A study in the AJO reports that thinner outer retinal thickness in the outer ETDRS ring is the most frequently reported variable that predicts lower brain measurements and is associated with atrophy in the of the brain regions involved in vision, memory and dementia.

The incidence of Alzheimer’s disease continues to grow exponentially, with some estimating it will affect more than 78 million people worldwide by 2030. However, imaging studies of brain aging have mostly been limited to neuroimaging, specifically MRI. Due to the cost associated with MRI, researchers have recognized retinal imaging to be a powerful, non-invasive and inexpensive way to study the brain via the eye. A new study in American Journal of Ophthalmology investigated how the outer retina in those with age-related macular degeneration would correlate with brain changes associated with Alzheimer’s.¹ The findings, which surprised the study authors themselves, reveal that a thinner outer retina was associated with the brain regions involved in memory.

Participants with thinner outer retina had significantly smaller hippocampus (β=0.019), lower occipital cortex regions of interest thickness (β=5.68) and lower cortical thickness in Alzheimer’s disease and related dementias (β=7.72). Significantly lower occipital cortex regions of interest (β=3.19) and dementia-related brain region (β=3.94) thickness were associated with participants with thinner total retina.

In AMD, the outer retina is impacted significantly and early, but little is known about its association with cognition or changes in brain morphometry. The authors noted the novelty of their study as it included patients with early or intermediate AMD, as well as those with normal retinal aging. “Limited literature exists on associations between neuroimaging and retinal imaging in older adults, particularly those with retinal diseases, such as AMD,” they wrote. “As retinal diseases are highly prevalent in aging populations, studies that include people with retinal disease are critical for understanding aging eyes and brain connections. In addition, several epidemiologic studies have shown that many retinal diseases are associated with higher risks of developing ADRD.”

The final cohort included 60 subjects (22 normal, 19 early AMD and 19 intermediate AMD) aged 70 to 87 (73 percent women). Seven participants were Black and the remainder were Caucasian. Linear regression was used to evaluate associations between retinal layer thickness measures (combined and averaged over central, inner, and outer ring) and dementia-related brain regions. MRI measurements included: total brain, cortex, cerebral white matter, gray matter and hippocampus volume, as well as occipital cortex thickness and cortical thickness in ADRD-related brain regions.

In this study, thinner outer retinal thickness in the outer ETDRS ring was the most frequently reported variable that predicted lower brain measurements, and most associated with atrophy of the brain regions involved in vision, memory and dementia. Thinner outer retina was associated with thinning of occipital regions of interest, lower hippocampal volume and brain regions known to show early structural and functional changes in dementia.

The association of outer retinal thinning with brain regions vulnerable to dementia and areas primarily involved in memory “was somewhat surprising,” the authors wrote in their paper. “It is possible that this association is unique to participants with normal macular aging and early and intermediate AMD. We recently published that in this cohort, outer retinal thickness was the only retinal layer that was significantly associated with cognition in this group.”

Study co-author Cecilia Lee, MD, Klorfine Family Endowed Chair in Ophthalmology at the University of Washington, Seattle, says the study’s findings involving the outer retinal layer were surprising. “We wanted to look at what’s the earliest changes we could detect,” she says, “and we were surprised that it was the outer retina and not the retinal nerve fiber layer as we had anticipated based on the literature.”

In terms of what’s behind the association, Dr. Lee says there are a couple possibilities. “This population is very different,” she says. “A lot of previous studies have excluded patients with AMD or any retinal diseases, so this is a different pilot study in that it includes people with and without AMD. Also, it could be related to the fact that AMD is the disease of the RPE and outer retina, and the outer retina is the first layer or first retinal location implicated in the early pathogenesis of AMD. So we’re not sure if it’s the early vascular disese that’s been picked up and there’s a thinning there. Also, we’re not really sure if it’s an AMD-related finding or if we’re following the normal aging population itself—these would be the first changes that we’d pick up in that case.

“If it’s actually the outer retinal layer, [that’s associated with brain atrophy] then that changes the focus of study,” Dr. Lee continues. “And if this is specific to the AMD population, that also changes everything because a lot of people are impacted by AMD.”

The authors point out that this pilot study, which had a small sample size, was meant to explore various relationships between retinal and brain health in people with early and intermediate AMD who are also at risk of developing age-related dementia. This “was not meant to study causal mechanisms,” they wrote. “Our study was not designed to investigate AD or any dementia specifically, and we used neuroimaging and cognitive proxy indicators of general brain health related to dementia. Thus, the generalizability of our results and hypothesized potential mechanisms should be interpreted with caution.

“Despite these limitations, the primary aim of our study was to identify associations and to highlight the predictive value of retinal layer thickness for brain atrophy, rather than to determine the exact magnitude of the associations,” the authors continued in their AJO paper. “Future research with larger sample sizes and independent replication studies will be crucial to confirm these associations, in which we also suggest exploring other retinal layer thickness variables that are highly correlated with the ‘marker’ identified in this study.”

In conclusion, the study suggests that imaging, particularly of outer retinal thickness, could be a complementary tool in evaluating risks of cognitive decline in individuals with normal retina aging, as well as early and intermediate AMD, but that “further research is warranted to determine whether these findings are specific to the AMD population or could generalize to populations with retinal diseases.”

^{1. Jiang, Yu et al. Outer retinal thinning is associated with brain atrophy in early age-related macular degeneration. American Journal of Ophthalmology. Oct. 3, 2024. [Epub ahead of print.]}

Atrial Fibrillation’s Association with Visual Field Loss

Cardiac arrhythmias like atrial fibrillation (AFib) can lead to stroke, heart failure and even sudden death, but this condition can harm more than a patient’s heart. In the past, studies have found an association between atrial fibrillation and glaucoma, but these reports never examined the effects on the progression of glaucoma. Research conducted at the University of California, recently published in Journal of Glaucoma, elaborates on how atrial fibrillation impacts the visual field of glaucoma patients.¹

Subjects had to be diagnosed with primary open-angle glaucoma but free of cardiac arrhythmia to be selected for this study. This allowed the researchers to measure a baseline visual field. Then, patients were followed for approximately 15 years before the final results were analyzed. A total of 144 eyes from 105 patients were selected, then divided into two groups. Patients that developed AFib during the study period were categorized as cases; all others were used as controls. The cases consisted of 48 eyes and the controls consisted of 96 eyes.

All subjects had an average baseline visual field worsening of -0.20 dB/year; in cases that developed AFib, it was -0.28 dB/year after the event. Control subjects showed an insignificant difference after the follow-up period, reporting an average visual field of -0.21 dB/year.

Researchers also assessed everyone’s scores on two common measures of stroke risk in AFib patients called CHADS₂ and CHA₂DS₂-VASc. These each assign point values based on the presence of various risk factors (e.g., congestive heart failure, hypertensions, diabetes). Higher scores indicate greater risk of stroke. “In this retrospective cohort study, we found that the presence of atrial fibrillation, and both higher CHADS₂ and CHA₂DS₂-VASc score were associated with a small but significantly faster rate of visual field progression in patients with glaucoma,” stated the researchers in their study.

On average, AFib patients in the study lost -0.07 dB/year more of their visual field for every unit of their CHADS₂ score. So, a CHADS₂ score of 0 would correspond with approximately -0.07 dB/year, while a score of 5 was measured at about -0.42 dB/year. This same principle was used when analyzing CHA₂DS₂-VASc scores, except the average visual field loss in correlation with this score was measured at -0.05 dB/year.

“Our findings may indicate that the presence of atrial fibrillation and related microvascular damage are associated with a faster visual field loss in patients with glaucoma, suggesting that impaired circulation has a role in glaucoma progression,” concluded the researchers in their paper on this study. “Our study underscores the need for comprehensive medical history assessment and the management of cardiovascular risk factors to mitigate the risk of fast disease progression.”

^{1. Nishida T, Moghimi S, Jin W, et al. Rates of visual field progression before and after the onset of atrial fibrillation. J Glaucoma. September 25, 2024. [Epub ahead of print].}

AAO Report: Intraoperative Aberrometry vs. Biometry

American Academy of Ophthalmology researchers evaluated the published literature to compare intraoperative aberrometry (IA) with preoperative biometry-based formulas with respect to intraocular lens power calculation accuracy for various clinical scenarios.

Literature searches in the PubMed database conducted in August 2022, July 2023 and February 2024 identified 157, 18 and six citations, respectively. These were reviewed in abstract form, and 61 articles were selected for full-text review. Of these, 29 met the criteria for inclusion in this assessment. The panel methodologists assigned a level of evidence rating to each of the articles; four were rated level I, 19 were rated level II and six were rated level III.

Here are some of the findings:

• Intraoperative aberrometry performed better than traditional vergence formulas, including the Haigis, HofferQ, Holladay and SRK/T; it performed similarly to the Barrett Universal II and Hill-RBF with respect to minimization of spherical equivalent refractive error. 

• For toric IOLs, IA outperformed formulas that only consider anterior corneal astigmatism and was similar to formulas like the Barrett Toric Calculator (BTC), which empirically account for the contribution from the posterior cornea. 

• In eyes with a history of corneal refractive surgery, IA performed similarly to the Barrett True-K and slightly better than other tested methods, including the Haigis-L, Shammas and Wang-Koch-Maloney formulas.

Scientists concluded that intraoperative aberrometry corresponded well with modern vergence formulas, including the Barrett Universal II, Hill-RBF, BTC and Barrett True-K. It had greater accuracy than traditional vergence-based intraocular lens power calculation formulas in eyes with and without a history of corneal refractive surgery. 

^{1. Pantanelli SM, Hatch K, Lin CC, et al. Intraoperative aberrometry versus preoperative biometry for intraocular lens power calculations: A Report by the American Academy of Ophthalmology. Ophthalmology 2024; Oct 3. [Epub ahead of print].}