(326 days)
The Valeda Light Delivery System is intended to provide improved visual acuity in patients with best-corrected visual acuity of 20/32 through 20/70 and who have dry age-related macular degeneration (AMD) characterized by:
- . The presence of at least 3 medium drusen (> 63 µm and ≤ 125 µm in diameter), or large drusen (> 125 um in diameter), or non-central geographic atrophy, AND
- The absence of neovascular maculopathy or center-involving geographic atrophy. ●
After about two years, the Valeda Light Delivery System treatment provides improved mean visual acuity of approximately one line of visual acuity (ETDRS) compared to those not receiving the treatment.
The Valeda Light Delivery System is a benchtop instrument emitting non-coherent light in the wavelengths of 590 nm (amber), 660 nm (red), and 850 nm (near infrared, i.e., NIR) from three light emitting diodes (LEDs). respectively. The system projects a beam spot with a diameter of approximately 30 mm at the corneal plane of the patient for each of the three wavelengths. The system is to be used by eye care professionals to treat certain population of patients with dry AMD as defined in the Indications for Use (IFU).
The operator interface (Operator View in Figure 1) consists of a touchscreen, start and stop buttons and a joystick to center the beam on the patient's eye. A USB port is used to load treatment credits into the system. The patient interface (Patient View in Figure 1) consists of a fixed forehead rest, the light aperture (exit window) and an adjustable chin rest.
Each treatment takes a total of 250 seconds and consists of four phases as described below.
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- Open Eye: Pulsed amber (590 nm, 3 Hz) and NIR (850 nm, 3 Hz) LEDs are turned on for 35 seconds.
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- Closed Eye: Continuous red LED (660 nm) is turned on for 90 seconds.
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- Open Eye: Pulsed amber (590 nm, 3 Hz) and NIR (850 nm, 3 Hz) LEDs are turned on for 35 seconds.
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- Closed Eye: Continuous red LED (660 nm) is turned on for 90 seconds.
For each treatment series, the patient receives 3 treatments each week for a total of 9 treatments over a period of 3-5 weeks.
Here's a breakdown of the acceptance criteria and study findings for the Valeda Light Delivery System, based on the provided text:
Acceptance Criteria and Device Performance
The provided document describes both non-clinical and clinical performance criteria. The non-clinical criteria generally focus on the physical characteristics and safety of the device's light output, material biocompatibility, and electrical/software safety. The clinical criteria are centered around the device's ability to improve visual acuity in patients with dry AMD and its safety profile.
Non-Clinical Acceptance Criteria and Reported Performance
| Test | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Beam diameter measurement | Between (b) (4) and (b) (4) mm | Passed: 7 of 7 tested devices, Average ~ 31 mm |
| Treatment beam divergence angle measurement | (b) (4) degrees | Passed: 7 of 7 tested devices, Average ~ 13 deg |
| Treatment beam irradiance measurement | Red: (b) (4) Amber: (b) (4) IR: (b) (4) | Passed: 7 of 7 tested devices |
| Long-term stability of device output | Calibrated power output at factory (b) (4) | Passed (devices tested 9 months to 5 years after previous calibration) |
| Optical Radiation Safety | Compliance with ANSI Z80.36-2021 | Acceptable: Test report provided and found acceptable |
| Biocompatibility | Compliance with ISO 10993-1:2018 | Acceptable: Evaluation found acceptable |
| Electromagnetic Compatibility (EMC) | Compliance with IEC 60601-1-2:2020 | Supported: Results support EMC |
| Electrical Safety | Compliance with IEC 60601-1: 2005, A1:2012, A2: 2020 | Supported: Results support electrical safety |
| Software Verification & Validation | Consistent with FDA guidance | Acceptable: Documentation and testing adequate |
Clinical Acceptance Criteria and Reported Performance (LIGHTSITE III Study)
The primary clinical acceptance criterion was the demonstration of statistical superiority in mean best-corrected visual acuity (BCVA) change from baseline between the PBM (active) and Sham (control) arms.
| Acceptance Criteria (Clinical) | Reported Device Performance (Primary Endpoint) |
|---|---|
| Primary Effectiveness Endpoint: | |
| Mean BCVA change from baseline to Month 13 | Not Met: Mean PBM result was 2.6 letters better than the mean Sham result (p=0.0548; non-significant). |
| Mean BCVA change from baseline to Month 21 | Met: Mean PBM result was 3.8 letters better than the mean Sham result (p=0.0036; significant). The 95% confidence interval on the difference was 1.2 to 6.3 letters. |
| Primary Safety Endpoint: | |
| Rule out inferiority for mean BCVA changes from baseline (PBM vs. Sham) to Month 24, with a non-inferiority margin of 2 letters. | Met: Superiority was achieved at Month 21 (p=0.0036), and maintained at Month 24 (p=0.0024), thus ruling out inferiority. (FDA noted this was considered an inappropriate primary safety endpoint due to being based on the same parameter as effectiveness, and preferred adverse event rates). |
| Overall Benefit/Risk Conclusion: | Positive: Probable benefits outweigh probable risks, as there is no existing approved treatment for this patient population. |
Study Details for Clinical Performance (LIGHTSITE III)
2. Sample Size and Data Provenance
- Test Set Sample Size: 100 subjects / 148 eyes were enrolled.
- PBM (Active) Group: 65 subjects / 93 eyes
- Sham (Control) Group: 35 subjects / 55 eyes
- mITT (modified Intent-to-Treat) Population for Effectiveness Analysis: 98 subjects / 145 eyes (34/54 for Sham, 64/91 for PBM).
- Data Provenance: The LIGHTSITE III study was a prospective, multi-site study conducted in the United States (up to 15 centers, 10-11 participating in the study).
3. Number of Experts and Qualifications for Ground Truth
The document mentions a "reading center" for confirmation of certain criteria, but does not specify the exact number of experts or their specific qualifications (e.g., years of experience, subspecialty) used to establish the ground truth for image-based classifications like drusen, GA, or neovascular maculopathy. It only states that diagnoses of dry AMD were confirmed by the reading center, and key exclusion criteria (e.g., CNV, central GA) were also confirmed by the reading center.
4. Adjudication Method
The document does not explicitly state an adjudication method (e.g., 2+1, 3+1) for the establishment of ground truth by the reading center.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, an MRMC comparative effectiveness study was not done. The LIGHTSITE III study was a clinical trial comparing a device (PBM) to a sham control, evaluating patient outcomes (BCVA), not comparing human readers with and without AI assistance. Therefore, there is no effect size reported for human readers improving with AI vs. without AI assistance.
6. Standalone Performance
No, a standalone (algorithm only without human-in-the-loop performance) study was not done. The Valeda Light Delivery System is a light-delivery device intended for direct patient treatment, not an AI-based diagnostic algorithm. Its performance is measured by its therapeutic effect on patients, not its ability to interpret medical images or data independently.
7. Type of Ground Truth Used
The ground truth for the clinical study was primarily established through:
- Clinical Assessments: Best-corrected visual acuity (BCVA) letter scores (ETDRS), low light BCVA (LLBCVA), contrast sensitivity, color vision testing. These are direct patient measurements.
- Imaging Data Interpretation: Confirmations by a "reading center" for:
- Presence of drusen (intermediate/large) and/or geographic atrophy (GA) on color fundus images, OCT, and/or FAF.
- Exclusion criteria like neovascular maculopathy (CNV, serous/hemorrhagic detachment, retinal hard exudates, subretinal/sub-RPE fibrovascular proliferation, disciform scar) and central-involving GA.
- Monitoring of AMD progression (drusen, pigmentary changes, GA, nAMD) and incident GA using OCT and FAF images.
- Adverse Event Reporting: Self-reported and clinically observed adverse events.
8. Training Set Sample Size
This is a medical device, not an AI/algorithm-based diagnostic tool that typically has a separate "training set" for model development. The concept of a "training set" as described in the prompt is not applicable here. The LIGHTSITE III study is the primary clinical evidence for the device's safety and effectiveness.
9. How the Ground Truth for the Training Set was Established
As noted above, there is no "training set" in the context of an AI algorithm. The LIGHTSITE III clinical trial serves as the pivotal study to demonstrate the device's performance, and the methods for establishing ground truth within that study are outlined in point 7.
N/A