Mohammad Ayoub

Overview

Ocular rosacea is a chronic inflammatory disorder affecting the eyelids, ocular surface, and periocular tissues. It is a recognised subtype of rosacea and may present with or without cutaneous involvement. Ocular rosacea is frequently underdiagnosed due to nonspecific symptoms and variable skin findings. Clinical features include chronic blepharitis, meibomian gland dysfunction and dry eye disease. There can also be recurrent chalazia, with potential progression to corneal ulceration, scarring and perforation if untreated. This overview summarises the epidemiology, pathophysiology, etiology, clinical presentation, diagnosis, differential diagnoses and current management strategies for ocular rosacea. Thus, emphasising the importance of early recognition and multidisciplinary care.

Introduction

Rosacea is a chronic inflammatory, acneiform condition that mostly affects the centrofacial and periocular skin. It affects mostly adults aged 30 to 60, with women being up to three times more likely than men. However, ocular involvement occurs at the same rate in both sexes. Rosacea affects an estimated 16 million people in the United States, with ocular symptoms reported in roughly 6-72% of cases (1-4).

In 20% of cases, ocular symptoms may exist in the absence of cutaneous disease (1-4).  The condition tends to be overlooked due to non-specific symptoms and subtle dermatological indications. This diagnostic challenge is seen in those with darker skin tones, where traditional cutaneous characteristics may be less apparent. (1, 2, 4)

Epidemiology and Risk Factors

The global prevalence of rosacea is estimated to be around 5.5%, with greater rates seen in fair-skinned Europeans (1,4). Ocular involvement has been observed in 6-58% of rosacea patients, with some studies indicating incidence rates of up to 72% (2,3) While cutaneous rosacea is more commonly diagnosed in women, men are more likely to develop severe phymatous changes (1-4).  In contrast, ocular rosacea affects both genders equally and might appear during childhood. In paediatric populations, it is commonly referred to as blepharokeratoconjunctivitis and is likely underreported (1-4).

Several risk factors for rosacea development have been noted, including genetic susceptibility, UV radiation exposure, obesity, dietary impacts and a positive family history. (2,4) Importantly, the degree of ocular involvement does not reliably correspond with the extent or severity of cutaneous disease, which may further add to diagnostic delay (1-4).

Pathophysiology

The pathophysiology of ocular rosacea is complex, multifactorial, and not yet fully understood. Current evidence suggests that it involves dysregulation of both innate and adaptive immune responses, vascular hyperreactivity, neurogenic inflammation, and microbial factors (1-4).

A key mechanism includes upregulation of Toll-like receptor 2 (TLR2) in epidermal keratinocytes, which leads to increased activity of the serine protease kallikrein 5 (KLK5). This results in excessive production of cathelicidins, particularly LL-37 (3,7). These antimicrobial peptides promote inflammation, stimulate angiogenesis through increased vascular endothelial growth factor (VEGF) expression, and contribute to vascular instability (3,7).

Additional inflammatory pathways are implicated, including elevated levels of interleukin-1α and interleukin-1β, tumour necrosis factor-α, and increased activity of matrix metalloproteinases, particularly MMP-8 and MMP-9. Increased expression of inflammatory markers such as ICAM-1 and HLA-DR has also been demonstrated in conjunctival epithelial cells (3). Enhanced metalloproteinase activity within the cornea contributes to stromal degradation, ulceration, scarring, and corneal neovascularisation (3).

Microbial factors also play a significant role. Demodex folliculorum and Demodex brevis are found in higher densities in patients with rosacea and may exacerbate inflammation through immune activation and the presence of associated bacteria, such as Bacillus oleronius (1,2). In addition, ocular surface microbiome dysbiosis and reduced levels of tear antimicrobial proteins may further contribute to disease progression (1-4).

Etiology

The aetiology of ocular rosacea is multifactorial and involves a combination of vascular dysregulation, immune dysfunction, microbial influences, genetic susceptibility, ultraviolet radiation exposure and neurovascular dysregulation (2,3,7). These interacting mechanisms contribute to chronic inflammation and disease persistence.

Several environmental and lifestyle triggers are known to exacerbate disease activity. Common triggers include sun exposure, extreme temperatures, spicy foods, alcohol, caffeine, emotional stress, strenuous exercise and the use of certain medications- such as topical or nasal corticosteroids, beta blockers, amiodarone and niacin (3,4). Identification and avoidance of these triggers are important components of long-term disease management and may help reduce symptom severity and flare frequency.

Clinical Presentation

Ocular rosacea most commonly presents with bilateral symptoms, including burning, stinging, foreign body sensation, dryness, photophobia, excessive tearing, and blurred vision  (1-4). On slit-lamp examination, lid margin erythema and telangiectasia are frequently observed, affecting approximately 50–94% of patients (3). Meibomian gland dysfunction is a prominent feature, reported in up to 92% of cases, and is characterised by inspissated and turbid secretions. This contributes to evaporative dry eye disease and is often associated with recurrent hordeola or chalazia (3).

Conjunctival involvement typically manifests as interpalpebral bulbar hyperaemia, often accompanied by papillary or follicular reactions. Corneal disease occurs in approximately 25–50% of patients and may range from punctate epithelial keratitis to more severe findings, including stromal infiltrates, corneal neovascularisation, thinning, scarring, ulceration and, in rare cases, perforation (3,5).

Cutaneous features commonly associated with rosacea include centrofacial erythema, telangiectasia, papules and pustules. In advanced disease, phymatous changes such as rhinophyma may develop. Morbihan syndrome is a rare but severe complication. It is characterised by persistent, solid oedema affecting the forehead, cheeks, glabella and periorbital regions (6).

Diagnosis

The diagnosis of ocular rosacea is primarily clinical and is based on a detailed history and slit-lamp examination, as no specific diagnostic biomarker has been identified (1,2,4). Traditionally, the National Rosacea Society classification describes four subtypes of rosacea: erythematotelangiectatic, papulopustular, phymatous, and ocular (7).

More recently, the Global Rosacea Consensus Panel has recommended a phenotype-based diagnostic approach. In this model, diagnostic features include persistent centrofacial erythema and phymatous changes. Major features include flushing, inflammatory papules and pustules, telangiectasia and ocular manifestations such as blepharitis, lid margin telangiectasia, keratitis and conjunctivitis (2, 7). Importantly, ocular manifestations may occur in the absence of clinically evident cutaneous disease, which can further complicate diagnosis (7).

Differential Diagnosis

The differential diagnosis of ocular rosacea includes seborrhoeic dermatitis, contact dermatitis, staphylococcal blepharitis, dry eye disease, herpes simplex keratitis, atopic dermatitis, lupus erythematosus, cellulitis, and blepharoconjunctivitis (3). These conditions may present with overlapping ocular and periocular features, making careful clinical assessment essential (6).

Morbihan syndrome should be considered in patients presenting with persistent facial and periorbital swelling, particularly when associated with features of chronic rosacea (6).

Management

Management is in stages and determined by illness severity, with early intervention aimed at preventing progression and complications (2-4).
Conservative care options include avoiding triggers, using warm compresses, cleaning the eyelids, massaging the meibomian gland and using artificial tears for dry eyes.(2-4, 8) Systemic sub-antimicrobial doses of tetracyclines, such as doxycycline or minocycline, are often used for moderate illness treatment due to their anti-inflammatory effects on cytokines, nitric oxide and matrix metalloproteinases. (2, 9, 10)

Macrolides, such as azithromycin, provide an alternative. Side effects should be considered, while low-dose regimens are typically well tolerated.(2) Topical treatments for rosacea include metronidazole for mild to moderate irritation and azithromycin or cyclosporine for eyelid and ocular surface inflammation (2-4).  

Interventional therapies include intense pulsed light (IPL), meibomian gland expression, and punctal occlusion. IPL has been shown to increase meibomian gland outflow, reduce bacterial load, decrease pro-inflammatory mediators and improve periocular erythema (11-13).

Surgical treatment is reserved for serious diseases and complications, such as non-healing ulcers or corneal perforation, and may involve amniotic membrane transplantation, conjunctival flaps, tissue adhesives, or penetrating keratoplasty (2,5). Chalazia may require incision and curettage.

Future Directions

Emerging therapies for ocular rosacea are increasingly aimed at specific cytokines, chemokines, and angiogenic pathways involved in disease progression. Chemodenervation using botulinum toxin has shown potential benefits, particularly by inhibiting vasodilatory processes and reducing facial flushing (14).

As our understanding of the molecular and immunological mechanisms driving ocular rosacea advances, future management techniques are anticipated to shift towards more focused and personalised therapeutic approaches, with the goal of enhancing disease control and long-term results.

Conclusion

Ocular rosacea is a common inflammatory condition that remains frequently under-diagnosed and has the potential to cause significant ocular morbidity. Its clinical presentation varies and may occur in the absence of skin manifestations, which can delay recognition. Early diagnosis, patient education focused on trigger avoidance and a structured, severity-based management approach are essential to reduce the risk of sight-threatening complications.

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