Quantitative assessments of retinal macular structure among rural-dwelling older adults in China: a population-based, cross-sectional, optical coherence tomography study

Objectives To quantitatively assess and compare retinal macular structures of rural-dwelling older adults in China using two different optical coherence tomography (OCT) scanners and to examine their associations with demographic, lifestyle, clinical and ocular factors. Design, setting and participants This population-based, cross-sectional study included 971 participants (age ≥60 years) derived from the Multimodal Interventions to Delay Dementia and Disability in Rural China study. We collected data on demographics, lifestyle factors, clinical conditions (eg, cardiovascular disease (CVD)) and ocular factors (eg, visual acuity and spherical equivalent). We used two models of spectral-domain OCT to measure macular parameters in nine Early Treatment Diabetic Retinopathy Study subﬁelds. Data were analysed using the multiple general linear models. Results Spectralis OCT demonstrated higher macular thickness but a lower macular volume than Primus 200 OCT (p<0.05). Nasal quadrant of the inner and outer subfields was the thickest, followed by superior quadrant. Adjusting for multiple potential confounding variables, older age was significantly correlated with lower average inner and outer macular thicknesses and overall macular volume. Men had higher macular parameters than women. The presence of CVD was correlated with lower central macular thickness (β=−6.83; 95% CI: −13.08 to −0.58; p=0.032). Middle school or above was associated with higher average inner macular thickness (β=7.85; 95% CI: 1.14 to 14.55; p=0.022) and higher spherical equivalent was correlated with lower average inner macular thickness (β=−1.78; 95% CI: −3.50 to −0.07; p=0.042). Conclusions Macular thickness and volume assessed by Spectralis and Primus 200 OCT scanners differ. Older age and female sex are associated with lower macular thickness and volume. Macular parameters are associated with education, CVD and spherical equivalent. Trial registeration number MIND-China study (ChiCTR1800017758).

Major 1) For factors such as achieving middle school and above and having CVD that were significantly different only in one model of OCT, it is questionable to conclude that "macular parameters were also affected by educational attainment, CVD, and spherical equivalent"(line343-344).What is your rationale for excluding the Primus results, which have a larger sample size?Please add that reason and revise your conclusion to what logically follows from the results.
Minor 2) line 214-(throughout the Results section) and Table 3 Instead of "P<0.05" and "P<0.01",please provide specific P values to enhance the clarity and precision of the reported statistical significance.
3) Figure 2 Please include an explanation of the statistical differences observed to better interpret the findings.

GENERAL COMMENTS
This article is well-written, with detailed methods and a sizable cohort.While it doesn't introduce many new insights into existing knowledge, there are some noteworthy points that could be value in Figure 2 in response to the Reviewer's comments (see page 27, Figure 2, and page 21, line 515).
Reviewer: 2 Dr. Alessio Antropoli, Università Vita Salute San Raffaele Comments to the Author: This article is well-written, with detailed methods and a sizable cohort.While it doesn't introduce many new insights into existing knowledge, there are some noteworthy points that could be highlighted more.For instance, the authors performed the same analyses with two different devices and found that the correlations between OCT parameters and various collected data, such as CVD, spherical equivalent, education level, and vision impairment, were only statistically significant with the Spectralis device.It would be helpful for the authors to explain why these correlations were only observed with the Spectralis device.
Response: We are grateful to the reviewer for the overall positive comments, along with kind suggestions for helping to improve our work.
(1) Indeed, previous population-based SD-OCT studies have shown that spherical equivalent was associated with thinner macular thickness1, which may correlate with axial elongation and loss of photoreceptor packing density in myopic eyes.However, as there was no autorefractor in Yanlou Town Hospital, spherical equivalent was not examined for participants scanned with the Primus 200 device.We have now briefly explained this in the text (see pages 13-14, lines 331-334).
(2) To our knowledge, very few studies have assessed the association of education and macular thickness2, and the underlying mechanism was unclear.The differences in demographics of both sample (e.g., mean age 68.1 for persons scanned with Spectralis vs. 70.4years for persons scanned with Primus 200; P<0.001) and the different sensitivity of the two scanners might partly contribute to the discrepant results.We now revised the discussion about the association of education and macular thickness (see page 12, lines 294-297).
(3) Previous case-control studies showed thinner retina thickness in participants with heart failure and stroke3 4, which may partially attribute to decrease in vessel density and regressive neuro-axonal damage.Our study showed that the presence of CVD was associated with thinner central macular thickness, but this association become statistically non-significant in the fully-adjusted model.Further population-based studies in diverse populations are needed to clarify the relationships of CVD with macular thickness.
Additionally, it's important to understand what the authors believe is the primary cause of visual impairment in their cohorts.Since they excluded retinal diseases, it's likely that cataracts were a common cause.Were cataracts investigated or reported in the study?Clarifying this aspect would enhance the completeness of the research.
Response: We appreciate the reviewer for valuable comments.We agree with the reviewer that cataracts were a common cause of visual impairment.We have excluded participants with low signal strength in the inclusion criteria of study participation.Therefore, we did not analyze the impact of cataract on macular parameters in our study.
Lastly, I will further clarify in the discussion the importance of their results and how and why they serve the purpose of the MIND-China study.
Response: We thank the reviewer for the very important comments.Our study engaged older adults who were living in rural communities in China and had received no or very limited school education and had relatively low socioeconomic status, and this sociodemographic group has been substantially under studied in the literature as we highlighted in the introduction.In addition, we studied a wider range of factors (e.g., demographic, lifestyle, and clinical and retinal factors) associated with retinal parameters in the current literature.Further, we compared retinal parameters measured with two most commonly used models of devices, which provided important information for studies using these two different models.We believe that these results from our study could contribute to the current literature.
One of the aims of the MIND-China study was to identify objective biomarkers for early detection of brain aging and cognitive impairment (e.g., MCI) and physical dysfunction (in addition to testing the effectiveness of multimodal interventions to delay dementia and functional dependence in rural older adults, as we previously described)5.Based on the current literature, we hypothesized that retinal measurements/biomarkers assessed with SD-OCT hold great potential for the early diagnosis, prognosis, and risk assessment of dementia/AD and MCI.We believe that the current descriptive study (e.g., methodological description and distribution of retinal parameters and related factors) will be very important for future research (including follow-up studies) regarding early diagnosis and prognosis of MCI, and their associations with brain aging markers (e.g., plasma and MRI biomarkers for brain aging and AD measured in MIND-China.See Dong Y, et al.J Alzheimer's Dis 6) in rural residents.We have now briefly highlighted this in the manuscript (see page 5, lines 94-98).