In this episode of Evidence Based Retina, Rishi P. Singh, MD, sits down with SriniVas R. Sadda, MD, FARVO, to discuss functional endpoints in geographic atrophy (GA) and the value of microperimetry as a measure of disease impact.
Dr. Sadda is the A. Ray Irvine, Jr., MD, Endowed Chair in Clinical Ophthalmology and Professor of Ophthalmology at the Doheny Eye Institute and the David Geffen School of Medicine at UCLA. He is set to join Duke University School of Medicine as chair of its Department of Ophthalmology in November 2026.
Microperimetry in GA fast facts:
- Foveal sparing in GA: Visual acuity may remain relatively preserved when GA spares the fovea, even as patients lose function elsewhere in the macula that can affect activities such as reading and driving.
- CHROMA and SPECTRI trials: Microperimetry correlated more strongly with GA lesion area than the other functional measures assessed, while visual acuity showed a weaker relationship.1
- Device options: Two microperimetry devices, the iCare MAIA and NIDEK MP-3, perform well in practice, though patient selection and testing strategy are critical, according to Dr. Sadda.
- AI-based sensitivity modeling: Functional OCT (OCT-F) uses AI to estimate retinal sensitivity at locations not directly tested with microperimetry, potentially providing a denser map of functional change while reducing the need for extensive direct testing.2
- Regulatory path: Dr. Sadda said a patient-education use might not require regulatory clearance, depending on the claims made, while using OCT-F to support a functional-benefit label claim would likely require validation acceptable to the FDA.
Microperimetry's correlation with functional loss in GA
Most retina trials rely on best-corrected visual acuity (BCVA) as a standard measure of visual function. Dr. Sadda noted that this can be problematic in GA because visual acuity may remain relatively preserved when an atrophic lesion spares the fovea, even as patients lose meaningful function elsewhere in the macula. These changes can affect activities such as reading and driving.
This limitation was evident in CHROMA and SPECTRI, two phase 3 trials of lampalizumab. Among the visual function tests assessed, microperimetry outcomes showed stronger correlations with GA lesion area, whereas visual acuity showed a weak correlation.1
“We were very confident that lampalizumab didn't work because we didn't see an impact on GA growth, but we also saw no impact on microperimetry, and the two curves really matched each other.”
For Dr. Sadda, those findings highlight the potential value of microperimetry as a functional measure in GA.
Choosing patients and devices for microperimetry
Dr. Sadda mentioned two available microperimetry devices, the iCare MAIA and the NIDEK MP-3. Both perform well, he said, but patient selection and testing strategy may matter more than the device choice.
Patient selection is important because microperimetry requires patients to maintain fixation and respond consistently throughout the test. Patients with poor fixation may struggle with microperimetry, which can make the test lengthy or frustrating.
“The ideal patient is someone who has good fixation, is alert, and doesn't have any physical limitations that impact their ability to push the button.”
Additionally, some clinical trials used standardized patterns that were not tailored to the GA lesion and required patients to respond to many stimulus points. Dr. Sadda said these testing approaches may have contributed to frustration and a negative perception of microperimetry despite its potential value.
Pairing microperimetry with AI-based OCT analysis
GA lesions typically enlarge slowly, and the spacing between microperimetry points may be wide enough that lesion growth does not reach a new test location during the course of a study. As a result, conventional testing may fail to detect a change in sensitivity even as the lesion expands, which is why standardized testing grids can be a challenge.
Dr. Sadda described an emerging approach, which he referred to as functional OCT (OCT-F), intended to address this limitation. The strategy combines OCT data with measured microperimetry sensitivity and uses artificial intelligence to estimate sensitivity at retinal locations not directly tested.
The AI model learns the relationship between OCT features and measured sensitivity at tested locations. That relationship can then be applied to untested locations across the macula. Peer-reviewed research has shown that machine-learning models can predict retinal sensitivity and generate high-resolution inferred-sensitivity maps.2
“The concept behind this OCT-F is a strategy that takes advantage of artificial intelligence techniques to infer the sensitivity in locations that you didn't test.”
The result is a denser estimate of retinal function that may better capture sensitivity loss as GA progresses while reducing the number of locations that need to be tested directly. Dr. Sadda said this inferred-sensitivity strategy has also been used to evaluate potential functional treatment effects.
The regulatory path to a functional endpoint
How OCT-F might ultimately be used in clinical practice will likely depend on its intended purpose and the claims made about the technology, according to Dr. Sadda.
As a patient-education tool, it might not require regulatory clearance, depending on the claims being made, although Dr. Sadda emphasized that he was not speaking as a regulatory expert. Using OCT-F as a clinical trial endpoint to demonstrate functional benefit and potentially support a functional claim on a product label would likely require validation acceptable to the FDA, including independent verification and assessment of the technology's reliability.
In Dr. Sadda's view, the supporting data are strong and robust, but it remains uncertain how regulatory agencies will evaluate the approach. That will become clearer as companies present the technology and supporting evidence to regulators.
Connecting functional measures with patient experience
Dr. Singh pointed to the NEI VFQ-25, a 25-item questionnaire used to assess vision-related function and quality of life, as an example of the type of patient-reported outcome that could be considered alongside microperimetry.3 He recalled pegcetacoplan data suggesting a relationship between preservation of central microperimetry and patient-reported outcomes.
The broader question, Dr. Sadda said, is whether changes detected by microperimetry correspond to meaningful changes for patients. Additional patient-reported outcome measures could therefore be studied alongside microperimetry to help establish the clinical relevance of the functional findings.
Pegcetacoplan data
OAKS, one of the two phase 3 pegcetacoplan trials, provides another example of microperimetry as a potential functional endpoint. A post-hoc analysis found a reduced rate of visual function loss in the central macula and GA junctional zone with pegcetacoplan treatment.4
Dr. Sadda also noted that the AI-based sensitivity model produced similar results when trained on treated versus untreated eyes. He considered this important because preserving retinal structure does not necessarily mean preserved photoreceptors remain functional.
In his view, testing fewer retinal locations directly and using OCT-F to estimate sensitivity elsewhere could make microperimetry more practical while still capturing functional change. To support a functional-benefit claim, however, the approach would need to be shown to be reliable and clinically meaningful to patients.
Key takeaways:
- BCVA may not capture the full functional impact of GA, particularly when the foveal center is spared.
- Microperimetry can provide localized measures of retinal sensitivity that more closely reflect GA-related structural change than visual acuity alone.
- Patient selection and testing strategy are major practical considerations, particularly when testing uses dense grids that are not tailored to the lesion.
- OCT-F may address some of these limitations by using OCT and AI to estimate sensitivity at untested locations, potentially reducing testing burden while providing a denser map of functional change.
- Establishing microperimetry or OCT-F as a clinical trial endpoint will require technical validation and evidence that measured functional changes correspond to clinically meaningful outcomes for patients.
This article was written by Sonia Kelley, OD, MS, based on the recorded video from Drs. Singh and Sadda.
