Author: Bethany Higgins (United Kingdom)
Co-authors: Giovanni Montesano, Timos Naskas, Usha Chakravarthy, Ruth Hogg, David Crabb
Purpose
Studies have suggested delayed rod-mediated dark adaptation (DA) to be a relevant diagnostic indicator of age-related macular degeneration (AMD) that worsens with disease severity. DA impairment has also been suggested to worsen in people with subretinal drusenoid deposits (SDDs), accretions of material within the retinal pigment epithelium (RPE) that extend through the ellipsoid zone. AMD severity is graded in a range of ways. The majority of published literature on DA relied on the Beckman classification, based on colour fundus photography (CFP), despite reported limitations of the technique. We aim to assess if differences in RIT are more discernible between different grades of AMD severity when a novel Optical Coherence Tomography (OCT) based criteria is used as compared to one using a CFP-based classification. A secondary aim is to investigate if SDD presence is associated with changes in rod-mediated DA at different AMD severity grades, according to an OCT-based severity scale.
Setting/Venue
Centre for Public Health, Queen's University Belfast and Royal Hospital, Belfast, Northern Ireland
Methods
We used prospectively collected data from the case-control Northern Ireland Sensory Aging studies (NISA) and Northern Ireland Sensory Aging-2 (NISA-2) studies conducted at Queen's University Belfast. Data for participants (≥50-years) with complete rod-intercept time (RIT) data, CFP and spectral domain OCT(SD-OCT) images and had been classified into both the Beckman grading and an OCT-based grading system were extracted, with demographic data. The eye with worse monocular visual acuity was designated the study eye. CFP and SD-OCT images were acquired with the Canon CX-1 Digital Fundus Camera (Canon,USA) and Heidelberg Spectralis SD-OCT (Heidelberg Engineering,Heidelberg,Germany) respectively. CFP and SD-OCT images were evaluated by TN and UC and participants were classified into the Beckman classification and OCT-based classification. SDD presence was identified via OCT. The OCT grading included: participants with no drusen/RPE abnormalities (OCT0), participants with drusen present but no RPE abnormalities (OCT1) and participants with drusen and RPE abnormalities present (OCT2). RIT was measured by the AdaptDx (Maculogix,USA). Time-to-event analysis assessed the magnitude of differences in RIT between groups of participants graded by the different imaging classifications. Simple summary statistics were calculated for RIT but comparisons between groups included age as a covariate and p-values were adjusted for multiple comparisons (Holm method).
Results
459 eyes (mean [standard deviation; SD] age 66[8] years) were stratified into 338 eyes in Beckman 0 (B0), 29 in Beckman 1 (B1), 20 in Beckman 2 (B2) and 72 in Beckman 3 (B3) Simple mean (SD) RIT for these four groups was 7.5 (5.3), 8.0 (4.3), 7.3 (4.7) and 15.6 (11.9) minutes respectively. The same 459 participants were split into 312 eyes in OCT0, 96 in OCT1 and 51 in OCT2. Simple mean (SD) RIT for these groupings appeared more distinct being 7.4 (5.5), 10.0 (7.2) and 15.3(21.0) minutes respectively. SDDs were detected in 55 eyes in OCT0, 30 in OCT1 and 24 in OCT2. Eyes with intermediate AMD (B3) had significantly longer RITs compared to each of the other Beckman groups (vs B0, B1, B2; p=<0.005 all). However, there were no statistically significant differences in RIT between any of the other Beckman groups. Eyes in OCT2 had slower RITs compared to OCT-defined controls (OCT0) (p=<0.001) and eyes in OCT1 (p=0.009). There was, however, no statistically significant difference between OCT0 and OCT1 (p=0.195). SDD presence significantly worsened RIT within OCT2 (p=0.002) but not within OCT1 (p=0.285). On the contrary, in OCT0 the presence of SDDs improved the RIT (p=0.012).
Conlusions
Our results provide some evidence of differences in RIT being marginally more apparent between different grades of AMD severity when a novel OCT-based criteria is used rather than a CFP-based classification. An OCT-based classification taking account of SDD presence seems relevant, too. We utilised a novel time-to-event analysis to assess RIT which allowed us to control for the effect of age under the assumption that age is a linear predictor of delayed DA. After controlling for age, the differences in RIT between the OCT grades were much less marked and this is noteworthy. These results are meaningful because RIT is a surrogate of a deficit in measurable loss of visual function (delayed DA) for a person. Our study had other strengths including a large sample size and a large cohort of people with SDDs which is uncommon when compared to recent DA research in people with AMD. An OCT-based classification, while partially mimicking Beckman, could account for structural abnormalities that CFP-based classifications cannot. For example presence of SDDs may be important when defining selection criteria for eyes entering prospective studies.
Financial Disclosure
Bethany E. Higgins - No Giovanni Montesano - Yes, consultant for CenterVue Timos T Naskas - No Usha Chakravarthy – Yes, part time visiting Professor and senior global medical director at Roche Ruth E. Hogg - Roche David P. Crabb - Speaker fees from Allergan, Bayer, Santen, THEA (Honoraria), Allergan, Apellis, Roche, Santen (Unrestricted funding), CenterVue (Consultant)
Comments
-
