Ocular Manifestations of Metabolic Syndrome: A Systemic Vascular Phenotype

ABSTRACT

Context

Metabolic syndrome (MetS) is defined by central obesity, insulin resistance, hypertension and dyslipidemia. MetS affects over one‐third of US adults. Beyond its cardiovascular burden, MetS has clinically relevant associations with ocular health and may contribute to a systemic vascular and neuro‐metabolic phenotype involving the retina, optic nerve, lens, ocular surface and choroid.

Evidence Acquisition

This narrative review searched PubMed through May 2026 using combinations of free‐text and MeSH‐based terms related to ‘metabolic syndrome’, ‘insulin resistance’, ‘obesity’, ‘hypertension’, ‘dyslipidemia’, ‘diabetes’, ‘diabetic retinopathy’, ‘diabetic macular edema’, ‘glaucoma’, ‘cataract’, ‘dry eye’, ‘macular degeneration’, ‘retinal vascular occlusion’ and ‘optic neuropathy’. Reference lists of relevant reviews and primary studies were also screened. English‐language human, translational, epidemiologic, clinical‐trial, systematic‐review and meta‐analysis articles were prioritized. This was not designed as a systematic review, and formal PRISMA screening, risk‐of‐bias grading and meta‐analysis were not performed.

Evidence Synthesis

MetS and its components are associated with diabetic retinopathy, diabetic macular edema (DME), non‐diabetic retinopathy, primary open‐angle glaucoma, cataract, dry eye disease, age‐related macular degeneration (AMD), retinal vascular occlusions and non‐arteritic anterior ischemic optic neuropathy (NAION). Shared mechanisms include chronic inflammation, oxidative stress, endothelial dysfunction, insulin resistance‐driven retinal neurodegeneration, dyslipidemia‐related lipotoxicity, hypertension‐related microvascular injury and microvascular rarefaction. Management requires both systemic risk‐factor optimization and disease‐specific ophthalmic therapy, including anti‐VEGF therapy, intraocular pressure reduction, laser or surgical procedures when indicated, ocular surface‐directed therapy and cataract surgery when visually significant.

Conclusions

Ocular complications associated with MetS are common and may be vision‐threatening. Risk‐based ocular surveillance and metabolic optimization are justified, particularly in patients with diabetes, hypertension, dyslipidemia, visual symptoms or established vascular disease. However, the strength of disease‐specific evidence varies: interventional evidence is strongest for diabetic retinopathy risk reduction and glaucoma treatment through intraocular pressure lowering, whereas evidence for AMD, NAION, RVO, cataract and dry eye disease is more frequently observational or indirect.

1. Introduction

Metabolic syndrome (MetS) is defined by the co‐occurrence of at least three of five criteria: abdominal obesity (waist circumference > 102 cm in men, > 88 cm in women), hypertriglyceridemia (> = 150 mg/dL), low HDL cholesterol (< 40 mg/dL in men, < 50 mg/dL in women), elevated fasting plasma glucose (> = 100 mg/dL) and hypertension (> = 130/85 mmHg) [1, 2]. These criteria were established by the NCEP‐ATP III and later refined by the harmonized international definition [2].

MetS affects over one‐third of US adults. Its prevalence rose from 32.5% in 2011–2012 to 36.9% in 2015–2016. Nearly 60% of Hispanic adults over 60 years are affected [3]. Globally, the Eastern Mediterranean region reports the highest prevalence at 36.6% [4]. MetS is increasingly common among children and adolescents [5].

The cardiovascular complications of MetS are well established. However, its ocular effects are less recognized. MetS and its individual components have been associated with retinopathy, glaucoma, cataract, dry eye disease, AMD, retinal vascular occlusions and ischemic optic neuropathy [6, 7]. These conditions share common mechanisms: inflammation, oxidative stress, microvascular injury and neurodegeneration [3, 6, 7, 8].

The eye is metabolically active and highly vascularized. It is uniquely vulnerable to systemic metabolic disturbances. Ocular complications may precede overt diabetes or cardiovascular events, making the eye a potential early indicator of systemic MetS‐related disease [6, 7].

This review examines the evidence linking MetS to ocular disease, describes the underlying mechanisms and outlines evidence‐based management strategies. The goal is to support a collaborative approach between endocrinologists and ophthalmologists while distinguishing established interventional evidence from associative observational data.

2. Evidence Acquisition

This article is a narrative review rather than a systematic review or scoping review. PubMed was searched for articles published through May 2026. Search concepts included metabolic syndrome and individual MetS components combined with ocular outcomes. Representative terms included: ‘metabolic syndrome’, ‘insulin resistance’, ‘obesity’, ‘central obesity’, ‘hypertension’, ‘dyslipidemia’, ‘diabetes mellitus’, ‘retinopathy’, ‘diabetic retinopathy’, ‘diabetic macular edema’, ‘glaucoma’, ‘primary open‐angle glaucoma’, ‘ocular hypertension’, ‘cataract’, ‘dry eye’, ‘meibomian gland dysfunction’, ‘age‐related macular degeneration’, ‘retinal vein occlusion’, ‘retinal artery occlusion’, ‘optic neuropathy’ and ‘non‐arteritic anterior ischemic optic neuropathy’. Where applicable, MeSH headings and free‐text synonyms were combined using Boolean operators.

Eligible literature included human epidemiologic studies, randomized clinical trials, systematic reviews, meta‐analyses, mechanistic studies, translational studies and clinically relevant reviews addressing associations, mechanisms, screening or treatment of MetS‐related ocular disease. Priority was given to recent evidence, large population‐based studies, meta‐analyses and practice‐relevant ophthalmic management literature. Exclusion criteria included non‐English‐language articles, studies not addressing MetS or its major components, articles without clinically relevant ocular outcomes and publications with insufficient methodological detail. Reference lists of relevant articles were searched manually to identify additional sources.

Because this narrative review was intended to synthesize clinically relevant evidence across several ocular disease domains, formal systematic screening, duplicate independent review, PRISMA flow reporting, risk‐of‐bias scoring and quantitative meta‐analysis were not performed. This limitation is considered when interpreting the strength of conclusions.

3. Pathophysiological Mechanisms

3.1. Chronic Inflammation

MetS is associated with chronic low‐grade inflammation. Visceral adipose tissue secretes pro‐inflammatory cytokines including IL‐6, TNF‐alpha and CRP, along with adipokines such as leptin, resistin and chemerin [3]. These mediators activate endothelial cells. They upregulate ICAM‐1 and VCAM‐1, reduce nitric oxide bioavailability and impair microvascular perfusion across ocular tissues [3].

In the retina, Muller cells and microglia amplify local inflammation. This promotes retinal ganglion cell degeneration and photoreceptor loss. On the ocular surface, inflammatory cytokines disrupt goblet cell function and destabilize the tear film, contributing to dry eye disease [9].

3.2. Oxidative Stress and Mitochondrial Dysfunction

Excess reactive oxygen species (ROS) and reactive nitrogen species (RNS) drive tissue injury in MetS. Under hyperglycemic and hyperlipidemic conditions, mitochondrial dysfunction activates four classical damage pathways: polyol pathway flux, protein kinase C (PKC) activation, advanced glycation end‐product (AGE) formation and hexosamine pathway activity [10].

In the retina, ROS cause pericyte loss, acellular capillary formation and Muller cell apoptosis. Due to their high metabolic demands, photoreceptors are particularly vulnerable. In the retinal pigment epithelium (RPE), lipofuscin accumulates under oxidative stress. This accelerates AMD progression [3, 11].

3.3. Insulin Resistance and Retinal Insulin Signalling

Insulin receptors are expressed throughout the retina, including in photoreceptors, Muller cells and retinal ganglion cells. Insulin resistance (IR) attenuates the PI3K/Akt survival pathway. MAPK signalling, which drives angiogenesis and inflammation, may be relatively preserved [8].

IR impairs retinal blood‐flow autoregulation, increases VEGF expression and disrupts the blood‐retinal barrier. These effects may increase susceptibility to diabetic retinopathy, AMD, and glaucomatous neurodegeneration [8, 11]. Direct retinal neuroprotection from improving insulin sensitivity remains biologically plausible but incompletely proven in clinical ocular‐outcome trials.

3.4. Endothelial Dysfunction and Microvascular Disease

MetS reduces nitric oxide synthase activity and increases endothelin‐1 production. Platelet hyperreactivity further promotes a pro‐thrombotic state. These changes cause microvascular injury including microaneurysms, haemorrhages and cotton wool spots and impair optic nerve head perfusion [6, 11].

Retinal arteriolar narrowing correlates with the number of MetS components. Hypertension and abdominal obesity are the main drivers [3]. Arteriolar narrowing is a recognized biomarker of systemic microvascular disease.

3.5. Dyslipidemia and Lipotoxicity

Elevated triglycerides and low HDL are central features of MetS dyslipidemia. Lipid deposition in retinal vessels causes hard exudates. Oxidized LDL damages endothelial cells. Complement pathway activation in the subretinal space promotes drusen formation and AMD progression [12, 13].

Hypertriglyceridemia alters meibum lipid composition. This increases evaporative tear loss and worsens dry eye symptoms. It also increases blood viscosity, contributing to NAION through small vessel occlusion [14, 15]. Fenofibrate, through lipid‐modulating and anti‐inflammatory effects, has shown retinal protective properties in large trials and recent systematic review evidence [16, 17].

4. Diabetic Retinopathy and Diabetic Macular Edema

Diabetic retinopathy (DR) is the most common and clinically significant ocular complication in MetS. Globally, DR affects approximately 34.6% of people with diabetes. Vision‐threatening forms, including proliferative DR and DME, occur in 10.2% and 6.8%, respectively [18]. MetS components increase DR risk beyond that attributable to hyperglycemia alone [7].

4.1. Pathophysiology

Chronic hyperglycemia causes pericyte apoptosis, breakdown of the inner blood‐retinal barrier, basement membrane thickening and VEGF‐driven neovascularization [19]. The Brownlee unifying hypothesis attributes diabetic microvascular injury to mitochondrial superoxide overproduction, which activates all four classical damage pathways [10].

MetS amplifies these pathways through multiple converging axes: hypertension increases retinal perfusion pressure and endothelial injury; dyslipidemia promotes hard exudates and inflammatory lipid deposition; insulin resistance reduces neurotrophic support and systemic inflammation enhances leukostasis and vascular permeability [7, 20]. Non‐diabetic retinopathy, including microaneurysms in normoglycemic patients with MetS, supports a contribution from non‐glycemic MetS components, although much of this evidence remains observational [7].

4.2. Classification and Ophthalmologic Findings

The international clinical DR severity scale classifies DR into five stages: no apparent DR, mild NPDR, moderate NPDR, severe NPDR and proliferative DR (PDR) [21]. DME is classified separately as center‐involving or non‐center‐involving based on OCT findings. Ophthalmic findings may include microaneurysms, dot‐blot haemorrhages, hard exudates, cotton wool spots, venous beading, intraretinal microvascular abnormalities, neovascularization and OCT evidence of macular edema.

4.3. Management

Management should distinguish prevention of DR onset/progression from treatment of vision‐threatening ocular disease. Glycemic and blood‐pressure control have the strongest interventional evidence for reducing DR incidence and progression. The Wisconsin Epidemiologic Study of Diabetic Retinopathy and subsequent trial evidence support intensive glycemic control, while lipid management may reduce hard exudates and DR progression in selected patients [16, 17, 22].

For center‐involving DME with visual impairment, intravitreal anti‐VEGF therapy with bevacizumab, ranibizumab, aflibercept, or faricimab is standard of care [23, 24]. Recent network meta‐analysis evidence supports anti‐VEGF‐based approaches for vision‐threatening DR, while recognizing that comparative benefits may vary by baseline vision, anatomic features and treatment burden [24, 25, 26]. Focal/grid laser may be considered for selected non‐center‐involving DME or adjunctive treatment; panretinal photocoagulation remains important for PDR, and vitrectomy is indicated for complications such as non‐clearing vitreous haemorrhage or tractional retinal detachment. Mechanistically, DR/DME represents the clearest ocular example of systemic MetS‐related microvascular injury translating into disease‐specific interventional evidence.

5. Glaucoma

Primary open‐angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide. It affects approximately 76 million people, with projections of 111.8 million by 2040 [27]. MetS is associated with glaucoma through elevated intraocular pressure (IOP), vascular dysregulation and optic nerve neurodegeneration. Evaluation should include tonometry, gonioscopy, pachymetry, optic nerve examination, OCT retinal nerve fibre layer/ganglion cell analysis and standard automated perimetry [28].

5.1. MetS and Intraocular Pressure

IR impairs trabecular meshwork outflow. Visceral obesity raises episcleral venous pressure. Dyslipidemia alters aqueous humour lipid composition. These mechanisms elevate IOP in MetS patients [29].

A retrospective population‐based study from the Rochester Epidemiology Project found a significant association between MetS and ocular hypertension. Central corneal thickness (CCT) was an important confounding variable. MetS patients with thicker corneas may have artificially elevated IOP readings, requiring corrected tonometry [29].

5.2. Vascular and Neurodegenerative Mechanisms

Beyond IOP, MetS may impair optic nerve head perfusion and increase retinal ganglion cell susceptibility through mitochondrial dysfunction, oxidative stress, endothelial dysfunction and altered amino‐acid metabolism [30]. Metabolomic studies have identified enrichment of arginine and proline metabolism pathways in aqueous humour and plasma of POAG patients, alongside amino‐acid changes linked to oxidative stress [30]. These findings support a neurovascular framework, but they do not establish metabolic optimization as a proven glaucoma treatment.

Type 2 diabetes independently increases POAG risk by approximately 40%. In the Nurses' Health Study, diabetes was associated with a hazard ratio of 1.82 for POAG [31].

5.3. Management

IOP reduction remains the only proven disease‐modifying treatment for POAG. First‐line therapy includes prostaglandin analogs, beta‐blockers, alpha‐agonists and carbonic anhydrase inhibitors. Laser trabeculoplasty and filtration surgery are used for refractory cases [32]. Blood pressure control, glycemic optimization and dyslipidemia management may support vascular risk reduction, but they should not be substitutes for evidence‐based IOP‐lowering therapy. Clinically, MetS should prompt careful glaucoma risk assessment and longitudinal monitoring.

6. Cataract

Cataract is the leading cause of reversible blindness worldwide [33]. MetS increases the risk of nuclear, cortical and posterior subcapsular (PSC) cataract through multiple mechanisms.

6.1. Pathophysiology

Hyperglycemia activates aldose reductase. Sorbitol accumulates in the lens, increasing osmotic stress. Crystallin proteins undergo glycation and lose their solubility, causing opacity [34].

Oxidative damage to lens epithelial cells from reduced glutathione and mitochondrial dysfunction accelerates nuclear and PSC cataract formation [34]. Hypertension may impair microvascular supply to the lens region, and dyslipidemia‐related lipid peroxidation may add further injury. A meta‐analysis confirmed a statistically significant association between MetS and cataract risk, with hyperglycemia and central obesity among the strongest contributors [35]. These data support association and biologic plausibility, but cataract prevention through MetS treatment remains less directly proven than DR prevention.

6.2. Management

Phacoemulsification with intraocular lens implantation is the definitive treatment for visually significant cataract. Perioperative glycemic and blood‐pressure optimization may reduce surgical risk and improve systemic safety. Nutritional strategies such as lutein, zeaxanthin, or omega‐3 supplementation act as general health or adjunctive preventive measures rather than established cataract treatment. The practical implication is that patients with MetS, particularly those with diabetes, should receive timely cataract evaluation when visual symptoms affect function.

7. Dry Eye Disease

Dry eye disease (DED) affects approximately 35% of the general population. MetS is an independent risk factor for DED through systemic and local mechanisms [15].

7.1. Pathophysiology

MetS may contribute to both aqueous‐deficient and evaporative DED through lacrimal gland inflammation, autonomic dysfunction, goblet cell loss, corneal nerve changes and meibomian gland lipid alteration [36, 37]. Pro‐inflammatory cytokines such as IL‐1beta and TNF‐alpha impair lacrimal gland function, cause conjunctival goblet cell loss and promote squamous metaplasia. Oxidative stress markers including malondialdehyde and xanthine oxidase are elevated in DED patients [3].

Hyperglycemia disrupts circadian gene expression and immune cell recruitment in the lacrimal gland. In a leptin receptor‐deficient diabetic mouse model, insulin treatment improved glycemia but failed to restore lacrimal gland function [9]. Hypertriglyceridemia alters meibum lipid composition, increasing evaporative tear loss [3, 15]. Thus, DED in MetS is not simply a nonspecific inflammatory manifestation but may involve disease‐specific meibomian gland lipotoxicity and neuro‐lacrimal dysfunction.

7.2. Clinical Features

In a prospective case–control study, MetS patients had significantly lower Schirmer I values (14.8 +/− 9.4 mm vs. 20.4 +/− 9.4 mm; p = 0.007) and nearly double the rate of lacrimal hypofunction compared with controls [15]. Women with MetS showed particularly high tear osmolarity (> 308 mOsm/L). Tear film break‐up time (TBUT) and OSDI scores were also worse in MetS patients [3].

7.3. Management

Management should be phenotype‐directed. Systemic treatment of MetS, including weight loss, glycemic control and lipid management, may reduce inflammatory burden but should be considered supportive rather than proven stand‐alone DED therapy [15, 37]. Topical treatments include preservative‐free artificial tears, topical cyclosporine, lifitegrast, short courses of topical anti‐inflammatory therapy when indicated and lid hygiene. Intense pulsed light therapy and meibomian gland expression may be considered for evaporative DED or meibomian gland dysfunction. Omega‐3 supplementation should be described cautiously because trial evidence is heterogeneous; it may be reasonable in selected patients but should not be generalized as uniformly effective.

8. Age‐Related Macular Degeneration (AMD)

AMD is the leading cause of irreversible visual impairment in adults over 55 years in developed countries. It affects approximately 196 million people globally, with projections of 288 million by 2040 [12]. MetS components of hypertension, dyslipidemia and insulin resistance contribute to AMD through overlapping metabolic and vascular pathways.

8.1. MetS and AMD Risk

A retrospective cohort study of 319 638 UK Biobank participants showed a dose‐dependent increase in AMD risk across cardiovascular‐kidney‐metabolic (CKM) syndrome stages. Hazard ratios were 1.15, 1.25, 1.22 and 1.48 for Stages 1–4, respectively, compared with stage 0. This was independent of genetic predisposition [13]. Individuals with both high CKM stage and high genetic AMD risk had the highest incidence (HR 2.67) [13]. These data suggest a strong association between systemic cardiometabolic burden and AMD risk, but they do not prove that metabolic optimization prevents AMD progression.

8.2. Pathophysiology

AMD involves RPE dysfunction, Bruch's membrane thickening, drusen deposition, complement dysregulation and choroidal neovascularization (CNV) in wet AMD [12, 13]. MetS‐driven oxidative stress impairs RPE autophagy and mitochondrial function. Lipofuscin accumulates and drusen form as a result [11]. Dyslipidemia promotes lipid accumulation in Bruch's membrane, reducing oxygen and nutrient transport to the RPE. Insulin resistance impairs IGF‐1 signalling in photoreceptors, reducing their survival capacity [8].

8.3. Management

Management differs by AMD stage. Early AMD is managed with risk‐factor modification and monitoring. Intermediate AMD may benefit from AREDS2 supplementation in appropriate patients. Neovascular AMD is treated with intravitreal anti‐VEGF therapy including ranibizumab, aflibercept, bevacizumab or faricimab. Geographic atrophy is now treated in selected patients with complement inhibitors such as pegcetacoplan or avacincaptad pegol. Smoking cessation, Mediterranean dietary patterns, blood‐pressure control and lipid management are clinically appropriate systemic recommendations, but the direct evidence that MetS treatment prevents AMD onset or progression remains less definitive than for DR.

9. Retinal Vascular Occlusions

Retinal vein occlusion (RVO) is the second most common retinal vascular disease after DR. MetS components including hypertension, diabetes, hyperlipidemia and central obesity increase RVO risk in a dose‐dependent manner [38].

9.1. MetS and RVO Risk

A nationwide Korean population‐based study of 1 408 093 young adults (aged 20–40 years) showed that cumulative MetS burden correlated with RVO incidence. All five MetS components were independently associated with increased RVO risk [38]. Women with MetS had disproportionately higher RVO risk (p < 0.001) [38]. A Mendelian randomization study identified low HDL cholesterol as an independent causal risk factor for RVO (OR 0.806 per genetically predicted HDL increment; p = 0.036) [39].

Retinal artery occlusion (RAO) shares risk factors with ischemic stroke. Atherosclerotic plaques at the central retinal artery origin promoted by MetS‐associated hyperlipidemia and hypertension are the primary driver of RAO [6]. Branch or central retinal vein occlusion may present with sectoral or diffuse retinal haemorrhages, venous tortuosity, cotton wool spots, macular edema and ischemic changes on fluorescein angiography or OCTA [40]. The retinal circulation offers a unique, non‐invasive view of systemic microvascular health [41]. Retinal arteriolar narrowing, venular dilation, capillary dropout and OCTA‐derived vessel density changes may represent ocular biomarkers of systemic endothelial dysfunction in MetS [42].

9.2. Management

Central RVO with macular edema is treated with intravitreal anti‐VEGF therapy. Branch RVO may respond to anti‐VEGF or laser photocoagulation depending on ischemia, edema and neovascular complications. Systemic management should address underlying MetS components through blood‐pressure control, lipid management, glycemic optimization and antiplatelet or vascular evaluation when clinically appropriate. RAO should be treated as an ocular stroke requiring urgent vascular assessment. The mechanistic implication is that RVO and RAO reflect systemic endothelial dysfunction and thrombogenic vascular risk, but ocular management remains disease‐specific and urgent when acute ischemia is suspected.

10. Non‐ARTERITIC Anterior Ischemic Optic Neuropathy

NAION is the most common acute optic neuropathy in adults over 50 years. It results from ischemia of the anterior optic nerve head. MetS is a strong and potentially modifiable risk factor [14, 43].

10.1. Evidence

A population‐based analysis from the Rochester Epidemiology Project (2005–2018) found that MetS patients had significantly higher odds of NAION (OR 6.17; p = 0.002) after adjustment for age, sex and race. Hypertriglyceridemia, low HDL and hyperglycemia were the primary drivers [14].

A systematic review and meta‐analysis of 21 studies confirmed that hypertension, diabetes mellitus and dyslipidemia are independently associated with NAION [43]. A matched cohort study found an increased NAION risk in patients prescribed semaglutide [44]. A more recent systematic review/meta‐analysis of emerging evidence also reported an association between semaglutide exposure and NAION risk, while emphasizing risk–benefit assessment and the limitations of observational evidence [45]. These findings raise an important clinical safety signal but do not by themselves prove causality.

10.2. Pathophysiology and Management

NAION arises from microvascular ischemia in the short posterior ciliary arteries supplying the optic nerve head. Nocturnal hypotension, obstructive sleep apnea and MetS‐related microvascular disease act as precipitating factors in structurally susceptible ‘disc‐at‐risk’ anatomy [43]. NAION typically presents with acute painless vision loss, relative afferent pupillary defect, optic disc edema, peripapillary haemorrhages and later optic atrophy [46]. No proven pharmacological treatment for acute NAION exists. Management focuses on urgent neuro‐ophthalmologic evaluation, exclusion of arteritic ischemic optic neuropathy when clinically indicated, risk‐factor control, sleep apnea evaluation and prevention of fellow‐eye involvement. Patients receiving GLP‐1 receptor agonists who develop acute visual symptoms require urgent ophthalmological evaluation, but decisions about continuing therapy should be individualized and based on overall cardiometabolic benefit and ophthalmic findings [44, 45].

11. Management Framework

11.1. Lifestyle Modification

Weight loss of 5%–7% or more improves all MetS components and reduces systemic inflammation. The Mediterranean diet lowers CRP, IL‐6 and oxidative stress markers. Aerobic exercise combined with resistance training (150 min/week or more) improves insulin sensitivity and endothelial function. These systemic benefits reduce ocular inflammatory burden and improve retinal perfusion [4, 6].

11.2. Pharmacological Management

11.2.1. Glycemic Control

GLP‐1 receptor agonists, SGLT‐2 inhibitors and metformin reduce HbA1c and provide cardiometabolic benefit. Their ocular relevance is strongest through systemic glycemic and vascular risk reduction. Rapid glycemic improvement can transiently worsen DR in susceptible patients and the emerging NAION safety signal with semaglutide requires balanced risk–benefit discussion rather than automatic discontinuation [44, 45].

11.2.2. Lipid‐Lowering Therapy

Statins reduce LDL and exert anti‐inflammatory effects. Fenofibrate has evidence for reducing DR progression and recent systematic review/meta‐analysis evidence supports its retinal relevance in diabetes [16, 17]. Omega‐3 fatty acids may help selected patients with meibomian gland dysfunction, but DED trial evidence is heterogeneous [36, 37].

11.2.3. Blood Pressure Control

ACE inhibitors and ARBs reduce retinal microvascular damage through RAAS blockade. They may independently reduce DR and AMD risk. A target blood pressure of less than 130/80 mmHg is recommended in MetS patients [6, 13].

11.3. Targeted Ophthalmic Interventions

Targeted ophthalmic treatment must be disease‐specific and should not be replaced by metabolic optimization alone. Table 1 summarizes a practical endocrinology–ophthalmology framework for screening, referral and co‐management.

TABLE 1.

Practical multidisciplinary framework for MetS‐related ocular disease.

Clinical scenario	Suggested ocular assessment	Urgent referral triggers	Cross‐specialty linkage
Known diabetes or suspected DR/DME	Dilated retinal examination; OCT when macular symptoms or DME suspected	Center‐involving DME, PDR, vitreous haemorrhage, tractional retinal detachment	Communicate HbA1c trend, BP, lipid therapy, anti‐VEGF/laser status
Ocular hypertension or glaucoma risk	IOP measurement, optic nerve exam, OCT RNFL/GCL, visual fields	New field defect, advanced cupping, very high IOP, acute symptoms	Endocrinology optimizes vascular risks; ophthalmology directs IOP‐lowering therapy
Dry eye symptoms or MetS with ocular surface complaints	TBUT, Schirmer testing, osmolarity, meibomian gland evaluation when available	Severe pain, corneal staining/ulceration, suspected neurotrophic keratitis	Coordinate glycemic/lipid control with phenotype‐directed DED therapy
AMD risk or new metamorphopsia	Dilated macular exam, OCT, Amsler grid counselling when appropriate	New metamorphopsia, subretinal/intraretinal fluid, haemorrhage	Risk‐factor modification plus stage‐specific AMD therapy
Acute monocular vision loss or vascular occlusion symptoms	Urgent retinal/neuro‐ophthalmic evaluation, OCT/OCTA/fluorescein angiography as indicated	Any suspected RAO, CRVO, BRVO with macular edema, or NAION	Urgent vascular‐risk evaluation; communicate antiplatelet/statin/BP/glucose plan

Abbreviations: AMD, age‐related macular degeneration; BP, blood pressure; BRVO, branch retinal vein occlusion; DED, dry eye disease; DME, diabetic macular edema; DR, diabetic retinopathy; GCL, ganglion cell layer; HbA1c, glycated haemoglobin; IOP, intraocular pressure; MetS, metabolic syndrome; NAION, non‐arteritic anterior ischemic optic neuropathy; OCT, optical coherence tomography; OCTA, optical coherence tomography angiography; PDR, proliferative diabetic retinopathy; RAO, retinal artery occlusion; RNFL, retinal nerve fibre layer; TBUT, tear film break‐up time; VEGF, vascular endothelial growth factor.

12. Screening and Prevention

Risk‐based ocular screening should be considered in patients with MetS, particularly those with diabetes, hypertension, dyslipidemia, visual symptoms, retinal vascular disease or additional vascular risk factors. Non‐diabetic retinopathy may precede overt diabetes, justifying early screening. OCT and OCTA enable early detection of DME, AMD and retinal nerve fibre layer thinning. IOP measurement and optic disc evaluation are required for glaucoma surveillance in patients with ocular hypertension. Ocular surface assessment with TBUT, Schirmer test and osmolarity should be performed in symptomatic MetS patients and in high‐risk patients, especially women [6, 7, 15, 36].

Urgent ophthalmology referral is warranted for acute vision loss, new visual field defect, symptoms of retinal vascular occlusion, suspected NAION, proliferative diabetic retinopathy, center‐involving DME, neovascular glaucoma, corneal epithelial breakdown or new metamorphopsia suggestive of neovascular AMD [47].

Multimodal imaging is central to the ophthalmic evaluation of MetS‐associated disease. Fundus photography documents retinopathy and vascular occlusions; OCT detects DME, AMD, retinal nerve fibre layer thinning and macular edema; OCTA may reveal capillary nonperfusion and microvascular rarefaction; fluorescein angiography remains useful for ischemia and neovascularization; and specular or Scheimpflug imaging may help characterize cataract and corneal/ocular surface comorbidities [48, 49, 50].

AI‐assisted retinal photography is emerging as a scalable screening tool. It can detect DR and predict cardiovascular risk from fundus images. Multidisciplinary endocrinology–ophthalmology co‐management improves screening adherence and early detection rates [51].

13. Future Directions

Retinal OCT and OCTA‐derived vascular metrics may serve as non‐invasive biomarkers of systemic MetS‐related microvascular disease [11]. Metabolomics including arginine/proline pathway dysregulation in aqueous humour and serum offers new diagnostic and therapeutic targets [11, 30]. Prospective studies are needed to define the NAION risk profile of GLP‐1 receptor agonists [44, 45]. Mitochondria‐targeted antioxidants and BDNF‐based neuroprotective agents are in early clinical development for MetS‐associated optic neuropathies. Deep learning algorithms trained on retinal images show promise in identifying MetS and detecting subclinical DR [6]. Sex‐stratified analyses are needed to inform tailored screening, as women with MetS show greater DED severity and RVO risk [15, 38].

14. Limitations

This review has several limitations. First, it is a narrative review and not a systematic review; therefore, formal PRISMA methods, duplicate independent screening, risk‐of‐bias assessment and meta‐analysis were not performed. Second, PubMed was the primary database, although reference lists of relevant articles were reviewed. Third, the underlying literature is heterogeneous, with variable definitions of MetS, inconsistent ocular endpoints, different imaging modalities and uneven adjustment for confounders. Fourth, many associations between MetS and ocular disease derive from cross‐sectional or observational cohort studies, which are vulnerable to residual confounding, shared risk factors, detection bias and reverse causality. Fifth, interventional evidence differs markedly by disease: evidence is strongest for glycemic and blood‐pressure control in DR and IOP‐lowering therapy in glaucoma, whereas evidence that MetS treatment prevents AMD, NAION, RVO, cataract or DED progression remains more indirect. Finally, sex‐, ethnicity‐ and age‐stratified data remain limited, despite evidence that demographic factors may modify risk for specific ocular outcomes.

15. Conclusions

MetS contributes to a wide range of ocular diseases through inflammation, oxidative stress, endothelial dysfunction, dyslipidemia, hypertension‐related microvascular injury and neurodegeneration. These conditions are common and may be vision‐threatening. The eye may show early signs of systemic vascular injury before other complications appear. Endocrinologists should consider risk‐based ocular screening as part of MetS care protocols, particularly for patients with diabetes, hypertension, dyslipidemia, visual symptoms or other vascular risk factors. Ophthalmologists should recognize the systemic metabolic context driving ocular pathology. Multidisciplinary management through lifestyle change, evidence‐based pharmacotherapy and targeted ocular treatment offers a rational strategy to reduce MetS‐associated visual impairment. However, causal inference and preventive effects should be interpreted according to disease‐specific evidence strength, with the clearest interventional evidence in diabetic retinopathy and glaucoma and more observational evidence for several other ocular outcomes.

Funding

The authors have nothing to report.

Conflicts of Interest

The authors declare no conflicts of interest.

Varghese R. T. and John A. A., “Ocular Manifestations of Metabolic Syndrome: A Systemic Vascular Phenotype,” Diabetes, Obesity and Metabolism 28, no. 11 (2026): 9809–9818, 10.1111/dom.71133.

Data Availability Statement

Data sharing not applicable – no new data generated, or the article describes entirely theoretical research.