Inflammatory Hyperreflective Retinal Foci: An OCT Biomarker of Neuroinflammation in Geographic Atrophy
Federico Parolini1, Elisabetta Pilotto1, Edoardo Midena1,2
1Department of Neuroscience-Ophthalmology, University of Padova, 35128 Padova, Italy.
Abstract:
Background: Inflammatory hyperreflective retinal foci (I-HRF) have been recognized as an optical coherence tomography (OCT) biomarker of aggregates of activated microglial cells. Microglia, the principal resident immune cells, are key players in geographic atrophy (GA) development and progression. Objective: To quantify I-HRF distribution across inner (IR) and outer (OR) retinal layers in GA compared with healthy controls. Methods: Retrospective observational study including patients aged ≥50 years with GA lesion area >1.25 mm2 and age-matched healthy subjects. GA eyes were classified as bilateral GA (B-GA) or unilateral GA (U-GA; fellow eye with macular neovascularization). Using Spectralis OCT, I-HRF (≤30 μm; RNFL-like reflectivity; no posterior shadowing) were identified and counted across IR and OR. Results: Sixty-eight eyes from 46 patients with GA (B-GA: 49 eyes; U-GA: 19 eyes) and 19 control eyes were studied. I-HRF were higher in IR than in OR in all groups (p < 0.001). I-HRF were higher in GA eyes in both layers compared with controls (p < 0.05). U-GA exhibited higher I-HRF than B-GA in IR (44.32 ± 8.47 vs. 30.10 ± 7.62; p < 0.001), while I-HRF were not significantly different in OR (9.58 ± 3.04 vs. 8.02 ± 3.33; p = 0.081). Conclusions: I-HRF are increased in GA. They are more numerous in IR, consistent with their proposed inflammatory origin. These findings further support the role microglia may play in GA pathology. I-HRF may become an OCT biomarker to track GA-associated neuroinflammation in different GA phenotypes. Longitudinal studies are needed to clarify I-HRF significance in GA progression.
Insights
Inflammatory hyperreflective foci (I-HRF) are elevated in geographic atrophy (GA) eyes, particularly in the inner retina, suggesting a role for microglia in GA pathology. These findings may establish I-HRF as an optical coherence tomography biomarker for neuroinflammation in GA.
Area of Science:
- Ophthalmology
- Neuroscience
- Medical Imaging
Background:
- Inflammatory hyperreflective foci (I-HRF) are recognized optical coherence tomography (OCT) biomarkers linked to activated microglial cells.
- Microglia are key immune cells implicated in the development and progression of geographic atrophy (GA).
- Understanding I-HRF distribution may elucidate the role of neuroinflammation in GA.
Purpose of the Study:
- To quantify and compare the distribution of I-HRF across the inner retinal (IR) and outer retinal (OR) layers in patients with GA versus healthy controls.
- To investigate potential differences in I-HRF distribution between bilateral GA (B-GA) and unilateral GA (U-GA) phenotypes.
Main Methods:
- Retrospective observational study involving patients aged ≥50 years with GA and age-matched healthy controls.
- Spectralis OCT was used to identify and count I-HRF (defined by size, reflectivity, and lack of posterior shadowing) in IR and OR.
- GA eyes were categorized as B-GA or U-GA (fellow eye with macular neovascularization).
Main Results:
- A total of 68 GA eyes and 19 control eyes were analyzed.
- I-HRF were significantly higher in the IR compared to the OR across all groups (p < 0.001).
- GA eyes showed higher I-HRF in both retinal layers compared to controls (p < 0.05).
- U-GA eyes exhibited significantly higher I-HRF in the IR than B-GA eyes (p < 0.001), with no significant difference in the OR (p = 0.081).
Conclusions:
- I-HRF are increased in geographic atrophy, predominantly in the inner retina, supporting their inflammatory origin and association with microglial activation.
- These findings suggest that I-HRF may serve as a valuable OCT biomarker for tracking GA-associated neuroinflammation across different GA phenotypes.
- Further longitudinal studies are warranted to determine the prognostic significance of I-HRF in GA progression.
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