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Evaluating Metabolic Changes Induced by PhotoBioModulation Through Spectrally Resolved Autofluorescence in Dry Age-Related Macular Degeneration Patients (PBM-dAMD)

F

Francesco Bandello

Status

Active, not recruiting

Conditions

Macular Degeneration, Age Related

Study type

Observational

Funder types

Other

Identifiers

NCT06582511
PBM-dAMD

Details and patient eligibility

About

The best treatment to prevent the evolution of early and intermediate forms of dAMD to atrophic degeneration is PhotoBioModulation (PBM). It is based on the principle that molecules can absorb light even if it is not part of specialized light-receiving organs. Irradiation of cells at certain wavelengths can be used to activate native molecules to modulate biochemical reactions and, consequently, whole cellular metabolism. One of the main targets of PBM is mitochondrial activity. Mitochondria are sensitive to irradiation with red-NIR light. PBM might also function by increasing the bioavailability of nitric oxide (NO) by prompting its release from intracellular stores. It is proposed that PBM causes the photodissociation NO from CCO15. NO is known to inhibit electron transport, so dissociation of NO can increase the mitochondrial membrane potential, increase O2, consumption, and thus the proton gradient, ultimately leading to an increase in ATP production. NO can also diffuse outside and act as a messenger capable of causing vasodilation and other effects.

PBM demonstrated a beneficial role in dAMD, characterized by mitochondrial dysfunction, oxidative stress, and inflammation. SrAF allows to assess of mitochondrial function, a target of PBM, as it allows the observation of minor fluorophores such as FAD. The SrAF is used to evaluate the effectiveness of the treatment.

Full description

This study is an observational, prospective, longitudinal, and monocentric study on Medical Device (CE marked, according to indications for use) on evaluating metabolic changes through Spectrally Resolved Autofluorescence in subjects with dry AMD.

Subjects will receive PBM treatments, as clinical practice, to stimulate metabolic mitochondrial activity which will be evaluated through Spectrally Resolved Autofluorescence.

Up to 30 subjects will be enrolled. The follow-up will last 6 months. Following the diagnosis of dAMD, the patient will be referred for photobiomodulation treatment.

Efficacy assessments will include slit lamp and fundus examinations, Intraocular pressure (IOP), ETDRS BCVA, CS, BAF, SR-AF, SD-OCT, Swept Source OCT-Angiography (SS-OCTA), and microperimetry. Whenever possible, the same person should perform the evaluations specified by the protocol at each study visit. Unless otherwise indicated, all ocular assessments should be performed on the study eye only.

Safety assessments include incidence of adverse events/serious adverse events, visual acuity, slit lamp findings, crystalline lens changes in phakic eyes, intraocular pressure, and fundus findings. The reporting period is from day 0 through the last study visit (Month 12).

The Primary Objective is to evaluate the modification of SrAF stimulated by the PBM treatment. The secondary objective is to evaluate the effectiveness of PBM treatment.

Enrollment

30 estimated patients

Sex

All

Ages

50+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

INCLUSION CRITERIA

  • Male or female at least 50 years;
  • Subjects with ETDRS BCVA letter scores of between 50 and 80 (Snellen equivalent of 20/100 to 20/25);
  • Subjects with a diagnosis of dry AMD as defined by the presence of drusen (regular or reticular pseudodrusen) and/or geographic atrophy (GA) visible on two of the following: color fundus images, OCT and/or Heidelberg FAF;
  • Able to communicate well with the Investigator and able to understand and comply with the requirements of the study; The subject is informed of the nature of this study and has provided written informed consent in accordance with institutional, local, and national regulatory guidelines.

EXCLUSION CRITERIA

  • Pregnant or lactating women

  • Current or history of neovascular maculopathy that includes any of the following:

    • Macular neovascularization (MNV) is defined as pathologic angiogenesis originating from the choroidal vasculature that extends through a defect in Bruch's membrane
    • Serous and/or hemorrhagic detachment of the neurosensory retina or retinal pigment epithelial (RPE)
    • Retinal hard exudates
    • Subretinal and sub-RPE fibrovascular proliferation
    • Disciform scar
  • Presence of center involving GA within the central ETDRS 500 μm diameter at diagnosis

  • Media opacities, including cataracts, which might interfere with visual acuity or imaging in the study eye(s). Subjects should not be entered if there is likelihood that they will require cataract surgery in the study eye in the next 24 months

  • Posterior capsule opacification, which might interfere with visual acuity or imaging in the study eye(s). Subjects should not be entered if there is likelihood that they will require surgery in the study eye in the next 24 months

  • Invasive eye surgery (e.g. cataract, capsulotomy) on a qualifying eye within three 3 months before treatment

  • Ocular disorder or disease that partially or completely obstructs the pupil (e.g., posterior synechia in uveitis)

  • A visually significant disease in any ocular structure apart from dry AMD (e.g., diabetic macular edema, glaucoma (using >2 eye drops medications, uncontrolled IOP and/or central/paracentral visual field loss), glaucoma surgery, active uveitis, active vitreous disease, intraocular tumor, retinal vascular diseases)

  • Has a serious medical illness that will prevent the subject from performing study activities (including cardiac, hepatic, renal, respiratory, endocrinologic, neurologic, or hematologic disease) or, in the judgment of the Investigator, is likely to require surgical intervention or hospitalization at any point during the study

  • Presence of or history of malignancy within the past 5 years other than non-melanoma skin or squamous cell cancer or cervical carcinoma in situ

  • Is non-ambulatory

  • Presence or history of known light sensitivity to yellow light, red light, or near-infrared radiation (NIR), or if there is a history of light-activated CNS disorders (e.g., epilepsy, migraine)

  • Use of any photosensitizing agent (e.g., topical, injectable) within 30 days of treatment without consulting the subject's physician

  • History of drug, alcohol, or substance abuse within 3 months before treatment

  • Has received an investigational drug or treatment with an investigational device within 3 months before treatment

  • If on any antioxidant or vitamin Age-Related Eye Disease Study (AREDS) supplement for dry AMD, has not been stabilized for a minimum of 1 month before Screening. Subjects are considered to be stable if they are taking the AREDS supplements consistently as prescribed by their treating doctor.

  • Has received Low Vision Rehab/Therapy within 30 days before Screening or intends to receive during the study

  • In the opinion of the Investigator, is unlikely to comply with the study protocol

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Data sourced from clinicaltrials.gov

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