In a new study published in Investigative Ophthalmology & Visual Science, researchers investigated whether the surface area of putative retinal gliosis (PRG) may be larger in patients with Alzheimer's disease (AD).
Give me some background first.
As a progressive neurodegenerative disease, AD is the most common cause of dementia in elderly individuals—accounting for an estimated 60% to 80% of all cases.
- Fact: In 2020, an estimated 5.8 million Americans had AD.
Symptoms of AD may include:
- Memory loss that disrupts daily life
- Decreased or poor judgment
- Changes in mood, personality, or behavior
- Difficulty handling money and paying bills
And what exactly is putative retinal gliosis?
Per the investigators: Putative retinal gliosis (activated retinal astrocytes, microglia, and Müller cells) is quantitatively characterized as hyper-reflective patches on spectral-domain optical coherence tomography (SD-OCT) en face images that correspond to similar structures on b-scans in the following diseases:
- Glaucoma
- Diabetic retinopathy (DR)
- Retinal vein occlusion (RVO)
Take note: The presence of these hyper-reflective structures (known as “putative gliotic changes”)—plus the extent of retinal region covered with them—have been reported to have a greater potential of being an indicator for glaucomatous degeneration.
Now, talk about the study.
Investigators conducted a cross-sectional multisite study to compare preclinical AD with controls on three points:
- The differences in the surface area of putative retinal gliosis
- The association between the surface area of putative retinal gliosis versus RNFL thickness
- To determine whether a multimodal model of the surface area of PRG and RNFL thickness would better distinguish between preclinical AD and controls compared to a model of the surface area of PRG alone.
Patients were recruited from:
- Butler Hospital Memory and Aging Program (MAP)
- University of Alabama at Birmingham (UAB) Alzheimer's Disease Research Center (ADRC)
Who was included in the study?
A total of 76 participants (132 eyes) comprised of:
- 22 patients with preclinical AD (40 eyes)
- Mean age: 69 years (range: 60 to 80 years)
- 20 control participants (32 eyes)
- Mean age: 66 years (range: 58 to 82 years, P = 0.11)
How was the study conducted?
The Spectralis Optical Coherence Tomography (OCT)2 Module (Heidelberg Engineering) was utilized to attain macular centered 20 × 20 and 30 × 25° spectral-domain OCT (SD-OCT) images of participants.
Then: The researchers used generalized linear mixed models to compare the surface area of putative retinal gliosis and RNFL thickness for the nine sectors of the Early Treatment Diabetic Retinopathy Study (ETDRS) map between treatment and control groups.
Findings?
The surface area of putative retinal gliosis was significantly greater in the pre-clinical AD group (0.97 ± 0.55 mm2) compared to controls (0.68 ± 0.40 mm2); F(1, 70) = 4.41, P = 0.039; Cohen's d = 0.61
- No significant difference was found between groups regarding RNFL thickness in the 9 ETDRS sectors (p > 0.05)
Limitations?
The authors noted that the study was cross-sectional in nature.
Additionally, en-face SD-OCT imaging did not have the lateral resolution necessary to resolve the types of glial cells in the areas of presumed gliosis.
Expert opinion?
The authors stated that the findings indicated the potential value of the surface area of putative retinal gliosis for:
- Early AD detection
- Monitoring disease progression
- Serving as surrogate endpoints for neuroinflammation in clinical trials related to AD
Take home.
Based on this data, putative retinal gliosis may be a biomarker for AD-related neuroinflammation.