Editor's Commentary

The curious link between gout and dry eye disease is a fascinating intersection of systemic and ocular health that warrants deeper exploration. Gout, a form of inflammatory arthritis characterized by elevated levels of uric acid in the blood, has long been known for its painful joint manifestations, often perceived as a condition primarily affecting the elderly and those with indulgent lifestyles. However, recent studies have begun to uncover its surprising impact on ocular health, particularly in the form of dry eye disease. Patients with gout are increasingly presenting with dry eye symptoms, suggesting a link between the two conditions.

One of the key mechanisms proposed to explain this link involves the accumulation of monosodium urate (MSU) crystals, which are the hallmark of gout and is explained in our columns this issue. These crystals, typically found in joints, can also deposit in extra-articular tissues, including ocular structures. Moreover, the inflammatory nature of gout itself may play a role in exacerbating dry eye disease. Gout is associated with systemic inflammation, and signaling pathways known to be involved in gout may also contribute to the development of dry eye disease, further linking the two conditions.

Interestingly, lifestyle factors that influence gout may also impact dry eye disease. For instance, dietary choices, alcohol consumption, and the use of visual display terminals are known to affect both conditions. This overlap suggests that managing these lifestyle factors could potentially mitigate the symptoms of both gout and dry eye disease, offering a holistic approach to patient care. As expected, the prevalence of gout varies significantly by age and is found more frequently in those over the age of 60. In the United States, roughly 9.2 million people are affected by gout, with the highest rates observed in older adults and males.1 Globally, the prevalence of gout has been rising, particularly in high-sociodemographic index regions and can be attributed to several factors. Firstly, dietary habits in these regions often include high consumption of purine-rich foods, such as red meat and seafood, which contribute to elevated uric acid levels. Additionally, the prevalence of obesity and metabolic syndrome, both significant risk factors for gout, is higher in these areas. Sedentary lifestyles and increased alcohol consumption further exacerbate the risk. Moreover, access to healthcare and diagnostic facilities in high-sociodemographic index regions leads to better detection and reporting of gout cases.

The rising prevalence of gout and its association with dry eye disease underscore the importance of early detection and treatment. Healthcare providers should consider the possibility of dry eye symptoms in patients with gout and conduct appropriate evaluations. Understanding the link between these two conditions can lead to better management strategies and improved quality of life for affected individuals. This intersection of systemic and ocular health reminds us of the intricate connections within the human body and the importance of a comprehensive approach to patient care.

Reference

1. Berman, J., Yip, K. What is gout? JAMA. 2021;326(24):2541. doi:10.1001/jama.2021.19770

Kelly K. Nichols, OD, MPH, PhD
Editor

Clinician's Corner

Jade Coats, OD, FAAO
McDonald Eye Associates, Bentonville, AR

The Dry Eye Office: A Scientific Approach to Managing Systemic Inflammation and Ocular Surface Disease

Dry eye disease (DED) is not simply an eye problem—it’s a complex condition shaped by a range of ocular and systemic influences. As highlighted in the Tear Film and Ocular Surface Society Dry Eye Workshop II (TFOS DEWS II) report, emerging research is increasingly pointing to systemic inflammation as a key player in the development and progression of DED, which affects tear film instability and can lead to persistent damage to the ocular surface.¹ Understanding the intricate relationship between systemic diseases and their influence on eye health not only deepens our insight into the pathogenesis of DED but also paves the way for more targeted evidence-driven treatment strategies that address the root causes.

Systemic Inflammation and Dry Eye Disease

Chronic systemic inflammatory conditions, including rheumatoid arthritis, lupus, diabetes, thyroid dysfunction, and inflammatory bowel disease, have been associated with an increased prevalence of DED.² Recent research by Chen et al. (2024) highlights gout as another possible systemic contributor, which demonstrates how elevated systemic uric acid and activation of the NLRP3-IL-1β signaling pathway may exacerbate systemic and ocular surface inflammation.³ Systemic inflammatory conditions have the potential to disrupt ocular surface homeostasis, increase pro-inflammatory cytokines, and impair tear film stability.³ Chronic inflammation of the ocular surface and eyelid tissues from these systemic diseases not only destabilizes the tear film but also increases meibomian gland dysfunction (MGD), which contributes to chronic ocular discomfort, photophobia, and blurred vision.^1,5

Inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and matrix metalloproteinases (MMPs) impact the corneal epithelium, leading to punctate keratopathy and changes to corneal nerve sensitivity.² Additionally, systemic oxidative stress damages the lacrimal and meibomian glands, which further exacerbates evaporative and aqueous-deficient dry eye.² Effectively managing DED necessitates addressing the underlying systemic inflammation to mitigate ocular surface damage and improve patient outcomes. 

Comprehensive Diagnostic and Treatment Strategies

A thorough DED diagnostic approach should include a tear film assessment, ocular surface staining meibography, and inflammatory biomarkers such as MMP-9 (when available) to assess disease severity. In addition, a complete review of systemic health and medications is an important consideration when assessing ocular surface inflammation related to systemic inflammation. Identifying underlying systemic contributors enables optometrists to provide more personalized treatment strategies.

Management of DED in the presence of systemic inflammation involves a multimodal approach:

• Ocular surface treatment: Topical anti-inflammatory agents such as cyclosporine A and lifitegrast play a key role in reducing chronic inflammation and improving tear film stability. Short-term use of corticosteroids may be necessary to rapidly suppress acute inflammation before transitioning to long-term therapies. Additionally, semifluorinated alkanes can be added to further support the tear film, which reduces friction at the ocular surface and helps to decrease ocular surface inflammation. Punctal occlusion can also be considered in some cases to retain tears and enhance treatment outcomes, followed by autologous serum tears and scleral lenses to help preserve the ocular surface and alleviate discomfort once active inflammation has been addressed. 
• Systemic anti-inflammatory interventions: Addressing systemic inflammation through dietary modifications, such as incorporating curcuminoids (a derivative of turmeric) and omega-3 fatty acids, has shown promise in reducing inflammatory mediators and improving tear quality.⁵ Pharmacologic interventions, including biologic agents and systemic corticosteroids prescribed for autoimmune conditions, may also provide indirect relief of ocular symptoms by mitigating systemic inflammatory activity.
• Lifestyle adjustments: Optimizing systemic health through hydration, regulating sleep, and minimizing inflammatory triggers—such as excessive alcohol consumption and high-glycemic diets—can support both systemic and ocular homeostasis and reduce the burden of DED.^1,5 Gout patients may have already undertaken dietary modifications such as reducing or eliminating foods high in purines (eg, organ meats and some seafood), which break down into uric acid. There is a suggestion that omega fatty acid consumption may also be beneficial in patients with gout.  

Collaborative Care for Optimal Outcomes

Given the widespread impact of systemic inflammation on various ocular diseases, a team-based approach is critical for achieving the best outcomes. Co-managing DED with rheumatologists, endocrinologists, and primary care physicians ensures comprehensive care and can control systemic inflammation while addressing ocular symptoms. Strong communication between providers fosters early detection of ocular complications related to systemic conditions, ultimately enhancing patient outcomes. It’s also important to educate patients that flare-ups of their systemic conditions may trigger changes in their ocular symptoms, which enables proactive management and improved quality of life.

Future Directions and Clinical Implications

Emerging research continues to elucidate the intricate relationship between systemic inflammation and DED. The development of novel systemic and topical anti-inflammatory therapies holds promise for improving patient outcomes. As optometrists, integrating these scientific advancements into clinical practice is crucial in delivering comprehensive care for patients suffering from DED and systemic inflammatory conditions.

References

1. Bron AJ, de Paiva CS, Chauhan SK, et al. TFOS DEWS II pathophysiology report. Ocul Surf. 2017 Jul;15(3):438-510. doi:10.1016/j.jtos.2017.05.011
2. Pflugfelder SC, de Paiva CS. The pathophysiology of dry eye disease: what we know and future directions for research. Ophthalmology. 2017;124(11S):S4-S13. doi:10.1016/j.ophtha.2017.07.010
3. Chen T, Chen J, Zhao C, Li X. Correlation between gout and dry eye disease. Int Ophthalmol. 2024 Feb 20;44(1):102. doi:10.1007/s10792-024-02965-6
4. Chen T, Chen J, Zhao C, Li X. Correction: Correlation between gout and dry eye disease. Int Ophthalmol. 2024 Sep 18;44(1):380. doi:10.1007/s10792-024-03156-z
5. Pellegrini M, Senni C, Bernabei F, et al. The role of nutrition and nutritional supplements in ocular surface diseases. Nutrients. 2020;12(4):952. Published 2020 Mar 30. doi:10.3390/nu12040952

Research Update: 
Commentary on Abstract of the Week

Blair Lonsberry, MS, OD, MEd, FAAO
Diplomate, American Board of Optometry

Gout is a form of inflammatory arthritis caused by the accumulation of uric acid crystals in the joints. These crystals trigger an immune response, leading to significant joint pain, swelling, and redness. The main risk factors for gout include hyperuricemia, genetics, medications (eg, blood pressure medications, aspirin, niacin), dietary factors (eg, red meat, seafood, alcohol, sugary drinks), with hyperuricemia being the most important risk factor for the development of gout.¹ Interestingly, gout can occur in someone without risk factors and may have a hereditary component. Patients typically experience sudden intense joint pain, often at night, which is described as throbbing, crushing, or excruciating. The affected joint becomes swollen, red, and warm to the touch with pain on movement or touch. Other symptoms include tophi (hard, white lumps of uric acid crystals that accumulate under the skin), joint deformity, and general feelings of fatigue that can wax and wane. 

Ocular manifestations of gout include tophaceous deposits in different locations of the eye including the eyelids, conjunctiva, cornea, iris, sclera, and orbit. Other ocular abnormalities include dry eye syndrome, red eye, uveitis, intraocular hypertension, glaucoma, and cataracts.² The link between dry eye disease (DED) and gout has not been clearly defined in particular with respect to whether the two conditions simply co-exist, whether there are common risk factors, or if DED is a complication of gout perhaps due to systemic inflammation. 

The purpose of this article was to perform a thorough literature search in the PubMed database, summarize the most recent information on the correlation between gout and DED, and explore the potential relationship between the pathogenesis of the two. The search terms used included dry eye disease, dry eye, gout, and gouty arthritis, with the search years between 1964 and 2023. In two of the landmark eye studies (Blue Mountain Eye Study [2003] and Beaver Dam Eye Study [2000]), authors reported that there was an association between patients having a history of gout and DED. In a study published in 2017, authors compared patients with and without gout, and those with gout had a significantly higher association with DED. The number of studies correlating gout and DED is limited, and there is bias toward patients with gout having an increased association with DED. Most of the studies were observational, so it was not possible to determine if there is a causative link. Research into the inflammatory mechanism and oxidative stress were found to be similar between gout and DED. Other factors that were found to potentially prevent gout and DED included reducing video display terminal use, limiting alcohol consumption, and moderating caffeine intake. 

The authors concluded that early detection and treatment of dry eye in gout patients are crucial, and ophthalmic assessment can be used to improve early recognition and management of dry eye in gout patients. Regular eye examinations are recommended for long-term gout patients with a view to early detection of DED and prompt treatment. As with other systemic inflammatory diseases, DED treatment options should target inflammation. In recalcitrant DED cases, a more thorough systemic health review may be needed because a patient may not make the connection between DED and gout.

References

1. Fenando A, Rednam M, Gujarathi R, et al. Gout. [Updated 2024 Feb 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK546606/
2. Sharon Y, Schlesinger N. Beyond joints: A review of ocular abnormalities in gout and hyperuricemia. Curr Rheumatol Rep. 2016 Jun;18(6):37. doi:10.1007/s11926-016-0586-8. PMID:27138165

Abstract

Correlation between gout and dry eye disease

Chen T, Chen J, Zhao C, Li X. Correlation between gout and dry eye disease. Int Ophthalmol. 2024 Feb 20;44(1):102. doi:10.1007/s10792-024-02965-6

BACKGROUND: Gout is a common form of inflammatory arthritis that can cause a number of serious complications. Complications are common in patients with gout and complicate their management and disease outcome. The recent literature has reported that an increasing number of gout patients are presenting with dry eye symptoms. However, until now, the link between gout and dry eye disease has not been clearly defined. (It is unclear whether the two conditions simply co-exist, whether there are common risk factors, or whether dry eye disease is a complication of gout.) 

METHODS: A thorough literature search was conducted in the PubMed database to summarize the most recent information on the correlation between gout and dry eye disease and to explore the potential relationship between the pathogenesis of the two. (Objective: Therefore, in this paper, we review the recent literature on the correlation between gout and dry eye disease and explore the potential association between the pathogenesis of both.) 

RESULTS: Studies in the last five years have shown a correlation between gout and dry eye, i.e., gout is associated with an increased risk of dry eye. The NLRP3-IL-1β signaling pathway may be a potential mechanism for the combination of gout and dry eye disease; factors such as high blood uric acid and xanthine oxidase activation in gout patients may aggravate the development of dry eye disease; reducing the use of visual display terminals; reducing or abstaining from alcohol consumption; and moderate coffee intake may effectively prevent gout and dry eye disease.

CONCLUSIONS: It is an undisputed fact that many gout patients present with dry eye manifestations that seriously affect the quality of life of gout patients, and early detection and treatment of dry eye in gout patients are crucial.

Technology

Jillian F. Ziemanski, OD, PhD, FAAO
Owner of InSight Eye Care, Oshkosh, WI

As a young optometry student, I recall being confused about gout—what it was, how it caused joint pain, etc. This confusion drove me into a “series of clicks”—a virtual rabbit hole some might say—to better understand the mechanisms underlying gout and the relationship of this disease to the eye. Although eventually I thought that I had figured it out, with time, science always yields more discoveries. Every handful of years or so, I have had to go down yet another rabbit hole to brush up on the latest information. Along the way, I have learned that one of the key players is the NLRP3–IL-1β signaling pathway.

First, it is important to understand that gout is triggered by the deposition of monosodium urate (MSU) crystals in the joints. These crystals elicit an immunological reaction, marked by an attempt to phagocytize the crystals by macrophages and monocytes followed by a subsequent inflammatory cascade. Central to this cascade is the NLRP3 inflammasome, a multiprotein complex that detects cellular stress and initiates immune activation. Once engaged, NLRP3 activates caspase-1, an enzyme that cleaves pro-IL-1β into its active form, IL-1β. This potent cytokine drives neutrophil recruitment, synovial inflammation, and the intense pain that is characteristic of gout flares.

The priming of the NLRP3 inflammasome often requires upstream signals, such as toll-like receptor (TLR) activation and NF-κB signaling, which upregulate NLRP3 and pro-IL-1β expression. The body is often priming the system for an inflammatory response, even before the flare occurs. This concept parallels many inflammatory cascades contributing to ocular surface disease.

Clinically, this pathway can serve as a therapeutic target, especially in recalcitrant gout cases. While serum urate–lowering therapies remain instrumental in preventing crystal formation and deposition, IL-1β inhibitors—such as anakinra, canakinumab, and rilonacept—provide targeted intervention. Of note, emerging NLRP3 inhibitors may soon offer even more precise control of gout-related inflammation.

In the same way that we tailor dry eye treatment based on the underlying cause—rather than only providing tear supplements to a poorly lubricated eye—effective gout management requires more than just lowering uric acid. By targeting the different elements of the NLRP3–IL-1β pathway, optometrists can provide better long-term outcomes for patients dealing with this painful recurrent disease.

This editorial content was supported via unrestricted sponsorship