Although lymphedema is not uncommon, our understanding of its basic underlying pathogenetic mechanisms is still limited. A brief overview of the lymphatic eyelid anatomy may shed some light on its etiology.⁴ Eyelid lymphatics lie superficial and deep to the orbicularis muscle forming superficial and deep systems that drain to the parotid and submaxillary nodes.²,⁶ The deep vessels traverse through the suborbicularis oculi fat and drain the conjunctiva and tarsus directly into the parotid (preauricular) lymph nodes. On the other hand, the superficial system which runs anterior to the orbicularis muscle drains the skin of the eyelids and orbicularis muscle.⁶ Medially, this superficial system collects lymphatic drainage from the medial aspects of both eyelids and drains into the submandibular lymph nodes, while the lateral aspect of both eyelids is drained by a separate system that flows into the parotid (preauricular) lymph nodes.⁶,⁷

If these channels are blocked, lymph stasis ensues which causes an accumulation of tissue protein and fluid, resulting in edema.² Accumulation of lymph increases oncotic pressure which draws even more fluid into the interstitium, which in turn may cause inflammation, further compromising support for lymphatic vessels. As the eyelid edema progresses, fibrotic changes ensue, and the already dysfunctional lymphatic channels are even more impaired by fibrosis of the surrounding tissues.⁸,⁹ This vicious cycle causes the initially soft eyelid subcutaneous tissue to become thickened, fibrotic, and solid.⁸

Lymphedema is subdivided into primary and secondary types. Primary or hereditary lymphedema due to aplasia or hypoplasia of the lymphatic vessels has not been reported in the eyelid; therefore eyelid lymphedema is usually a localized form of secondary lymphedema. The list of periocular conditions associated with lymphedema includes (1) chronic inflammatory conditions like rosacea, Melkersson-Rosenthal syndrome (MRS), or oculofacial granulomatosis; (2) trauma either surgical or nonsurgical; (3) infections like erysipelas; (4) conditions including giant cell angiofibroma or neurofibroma; and (5) miscellaneous causes, including hypothyroidism, amyloidosis, nephrotic syndrome, alcoholism, continuous positive airway pressure nasal masks, malar festoons, or it may be idiopathic.⁸,¹⁰,¹¹,¹²,¹³,¹⁴,¹⁵,¹⁶,¹⁷,¹⁸,¹⁹,²⁰,²¹,²²,²³

Concomitant injury to both the deep and superficial lymphatic drainage systems explains the increase in the rate of persistent chemosis/eyelid edema that has become more prevalent as cosmetic procedures that combine traditional transcutaneous blepharoplasty with trans-eyelid midface suspension have become more common.⁶ Historically, placement of surgical incisions over the inferior orbital margin to access the anterior orbit not only resulted in an unsightly scar but these incisions caused significant lymphedema as well.¹⁷ Another procedure that can be associated with considerable lymphedema is myectomy for essential blepharospasm.¹⁸ Eyelid lymphedema does not occur only from trauma or surgery involving the periocular region, and several cases have been reported following modified radical neck dissection for head and neck cancer metastases.²,⁸

Rosacea is a chronic inflammatory skin condition affecting approximately 10% of adults and is characterized by
facial erythema, papules, pustules, telangiectasia, sebaceous gland hyperplasia, and meibomian gland dysfunction.¹³,¹⁴,¹⁵ In the absence of a history of a surgical or a nonsurgical traumatic insult, rosacea is by far the most common underlying etiologic condition associated with lymphedema and is observed in roughly 50% of patients. While ophthalmologists are familiar with the classic ocular manifestations of rosacea, such as conjunctivitis or blepharitis, rosacea is often overlooked as a common cause of eyelid lymphedema.²⁴

MRS is a rare locally infiltrative granulomatous disease of obscure etiology, which is characterized by a triad of idiopathic eyelid or lip edema, facial palsy, and fissured tongue. However, the classic triad is encountered in one-third of patients only,¹¹,¹²,²⁵ and patients can present solely with eyelid lymphedema (Figure 85.1). The disease has a worldwide distribution, with no racial predilection, but is diagnosed more often in females.²⁵

Orofacial granulomatosis (OFG) is an uncommon non-necrotizing granulomatous disorder of the orofacial tissues. The term is a catch-all term that was coined in 1985²⁵ to encompass several entities that share two common features: orofacial swelling and the histologic evidence of noncaseating granulomas.²⁶ This condition has a multifactorial etiology and uncertain pathogenesis, but an underlying genetic or immunologic (delayed hypersensitivity) mechanism that favors a granulomatous inflammatory response is possible.²⁵,²⁶,²⁷,²⁸,²⁹ Although the term is nonspecific, establishing the diagnosis of OFG is still important because it should prompt the clinician to thoroughly search for the underlying disease, including granulomatous cheilitis, Miescher cheilitis, Crohn disease, or MRS.²⁶ Unfortunately, the diagnosis remains elusive in a significant proportion of patients,²⁶ and in these individuals, the term “OFG” can be used alone, a situation which is not quite dissimilar to the use of the term “idiopathic orbital inflammation” in orbital disease.

An often overlooked clinical condition that is at least partially attributable to lymph stasis is malar mounds, the other contributory or comorbid mechanism being anatomical laxity of dermal attachments. Both factors (laxity and lymph stasis) contribute to the characteristic clinical appearance of festoons.¹⁶

Comorbid factors that may increase the risk of developing lymphedema include genetic factors, obesity, radiation, and infections.¹,²,³,⁴ Interestingly, genetic factors do not only play a role in primary lymphedema but may be implicated in cases of secondary lymphedema.⁴ An increased rate of mutations in the HGF/MET pathways which regulate lymphangiogenesis, as well as mutations in the CJC2 protein which regulates lymphatic flow, have been observed in patients with secondary lymphedema.³⁰,³¹ Obesity has repeatedly been shown to impair lymphatic function and patients with a higher body mass index have a higher incidence of lymphedema, but this may be reversible after weight loss.⁴ Radiation per se is associated with an increased risk of lymphedema but is an important comorbid risk factor if performed following surgery.⁴ Infections can also cause significant destruction of the lymphatic system.

The prevalence of lymphedema is unknown because lymphedema is not a reportable disease.²⁰ Pain is usually absent, but patients are concerned about the nature of the edema and the associated cosmetic disfigurement which is bothersome because chronic lymphedema may cause a significant change in orbital and facial contour.⁵ On physical examination, the eyelid tissue initially shows a variable degree of mild edema, which later progresses to severe or profound lymphedema (Figure 85.2). If the upper eyelid is involved, the visual axis may partially or completely be occluded, but the levator function is difficult to assess amidst the edema.²