To investigate the effect of age, sex, and the Y402H variant in the complement factor H (CFH) gene on the incidence, progression, and regression of age-related macular degeneration (AMD) as well as the effect of these factors and AMD on mortality, using multistate models, 4,379 persons aged 43 to 84 years at the time of the census were analyzed.

The status of AMD on a 5-level severity scale was graded from retinal photographs taken at up to 5 study visits between 1988 and 2010 and multistate models in continuous time were used to model the effects of age, sex, and CFH genotype on the incidence, progression, and regression of AMD and mortality.

The CFH Y402H genotype CC was associated, relative to genotype TT (reported as hazard ratio; 95% CI), with increased incidence of AMD (no to minimally severe early AMD, 1.98; 1.57–2.49), progression of AMD (minimally severe early to moderately severe early AMD, 1.73; 1.29–2.33; moderately severe early to severe early AMD, 1.30; 0.86–1.94; and severe early to late AMD, 1.72; 1.01–2.91) but not with regression of AMD or mortality. It was also noted that late AMD was associated with increased mortality (1.37; 1.15–1.62) relative to no AMD, but earlier stages of AMD were not.

Using the multistate models, this study showed that the Y402H risk variant is associated with lifetime incidence of early AMD and progression of early to late AMD and that late AMD is associated with mortality risk.

Australia researchers investigated the relationship between clinical macular changes and retinal function in age-related macular degeneration (AMD). They found that steady state thresholds (14Hz Flicker and Blue Color) and clinical signs showed significant concordance across the spectrum of early AMD fundus changes, which suggests that these tests may be an effective tool for monitoring progression of AMD to supplement clinical grading.

The researchers recruited 357 participants with visual acuity of better than 20/60 in the study eye, including 64 individuals with normal fundi and 293 AMD participants classified into 12 subgroups based upon the International Classification and Grading System. They assessed visual function in the study eye using two steady-state tests (achromatic 14Hz flicker, F14Hz and isoluminant Blue color, BCT) and two adaptation measurements (Cone Photo-Stress Recovery Rate, CRR; and Rod Dark Adaptation Recovery Rate, RRR). They then compared the groups on their average psychophysical measurements and ranked them according to functional deficiency.

According to the researchers, both adaptation parameters were significantly abnormal when only hard and/or intermediate drusen were evident (compared with controls, p<0.023) and yield considerably worse outcomes in cases with more advanced fundus changes (p<0.001) providing limited ability to discriminate between them (linear trend, CRR, t=0.68, p=0.50 and RRR, t=1.76, p=0.08). Steady-state measurements, however, declined gradually along the entire hierarchy of fundus changes (linear trend, F14Hz, t=10.16, p<0.001 and BCT, t=11.19, p<0.001) with flicker (14Hz) being able to detect significant functional change as early as in the intermediate drusen group, when compared to controls (p=0.003).

The authors of the following Korean case-control study investigated cognitive function in patients with early and late age-related macular degeneration (AMD) compared with an elderly, community-dwelling Korean population without AMD.

They enrolled 170 AMD patients and 190 non-AMD community-based controls and a comprehensive battery for cognitive function evaluation consisting of 15 psychological tests, including a depression evaluation test, was used. They adjusted cognitive function scores for age, gender, education, and visual acuity (VA) and categorized AMD as early AMD, exudative AMD, or geographic atrophy. The primary outcome measure was the degree of cognitive impairment, as assessed by the Korean versions of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery, Benton Visual Retention Test, and Digit Span Test Forward and Backward.

Patients with AMD showed lower global cognition scores than did normal controls (mean Mini-Mental State Examination [MMSE] score, 24.97 vs 25.99; p<0.001), the authors noted. They also reported that, among cognitive functions, visuospatial function, verbal memory, visual memory, and frontal function were impaired in AMD patients relative to normal controls. Additionally, the study authors found that the rate of mild cognitive impairment (MCI) was higher in AMD patients than in controls (52.4% vs 26.8%; p<0.001), with an odds ratio (OR) of 3.127 (95% confidence interval, 1.855–5.271) after adjustment for age, education, and VA. Geographic atrophy was associated with the highest risk of MCI (OR, 4.431; 95% confidence interval, 1.413–13.898) and a clinically significant reduction in MMSE scores (23.42) relative to the controls. Furthermore, the authors observed a trend of worsening cognitive function test scores from the controls to the early AMD, then the exudative AMD, and finally the geographic atrophy patients, after adjustment for covariates. AMD patients with poor VA (≤20/100) had 6 times the risk of MCI as AMD patients with good or moderate VA (>20/100).

To conclude, patients with AMD—especially those with the geographic atrophy subtype—are at greater risk for cognitive impairment than are non-AMD control subjects. In the visual rehabilitation of AMD patients, potential cognitive impairment should be taken into consideration.

Investigators conducted the following study to describe the pathoanatomy of diabetic macular edema (DME) in optical coherence tomography (OCT) and its correlation with fluorescein angiography patterns.

They analyzed 60 eyes of 56 patients and classified DME into typical focal leakage (from microaneurysm), typical diffuse leakage (the capillary plexus), or combined/questionable leakage using fluorescein angiography and retinal thickness profiles. They then matched the leakage and pooling patterns in fluorescein angiography to the corresponding OCT images.

The investigators noted that focal leakage shows swelling predominantly in the outer plexiform layer (OPL) and that deeply located microaneurysms directly leak into the loose fiber portion of OPL (Henle layer) through the “fluid conductivity barrier” (synaptic portion of OPL). They also found that diffuse leakage caused swelling predominantly in the inner nuclear layer and secondarily in the OPL. The deep capillary plexus is located between the two “fluid barriers” (inner plexiform layer and OPL); thus, diffuse leakage is primarily related with swelling in the inner nuclear layer. In the combined/questionable leakage, partial sections consisting of inner nuclear layer swelling and much larger areas of OPL/outer nuclear layer swelling are noticed.

Based on the concept of the fluid conductivity barrier, the study investigators revealed a correlation between the intraretinal location of the leakage source and where the fluid accumulated within the retinal layers.