Age-related macular degeneration (AMD) is a leading cause of vision loss, and understanding its progression is critical for early intervention. A recent study published in the American Journal of Ophthalmology sheds new light on a powerful biomarker that could revolutionize how we predict retinal atrophy: hyperreflective foci along the retinal pigment epithelium (rpeHRF).
🧠 What Are HRF and Why Do They Matter?
Hyperreflective foci (HRF) are bright spots seen on optical coherence tomography (OCT) scans. They come in two flavors:
- rpeHRF: Located along the retinal pigment epithelium (RPE), often indicating thickening or dysfunction.
- iHRF: Found within the neurosensory retina, detached from the RPE.
These tiny lesions may look subtle, but they carry big implications for disease progression.
📈 The Study: Tracking AMD Over Time
Researchers followed 171 eyes with intermediate AMD (iAMD) for nearly five years using swept-source OCT imaging. Their goal? To determine which type of HRF better predicts the onset of large choroidal hypertransmission defects (hyperTDs)—a precursor to geographic atrophy.
Key Findings:
- rpeHRF area was the strongest predictor of hyperTD onset, outperforming both iHRF and drusen volume.
- iHRF always appeared after or alongside rpeHRF, never before.
- Eyes with only rpeHRF still progressed to hyperTDs, highlighting its early warning potential.
🧪 Figure 1: The Method Behind the Magic
Figure 1 in the study illustrates how researchers separated and quantified iHRF and rpeHRF using en face and B-scan OCT images. This meticulous workflow enabled them to analyze each HRF type independently and confirm rpeHRF’s predictive power.
🧠 Study Workflow (Figure 1)
Step-by-step HRF classification:
- Start with total HRF outlines on en face OCT.
- Review B-scans to locate each HRF.
- Separate into:
- rpeHRF (yellow arrows)
- iHRF (blue arrows)
- Quantify each type within a 5-mm fovea-centered circle.
⏳ Figure 2: A Case Study in Progression
Figure 2 tracks a 65-year-old woman’s eye over 44 months:
- Baseline: Large drusen and rpeHRF present; no iHRF.
- 21 Months: iHRF emerges; drusen and rpeHRF grow.
- 29 Months: HyperTDs appear as drusen and rpeHRF shrink.
- 44 Months: HRF regress, but hyperTDs persist and expand.
This timeline reinforces the idea that rpeHRF precedes iHRF and hyperTDs, making it a critical biomarker for early detection.
| Time Point | Drusen Volume | rpeHRF | iHRF | HyperTDs |
|---|---|---|---|---|
| Baseline | High | Present | Absent | None |
| 21 Months | Increased | Increased | Appears | None |
| 29 Months | Decreased | Shrinks | Enlarges | First signs |
| 44 Months | Nearly gone | Minimal | Minimal | Expanded |
🧩 Interpretation: rpeHRF appears first → iHRF follows → hyperTDs emerge → HRF regress but damage persists.
🧬 Why This Matters
The study’s findings suggest that rpeHRF may represent early RPE dysfunction and serve as a harbinger of retinal atrophy. By identifying and monitoring rpeHRF, clinicians can better predict which patients are at highest risk—and potentially intervene before irreversible damage occurs.
👁️ Clinical Takeaway
- rpeHRF should be prioritized in AMD monitoring and clinical trials.
- En face imaging offers a fast, reliable way to detect HRF and hypoTDs.
- Total HRF burden remains a robust predictor, even without separating HRF types.
Berni, A., Kastner, J.D., Shen, M., Cheng, Y., Herrera, G., Hiya, F., Liu, J., Wang, L., Li, J., El-Mulki, O.S., Beqiri, S., Trivizki, O., Waheed, N.K., O’Brien, R., Gregori, G., Wang, R.K., & Rosenfeld, P.J. (2025). Hyperreflective Foci Along the Retinal Pigment Epithelium Predict the Onset of Large Choroidal Hypertransmission Defects in Age-Related Macular Degeneration. American Journal of Ophthalmology, 274, 76–90.
