Chronic obstructive pulmonary disease (COPD) is a slowly progressive chronic respiratory disorder, recognized as a leading global cause of mortality, with a prevalence of 10.3% among individuals aged 30–79 years worldwide (1), and contributing to 74.4 million disability-adjusted life years lost and 3.3 million deaths (2). COPD impacts ocular fundus structures via mechanisms including chronic hypoxia, systemic inflammation, and vascular dysfunction, resulting in alterations to retinal layer thickness. These changes are typically assessed using imaging modalities such as optical coherence tomography (OCT) (3).

Hypertension is globally recognized as the leading modifiable risk factor for premature mortality (4). Beyond its well-established role in cardiovascular, renal, and cerebrovascular diseases, hypertension induces retinal microvascular damage characterized by impaired vasomotor regulation and increased wall-to-lumen ratio (5). These alterations manifest as significant changes in multiple retinal nerve fiber layers in hypertensive patients compared with normotensive controls, ultimately affecting total retinal thickness (6).

Retinal thickness (RT) reflects the structural integrity, functional status, and pathological changes of the macular region, and serves as a core quantitative indicator for the progression of various ocular diseases. Central macular thickness (CMT) directly affects the density and function of cone cells, with a thickness of approximately 300 μm in this area (7, 8). CMT is not an isolated indicator; it can integratively reflect the effects of multiple influencing factors, and any abnormality in it may lead to decreased central visual acuity. Increased CMT thickness is often associated with local inflammation, vascular leakage, and fluid accumulation, and serves as an early marker for the active phase of vision-threatening diseases (9–11) such as diabetic retinopathy, retinal vein occlusion, and uveitis. In contrast, decreased thickness is often associated with high myopia and neurodegenerative diseases, such as optic neuropathy, late-stage dry age-related macular degeneration (AMD) (geographic atrophy), as well as some hereditary retinal diseases. CMT, measured by OCT, is an important parameter for diagnosing different types of retinal diseases (12–14).

The standardized segmentation of the fovea centralis of the macula and its surrounding areas is an important foundation for research on retinal structure and function. This segmentation was first mentioned in the 1985 Early Treatment Diabetic Retinopathy Study (ETDRS) (15) and is referred to as the ETDRS grid. It is divided into three concentric rings based on diameters of 1 mm, 3 mm, and 6 mm, and is further subdivided into four quadrants: superior, inferior, temporal, and nasal (16). The 1-mm foveal centralis region of the macula is a circular area with the fovea centralis as the center and a diameter of 1 mm, corresponding to an approximate range of 5° in the central visual field, and serves as the core region with the sharpest visual acuity. The 3-mm perifoveal region of the macular fovea is a ring-shaped area with the fovea as the center and a radius ranging from 1 mm to 3 mm. It corresponds to an approximate range of 10° in the central visual field and belongs to the parafovea. The 6-mm perifoveal region of the macular fovea is a ring-shaped area with the fovea as the center and a radius ranging from 3 mm to 6 mm, and corresponds to a range of 20° in the central visual field. The entire standardized segmentation with a 6-mm diameter fully covers the macular region. The retina in the fovea centralis of the macula and its surrounding superior, inferior, temporal, and nasal regions at different distances exhibits significant differences in structure, cell distribution, vascular supply, and function— differences that are closely associated with visual sensitivity and disease susceptibility (17). Understanding the influencing factors of retinal thickness in different macular regions provides a theoretical foundation for the risk assessment, staging, and treatment of macular-related diseases, and is of great significance for enhancing diagnostic and therapeutic efficiency and improving visual prognosis.

The thickness of different retinal nerve layers and the choroid in the population changes with increasing age and is influenced by multiple factors such as gender, lifestyle, disease status, and ocular factors (18, 19). However, existing studies mostly focus on different retinal nerve layers based on clinic-based patient studies (20, 21), and lack investigations on the full-thickness retinal thickness in all orientations of CMT among community-dwelling middle-aged and elderly populations.

This study is a cross-sectional study on community-dwelling middle-aged and elderly populations, accurately measuring retinal thickness in all orientations via OCT, while simultaneously collecting demographic data, lifestyle factors, comorbidities, and ocular indicators. It aims to establish age-specific reference ranges for retinal thickness in this population, to determine whether hypertension is a key risk factor for abnormal retinal thickness and to explore the impact of blood pressure control on RT. This study not only fills gaps in community-based research and provides appropriate assessment benchmarks for clinical practice, but also supports the development of ocular health screening strategies for community-dwelling middle-aged and elderly individuals and early warning of relevant ocular disease risks, contributing to the improvement of ocular health among middle-aged and elderly populations in the context of healthy aging.

In recent years, studies have found that as an extension of the central nervous system, the retinal thickness changes could reflect the health status of the nervous system and the whole body (24). RT is not an isolated indicator. It integrates and reflects the combined effects of multiple influencing factors. For instance, vascular factors (such as hypertensive retinopathy) cause leakage or ischemia; inflammatory factors damage the blood-retinal barrier and induce fluid accumulation; neurodegenerative factors (such as glaucoma and Alzheimer’s disease) lead to the loss of the ganglion cell layer; and age-related and genetic factors also exert an impact on RT within a certain range. Investigating the influencing factors of RT essentially involves exploring the ultimate manifestation of the interactions among the aforementioned multiple systems, including vascular, neurological, inflammatory, and genetic systems (24–27).

Consistent with previous studies (28), we found that increasing age is associated with retinal thinning. This phenomenon is primarily attributed to age-related neuronal loss, gliosis, and degeneration of the retinal pigment epithelium (RPE) layer. These processes lead to cell apoptosis and structural atrophy, which in turn accelerate local microcirculatory disturbances and impaired metabolic function. Among these regions, the central region—being a macular area with high neuronal density—is more susceptible to accumulated oxidative stress, resulting in significant thinning.

Our findings indicate that in multivariable logistics regression model history of hypertension serves as an independent risk factor for retinal thinning in the inner temporal and superior outer regions, while COPD independently contributes to thinning in the inferior outer region. Notably, stratification by hypertension status revealed no association between COPD and retinal thickness across any regions in the hypertensive subgroup, whereas in the non-hypertensive subgroup, COPD was significantly linked to thinning in the central, inner nasal, inferior outer, and outer nasal regions (chi-square analysis). These observations underscore a potential interaction wherein hypertension may modulate COPD’s ocular effects. Focusing on COPD’s influence on retinal thickness, our results align with emerging evidence that COPD was associated with reduced retinal nerve fiber layer (RNFL) thickness, correlating with disease severity and hypoxemia levels, as detected via OCT. (3, 29) These changes likely stem from hypoxia-induced neuronal damage and vascular remodeling, disproportionately affecting outer retinal zones where oxygen demand is high (30). Furthermore, COPD’s microvascular retinopathy persists even after adjusting for comorbidities like hypertension, suggesting an intrinsic pathological pathway.

The stratified analysis highlights a novel interaction: COPD’s impact on retinal thickness appears confined to non-hypertensive individuals, potentially due to hypertension’s dominant vascular pathology overshadows COPD-related effects in comorbid cases. This could reflect additive or synergistic mechanisms in isolated COPD, where unmasked hypoxemia drives regional thinning, versus a ceiling effect in hypertensive patients with pre-existing endothelial impairment (31, 32). COPD and hypertension may synergistically affect retinal thickness through chronic hypoxia, systemic inflammation, and vascular endothelial dysfunction, collectively exacerbating microcirculatory impairment and neurodegeneration in specific retinal regions (20, 29).

Beyond the above findings, this study focused on the impact of hypertension on RT. After adjusting for lifestyle and medical history factors—including gender, age, alcohol consumption history, history of coronary heart disease, history of diabetes, history of hyperlipidemia, 30-min moderate-intensity exercise per week, weekly intake of fruits and vegetables, preference for salty food, and regular consumption of pickled foods—we found that participants with a previous history of hypertension were prone to thinning in the temporal inner region and superior outer region. Furthermore, based on further measurements of participants’ daily blood pressure, DBP was positively correlated with the thickness of the inner retinal region, while its impact on other retinal regions was not statistically significant. In contrast, SBP had no statistically significant effect on any retinal region. This indicated that a previous history of hypertension only induces changes in RT in specific regions. In contrast, daily blood pressure control—particularly of DBP rather than SBP—was associated with RT, especially in the inner retinal region. This provides guidance for retinal protection in patients with hypertension.

Patients with hypertension exhibit relatively lower vascular density (33). Retinal microvascular stenosis may increase microcirculatory resistance, cause impaired autoregulation of retinal blood flow, reduce microvascular blood flow, and easily lead to insufficient perfusion of the optic nerve, thereby resulting in retinal ischemia (34). Meanwhile, chronic elevated blood pressure induces retinal microvascular remodeling, endothelial damage, and local ischemia-hypoxia. These processes accelerate the degenerative changes of the outer plexiform layer, photoreceptor layer, and RPE, leading to cell apoptosis and structural atrophy, which further thin the retina. Retinal thinning may in turn reduce the oxygen consumption and blood flow of retinal blood vessels, triggering a vicious cycle of retinal structural atrophy and functional impairment (22). Previous studies have also found that long-term hypertension is associated with reduced retinal blood flow and thinning of the ganglion cell-inner plexiform layer (GC-IPL), RNFL, and other layers (33, 35, 36). This is consistent with our finding that participants with a history of hypertension showed thinning in the temporal inner region and superior outer region.

Our study found that a history of hypertension is a potential risk factor for thinning of the temporal inner and superior outer retina. Further assessment of daily blood pressure revealed that, compared with the limited effect of SBP on RT, DBP exerts an impact on the thickness of the inner retina across the entire macular region. DBP reflects the sustained pressure load on vascular walls during diastole and regulates continuous perfusion levels and basal vascular tone (37). The central retinal artery and its branches are classified as small-to-medium arteries and capillaries, which have thin vessel walls and weak regulatory capacity. In contrast, choroidal vessels belong to a “large vessel-sinusoidal capillary” system, characterized by thicker walls, larger diameters, and regulation by the autonomic nervous system and local metabolic factors. These features enable choroidal vessels to rapidly buffer blood pressure fluctuations through self-constriction and dilation (38, 39). Among different retinal regions based on the ETDRS 9-field grid, the inner retina relies on blood supply from the central retinal artery. Its vascular structure is more susceptible to systemic blood pressure fluctuations than the outer retina (which depends on choroidal perfusion) and the avascular foveal center. The core cells in the foveal center are cone cells, whose metabolic needs primarily rely on oxygen and nutrients supplied by the choroid. The key cell layers in the inner retina include the nerve fiber layer, inner nuclear layer, and Müller glial cells, while those in the outer retina consist of the photoreceptor layer and RPE layer. Therefore, the cell layers of the foveal center and outer retina lack the conditions to be affected by DBP (40, 41). The nerve fiber layer and ganglion cell layer in the inner retina are sensitive to hypoxia and oxidative stress. Elevated DBP can increase vascular permeability, leading to leakage of plasma components into the interstitial space and subsequent thickening. Meanwhile, retinal arteriolosclerosis reduces blood perfusion, prompting local compensatory thickening to maintain function. Sustained mechanical stress and ischemia-hypoxia further stimulate the proliferation of glial cells (e.g., Müller cells), which exacerbates inner retinal thickening (42, 43). SBP primarily reflects peak arterial pressure, and its elevation lasts only 0.2–0.3 s. This short-term peak cannot trigger cellular compensatory responses, resulting in a minimal independent contribution to chronic retinal structural changes. Thus, the effect of SBP is often masked by factors such as age, lifestyle, and comorbidities, leading to no significant linear association (44, 45). Both the central retinal artery and choroidal vessels possess myogenic autoregulatory capacity. In addition to myogenic regulation, choroidal vessels are also controlled by the autonomic nervous system and local metabolic factors. When SBP increases, the smooth muscles of the supplying arteries rapidly adjust blood flow through relaxation or contraction, thereby reducing the actual intravascular perfusion pressure. This mechanism ensures stable perfusion and prevents vascular damage or edema caused by sudden increases in blood flow (44, 46).

However, in other studies, elevated DBP often exhibits a negative correlation with the thickness of most retinal neural layers, including the RNFL, GCL, and outer segments of photoreceptors (POS). This is likely due to vasospasm and neuronal loss under high pressure dominating degenerative changes. In contrast, DBP shows a positive correlation with the thickness of the inner nuclear layer (INL), possibly resulting from inflammatory thickening of bipolar cells and glial cells in the INL that serves as a protective response (47). The positive correlation observed in this study may reflect the comprehensive effect on total RT, in which the positive contribution of the INL predominates in the multivariable model, masking the negative effects of other layers. This discrepancy may be attributed to differences in measurement methods between OCT-based measurements of total thickness in segmented regions and neural layer-specific analysis, which requires further verification.

In participants with a history of hypertension who were taking antihypertensive medications, the impact of blood pressure on inner retinal thickness was generally significantly limited. Antihypertensive medications protect the retina from chronic high-pressure damage by reducing overall blood pressure load, improving vascular compliance, and mitigating oxidative stress. The superior inner region has higher vascular density and blood flow, making it more sensitive to short-term variability in DBP (48). Even if medications control average blood pressure, residual fluctuations may still affect the microcirculation in this region, leading to tissue thickening. Compared with other regions, the vascular walls in the superior inner region may be more prone to remodeling (49, 50), which manifests as a positive correlation rather than a negative one in treated patients. The retinal vascular distribution in the temporal outer region is relatively sparse, making it more vulnerable to high pressure-induced local ischemia or oxidative stress. Chronic atrophy of nerve fibers results in reduced thickness. Although antihypertensive medications reduce overall blood pressure load, they cannot completely eliminate the residual effects of chronic hypertension on local microcirculation, ultimately leading to a negative correlation between blood pressure and thickness in this region (44). Elevated DBP showed a positive correlation only in the superior inner region, with no significant impact observed in other regions. This indicates that the potential negative effects of elevated DBP are attenuated and confined to specific local areas. Similarly, SBP exhibited a negative correlation only in the temporal outer region, with no obvious association detected in other sites. Overall, these findings highlight the protective role of antihypertensive therapy in alleviating the impact of blood pressure on retinal structure, reducing the global effect of blood pressure changes on the retina to specific anatomical regions.

This study also has several limitations. First, the study sample was derived from a single center and employed a cross-sectional design. Consequently, it can only identify associations rather than establish causality. Although we adjusted for multiple demographic and clinical confounders in the analysis, the single-center design may still limit the direct generalizability of our conclusions to other regions or broader populations due to factors such as regional demographic composition, genetic background, environmental exposures, and healthcare practices. Future multi-center, large-sample prospective studies are needed to further validate and extend our findings. Second, a notable limitation of this study is the lack of detailed information on the class, dosage, and duration of antihypertensive medications. Growing evidence suggests that different classes of antihypertensive agents (e.g., calcium channel blockers, ACE inhibitors/angiotensin receptor blockers, β-blockers) exert distinct effects on retinal vessel diameter, blood flow, and retinal nerve fiber layer thickness. Future studies will systematically collect these medication details and conduct subgroup analyses to elucidate the specific impact of different antihypertensive drug classes and dosages on retinal structure and function. This would provide more precise ophthalmological evidence for personalized management of hypertensive patients. Tirdly, this study has mentioned limitations including single-center setting, cross-sectional design, and lack of detailed information on antihypertensive medications. It is recommended to further supplement: The study did not include COPD severity classification (e.g., GOLD grade) and pulmonary function indicators (e.g., FEV1/FVC), making it impossible to clarify the dose–response relationship between COPD progression and retinal thickness.

This study holds great significance. It analyzed the differential effects of a history of hypertension, SBP, and DBP on the thickness of the nine retinal regions using multivariable linear and multivariable logistic regression analyses. Given the limited availability of ophthalmic examination equipment in settings such as community screenings, and considering that previous studies have focused on the impact of hypertension on individual retinal layers, this study centered on the relationship between total RT and hypertension. It revealed the independent positive correlation effect of DBP and further suggested that the use of antihypertensive medications can restrict this positive correlation. This finding not only deepens the understanding of the microscopic ocular effects of hypertension but also highlights the value of refined blood pressure assessment in preventing eye diseases. Furthermore, it provides new insights for community screening and the prevention of ocular disorders.

The study found that a history of hypertension is a potential risk factor for thinning of the temporal inner and superior outer retina. COPD and hypertension are independent risk factors for changes in retinal thickness, with heterogeneous effects across different retinal regions. Further evaluation of daily blood pressure levels revealed that, compared with the limited impact of SBP on RT, DBP exhibits a positive correlation with the thickness of the inner region of the entire macular region. In the subgroup of participants with a history of hypertension who were taking antihypertensive medications, the impact of DBP on inner retinal thickness was only observed in its positive correlation with the thickness of the inferior inner region. This indicates that elevated DBP affects the thickness of the inner retinal region, but this potential positive effect is attenuated after the use of antihypertensive medications and confined to specific local regions. It provides new insights into the impact of hypertension prevention and management on the retinal and optic nerve in the eye.