New findings from a study published in Investigative Ophthalmology & Visual Science suggest that the appearance of intraretinal hyper-reflective foci (IHRF) in the outer retina signals risk for the progression of age-related macular degeneration (AMD).
Tell me about IHRF first.
IHRF can be photographed as hyperpigmentation via optical coherence tomography (OCT), and is found in both the outer and inner layers of the retina.
Previous studies have shown that the presence, increase in count, and location of IHRF are risk factors for progression to late AMD.
IHRF cells may migrate towards the deep capillary vascular plexus (DCP), which is thought to cause the development of macular neovascularization (MNV)—the process largely responsible for AMD.
And the connection to this research?
The study authors hypothesized that IHRF within the retina may have different sources, as IHRF in the outer retinal layers have been found to be more strongly associated with the risk of AMD progression.
This study was conducted to further investigate the spread of IHRF over time and what it may indicate regarding AMD.
Now, talk about the study.
Subjects were recruited from the Amish Eye Study, a longitudinal observational study that explored the genetic association between OCT-based risk factors and AMD progressionOut of the 1,339 participants, 52 eyes had both intermediate AMD (iAMD) and IHRF. Changes in the number and distribution of IHRF were compared over 2 years.
Patients with the following characteristics were excluded:
- Eyes with retinal disease other than iAMD
- OCT scans with segmentation errors
How were the OCT scans analyzed?
The following steps were performed to analyze the OCT scans at baseline and after 24 months:
- Identification of IHRF on OCT scans
- Division of retina into five equidistant slabs from the outer border of the internal limiting membrane (ILM) to the inner border of the retinal pigment epithelium (RPE)
- Binarization of slabs using thresholding in ImageJ software
- Removal of other hyper-reflective particles besides IHRF
- Count of IHRF generated
Findings?
The mean total number of IHRF increased from 4.67 to 11.61 over 24 months, and the majority of IHRF persisted over 24 months. Although IHRF count rose overall, lesions at a given location could drastically change at any particular time.
The most increase in IHRF was found in the outer retinal slabs, while inner slabs typically maintained a more constant count.
Meaning?
This suggests that there was an increase of IHRF up to the DCP, though not beyond it, which could imply that the risk of AMD progression is mainly linked to IHRF found in the outer retinal layers.
Expert opinion?
The results suggest that the appearance of an IHRF signals the development of many more IHRF— potentially becoming a marker to start treatment.
Future therapies may aim to treat early appearances of IHRF, and these therapies can help assess the effectiveness of IHRF treatment in delaying AMD.
Any limitations to know about?
A few … especially regarding the sample of the study.
A relatively small number of eyes with both iAMD and IHRF was collected, and the relatively uniform population of the Amish from which the sample was taken may have limited the degree of generalization of the findings.
Other limitations included the difficulty in consistently defining retinal slabs depending on the eye and the lack of analysis of the progression of individual lesions, though the overall number of IHRF within an eye were counted.
Take home.
The researchers summarized that “IHRF counts over time may be a quantitative measure of disease progression and may serve as biomarkers or endpoints in future therapeutic trials.”
Next steps?
Future research should explore the different sources of IHRF in inner and outer retinal layers to further understand the association between IHRF and AMD progression.
Studies may also investigate the potential for IHRF counts as an indicator of disease progression and intervening therapies.