In AMD, Cone Densities Decline Across Clinically Unremarkable Retinal Regions

In patients with age-related macular degeneration (AMD), cone density declines in clinically unremarkable retinal regions, which may explain the loss of mesopic sensitivity reported in such areas, according to research published in the American Journal of Ophthalmology. The study shows that, in some AMD eyes, retinal regions that are not clinically affected by AMD lesions experience accelerated cone density reductions. Although this occurs in both eyes with predominantly subretinal drusenoid deposits (SDD) and eyes with drusen and no SDD, researchers say a higher rate of loss occurs in eyes with SDD.

“[C]one degeneration or loss causes major visual impairment since cones are responsible for color vision and fine visual acuity, which are essential for many activities of daily living,” the researchers explain. “Therefore, accurate assessment of cone photoreceptor survival in patients with AMD is essential, and formulating strategies for preserving or rescuing cones is of critical value.”

They compared cone density in 1174 clinically unremarkable regions within the central subfield, inner ring, and outer ring of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid for 39.6±3.3 months and compared the values of the AMD group with those of an age-matched normal values of a control group.

The researchers conducted a prospective case series to evaluate cone photoreceptor density in clinically unremarkable retinal regions of patients with intermediate AMD using adaptive optics scanning laser ophthalmoscopy (AOSLO) and optical coherence tomography (OCT). 

The study included 10 eyes of 7 patients with intermediate AMD, including 5 eyes of 4 patients with predominantly subretinal drusenoid deposits (SDD; aged 74-85 years) and 5 eyes of 3 patients with drusen but without SDD (aged 60-69 years), and 27 eyes of 17 participants without AMD. 

For age matching and subsequent comparison with the AMD groups, the researchers divided participants into 2 control groups; a younger group (aged 54-72 years; 17 eyes of 11 participants; compared with the AMD-drusen group) and an older group (aged 72-84 years; 12 eyes of 7 participants; compared with the AMD-SDD group).

In the eyes with AMD, the researchers found cone density decreased at 98.3% of the examined locations. In the central subfield, inner ring, and outer ring, they found cones declined by -255±135, -133±45, and -59±24 cones/degree²/year, respectively, in AMD-SDD eyes and by -212±89, -83±37, and -27±18 cones/degree²/year, respectively, in AMD-drusen eyes. 

The team noted the percentage of retinal loci with cone density lower than normal increased over the follow-up period from 42% at baseline to 80% at the last visit in the AMD-SDD eyes and from 31% to 70% in the AMD-drusen eyes.

“In retinal regions that were not clinically affected by AMD lesions, eyes with SDD and drusen both showed an accelerated cone density reduction albeit the rate of loss was even greater in eyes with SDD,” according to the researchers “Because SDD and drusen represent 2 independent risk factors for vision loss in AMD, longitudinal quantification of the natural history of photoreceptor degeneration in AMD of different phenotypes merits attention.”.

Limitations of the study include lack of a linear scale cone density due to lack of an axial length measurement, relatively few eyes with AMD studied, lack of correlative longitudinal functional data and OCT-angiography choriocapillaris flow deficit measurements, and images of cones acquired using a confocal AOSLO device.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.