Reading Vision in Adults With Early and Intermediate Age-Related Macular Degeneration Under Mesopic and Photopic Conditions

Abstract

Purpose: Reading is involved in various daily activities that operate under a wide range of luminance levels. Rod- and cone-mediated mesopic visual function is known to be impaired even in early/intermediate age-related macular degeneration (AMD). It remains unclear whether and to what extent mesopic reading is impaired in early/intermediate AMD. Here, we assessed differences in reading vision between photopic and mesopic conditions in early/intermediate AMD and compared their performance to those in older adults with normal macular health.

Methods: The study included 30 patients with early/intermediate AMD and 30 healthy controls. Reading performance was tested on the MNREAD iPad app under mesopic (2 cd/m² with a neural-density filter) and photopic (220 cd/m²) conditions. Four reading indices—maximum reading speed (MRS), critical print size (CPS), reading acuity (RA), and reading accessibility index (ACC)—were obtained from the MNREAD test, yielding a function representing reading speed versus print size.

Results: Compared to photopic conditions, patients with AMD and healthy controls both exhibited noticeable decreases in reading vision under mesopic conditions (P < 0.001) despite normal photopic visual acuity. This decrease was more pronounced in AMD even after adjusting for age (P < 0.001): Under mesopic conditions, MRS and ACC decreased by 8 words per minute and 0.1, respectively; CPS and RA were enlarged by 0.27 and 0.24 logMAR, respectively.

Conclusions: Reading vision deteriorates under mesopic conditions compared to photopic conditions in early/intermediate AMD and is accentuated compared to this difference in healthy controls.

Translational Relevance: A mesopic reading test may provide a more sensitive and comprehensive assessment of a patient's reading impairment.

Introduction

Age-related macular degeneration (AMD) is a complex, multifactorial disease of aging in which central retinal photoreceptors are lost or dysfunctional due to a neovascular event or an atrophic process. AMD is the leading cause of irreversible blindness in older adults in developed countries.¹ AMD is associated with a wide range of difficulties in everyday life, such as reading, face recognition, visual search, driving, and mobility.^2–11 In particular, reading difficulty is one of the major complaints among patients with AMD.^12,13 Reading is indispensable to many daily activities and affects a person's ability to function at work and at home⁴; thus, reading is a major component of vision-related quality of life.¹⁴ 

Although most functional measurements are assessed under ideal photopic conditions in the clinic, people often perform daily activities under dimly lit environments. For example, the median home ambient lighting was shown to be three to four times dimmer,¹⁵ with some evidence suggesting up to 10 times, lower than clinic lighting¹⁶ (e.g., 200–550 lux).¹⁶ Patients with AMD often report a great deal of difficulty in performing daily activities under dim light conditions despite relatively good photopic visual acuity,^17–24 highlighting additional impairment in dimly lit environments. In particular, the reading performance of patients with AMD becomes further impaired when illumination decreases down to low photopic levels (∼50 lux or <30 cd/m²), supporting the importance of lighting with regard to reading vision with AMD.^25–29 

Mesopic vision operates under low or dim light levels at a luminance level ranging between approximately 0.01 cd/m² and 3 cd/m².³⁰ The additional impairment under mesopic luminance levels (1 or 3.5 cd/m²) observed in AMD^25,29 is indeed consistent with functional abnormalities of both rods and cones shown in AMD. Early and intermediate stages of AMD result in central vision changes in the macula, with rod photoreceptor loss or dysfunction being the primary cause of visual impairment.^31,32 Studies have shown that the rod loss of AMD is maximal around 4° to 5° degrees in the macula, although rod density is higher further out in the periphery. It has been shown that rod- and cone-mediated mesopic visual function is significantly reduced in patients with AMD.^23,33–37 Furthermore, delayed rod-mediated dark adaptation is the first identified functional biomarker for early AMD.³⁸ More specifically, a study done by Owsley et al.³⁸ showed that older adults with normal macular health who exhibited abnormal dark adaptation at baseline were two times more likely to develop AMD as compared to those who did not have abnormal dark adaptation at baseline. Furthermore, studies^39,40 have demonstrated a longitudinal decline in dark adaptation over time in patients with intermediate AMD. 

As dysfunction of rods and cones has been well established even in early and intermediate AMD, a mesopic reading test mediated by both cone and rod vision is likely to provide a more sensitive and comprehensive assessment of a patient's reading impairment while serving as a potentially useful tool to evaluate the efficacy of interventions and disease progression of early/intermediate AMD. However, relatively little is known about detailed reading vision, including the maximum reading speed (MRS), reading acuity (RA), and print size required for optimal reading performance, in persons with early and intermediate AMD at mesopic luminance levels. Furthermore, it still remains unclear whether additional impairment under mesopic conditions in persons with early and intermediate AMD (if any) would significantly differ from that of older adults with normal macular health. 

Thus, here we aim to evaluate the effect of mesopic luminance level (<3 cd/m²) on reading vision in persons with early and intermediate AMD, particularly using the detailed characteristics of reading vision such as print size requirements for optimal reading. Reading vision was assessed with the MNREAD iPad app,⁴¹ a digital version of the MNREAD chart under photopic and mesopic conditions. The MNREAD chart is a continuous-text reading acuity test designed to measure the reading performance of people with normal and low vision.⁴² The MNREAD chart uses sentences of 10 standard word length (60 characters) to determine reading speed across print sizes that decrease logarithmically in steps of 0.1 log units.⁴² Thus, the MNREAD chart allows for the examination of how visual factors such as print size or eye health conditions affect a person's reading vision while minimizing the influence of higher level linguistic or cognitive factors. The MNREAD chart is widely used to evaluate the impact of eye disorders, treatment, or visual rehabilitation on reading vision and also to prescribe optical corrections/prescriptions for reading or other reading aids in the clinic.^12,43–49 Like the standard MNREAD print chart, the iPad app uses the same short sentences and the same sentence layout (three lines per sentence) as the chart but with a reduced range of print sizes (14 sentences compared to 19 in the printed version).⁴¹ As shown in Figure 1, four MNREAD measures can be obtained from the MNREAD test: (1) MRS in words per minute (wpm), a person's reading speed when reading is not limited by print size; (2) critical print size (CPS), the smallest print that the person can read with maximum speed; (3) RA the smallest print that the person can read without making significant errors; and (4) reading accessibility index (ACC),⁵⁰ the person's access to text across the range of print sizes found in everyday life. Calabrèse et al.⁴¹ demonstrated that, overall, MNREAD parameters measured with the printed chart and the iPad app are comparable based on the data collected from both normal and low vision populations. 

Figure 1.

 

An example MNREAD curve (i.e., reading speed as a function of print size) from which the four MNREAD parameters are extracted: maximum reading speed (MRS), reading accessibility index (ACC), critical print size (CPS), and reading acuity (RA).

In the current study, reading vision was assessed in patients with early and intermediate AMD under both mesopic (i.e., luminance of 2 cd/m²) and photopic (i.e., luminance of 220 cd/m²) conditions. The study design also included age-similar older adults with normal macular health. The resulting four MNREAD indices were compared between mesopic and photopic conditions in patients with AMD and healthy controls to see if the adverse effects (if any) of mesopic conditions were more prominent in patients with AMD. 

The outcome of the current study may help us better understand whether mesopic reading performance mediated by both cones and rods is impacted by early and intermediate stages of AMD. Furthermore, it may also help us determine whether mesopic reading vision may serve as a clinical outcome measure for treatment effectiveness relevant to real life tasks. 

Methods

Participants

All AMD participants were recruited from the University of Alabama at Birmingham Callahan Eye Hospital Clinics, whereas all healthy older adults were recruited from the Northeastern University community and the greater Boston area. All participants were native or fluent English speakers without known cognitive or neurologic impairments, confirmed by the Mini Mental Status Exam (MMSE; ≥25 MMSE score for those aged 65 and over). 

The presence of AMD was initially confirmed through medical records. In addition, an experienced grader evaluated fundus photographs in each eye under dilated conditions using the Age-Related Eye Disease Study (AREDS) nine-step classification system⁵¹ and determined that all AMD eyes had early or intermediate AMD and did not have geographic atrophy or choroidal neovascularization. Exclusion criteria for participants included the following diagnoses or conditions: (1) glaucoma, other retinal conditions, optic nerve disease, or corneal disease; (2) diabetes; (3) Alzheimer's disease, Parkinson's disease, brain injury, or other neurological or psychiatric conditions as revealed by the medical record or self-report; and (4) known dyslexia. All participants were native English speakers. Healthy control participants had normal macular health (i.e., no AMD or glaucoma in either eye) and normal binocular vision with no known history of ocular or neurologic disease other than cataracts or cataract surgery. For all participants, contrast sensitivity and visual acuity were tested on each eye, and one at a time. Visual acuity was measured at 2 meters using Early Treatment Diabetic Retinopathy Study (ETDRS) charts and was reported in logarithm of the minimum angle of resolution (logMAR). Contrast sensitivity was measured at 1 meter using Pelli–Robson contrast sensitivity charts and was expressed as log sensitivity. Pelli–Robson contrast sensitivity was scored based on the letter-by-letter method,⁵² whereby each letter correctly identified was scored as 0.05 log units. Proper refractive correction for the viewing distance was used. The chart luminance for ETDRS visual acuity and Pelli–Robson contrast sensitivity ranged from 120 to 145 cd/m². 

The protocol followed the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board of either the University of Alabama at Birmingham or Northeastern University. Written informed consent was obtained from all participants prior to the study and after explanation of the nature and possible consequences of the study. 

Apparatus

The MNREAD test was administered with the MNREAD iPad app (1.2 version; University of Minnesota, Minneapolis, MN; https://apps.apple.com/us/app/mnread/id1196638274) running on an iPad Air 2 tablet (Apple, Cupertino, CA) with retina display (2048 × 1536-pixel resolution at 264 ppi). The iPad was mounted vertically on a stand in landscape mode. Height was adjusted individually so the center of the screen was at the appropriate eye level. For photopic conditions, iPad screen brightness was set to 75 (equivalent to 220 cd/m²). Mesopic screen luminance (2 cd/m²) was achieved by setting the iPad screen brightness to a value of 0 (equivalent to 3.9 cd/m²) in combination with a neutral density filter (Kodak ND 0.30; Eastman Kodak, Rochester, NY) applied on the screen. The filter has a factor of 2 luminance reduction, and the luminance attenuation of the filter was confirmed with photometric readings from a luminance meter (Minolta LS-110 Luminance Meter; Konica Minolta, Tokyo, Japan). 

Study Design and Task Procedure

A within-subject design was used to compare reading vision between mesopic and photopic conditions within each group (AMD, normal controls). For each participant, the MNREAD test was administered in sequences of photopic–mesopic–mesopic–photopic. This reverse order was used to minimize any potential confounding effects such as fatigue and/or training effects. However, for each test, a different MNREAD chart was used so that a participant never read the same text more than once. We reported the average value of the two measurements for each viewing condition. 

Participants read binocularly at a viewing distance of 40 cm (16 inches) up to 80 cm (32 inches). In order to reliably extract the four MNREAD indices from the MNREAD curve, it is important to test a participant's reading performance on a wide range of print sizes illustrated in Figure 1. However, the range of physical print sizes that can be displayed on the iPad screen is limited. Therefore, we adjusted the viewing distance to vary the angular size of the font subtended at the eye if needed. We used a viewing distance of 40 cm as our default distance. We, however, determined each participant's viewing distance based on his or her practice trials conducted prior to the main task. We made sure to use an appropriate viewing distance that yielded a proper plateau and drop-off point on the MNREAD curve as illustrated in Figure 1. Each participant's near refractive error was corrected for their testing distance with either their habitual reading glasses or trial lens refraction. We only fitted those who did not present with reading glasses or were unable to achieve 20/20 visual acuity with near prescription in addition to a trial lens refraction. They were also given a short adaptation period to adapt to the trial lens prescription before the reading test. If participants wore bifocal or progressive lenses, they were instructed to use the correct portion of their lens to read the text on the screen. 

Participants performed the reading task in a dimly lit room while they were seated in a comfortable position. The ambient light level of the dimly lit testing room was 4.5 lux, and the illuminance values of the photopic viewing condition and mesopic viewing condition were approximately 22 lux and 1 lux, respectively. Participants were given on average 8 minutes to adapt to the room illumination before the first reading test, as well as between test conditions, while the room illumination remained dim. 

Sentences were presented one at a time, centered on the iPad screen, and they were displayed in three lines in the Times Roman font, with print size decreasing in steps of 0.1 log units. The physical print size ranges from 6.3 M to 0.32 M (in Sloan M notation) or 9.3 mm to 0.5 mm (in x height), corresponding to angular print size ranges from 1.2 to −0.1 logMAR (Snellen equivalents 20/320 to 20/16) at the recommended viewing distance of 40 cm.⁴¹ Sentence presentation was initiated by the experimenter using an external keyboard, and each sentence was displayed instantly. Participants were instructed to read the test sentences aloud as quickly and accurately as possible, beginning with the largest print size and progressing to the smallest print size that could be read. After each sentence was read, a score screen was displayed to the experimenter, who entered the number of errors via the external keyboard (if any had occurred during testing). The testing stopped when the print size was so small that the participant could no longer read any words. When reading was completed, the experimenter ended the trial, and the app recorded the reading time. As shown in Figure 1, the iPad app then displayed the corresponding MNREAD curve of log reading speed as a function of print size, along with the following four MNREAD parameters: MRS (wpm), CPS (logMAR), RA (logMAR), and ACC. The same procedure was used for both mesopic and photopic conditions. Note that reading speed was estimated by excluding words that were missed or read incorrectly. If more than 10 errors were made, then reading speed was assumed to be zero. The number of errors was also taken into account to estimate RA, where Acuity = 1.4 – (sentences × 0.1) + (errors × 0.01). 

Data Analysis

We used the within-group analysis to compare reading vision between mesopic and photopic viewing conditions for both AMD and normal controls. We also performed the between-group analysis after adjusting for age to compare reading vision between AMD and normal controls. More specifically, to examine if there are any significant differences in reading vision (i.e., four MNREAD parameters) between (1) two viewing conditions and between (2) patients with AMD and normal older adults, we performed an analysis of covariance (ANCOVA) on reading vision: two viewing conditions (mesopic and photopic) × two subject groups (AMD and normal controls). The repeated-measures ANCOVA was performed with viewing condition as a within-subject factor, subject group as a between-subject factor, and age as a covariate. 

We performed a separate ANCOVA analysis for each MNREAD parameter: MRS, ACC, CPS, and RA. To determine which specific level differed from each other while controlling for multiple comparisons, we also performed post hoc tests with Bonferroni correction. The normality of the data was checked using the quantile–quantile plot. Statistical analyses and data visualization were performed using SPSS Statistics 28.0.0.0 (IBM, Chicago, IL) and MATLAB R2020b (MathWorks, Natick, MA). 

Results

Table 1 summarizes the characteristics of the study participants, including the mean values of age, visual acuity, and contrast sensitivity for both patients with AMD and normal controls. The study had a total of 60 older adult participants: 30 patients with early (n = 11) or intermediate (n = 19) AMD (14 males) and 30 controls with normal macular health (15 males). The mean age ± SD of patients with early and intermediate AMD (n = 30) was 74 ± 6 years, whereas the mean age of normal controls was 66 ± 6 years. The age distribution differed between the two groups, t₍₅₈₎ = −4.93, P < 0.001, and thus we controlled for age in between-group comparisons. 

Table 1.

 

Characteristics of Study Participants (Mean ± SD)

 

For patients with AMD, the mean visual acuity was 0.04 ± 0.16 logMAR (or 20/20 Snellen equivalent) for the right eye and 0.07 ± 0.22 logMAR (or 20/24 Snellen equivalent) for the left eye. The mean log contrast sensitivity of patients with AMD was 1.56 ± 0.12 for the right eye and 1.55 ± 0.14 for the left eye. For healthy controls, the mean visual acuity was 0.11 ± 0.17 logMAR (or 20/26 Snellen equivalent) for the right eye and 0.09 ± 0.11 logMAR (or 20/25 Snellen equivalent) for the left eye. The mean log contrast sensitivity of healthy controls was 1.54 ± 0.16 for the right eye and 1.70 ± 0.19 for the left eye. 

Reading Vision Is Significantly Deteriorated Under Mesopic Conditions for Patients With AMD and Healthy Controls

Figure 2 plots the mean MNREAD parameter values for mesopic and photopic viewing conditions for patients with AMD and normal controls. We observed that mesopic reading vision significantly differs from photopic reading vision, further confirmed by the significant main effect of viewing condition on reading vision for all four MNREAD parameters: MRS, F_{(1, 57)} = 12.03, P = 0.001; ACC, F_{(1, 57)} = 80.57, P < 0.001; CPS, F_{(1, 57)} = 348.15, P < 0.001; RA, F_{(1, 57)} = 383.62, P < 0.001. More specifically, patients with AMD exhibited slower reading speed by 8 wpm, F_{(1, 57)} = 18.70, P < 0.001; reduced reading accessibility by 0.1, F_{(1, 57)} = 40.77, P < 0.001; larger CPS by 0.27 logMAR, F_{(1, 57)} = 119.58, P < 0.001; and worse RA by 0.24 logMAR, F_{(1, 57)} = 203.23, P < 0.001, under mesopic conditions compared to photopic conditions. It is also worth noting that, even though patients’ visual acuity was considered fairly normal—0.04 ± 0.16 logMAR (or 20/20 Snellen equivalent) for the right eye and 0.07 ± 0.22 logMAR (or 20/24 Snellen equivalent) for the left eye—both CPS and RA were markedly larger than visual acuity for both photopic and mesopic conditions. 

Figure 2.

 

The differences in MNREAD parameter values between mesopic (solid bars) and photopic (open bars) conditions for patients with AMD (blue color) and normal controls (coral color). The bar graph indicates the mean value of each MNREAD parameter collapsed across participants (n = 30). (A) Maximum reading speed (wpm). (B) Reading accessibility index. (C) Critical print size (logMAR). (D) Reading acuity (logMAR). Error bars represent ±1 SEM. ***P < 0.001. n.s., no statistical significance.

These findings are consistent with previous research showing that the print size requirement for reading is much larger than what is expected from visual acuity.^3,53,54 It is also important to note that patients’ MRS decreases even with enlarged print sizes under mesopic conditions compared to photopic conditions. Larger print size requirements for mesopic conditions were also observed in normal controls, as shown in Figure 2C and 2D. Table 2 summarizes the mean values of MNREAD parameters for mesopic and photopic conditions for both AMD and normal controls. 

Table 2.

 

Mean Values for MNREAD Parameters for Two Viewing Conditions and Statistical Results

 

The Adverse Effect of Mesopic Conditions Is More Pronounced in AMD Even After Adjusting for Age

As shown in Figure 2, the difference in reading vision between the two viewing conditions was more evident for patients with AMD compared to normal controls even after controlling for age. The pattern of the results was further confirmed by the significant interaction effect of viewing condition and subject group for MRS, F_{(1, 57)} = 7.47, P = 0.008, and RA, F_{(1, 57)} = 4.70, P = 0.034. In other words, the differences in MNREAD reading vision between mesopic and photopic conditions were significantly greater for patients with AMD compared to the differences for normal controls even after controlling for age. For example, the reading speed of patients with AMD was decreased by 8 wpm, F_{(1, 57)} = 18.70, P < 0.001, under mesopic conditions, but the reading speed of normal controls remained unchanged, F_{(1, 57)} = 0.02, P = 0.891. Similarly, the average RA of patients with AMD increased by 0.24 logMAR, F_{(1, 57)} = 203.23, P < 0.001, whereas the average RA of normal controls increased by 0.19, F_{(1, 57)} = 119.56, P < 0.001. We, however, did not find any significant interaction effect for the ACC, F_{(1, 57)} = 0.64, P = 0.43 or CPS, F_{(1, 57)} = 1.93, P = 0.17. 

Discussion

Although most functional measurements in the clinic are assessed under photopic conditions (200–550 lux), humans often function under low or dim lighting conditions, including dusk and overcast weather conditions and in dim indoor environments.¹⁶ Visual function such as visual acuity or contrast sensitivity has been shown to be compromised under dim light conditions in both aging and clinical populations.^{23,37,55–57} For this reason, patients with visual impairment often report difficulty in performing daily activities under low or dim illuminations.^18,58 This issue becomes more pronounced in those with rod dysfunction, as mesopic vision is mediated by both cone and rod photoreceptors.^17,19,37,59 

Rod function is impaired in early and intermediate AMD, a leading cause of irreversible visual impairment in the elderly.⁴ Due to loss of rod photoreceptors present even in early stages of AMD, mesopic visual function, which relies on both rods and cones, is known to be affected in AMD.^{18,19,23,27,35,36} Puell et al.³⁶ showed that the difference in visual acuity between mesopic (0.1–0.2 cd/m²) and photopic (85 cd/m²) conditions was significantly greater for early AMD compared to healthy controls. The mean drops in high-contrast visual acuity observed under mesopic compared to photopic conditions were 5.1 lines in the early AMD and 3.8 lines in controls; the mean drops in low-contrast visual acuity were 7.6 lines in early AMD and 4.4 lines in the controls. Sunness et al.²⁴ further showed that low-luminance visual dysfunction is a strong predictor of subsequent visual acuity loss in AMD. 

Reading is involved in a variety of daily activities such as reading books, street signs, and product labels. Various tasks involving reading are performed while operating under a wide range of luminance levels. Reading difficulty has been cited as one of the major complaints among patients with AMD.¹² Importantly, a number of studies have shown that higher lighting/luminance levels are required for persons with AMD to achieve their maximum reading or acuity performance using a wide range of photopic lighting levels,^25–29 indicating the importance of lighting on reading vision in patients with AMD. For example, using MNREAD charts, Bowers et al.²⁶ investigated the effects of illumination, in the range of 50 lux (typical home environment) to 5000 lux (clear daylight), on reading vision in patients with AMD. They showed that task illuminance of at least 2000 lux is required for patients with AMD to maximize reading performance. Particularly, the improvement in RA (by 0.32 logMAR) and CPS (by 0.31 logMAR) was greatest in the range of 50 to 2000 lux. However, the majority of these aforementioned studies used a range of photopic luminance levels. The few studies^25,29 that included mesopic luminance levels (e.g., 1 or 3.5 cd/m²) studied relatively advanced AMD (although not explicitly stated, the majority of their study participants had advanced stages of AMD in terms of visual acuity and non-foveal viewing).^25,29 

As functional abnormalities of rods and cones have been well established in early and intermediate AMD, a mesopic reading test likely provides a more sensitive and comprehensive assessment of a patient's reading impairment even in the early stages of disease progression. Despite its significance, it is still unclear whether and to what extent rod- and cone-mediated mesopic reading vision is impaired in early/intermediate AMD. 

Thus, the current study aimed to fill this knowledge gap by investigating the effects of mesopic luminance conditions on reading in patients with early and intermediate AMD. For detailed characterization of reading vision, we evaluated reading performance with the MNREAD iPad app.⁴¹ The resulting four MNREAD indices—MRS, CPS, RA, and ACC—were compared between mesopic and photopic conditions. As a reference, we also compared MNREAD test results of our patients with AMD to those of healthy controls. We were particularly interested in whether the differences (if any) in reading vision measured by the MNREAD test between mesopic and photopic conditions would be more pronounced in patients with early and intermediate AMD as compared to healthy controls after adjusting for age. Our main findings can be summarized as follows. 

First, our results showed that overall reading vision of patients with early and intermediate AMD indicated by MNREAD parameters deteriorated under mesopic conditions. Compared to photopic conditions, mesopic reading speed decreased by 8 wpm on average; CPS and RA increased by 0.27 logMAR and by 0.24 logMAR (i.e., more than a two-line difference on the acuity chart), respectively; the ACC decreased by approximately 0.1 under mesopic conditions (p < 0.001). It is, thus, apparent that under low luminance conditions, patients with early and intermediate AMD require a much larger print size, at least 2.5 times larger than that of photopic viewing, to achieve their MRS. However, it is important to note that even with a larger print size, their MRS is still compromised compared to photopic conditions. 

Second, we observed a similar pattern of the results in healthy controls. The reading vision of older adults with normal macular health was also significantly affected by low luminance conditions. Although no significant difference was found in MRS (P = 0.89), both CPS and RA increased by 0.28 logMAR and 0.19 logMAR (i.e., a two-line difference on the acuity chart), respectively, under dim light. Our results are well aligned with previous findings of questionnaire studies and structured focus groups showing that older adults are more likely to cite vision problems at night and under low luminance conditions compared to young adults.^14,60–62 It has been attributed to age-related changes in the optical properties of the eye (e.g., pupillary miosis, increasing lens optical density),^63,64 a loss of rod photoreceptors,^65,66 as well as delayed dark adaptation resulting from age-related disturbance in regeneration of rhodopsin.^62,67 These results together demonstrate that overall reading vision becomes impaired under low luminance conditions compared to photopic conditions in older adults even in the absence of retinal disorders. However, to further confirm the aging effect, a future study should compare the MNREAD reading vision between mesopic and photopic conditions in healthy young adults in addition to healthy older adults. 

Third, the adverse effect of mesopic conditions was more pronounced in patients with early and intermediate AMD even after adjusting for age. The difference in reading vision between the two viewing conditions was more prominent for patients with AMD compared to normal controls for MRS, F_{(1, 57)} = 7.47, P = 0.008, and RA, F_{(1, 57)} = 4.70, P = 0.034. Our findings are consistent with previous work showing that reading with small print was more affected by low light conditions in patients with more advanced AMD compared to healthy controls.^25,29 For example, Seiple et al.²⁵ investigated how the reading speed would depend on print size under luminance levels ranging from 3.5 to 696 cd/m² for patients with relatively advanced AMD (e.g., six out of nine patients with AMD had non-foveal preferred retinal locus [PRL] for viewing and VA worse than 0.7 logMAR) and healthy controls. They found that, for patients with AMD, a plot of reading speed versus print size was shifted to larger print sizes and slower reading speeds as compared to healthy controls across luminance levels. More importantly, at the dimmest luminance level (3.5 cd/m²), reading speeds were slowest at letter sizes near a patient's threshold and reached a plateau for larger sizes. When luminance was increased up to 30 cd/m², reading speed increased only for the smaller letter sizes, suggesting the interaction effect of print size and luminance for reading. Taken together, the results of our current study further show that additional reading impairment observed in patients with AMD at mesopic luminance levels appears to be present even in patients with early and intermediate AMD typically known to have good photopic visual acuity (better than 20/25 Snellen equivalent).^40,68 

Finally, our results show that CPS measured under photopic conditions was markedly larger than photopic visual acuity for patients with AMD (CPS of 0.24 logMAR vs. VA of 0.04 [right eye] or 0.07 [left eye] logMAR) and for healthy controls (CPS of 0.21 logMAR vs. VA of 0.11 [right eye] or 0.09 [left eye] logMAR). This finding is in line with previous work showing that the print size requirement for reading is much larger than what is expected from visual acuity,^3,53,54 thereby highlighting the importance of measuring reading vision to better characterize a patient's functional vision.⁶⁹ 

It is also noteworthy that the photopic reading speed of our healthy older adults (145 ± 20 wpm) is noticeably slower by 21% compared to that of healthy older adults in a similar age range (66 years old on average) reported in Calabrèse et al.⁵⁴ (approximately 184 wpm). Although speculative, this observed discrepancy between the two studies might be due to the difference in the way the MNREAD test was measured (i.e., MNREAD iPad app-based vs. chart-based tests). Indeed, Calabrèse et al.⁴¹ compared MNREAD reading performance measured with the MNREAD chart and an iPad app version of the same test for both normally sighted individuals and low-vision patients. Despite overall high correlations between the two tests, they reported that the iPad app provided noticeably slower estimates of MRS than the chart, with the difference being up to 25% (see Fig. 5 of Calabrèse et al.⁴¹). 

We also acknowledge that a future study should consider using other reading speed measures (e.g., relatively long passage reading as opposed to single sentence reading like the MNREAD test) to see if the observed pattern of results is generalized to other types of reading measures. Although reading or word recognition is known to be facilitated by contextual and sematic information provided by passages,⁷⁰ we expect that the burden of mesopic conditions on reading for patients with AMD is likely to be more exacerbated with long passage reading. Previous studies indeed demonstrated that visually impaired individuals exhibit more pronounced deficits in sustained reading in terms of reading speed⁷¹ or comprehension.⁷² 

Also, as larger sample sizes provide more accurate and reliable estimates of the population, future studies with a larger sample size may not only help further confirm the relationship between early/intermediate AMD and mesopic reading deficits observed in the current study but also help us understand whether mesopic reading deficits are present as early as in the early stage of AMD via the subgroup analysis comparing between early and intermediate AMD. 

Furthermore, the current study relied on a person's self-reported ocular history (e.g., surgical history of cataract, use of intraocular lens) for the normal control group. We, thus, cannot rule out the fact that some of our healthy controls might have had unknown ocular conditions that might have affected their results. We, however, believe that such a case may have led to an underestimation of the differences between patients with AMD and healthy controls, not the other way around. Also, in the current study, the MNREAD reading vision was evaluated under one mesopic luminance level (i.e., a luminance of 2 cd/m²). However, to better characterize the dependency of reading vision of patients with early and intermediate AMD on low luminance, a future study may consider testing various photopic and mesopic light levels parametrically. This may help us determine whether there will be any critical luminance level from which reading vision of patients with early and intermediate AMD starts to substantially deteriorate (i.e., a drop-off point). Finally, we used photopic visual acuity as one of the criteria for screening normal vision, as well as an additional means to confirm the degree of vision loss in AMD. This is the reason we chose to measure photopic acuity on each eye monocularly. However, it would have been more informative if we had both photopic and mesopic binocular acuities to see how these binocular acuities are related to binocular mesopic reading vision. Therefore, future studies are called for to address these limitations. 

In summary, our results suggest that reading vision is deteriorated under mesopic conditions requiring a larger print size for reading in persons with early and intermediate stages of AMD and older adults with normal macular health. However, this impact on reading performance is significantly accentuated in persons with AMD. Our findings further suggest that a mesopic reading test mediated by both cone and rod vision may provide a more sensitive and comprehensive assessment of a patient's reading impairment while serving as a potentially useful tool to evaluate the efficacy of interventions and disease progression of early and intermediate AMD. 

Acknowledgments

The authors thank Lindsay Washington and Traci-Lin Goddin for their help with participant recruitment and data collection. We also thank Mark Clark for his help with the AREDS grading. 

Supported by a grant from the National Institute on Aging, National Institutes of Health (P30AG22838); Research to Prevent Blindness and Lions’ Clubs International Foundation Low Vision Research Award; and grants from the National Eye Institute, National Institutes of Health (R01 EY027857, R01EY029595). The sponsor or funding organization had no role in the design or conduct of this research. 

Disclosure: M. Kwon, None; C. Owsley, None