The present study examining associations between bariatric surgery and common ocular pathology across a large national database, suggests bariatric surgery and associated systemic improvements may serve a protective role in development of ocular morbidity and mortality. Patients whose morbid obesity was managed surgery were significantly less likely to experience diabetic retinopathy, vitreous hemorrhage, intravitreal injection, vitrectomy, ocular hypertension, glaucoma, glaucomatous surgeries, use of ocular pressure lowering medications, age-related macular degeneration, cataract formation, cataract surgery, low vision, and blindness compared to patients who were not treated surgically.

This study largely supports and adds clarity to what has been reported in the literature regarding patients undergoing bariatric surgery and ocular pathology. With respect to diabetic retinopathy, this study supports findings of Akerblom et al. who found bariatric surgery to reduce future development of diabetic retinopathy in 5321 Swedish patients with diabetes. However, Akerblom et al also reported no difference in diabetic retinopathy complications such as development of proliferative DR, need for PRP, or IVI, which the present study finds to be reduced, possibly due to larger sample sizes leading to an appropriately powered analysis [15]. The present study also examines additional complications of DR not examined by Akerblom et al. such as development VH, finding reduced frequency in those whose obesity was managed surgically. The present data runs contrary to analyses of the STAMPEDE trial, which found no difference in DR incidence comparing patients who underwent bariatric surgery to intensive medical management. While these differences may be due to larger sample size in the present study, it is also plausible these differences are due to variations in the comparator group. In the STAMPEDE trial, patients undergoing surgery were compared to those undergoing intensive medical management of systemic disease while the present study compared outcomes to real world morbidly obese patients who were not managed surgically. Therefore, it is plausible the control cohort in the present study may have reduced access to care, decreased long term follow up, were poor candidates for surgery, or other differences unable to be controlled for in the study design. However, if this were the driving factor, it would be expected for this population to have reduced ophthalmic visits and diagnoses relative to the surgical cohort, potentially diminishing true effect of the surgical intervention. The diabetic cohorts as a whole suggest that treatment with bariatric surgery may be associated with reduced future development of diabetic retinopathy in morbidly obese patients along with sight-threatening complications of DR such as development of VH, TRD, DME, and need for treatment with IVI, and PRP.

The present study is also one of the first to examine bariatric surgery and associations with development of glaucomatous disease. To date, a retrospective study of 22 bariatric surgery patients by Shimonov et al. showed that BMI reduction was associated with significant and continued decline in IOP beyond 1 year after surgery. Specifically it was found that average BMI decreased from 41.9  ±  7.3 to 25.5  ±  5.7 kg/m2 at 1-year follow-up from bariatric surgery, which corresponded to a mean IOP decrease of 21% [16]. Additionally, small clinical cohorts examined by Burgansky-Eliash et al. have also shown bariatric surgery to reduce intraocular pressure [10]. Mechanistically, obesity associated orbital adipose tissue may elevate episcleral venous pressure, decreasing aqueous humor outflow resulting in IOP elevation [17]. Strong associations also exist between glaucoma and OSA, as carrying a diagnosis of OSA significantly increases the likelihood of being diagnosed with glaucoma [18]. These associations are thought to be a result of increased hypoxia in OSA, leading to optic nerve hypoxic damage and glaucomatous phenotype. Supporting these associations, patients who elected surgery were found to have lower incidences of being diagnosed with glaucomatous diseases such as ocular hypertension, glaucoma suspect, glaucoma, primary open angle glaucoma, and glaucomatous optic atrophy. Interestingly patients who underwent bariatric surgery were found to have significantly decreased incidence of OSA, in line with the above proposed mechanistic links between the two. In terms of clinical outcomes, surgically managed patients were less likely to use pressure lowering drops or undergo glaucoma surgeries in the future, highlighting relevant metrics for future analyses of clinical trials. The present study did not investigate secondary glaucoma mechanisms, such as neovascular glaucoma, which may also be affected by the many metabolic syndromes seen in morbidly obese patients.

While obesity has been identified as a risk factor for likelihood of being diagnosed with AMD, bariatric surgery has not been explored with respect to future development of disease. Although literature that explores the effect of bariatric surgery on ocular anatomy exists, there is a paucity of literature that explores AMD and bariatric surgery specifically. A prospective controlled study by Ozcelik-Kose et al. showed that total choroidal area and the choroidal vascularity index (CVI) exhibited significant increases when comparing the values 6 months before surgery and 6 months after surgery [19]. Similarly, in a prospective study of 40 patients, ElShazly et al. found significant increases in macular thickness and macular vascular density of the deep capillary plexus when compared 3 months before and 3 months after bariatric surgery [20]. Taken together these early studies may suggest systemic effects of bariatric surgery may include improvement in retinal microvascular circulation. Supporting these early associations, patients who underwent bariatric surgery were significantly less likely to develop nonexudative and exudative AMD. To more thoroughly examine these associations and impact on clinical treatment course, larger cohorts of surgical patients with long term follow up would be necessary.

Our study supports findings of Burkard et al., showing bariatric surgery to be associated with decreased risk of cataract diagnoses. However, the present study further adds novelty with the utilization of a large cohort of US patients, while also examining type of cataract developed and future need for cataract surgery [14]. Obesity has been identified as a significant risk factor for cataract formation, thought to be mediated through increases in reactive oxygen species and high circulating leptin in these patients, clouding the lens over time [21]. Diabetes is also a significant risk factor for cataract development, especially in those under 65 years of age, thought to be a result of increased osmotic and oxidative stress [22]. Because our cohorts are similar with respect to age and BMI at baseline, it is reasonable to assume that weight loss and systemic effects from bariatric surgery such as improved glycaemic control may have reduced likelihood of cataract development in our cohorts [4]. Furthermore, our findings show a reduction in incidence of all types of cataract including nuclear sclerotic, cortical, posterior subcapsular, and diabetic which have all been associated with obesity or diabetes [5, 22].

Supporting reductions seen in various ocular pathologies, patients in the bariatric cohort were found to be at significantly decreased risk of experiencing low vision or blindness post operatively. This finding largely aligns with data reported in the present study, as patients with bariatric surgery were less likely to develop DR, glaucomatous pathology, and AMD, all of which in isolation may contribute to low vision or blindness. While low vision and blindness is multifactorial in etiology and not all causes are investigated in the present study design, this finding is imperative to highlight that bariatric surgery not only results in reduced disease burden, but also reduces in visual decline in the process.

The findings of the present study, that morbidly obese patients who undergo bariatric surgery experience decreases in ocular morbidity and mortality, may be largely explained by improvements in systemic health as a result of the surgical intervention. Bariatric surgery has been shown long term to reduce BMI, improve glycaemic control, and reduce cardiovascular disease risk factors. Since DR is a microvascular complication of poor systemic diabetic health, it is reasonable to assume that the reduction in DR incidence may be explained by overall glycaemic improvement in this cohort. Reductions in incidence of glaucoma may be attributed to decreases in IOP or OSA over time in hand resulting in less disease development. Although the mechanistic link between obesity and AMD remains less clear, it is plausible to assume reductions in obesity, a studied risk factor for patients with AMD, is contributing to decreases in disease incidence observed. Future long term high powered clinical studies examining bariatric surgery and development of ocular pathology may add credence to the associations presented.

Strengths of the present study lie in the utilization of a national database to investigate bariatric surgery and its effect on the development of DR, glaucoma, AMD, and low vision and blindness in the future. To date, this is the largest longitudinal cohort to date examining these associations, allowing for analysis of a variety of pertinent ocular outcomes with respect to the above disease states. However, the present study is not without its limitations. Length of follow up is unable to be ascertained from the present data set, making it difficult to associate decreases in disease state seen with set chronologic time points. Even after utilization of propensity score matching, small baseline differences still existed in the two populations. However, these small differences may have been significant due to the large cohort sizes used, overpowering the measure of association. Because the data obtained through TriNetX is presented in aggregated form, it is difficult to assess patient-level data such as individual visual acuity, disease progression, and treatment course. While the present study reports univariate analysis as allowed by the TrinetX platform, subsequent analyses with incorporation of multivariate analysis would be of interest to further explore these associations. Additionally, it is also possible that patients receiving surgery may have been of higher socioeconomic status than those who did not pursue surgery. Unfortunately, this level of patient data was unable to be extracted as only ICD10 associated data was pulled. Finally, as TriNetX relies on ICD-10 and procedural codes to categorize variables, the conclusions drawn from such data is contingent on proper physician coding, leaving room for bias if disease states are coded inconsistently across health care organizations.

This study provides novel insight examining bariatric surgery and ocular pathology across a large national cohort in the US, uncovering a protective association between the surgery and ocular disease. The associations herein suggest a need for further investigation of bariatric surgery and obesity reduction on development of ocular morbidity and mortality in large long term clinical settings.