Cigada M, Choudhry N, Deiro AP, Oldani M, Pellegrini M, Invernizzi A, Duca P, Miller JW, Staurenghi G. Reproducibility of retinal thickness measurements on normal and pathologic eyes by different optical coherence tomography instruments. Am J Ophthalmol. 2010 Dec;150(6):815-24. doi: 10.1016/j.ajo.2010.06.025. Epub 2010 Oct \\u003c/li\\u003e\\n\\u003cli\\u003eErratum in: Am J Ophthalmol. 2011 Apr;151(4):737. PMID: 20965494.\\u003c/li\\u003e\\n\\u003cli\\u003eSamanta A, Aziz AA, Jhingan M, Singh SR, Khanani AM, Chhablani J. Emerging Therapies in Nonexudative Age-Related Macular Degeneration in 2020. Asia Pac J Ophthalmol (Phila). 2021 Jan 28;10(4):408-416. doi: 10.1097/APO.0000000000000355. PMID: 33512911.\\u003c/li\\u003e\\n\\u003cli\\u003eKim JE, Glassman AR, Josic K, Melia M, Aiello LP, Baker C, Eells JT, Jampol LM, Kern TS, Marcus D, Salehi-Had H, Shah SN, Martin DF, Stockdale CR, Sun JK; DRCR Retina Network. A Randomized Trial of Photobiomodulation Therapy for Center-Involved Diabetic Macular Edema with Good Visual Acuity (Protocol AE). Ophthalmol Retina. 2022 Apr;6(4):298-307. doi: 10.1016/j.oret.2021.10.003. Epub 2021 Oct 8. PMID: 34628066; PMCID: PMC9011341.\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"},{\"header\":\"Tables\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eTable 1 \\u0026ndash; Demographic and Ocular Characteristics\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003ctable border=\\\"0\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"328\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003ePatients (N=19)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 114px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eSex\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 114px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003eFemale:\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 114px;\\\"\\u003e\\n \\u003cp\\u003e9 (47,4%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003eMale\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 114px;\\\"\\u003e\\n \\u003cp\\u003e10 (52,6%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003eLaterality\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 114px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003eBilateral\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 114px;\\\"\\u003e\\n \\u003cp\\u003e6 (31,6%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003eUnilateral\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 114px;\\\"\\u003e\\n \\u003cp\\u003e13 (68,4%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003eAge (years)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 114px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003eMean \\u0026plusmn; SD\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 114px;\\\"\\u003e\\n \\u003cp\\u003e72,6 \\u0026plusmn; 11,2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003eMedian (Min to Max):\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 114px;\\\"\\u003e\\n \\u003cp\\u003e72,0 (56,0 a 94,0)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 114px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003eEyes (N=25)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 114px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eSide\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 114px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003eRight Eye (OD):\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 114px;\\\"\\u003e\\n \\u003cp\\u003e12 (48,0%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003eLeft Eye (OS):\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 114px;\\\"\\u003e\\n \\u003cp\\u003e13 (52,0%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 114px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eNote\\u003c/strong\\u003e: OD: right eye; OS: left eye.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cbr\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTable 2 \\u0026ndash; AREDS Classification.\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003ctable border=\\\"0\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"75%\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eCategory AREDS\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eNumber of Eyes\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ePercentage\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33px;\\\"\\u003e\\n \\u003cp\\u003e1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33px;\\\"\\u003e\\n \\u003cp\\u003e0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33px;\\\"\\u003e\\n \\u003cp\\u003e0 %\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33px;\\\"\\u003e\\n \\u003cp\\u003e2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33px;\\\"\\u003e\\n \\u003cp\\u003e16\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33px;\\\"\\u003e\\n \\u003cp\\u003e64 %\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33px;\\\"\\u003e\\n \\u003cp\\u003e3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33px;\\\"\\u003e\\n \\u003cp\\u003e9\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33px;\\\"\\u003e\\n \\u003cp\\u003e36 %\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33px;\\\"\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33px;\\\"\\u003e\\n \\u003cp\\u003e0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33px;\\\"\\u003e\\n \\u003cp\\u003e0 %\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTable 3 \\u0026ndash; Summary Measurements of VA LogMAR and Anatomical Characteristics\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003ctable border=\\\"0\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"708\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 219px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 148px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ePre\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 148px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ePost\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 135px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eD (Post \\u0026ndash; Pre)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 59px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ep\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 219px;\\\"\\u003e\\n \\u003cp\\u003eAV \\u0026nbsp;LogMAR\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 148px;\\\"\\u003e\\n \\u003cp\\u003e0,38 \\u0026plusmn; 0,20\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 148px;\\\"\\u003e\\n \\u003cp\\u003e0,32 \\u0026plusmn; 0,20\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 135px;\\\"\\u003e\\n \\u003cp\\u003e-0,06 \\u0026plusmn; 0,05\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 59px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e0,001\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 219px;\\\"\\u003e\\n \\u003cp\\u003eCMT\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 148px;\\\"\\u003e\\n \\u003cp\\u003e234,56 \\u0026plusmn; 28,94\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 148px;\\\"\\u003e\\n \\u003cp\\u003e236,08 \\u0026plusmn; 30,28\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 135px;\\\"\\u003e\\n \\u003cp\\u003e1,52 \\u0026plusmn; 6,02\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 59px;\\\"\\u003e\\n \\u003cp\\u003e0,198\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 219px;\\\"\\u003e\\n \\u003cp\\u003eSCT\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 148px;\\\"\\u003e\\n \\u003cp\\u003e163,00 \\u0026plusmn; 103,68\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 148px;\\\"\\u003e\\n \\u003cp\\u003e161,80 \\u0026plusmn; 102,85\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 135px;\\\"\\u003e\\n \\u003cp\\u003e-1,20 \\u0026plusmn; 10,14\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 59px;\\\"\\u003e\\n \\u003cp\\u003e0,546\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 219px;\\\"\\u003e\\n \\u003cp\\u003eCD\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 148px;\\\"\\u003e\\n \\u003cp\\u003e15,08 \\u0026plusmn; 4,18\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 148px;\\\"\\u003e\\n \\u003cp\\u003e15,62 \\u0026plusmn; 4,63\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 135px;\\\"\\u003e\\n \\u003cp\\u003e0,54 \\u0026plusmn; 4,79\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 59px;\\\"\\u003e\\n \\u003cp\\u003e0,567\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 219px;\\\"\\u003e\\n \\u003cp\\u003eAASP\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 148px;\\\"\\u003e\\n \\u003cp\\u003e187.644,80 \\u0026plusmn; 109.506,53\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 148px;\\\"\\u003e\\n \\u003cp\\u003e177.198,24 \\u0026plusmn; 120.992,85\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 135px;\\\"\\u003e\\n \\u003cp\\u003e-10.446,56 \\u0026plusmn; 73.135,47\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 59px;\\\"\\u003e\\n \\u003cp\\u003e0,466\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 219px;\\\"\\u003e\\n \\u003cp\\u003eAADP\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 148px;\\\"\\u003e\\n \\u003cp\\u003e268.296,72 \\u0026plusmn; 171.163,09\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 148px;\\\"\\u003e\\n \\u003cp\\u003e270.879,44 \\u0026plusmn; 196.084,36\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 135px;\\\"\\u003e\\n \\u003cp\\u003e2.582,72 \\u0026plusmn; 77.550,21\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 59px;\\\"\\u003e\\n \\u003cp\\u003e0,865\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003eNumber of patients \\u0026ndash; N = 19. Number of eyes \\u0026ndash; N = 25.\\u003c/p\\u003e\\n\\u003cp\\u003ep \\u0026ndash; descriptive level of the linear model with random effects.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eVA LogMAR\\u003c/strong\\u003e: Visual Acuity in LogMAR; \\u003cstrong\\u003eCMT\\u003c/strong\\u003e: Central Macular Thickness; \\u003cstrong\\u003eSCT\\u003c/strong\\u003e: Subfoveal Choroidal Thickness;\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAASP\\u003c/strong\\u003e: Avascular Area of the Superficial Plexus; \\u003cstrong\\u003eAADP\\u003c/strong\\u003e: Avascular Area of the Deep Plexus; \\u003cstrong\\u003eCD\\u003c/strong\\u003e: Capillary Density.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cbr\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTable 4 \\u0026ndash; Summary Measures of Characteristics\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003ctable border=\\\"0\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"766\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 223px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eMean\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eStandard Deviation\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eMinimum\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 77px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eMaximum\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e1st Quartile\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eMedian\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e3rd Quartile\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eN\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 223px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eAge (years)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e72,6\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e11,2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e56,0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 77px;\\\"\\u003e\\n \\u003cp\\u003e94,0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e64,0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e72,0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e82,0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003e19\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 223px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eVA Logmar\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 77px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 223px;\\\"\\u003e\\n \\u003cp\\u003ePre\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e0,38\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e0,20\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e0,18\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 77px;\\\"\\u003e\\n \\u003cp\\u003e1,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e0,24\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e0,30\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e0,48\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003e25\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 223px;\\\"\\u003e\\n \\u003cp\\u003ePost\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e0,32\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e0,20\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e0,10\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 77px;\\\"\\u003e\\n \\u003cp\\u003e1,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e0,18\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e0,30\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e0,40\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003e25\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 223px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eCMT\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 77px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 223px;\\\"\\u003e\\n \\u003cp\\u003ePre\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e234,56\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e28,94\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e194,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 77px;\\\"\\u003e\\n \\u003cp\\u003e290,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e210,50\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e226,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e256,50\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003e25\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 223px;\\\"\\u003e\\n \\u003cp\\u003ePost\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e236,08\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e30,28\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e194,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 77px;\\\"\\u003e\\n \\u003cp\\u003e292,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e213,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e229,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e259,50\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003e25\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 223px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eSCT\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 77px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 223px;\\\"\\u003e\\n \\u003cp\\u003ePre\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e163,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e103,68\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e49,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 77px;\\\"\\u003e\\n \\u003cp\\u003e355,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e62,50\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e128,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e242,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003e25\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 223px;\\\"\\u003e\\n \\u003cp\\u003ePost\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e161,80\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e102,85\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e49,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 77px;\\\"\\u003e\\n \\u003cp\\u003e365,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e62,50\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e128,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e242,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003e25\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 223px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eCD\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 77px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n 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style=\\\"width: 223px;\\\"\\u003e\\n \\u003cp\\u003ePost\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e177.198,24\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e120.992,85\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e69,02\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 77px;\\\"\\u003e\\n \\u003cp\\u003e499.922,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e86.814,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e146.338,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e253.817,50\\u003c/p\\u003e\\n 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valign=\\\"bottom\\\" style=\\\"width: 223px;\\\"\\u003e\\n \\u003cp\\u003ePost \\u0026ndash; Pre Variation\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 77px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 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style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e13.843,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003e25\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 223px;\\\"\\u003e\\n \\u003cp\\u003eAADP\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e2.582,72\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e77.550,21\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 82px;\\\"\\u003e\\n \\u003cp\\u003e-198.150,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 77px;\\\"\\u003e\\n \\u003cp\\u003e190.634,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e-24.817,50\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e3.164,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 70px;\\\"\\u003e\\n \\u003cp\\u003e26.400,00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003e25\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003e\\u0026nbsp;\\u003cstrong\\u003eVA LogMAR\\u003c/strong\\u003e: Visual Acuity in LogMAR; \\u003cstrong\\u003eCMT\\u003c/strong\\u003e: Central Macular Thickness; \\u003cstrong\\u003eSCT\\u003c/strong\\u003e: Subfoveal Choroidal Thickness; \\u003cstrong\\u003eAASP\\u003c/strong\\u003e: Avascular Area of the Superficial Plexus; \\u003cstrong\\u003eAADP\\u003c/strong\\u003e: Avascular Area of the Deep Plexus; \\u003cstrong\\u003eCD\\u003c/strong\\u003e: Capillary Density. Pre: pre-treatment. Post: post-treatment.\\u003c/p\\u003e\"},{\"header\":\"Graphs\",\"content\":\"\\u003cp\\u003eGraphs 1 to 6 are available in the Supplementary Files section.\\u003c/p\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"photobiomodulation, multiwavelength, dry age-related macular degeneration, swept-source optical coherence tomography, OCT, OCT-A, OCT angiography, ocular disease, vision, retina\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-5424107/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-5424107/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003ch2\\u003eBackground:\\u003c/h2\\u003e \\u003cp\\u003eThe Photobiomodulation-Valeda device is an innovative approach for treating dry age-related macular degeneration (AMD). The main objective of this study was to conduct a multimodal imaging analysis using swept-source technology in OCT (SS-OCT) and OCT-Angiography (SS-OCTA) in patients with dry AMD treated with Photobiomodulation (PBM), focusing primarily on safety and biomarkers.\\u003c/p\\u003e\\u003ch2\\u003eMaterials and Methods:\\u003c/h2\\u003e \\u003cp\\u003eA prospective interventional study was conducted involving 19 patients (25 eyes) diagnosed with dry AMD. The treatment consisted of nine sessions of PBM using the Valeda Light Delivery System. Various biomarkers were assessed before and one week after the treatment, including Best Corrected Visual Acuity (BCVA) for logMAR, central macular thickness (CMT), subfoveal choroidal thickness (SCT), capillary density (CD), and avascular areas of the superficial (AASP) and deep plexus (AADP).\\u003c/p\\u003e\\u003ch2\\u003eResults:\\u003c/h2\\u003e \\u003cp\\u003eThe study included 25 eyes, predominantly in AREDS category II. Significant improvements were observed in BCVA (p\\u0026thinsp;=\\u0026thinsp;0.001). No significant changes were observed in CMT, SCT, CD, AASP, and AADP (p\\u0026thinsp;\\u0026gt;\\u0026thinsp;0,05). The treatment was well tolerated, with few mild side effects, and no patient developed wet AMD.\\u003c/p\\u003e\\u003ch2\\u003eConclusion:\\u003c/h2\\u003e \\u003cp\\u003ePBM-Valeda therapy shows promise as a treatment strategy for dry AMD, resulting in improved visual acuity (as previously demonstrated in Lightsite I, II, and III). It is important to emphasize the safety of the treatment, as none of the biomarkers (CMT, SCT, CD, AASP, and AADP) exhibited harmful changes. Side effects were minimal, there were no signs of retinotoxicity, and no patient developed exudative AMD, after 1 cycle: 9 sessions of PBM treatment.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Prospective Study of Safety and Biomarkers Using Multimodal Analysis with Swept-Source Oct and Oct-Angiography in Patients with Dry Age Related Macular Degeneration Treated with Photobiomodulation.\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2024-12-17 06:46:18\",\"doi\":\"10.21203/rs.3.rs-5424107/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"01c5f8bd-29bd-46b0-a983-210dc59cca8a\",\"owner\":[],\"postedDate\":\"December 17th, 2024\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2024-12-17T06:46:20+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2024-12-17 06:46:18\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-5424107\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-5424107\",\"identity\":\"rs-5424107\",\"version\":[\"v1\"]},\"buildId\":\"qtupq5eGEP_6zYnWcrvyt\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}