There is a limited number of studies evaluating the association between air pollution and ocular diseases as this research requires long-term evaluation and large sample sizes. Different studies included various pollutants and evaluated different parameters, thus making the comparison and generalized conclusions challenging.

Ambient PM_2.5 is reported to be the fifth-ranked risk factor of mortality globally [14]; furthermore, it may play a significant role in the development of vision-threatening posterior segment ocular diseases. Our reviewed studies showed that increased exposure to PM_2.5 is linked to the increased incidence of glaucoma, suggesting that this pollutant is an independent risk factor for the disease [9,10,12,14,15,17]. Several studies indicated significant primary findings of possible associations between exposure to PM_2.5 and increased incidence of subtypes of glaucoma, including PACG [14], NTG [17], and acute glaucoma [18]. Evidence of the association between increased exposure to PM_2.5 and glaucoma was verified by the results of a recently published systematic review and meta-analysis by Grant and colleagues [9].

Grant et al. found that IOP was significantly associated with increased levels of O₃ and PM_2.5 in the multi-pollutant model, suggesting increased toxic effects by correlation of different pollutants [15]. More evidence of the pathogenic mechanisms of air pollutants’ effect on IOP arises from animal and in vitro studies [30]. IOP increased gradually after mouse eyes were exposed to topical PM_2.5 suspension for 3 months [30]. Human trabecular meshwork (HTM) cells subjected to various PM_2.5 concentrations in vitro resulted in decreased cell viability (concentration-dependent decrease) and affected its contraction, increased oxidative stress, and increased the subsequent induction of NLRP3 inflammasome-mediated pyroptosis [30]. This may damage the trabecular meshwork, leading to an increased aqueous outflow resistance, thereby causing IOP elevation and glaucoma [30]. Furthermore, black carbon was significantly linked to an increased IOP when the oxidative stress allelic score was increased [31]. The authors suggested that susceptibility to black carbon exposure might be determined biologically and there is a possibility of gene–environment interactions [31]. There is increasing evidence that oxidative stress could be one of the possible pathogenetic mechanisms in the association between air pollution and IOP [30,31]. To the contrary, Chua et al. proposed neurotoxicity or vascular dysfunction as possible pathogenetic mechanisms as they did not find a significant relationship between PM_2.5 and IOP [10].

It was noticed that patients with comorbidities such as diabetes might have a higher risk of glaucoma when exposure to PM_2.5 is increased [13]. Likewise, children may be more susceptible to air pollution, as Min et al. found that increased exposure to PM₁₀ is associated with an increased risk of childhood glaucoma [11]. Furthermore, increased exposure to air pollutants may affect retinal vascular changes in children. Korsiak et al. found that the combined oxidant capacity of O₃ and NO₂ (Ox) was associated with the reduction in retinal arteriolar diameter, while PM_2.5 was linked to a slight increase in arteriolar diameter [32]. The identified changes in microvasculature can be a significant factor in the further determination of possible pathogenetic mechanisms between air pollution and posterior segment ocular diseases.

Several studies aimed to evaluate ambient air pollutants’ effect on AMD. There has been a lack of consolidated findings on the exact pathogenetic mechanisms between air pollutants and AMD. Increased levels of PM₁₀, NO₂, and CO were found to be associated with early AMD [21], while PM_2.5 was more related to late AMD and visual impairment [15]. Similarly, the risk of AMD increased with the increased levels of PM_2.5 [22]. A study by Chua et al. confirmed that greater exposure to PM_2.5 was associated with self-reported AMD; furthermore, exposure to higher concentrations of PM_2.5, PM₁₀, and PM_2.5 absorbance were associated with inner and outer retinal layer thinning evaluated by SD-OCT [20], suggesting toxic pollutants’ effect on retinal structures. Ambient PM_2.5 was reported to be positively associated with pro-angiogenesis molecules; thus, it could induce vascular dysfunction and the AMD neovascularization process, possibly leading to a visual impairment [15].

The results of the evaluation of other pollutants’ effects were not consistent enough; nevertheless, possible associations cannot be denied. Increased levels of NO₂ were associated with an increased risk of early AMD [21], active exudative AMD [23], and AMD [19]; however, Chua et al. did not find a significant association [20]. The link between the risk of AMD and increased levels of CO was found in two studies [19,21]. NO₂ is known to be a component of reactive nitrogen species (RNS) that can act together with reactive oxygen species and damage cells, while CO can promote oxidative stress; thus, these pollutants could significantly impact the pathogenesis of AMD [19]. We have observed rising evidence that increased levels of PM_2.5, NO₂, and CO could be validated as risk factors for AMD.

AMD can be caused by interactions between genetic and environmental risk factors. It is known that the retina is one of the most metabolically active tissues, making it more susceptible to oxidative stress. The damage increases with age, thus leading to retinal dysfunction and cell loss [29]. As no exact pathogenetic mechanisms between air pollution and AMD have been established, some authors even described a possible link between air pollution and toxicity to retinal ganglion cells and other parts of the retina as “pollution retinopathy” or “particulate pollution-induced retinopathy” [10]. It was reported that air pollution exposure is associated with increased oxidative stress, inflammation, hypercoagulation, and disruption of the blood–brain barrier [33,34]. Specifically, PM-induced changes in endothelial cells and vascular flow were reported to contribute to systemic inflammatory responses through circulating plasma proteins, decreased vascular tone, changes in endothelial cell dynamics, and blood–brain barrier alterations [35].

These mechanisms are known to be associated with AMD as well as with retinal vascular diseases. Single studies showed that increased exposure to PM_2.5 and PM_2.5–10 can be associated with an increased risk of DR [24,25]; THC and NMHC can increase the risk of RVO [26], while CO, NO₂, and PM₁₀ were associated with increased risk of CRAO [27]. It is reported that air pollutants can be associated with arterial narrowing, retinal microvascular dysfunction, and inflammatory responses altering endothelial dysfunction, leading to retinal vascular diseases [26,27,36,37].

The exact pathogenetic mechanisms of air pollutants’ effect on posterior segment ocular diseases have not been elucidated to date. Nevertheless, it is believed to be linked to an oxidative stress associated with elevated intracellular levels of reactive oxygen species (ROS) [38]. Excessive ROS formation can lead to vascular endothelial dysfunction and inflammation in the retina [38]. Furthermore, ROS can stimulate the production of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), causing inflammation and cell death [38]. Increased levels of ROS have been associated with diabetic retinopathy, glaucoma, and AMD [38].

Laboratory studies by Lee et al. found that PM_2.5 induced the epithelial–mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells, which resulted in a changed phenotype of RPE cells from epithelial to fibroblast-like mesenchymal, and increased cell migration [39]. The pathogenetic pathway was activated by cellular ROS production during PM_2.5-induced EMT which was reported to be implicated in the development of intraocular fibrotic disorders, including AMD, proliferative vitreoretinopathy, and diabetic retinopathy [39].

Although our reviewed studies included large sample sizes, the majority of them are observational. We found only one experimental study and one systematic review and meta-analysis. Different studies used different methodologies, analysis methods, adjustments of confounding variables, and concentrations of air pollutants varied. The epidemiological studies mainly considered the residential address of the participants but did not account for exposure to pollutants at place of employment, where participants may have spent considerable time. The authors of a recent systematic review [9] reported high heterogeneity among the research studies and found a low certainty of their evidence ratings. However, there is an undoubtable association between several air pollutants and posterior segment ocular diseases, including glaucoma, AMD, and retinal vascular diseases, that are significantly associated with vision impairment. There is a need for further longitudinal, comprehensive studies on air pollution’s effects on ocular diseases seeking generalized conclusions and preventative recommendations.

The most common pollutants that were reported to be significantly associated with ocular posterior segment diseases included NO₂, CO, PM_2.5, and PM₁₀. These are generally considered the most dangerous to various health conditions, as well as for the environment and even mortality. We observed that the majority of our reviewed studies were performed in highly urbanized cities. Urbanization is significantly associated with the increase in air pollution, leading to the previously discussed diseases, increased outpatient visits, and healthcare costs.

There are inherent connections between air pollution, climate change, health issues, and increased costs in different spheres. It was reported in the studies that the most vulnerable to climate-related health problems are children, older people, people in lower socioeconomic groups, and future generations [40]. Significant regulatory changes are urgently needed to effectively control ambient and household air pollution, as well as climate change. It was reported that keeping the air temperature rise below 2°C over the next 50 years would prevent about 4.5 million premature deaths, about 3.5 million hospitalizations and emergency room visits, and approximately 300 million lost workdays in the United States [41]. Policies, technologies, specific emission regulations, and cooperative international efforts have been implemented against air pollutants; however, there is evidence that the results are not effective enough.