Rod Intercept Time Research Articles

Visual Function in Pentosan Polysulfate Sodium Maculopathy.

PurposeIndividuals with pentosan polysulfate sodium (PPS) maculopathy commonly report symptoms of prolonged dark adaptation and difficulty reading. We hypothesize that PPS maculopathy causes degradation of visual function not fully captured with visual acuity testing.MethodsSubjects with PPS maculopathy underwent multimodal evaluation of retinal structure and function. Structural changes were graded as moderate or advanced. Patient-reported visual function was assessed with the National Eye Institute Visual Function Questionnaire 39 (NEI-VFQ-39) and Low Luminance Questionnaire (LLQ). Objective functional evaluations included Early Treatment of Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), Pelli–Robson contrast sensitivity, mesopic microperimetry, and dark adaptometry. Functional testing results were correlated with structural disease category.ResultsThirteen patients (26 eyes), median age 62 years (range, 37–76), completed the study. Median ETDRS letter score was 82 (Snellen equivalent 20/25). Median NEI-VFQ-39 and LLQ composite scores were 65 (range, 33–88) and 41 (range, 20–92), respectively. Median contrast sensitivity was 1.65 (range, 0.15–1.95), and median mesopic microperimetry average thresholds and percent reduced thresholds were 26 decibels (range, 0.4–28.6) and 21.6% (range, 0–100%), respectively. Median rod intercept time was 14.1 minutes (range, 4.4–20.0). Eyes with advanced disease based on retinal structure had significantly worse retinal function for several testing modalities.ConclusionsPPS maculopathy causes considerable visual function degradation that is not fully captured with BCVA testing. There was good correlation between other measures of visual function and disease severity. These findings deepen our concern regarding this patient safety issue.

Repeatability of Scotopic Sensitivity and Dark Adaptation Using a Medmont Dark-Adapted Chromatic Perimeter in Age-related Macular Degeneration.

PurposeFunctional studies of rods in age-related macular degeneration using the Medmont Dark-Adapted Chromatic Perimeter (DACP) have demonstrated impairments in scotopic sensitivities and dark adaptation (DA). We investigated the intersession repeatability of scotopic sensitivity and DA parameters including the rod intercept time recorded from the Medmont DACP.MethodsScotopic thresholds (14 test points) and DA using a 30% photobleach (eight test points) were measured on two separate days from participants 50 years of age or older with a range of age-related macular degeneration severity at loci superior and inferior to the fovea. Repeatability coefficients were calculated for prebleach scotopic sensitivity, and for DA parameters including rod intercept time.ResultsTwelve participants (mean age, 79.7 ± 8.1 years) repeated Medmont DACP testing within 50 days. Repeatability coefficients for prebleach scotopic sensitivity to long wavelength (red, 625 nm) and short wavelength (cyan, 505 nm) were 5.9 dB and 7.2 dB, respectively. The DA curve-derived repeatability coefficients for cone threshold was 3.9 dB, final threshold 5.3 dB, with an R value of 0.075 decades/min, rod intercept time 7.6 minutes, and RITslope 0.54 min/degree.ConclusionsThis study establishes repeatability coefficients for scotopic thresholds and multiple DA parameters obtained with the Medmont DACP in patients with age-related macular degeneration. These repeatability coefficients will serve as the basis for determining clinically meaningful change in rod function in future clinical trials.Translational RelevanceMeasures of repeatability parameters of scotopic thresholds and DA are essential to the accurate interpretation of results in future studies and trials using these measures.

Relationship Between Rod-Mediated Sensitivity, Low-Luminance Visual Acuity, and Night Vision Questionnaire in Age-Related Macular Degeneration

PurposeTo quantify the association between dark adaptation parameters and other clinical measures of visual function among people with and without early and intermediate age-related macular degeneration (AMD).MethodsIn this cross-sectional study, participants underwent multimodal imaging and visual function testing, including best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), low-luminance deficit (LLD = BCVA – LLVA) and the 10-item Night Vision Questionnaire (NVQ-10). Dynamic and static dark-adapted chromatic perimetry (DACP) was performed. Sensitivity difference was defined as the difference in sensitivity between the 505-nm and 625-nm stimuli. Rod intercept time (RIT) was estimated as the time required to reach a threshold of −3 log candelas/meter2 with the 505-nm stimulus following bleaching. The magnitude of association between the DACP parameters and other clinical tests was estimated via mixed-effects regression.ResultsA total of 51 participants (aged 51–88 years, 65% female, 39% with AMD) were included. RIT was found to be negatively associated with BCVA (P < 0.001), LLVA (P = 0.005), and NVQ-10 score (P = 0.028) but not LLD (P = 0.763). There was no evidence of an association between sensitivity difference and any of the clinical measures (P ≥ 0.081).ConclusionsReduced rod function, as determined by RIT, was associated with lower NVQ-10 scores (designed to interrogate rod-mediated function) and with worse BCVA and LLVA (measures of cone function).Translational RelevanceDecreasing rod function maybe indicative of more generalized photoreceptor dysfunction involving cones. Further development of questionnaires to target function in scotopic conditions may provide an easier to administer test without the need to perform perimetric tests of rod function.

A Pilot Study Evaluating the Effects of 670 nm Photobiomodulation in Healthy Ageing and Age-Related Macular Degeneration.

Limited evidence suggests that the application of 670 nm of red light alters the course of aged decline. A previous report on 18 patients showed regression of drusen and improvement in visual functions in patients with intermediate age-related macular degeneration (AMD) by 12 months. We evaluated the functional and structural effects of applying 670 nm light to 31 patients with intermediate AMD and 11 people aged 55 years or above with normal retina. The study eyes were treated daily in the morning with a 670 nm hand-held light source housed in a torch-like tube that emitted energy equivalent to 40 mW/cm2 or 4.8J/ cm2 for 2 min at the viewing aperture. Visual function in terms of best-corrected visual acuity, low luminance visual acuity, scotopic thresholds and rod-intercept time were compared between baseline and 1, 3, 6 and 12 months. Structural changes on optical coherence tomography OCT and colour photographs were also assessed. Five withdrew consent voluntarily due to the intensity of the study visit assessments and two developed neovascular AMD and were excluded from further treatment and the analysis. In normal ageing, there was an improvement in scotopic thresholds in the group with no AMD by 1.77dB (p = 0.03) and no other parameters showed any clinically significant change. In eyes with intermediate AMD, there was no significant improvement in any functional or structural changes at any time point up to 12 months although the compliance was good. This pilot study shows that photobiomodulation with 670 nm has no effect in patients who have already progressed to intermediate AMD.

DARK ADAPTATION IN MACULAR TELANGIECTASIA TYPE 2.

To evaluate dark adaptation (DA) in patients with macular telangiectasia Type 2 (MacTel). After a local photobleach (4 × 4° size, 83% bleach), DA was measured using a test stimulus (2° diameter) projected at 5° eccentricity horizontal from the foveal center within the temporal parafovea. Cone plateau, rod intercept time, and rod recovery rate (S2) were calculated from the resulting DA curves. Findings were correlated with disease stages (according to Gass and Blodi), the area of ellipsoid zone loss in optical coherence tomography, and macular pigment loss ("MP-Classes 1-3"). Fifty-nine eyes of 59 patients were compared with 18 eyes of 18 healthy controls. Dark adaptation was significantly impaired in patients with MacTel. Although differences were most pronounced for parameters indicating rod-mediated recovery, cone-mediated recovery was also decreased, yet to a lesser extent. Dark adaptation parameters were only weakly associated with disease stages and ellipsoid zone loss. A better association was found between rod-mediated recovery (S2 and rod intercept time) and macular pigment loss (Kendall's tau for rod intercept time: 0.69 and S2: -0.51; both P < 0.0001). Dark adaptation is significantly impaired in patients with MacTel. Our results indicate an association of reduced macular pigment and rod dysfunction in MacTel.

Investigation of the relationship between macular pigment levels and rod‐mediated dark adaptation in intermediate age‐related macular degeneration

BackgroundIt has been shown that rod‐mediated dark adaptation is significantly delayed in ageing, a change which is exacerbated in age‐related macular degeneration (AMD). Levels of lutein and zeaxanthin, the two main constituents of macular pigment have been found in rod outer segments, indicating that the macular pigment may have an influence on rod‐mediated dark adaptation. The aim of this study was to determine if rod‐mediated dark adaptation is associated with central macular pigment levels in individuals with intermediate stage AMD.MethodsA cross‐sectional observational study included individuals with acuity better than 6/15 Snellen and intermediate stage AMD based on graded fundus photographs using an internationally accepted grading scale. Rod‐mediated dark adaptation was assessed at five degrees eccentricity in the superior retina (inferior visual field) using the rod intercept time measure from the MacuLogix AdaptDx. Macular pigment optical density was measured at 0.5 degrees eccentricity using a heterochromatic flicker photometry‐based method.ResultsTwenty‐seven individuals (mean age 76.7-years) with intermediate stage AMD and 23 age‐matched normal controls (mean age 74.0-years) were recruited. Rod‐mediated dark adaptation was significantly delayed in intermediate stage AMD compared with healthy controls (32.9-minutes versus 10.7-minutes, p < 0.01). There was no statistically significant correlation between the rod intercept time and the level of macular pigment in those with intermediate AMD (r = −0.04, p = 0.85).ConclusionThe results did not support the hypothesis that higher macular pigment is associated with improved rod‐mediated performance or that higher levels of macular pigment protect rod‐mediated function in intermediate AMD.

Longitudinal Assessment of Rod Function in Intermediate Age-Related Macular Degeneration With and Without Reticular Pseudodrusen.

To evaluate rod function longitudinally in intermediate age-related macular degeneration subjects with reticular pseudodrusen (RPD) and without RPD (AMD). Retinal sensitivities (505 and 625 nm) during dark adaptation, at 14 locations within the central 12° macula were obtained after photobleaching at baseline and 12-month visits. Pointwise sensitivity differences between both stimuli were used to assess static rod function, while rod intercept time (RIT) and rod recovery rate (RRR) were used to evaluate dynamic function. Changes in function over time were compared between groups. A total of 23 controls, 12 AMD, and 13 RPD cases were followed-up. At baseline, the RPD group had significantly worst static and dynamic rod function compared to AMD and control groups. Static function in AMD was similar to controls. Static and dynamic function across the central 12° was consistent in controls; however, it was most impaired at 4° compared to 12° eccentricity in disease groups. Over 12 months, no AMD cases progressed clinically and static function in AMD improved (P ≤ 0.04), but remained unchanged in control and RPD groups (P ≥ 0.17). The RRR for control and RPD groups remained stable, while the AMD group deteriorated, but only at 12° (P = 0.02). The RIT was stable in AMD (P = 0.75) and RPD (P = 0.71) groups but improved in the control group (P = 0.002). A decrease in RRR was detected over 12 months at 12° eccentricity in the AMD group. Evaluating changes in rod function requires testing at multiple locations including the peripheral macula.

The ARMS2 A69S Polymorphism Is Associated with Delayed Rod-Mediated Dark Adaptation in Eyes at Risk for Incident Age-Related Macular Degeneration

To examine the association between sequence variants in genetic risk factors for age-related macular degeneration (AMD) and delayed rod-mediated dark adaptation (RMDA), the first functional biomarker for incident AMD, in older adults with normal macular health and early AMD. Cross-sectional. Adults 60 years of age or older showing normal macular health (defined as both eyes at step 1 on the Age-Related Eye Disease Study 9-step AMD classification system) and those with AMD in one or both eyes (defined as steps 2-9). Single nucleotide polymorphisms were genotyped in the complement factor H (CFH) and ARMS2 genes using a Taqman assay. Rod-mediated dark adaptation was assessed in 1 eye after photobleach with targets centered at 5° on the inferior vertical meridian. Rate of dark adaptation was defined by rod intercept time (RIT), duration (in minutes) required for sensitivity to reach a criterion sensitivity level in the latter half of the second component of rod recovery. Associations between CFH and ARMS2 polymorphisms and RMDA were adjusted for age and smoking. Rod intercept time. The sample consisted of 543 participants having both genotype and RIT determination; 408 showed normal macular health and 135 demonstrated AMD, most having early AMD (124 of 135). For the combined sample, higher RIT (slower RMDA) was observed for both the A69S variant in ARMS2 and the Y402H variant in CFH (adjusted P= 0.0001 and P= 0.0023, respectively). For healthy participants, the A69S variant in ARMS2 was associated with higher RIT (adjusted P= 0.0011), whereas the Y402H variant in CFH was not (adjusted P=0.2175). For AMD patients, the A69S variant of ARMS2 and the Y402H variant of CFH were associated with higher RIT (adjusted P=0.0182 and P= 0.0222, respectively). Those with a larger number of high-risk ARMS2 and CFH alleles showed higher RIT, in both healthy and AMD groups (adjusted P= 0.0002 and P < 0.0001, respectively). We report a novel association wherein older adults with high-risk ARMS2 and CFH genotypes are more likely to demonstrate delayed RMDA, the first functional biomarker for incident early AMD. Before the AMD clinical phenotype is present, those showing normal macular health with the ARMS2 A69S allele demonstrate delayed RMDA. Understanding ARMS2 function is a research priority.

Longitudinal Study of Dark Adaptation as a Functional Outcome Measure for Age-Related Macular Degeneration

To investigate the natural history of dark adaptation (DA) function as measured by the change in rod intercept time (RIT) over 4 years and to correlate RIT change with age-related macular degeneration (AMD) severity. Longitudinal, single-center, observational study. A total of 77 participants aged ≥50 years with a range of AMD severities. Participants each contributing a single study eye to the analysis were assigned into person-based AMD severity groups based on fundus characteristics (drusen, pigmentary changes, late AMD, and subretinal drusenoid deposits [SDDs]). The DA function was assessed in study eyes at baseline and 3, 6, 12, 18, 24, 36, and 48 months. Mean change in DA function over time was calculated using the slope of linear regression fits of longitudinal RIT data. Patient-reported responses on a Low Luminance Questionnaire (LLQ) were obtained at baseline and yearly. Nonparametric statistical testing was performed on all comparisons. The RIT, defined as the time taken after a photobleach for visual sensitivity to recover detection of a 5×10-3 cd/m2 stimulus (a decrease of 3 log units), was monitored in study eyes over 4 years, and the mean rate of change was computed. Longitudinal analysis of 65 study eyes followed on the standard testing protocol (mean age, 71±9.3 years; 49% were female) revealed that higher rates of RIT prolongation were correlated with AMD severity group assignment at baseline (P= 0.026) and with severity group assignments at year 4 (P= 0.0011). Study eyes that developed SDD during follow-up demonstrated higher rates of RIT prolongation relative to those that did not (P<0.0001). Overall, higher rates of RIT prolongation were significantly correlated with greater 4-year decreases in LLQ scores (total mean score, P= 0.0032). Longitudinal decline in DA function, which correlated with patient-reported functional deficits, was accelerated in eyes with greater AMD severity and especially in eyes with SDD both at baseline and at 4 years. The RIT prolongation as a measure of changing DA function may be a functional outcome measure in AMD clinical studies.

Determining Optimal Test Parameters for Assessing Dark Adaptation in People With Intermediate Age-Related Macular Degeneration.

The primary aim was to determine optimal test conditions for evaluating dark adaptation in intermediate age-related macular degeneration (iAMD) in order to minimize test time while maintaining diagnostic sensitivity. People with AMD and age-similar controls were recruited (aged >55 years). Rod intercept time (RIT) was assessed after a 76%, 70%, and 65% rhodopsin bleach at 5° eccentricity and 76% and 70% bleach at 12°. Test order was randomized and a 30-minute washout period added between tests. Results were compared between control and iAMD groups and receiver operating characteristics (ROC) curves were constructed. A total of 26 participants with variable grades of macular health attended for two visits. There was a statistically significant difference in average RIT between the control and iAMD groups at 5° (median, IQR controls = 5.8 minutes, 3.8-7.5; iAMD = 20.6 minutes, 11.1-30.0; Mann-Whitney, P = 0.01) and at 12° (mean, controls: 4.54 minutes ± 2.12 SD, iAMD = 7.72 minutes ± 3.37 SD; independent samples t-test, P = 0.03) following a 76% bleach. Area under the ROC curves was 0.83 (confidence interval [CI]: 0.64-1.0) and 0.79 (CI: 0.59-0.99) for these two test conditions, respectively. Five participants (45%) in the iAMD group had RITs >20 minutes for 76% bleach at 5°, but none for any other test condition. Nearly half of the participants with iAMD produced unacceptably long recovery times (>20 minutes) using a 76% bleach at 5° eccentricity. The 76% bleach at 12° provided almost equivalent separation between AMD and controls but recovery was achieved within 20 minutes.

HEALTH CONDITIONS LINKED TO AGE-RELATED MACULAR DEGENERATION ASSOCIATED WITH DARK ADAPTATION.

To determine the association between dark adaption (DA) and different health conditions linked with age-related macular degeneration (AMD). Cross-sectional study, including patients with AMD and a control group. Age-related macular degeneration was graded according to the Age-Related Eye Disease Study (AREDS) classification. We obtained data on medical history, medications, and lifestyle. Dark adaption was assessed with the extended protocol (20 minutes) of AdaptDx (MacuLogix). For analyses, the right eye or the eye with more advanced AMD was selected. Multivariate linear and logistic regressions were performed, accounting for age and AMD stage. Seventy-eight subjects (75.6% AMD; 24.4% controls) were included. Multivariate assessments revealed that body mass index (BMI; β = 0.30, P = 0.045), taking AREDS vitamins (β = 5.51, P < 0.001), and family history of AMD (β = 2.68, P = 0.039) were significantly associated with worse rod intercept times. Abnormal DA (rod intercept time ≥ 6.5 minutes) was significantly associated with family history of AMD (β = 1.84, P = 0.006), taking AREDS supplements (β = 1.67, P = 0.021) and alcohol intake (β = 0.07, P = 0.017). Besides age and AMD stage, a higher body mass index, higher alcohol intake, and a family history of AMD seem to impair DA. In this cohort, the use of AREDS vitamins was also statistically linked with impaired DA, most likely because of an increased severity of disease in subjects taking them.

Characterization of Rod Function Phenotypes Across a Range of Age-Related Macular Degeneration Severities and Subretinal Drusenoid Deposits

PurposeTo examine spatial changes in rod-mediated function in relationship to local structural changes across the central retina in eyes with a spectrum of age-related macular degeneration (AMD) disease severity.MethodsParticipants were categorized into five AMD severity groups based on fundus features. Scotopic thresholds were measured at 14 loci spanning ±18° along the vertical meridian from one eye of each of 42 participants (mean = 71.7 ± 9.9 years). Following a 30% bleach, dark adaptation was measured at eight loci (±12°). Rod intercept time (RIT) was defined from the time to detect a −3.1 log cd/m2 stimulus. RITslope was defined from the linear fit of RIT with decreasing retinal eccentricity. The presence of subretinal drusenoid deposits (SDD), ellipsoid (EZ) band disruption, and drusen at the test loci was evaluated using optical coherence tomography.ResultsScotopic thresholds indicated greater rod function loss in the macula, which correlated with increasing AMD group severity. RITslope, which captures the spatial change in the rate of dark adaptation, increased with AMD severity (P < 0.0001). Three rod function phenotypes emerged: RF1, normal rod function; RF2, normal scotopic thresholds but slowed dark adaptation; and RF3, elevated scotopic thresholds with slowed dark adaptation. Dark adaptation was slowed at all loci with SDD or EZ band disruption, and at 32% of loci with no local structural changes.ConclusionsThree rod function phenotypes were defined from combined measurement of scotopic threshold and dark adaptation. Spatial changes in dark adaptation across the macula were captured with RITslope, which may be a useful outcome measure for functional studies of AMD.

Longitudinal Changes in Retinotopic Rod Function in Intermediate Age-Related Macular Degeneration.

Although impairment of rod function in the early stages of age-related macular degeneration (AMD) has been well recognized, data on longitudinal changes in rod function at multiple retinal locations remain limited. This study investigated the longitudinal changes in retinotopic rod function in eyes with intermediate AMD (iAMD). Complete ophthalmic examination, multimodal imaging, and scotopic perimetry were performed at baseline and at 12-month follow-up. Perimetric scotopic retinal sensitivities for the 505-nm stimulus were repeatedly measured for 20 minutes after exposing to a single photobleach (∼30%). The rod intercept time (RIT) and retinal sensitivity at seven retinal loci within the central 12° were ascertained. Using the 95% limit of measurement variability derived from the control eyes as a reference, the proportion of test points with a significant change in retinal sensitivity or RIT at follow-up was determined. Twenty iAMD and 6 control eyes were included. Decline in rod function was detected at 12-month follow-up in eyes with iAMD, but not in control eyes. Approximately 25% of test points in iAMD eyes showed a significant increase in RIT compared to 6% of test points with a decrease in RIT over the 12-month period (P < 0.001). Similarly, 40% of test points demonstrated a reduction in retinal sensitivity compared to the 7% of test points with an increase in retinal sensitivity at follow-up (P < 0.001). There are detectable retinotopic changes in rod function over 12 months in iAMD eyes, indicating an ongoing disease progression in rod impairment or loss with time.

Decreased Visual Function Scores on a Low Luminance Questionnaire Is Associated with Impaired Dark Adaptation

We investigate whether responses on a Low Luminance Questionnaire (LLQ) in patients with a range of age-related macular degeneration (AMD) severity are associated with their performance on focal dark adaptation (DA) testing and with choroidal thickness. Cross-sectional, single-center, observational study. A total of 113 participants older than 50 years of age with a range of AMD severity. Participants answered the LLQ on the same day they underwent DA testing using a focal dark adaptometer measuring rod intercept time (RIT). We performed univariable and multivariable analyses of the LLQ scores and age, RIT, AMD severity, subfoveal choroidal thickness [SFCT], phakic status, and best-corrected visual acuity. The primary outcome of this study was the score on the 32-question LLQ. Each item in the LLQ is designated to 1 of 6 subscales describing functional problems in low luminance: driving, emotional distress, mobility, extreme lighting, peripheral vision, and general dim lighting. Scores were computed for each subscale, in addition to a weighted total mean score. Responses from 113 participants (mean age, 76.2±9.3 years; 58.4% were female) and 113 study eyes were analyzed. Univariable analysis demonstrated that lower scores on all LLQ subscales were correlated with prolonged DA testing (longer RIT) and decreased choroidal thickness. All associations were statistically significant except for the association of choroidal thickness and "peripheral vision." The strongest association was the LLQ subscale of driving with RIT (r=-0.97, P < 0.001). Multivariable analysis for each of the LLQ subscale outcomes, adjusted for age, included RIT, with total LLQ score, "driving," "extreme lighting," and "mobility" also including choroidal thickness. In all multivariable analyses, RIT had a stronger association than choroidal thickness. This cross-sectional analysis demonstrates associations of patient-reported functional deficits, as assessed on the LLQ, with both reduced DA and reduced choroidal thickness, in a population of older adults with varying degrees of AMD severity and good visual acuity in at least 1 eye. These analyses suggest that local functional measurements of DA testing (RIT) and choroidal thickness are associated with patient-reported functional deficits.

Natural History of Rod-Mediated Dark Adaptation over 2 Years in Intermediate Age-Related Macular Degeneration.

PurposeTo characterize the natural history of rod-mediated dark adaptation (RMDA) over 2 years in eyes with intermediate age-related macular degeneration (AMD). This information will be useful in understanding the potential of RMDA to serve as a functional endpoint in proof-of-concept studies and clinical trials on intermediate AMD.MethodsRMDA was measured in eyes with intermediate AMD at baseline and follow-up visits over 2 years at 6, 12, 18, and 24 months. A computerized dark adaptometer measured sensitivity for targets centered at 11° on the superior vertical meridian of the retina. Rod intercept time (RIT) characterized the speed of dark adaptation and was defined as the duration (in minutes) required for sensitivity to reach a criterion level of 3.0 log units of attenuation of the stimulus.ResultsMean change in RIT over 24 months for 30 eyes was 10.5 minutes (standard deviation 19.4), p < 0.0001; 73.3% of eyes had a RIT increase >1 minute, 56.7% had an increase >3 minutes, and 36.7% had an increase >6 minutes; for 26.7% RIT was unchanged (0- to 1-minute increase) or decreased. Greater increase in RIT over 24 months was associated with smoking.ConclusionsRMDA slows in intermediate AMD over 2 years in most eyes. There was wide variability in RIT at both baseline and in the extent to which it increased over 24 months. A major risk factor for AMD, smoking, exacerbated RMDA slowing.Translational RelevanceRMDA as assessed by RIT may be useful as a functional endpoint in proof-of-concept studies and clinical trials on intermediate AMD with 2-year designs.

Structural Changes Associated with Delayed Dark Adaptation in Age-Related Macular Degeneration

To examine the relationship between dark adaptation (DA) and optical coherence tomography (OCT)-based macular morphology in age-related macular degeneration (AMD). Prospective, cross-sectional study. Patients with AMD and a comparison group (>50 years) without any vitreoretinal disease. All participants were imaged with spectral-domain OCT and color fundus photographs, and then staged for AMD (Age-related Eye Disease Study system). Both eyes were tested with the AdaptDx (MacuLogix, Middletown, PA) DA extended protocol (20 minutes). A software program was developed to map the DA testing spot (2° circle, 5° superior to the fovea) to the OCT B-scans. Two independent graders evaluated the B-scans within this testing spot, as well as the entire macula, recording the presence of several AMD-associated abnormalities. Multilevel mixed-effects models (accounting for correlated outcomes between 2 eyes) were used for analyses. The primary outcome was rod-intercept time (RIT), defined in minutes, as a continuous variable. For subjects unable to reach RIT within the 20 minutes of testing, the value of 20 was assigned. We included 137 eyes (n= 77 subjects), 72.3% (n= 99 eyes) with AMD and the remainder belonging to the comparison group. Multivariable analysis revealed that even after adjusting for age and AMD stage, the presence of any abnormalities within the DA testing spot (ß= 4.8, P < 0.001), as well as any abnormalities in the macula (ß= 2.4, P= 0.047), were significantly associated with delayed RITs and therefore impaired DA. In eyes with no structural changes within the DA testing spot (n= 76, 55.5%), the presence of any abnormalities in the remaining macula was still associated with delayed RITs (ß= 2.00, P= 0.046). Presence of subretinal drusenoid deposits and ellipsoid zone disruption were a consistent predictor of RIT, whether located within the DA testing spot (P= 0.001 for both) or anywhere in the macula (P < 0.001 for both). Within the testing spot, the presence of classic drusen or serous pigment epithelium detachment was also significantly associated with impairments in DA (P ≤ 0.018). Our results suggest a significant association between macular morphology evaluated by OCT and time to dark-adapt. Subretinal drusenoid deposits and ellipsoid zone changes seem to be strongly associated with impaired dark adaptation.

Impairments in Dark Adaptation Are Associated with Age-Related Macular Degeneration Severity and Reticular Pseudodrusen

We investigate whether ocular and person-based characteristics were associated with dark adaptation (DA). Cross-sectional, single-center, observational study. One hundred sixteen participants older than 50 years of age with a range of age-related macular degeneration (AMD) severity. Participants underwent best-corrected visual acuity (BCVA) testing, ophthalmoscopic examination, and multimodal imaging. Presence of reticular pseudodrusen (RPD) was assessed by masked grading of fundus images and was confirmed with optical coherence tomography. Eyes also were graded for AMD features (drusen, pigmentary changes, late AMD) to generate person-based AMD severity groups. One eye was designated the study eye for DA testing. Nonparametric statistical testing was performed on all comparisons. The primary outcome of this study was the rod intercept time (RIT), which is defined as the time for a participant's visual sensitivity to recover to a stimulus intensity of 5×10(-3) cd/m(2) (a decrease of 3 log units), or until a maximum test duration of 40 minutes was reached. A total of 116 study eyes from 116 participants (mean age, 75.4±9.4 years; 58% female) were analyzed. Increased RIT was associated significantly with increasing AMD severity, increasing age (r = 0.34; P = 0.0002), decreasing BCVA (r = -0.54; P < 0.0001), pseudophakia (P = 0.03), and decreasing subfoveal choroidal thickness (r = -0.27; P = 0.003). Study eyes with RPD (15/116 [13%]) had a significantly greater mean RIT compared with eyes without RPD in any AMD severity group (P < 0.02 for all comparisons), with 80% reaching the DA test ceiling. Impairments in DA increased with age, worse visual acuity, presence of RPD, AMD severity, and decreased subfoveal choroidal thickness. Analysis of covariance found the multivariate model that best fit the data included age, AMD group, and presence of RPD (R(2) = 0.56), with the presence of RPD conferring the largest parameter estimate.