In contrast to hair growth elsewhere in the body, very little is known about the biology of growth of the eyelashes, and knowledge in this field is still rudimentary. As a result, there are conflicting data in the literature about basic physiologic processes like the length of each phase of the eyelash growth cycle.¹³,¹⁴ Confusion also exists about the exact number of eyelashes in each eyelid.¹⁴,¹⁵ A brief overview of the physiology of eyelash growth may help shed some light on the underlying causes of hair follicle abnormalities.

Although the eyelid skin is the thinnest in the body, eyelashes are the thickest hairs in the body with the widest recorded diameter.¹⁵,¹⁶ This is probably significant from an evolutionary point of view because eyelashes subserve an important protective function preventing debris from entering the eye.¹⁷ The absolute number of eyelashes may vary according to the hair growth cycle but overall, the eyelashes are more or less constant in number from birth, and retain their pigmentation throughout life, therefore eyelashes are classified as terminal hairs (thick, coarse, pigmented hairs) and not vellus hairs (the fine short, nonpigmented hairs, which are observed elsewhere in the face before puberty).¹¹,¹⁸ There are approximately 75 to 150 eyelashes in each upper eyelid arranged in multiple rows, whereas the eyelashes in the lower eyelid are lesser in number (75-80), arranged in fewer rows, and shorter in length than those in the upper eyelids (6-8 mm vs 8-12 mm).⁹,¹²,¹⁵,¹⁷ Eyelashes are typically darker than eyebrow hairs and are resistant to graying.⁹

The human hair growth cycle is divided into three or four phases, anagen, telogen, catagen, and possibly the exogen phase.¹⁷ The eyelash anagen phase (growth phase), which is a phase of rapid cellular growth and proliferation, is approximately 1 to 2 months long (25-70 days) wherein the eyelashes grow at a rate of 0.12 to 0.15 mm/day.¹³,¹⁴,¹⁵ This contrasts with the arrested development during the apoptosis-driven catagen phase (involutional or transition phase) of eyelash growth, which takes about 15 days, during which keratinocytes (epithelial elements of the follicle) undergo apoptosis.¹⁵ The telogen phase (resting or dormant phase) is the phase where no significant changes are observed, and is estimated
to last between 3 and 8 months (100-270 days).¹⁵ Whether the exogen phase, where eyelash fallout or shedding is observed, is a separate phase or a part of the anagen or catagen phase is unknown.¹³,¹⁹

The total duration of the eyelash growth cycle is controversial in the literature as it reportedly varies between 3 and 12 months, but the average is around 5 to 7 months.³,⁹,¹⁵,¹⁷,²⁰ The cycle is asynchronous meaning that at any one moment in time, individual eyelashes are at different phases of the growth cycle.¹⁷,²⁰ Approximately 41% to 50% of upper eyelid lashes are in the anagen phase at all times, which contrasts with the denser scalp hairs where 85% to 90% of hair follicles are in the anagen phase at any point in time.³ The anagen-totelogen ratio in the lower eyelids is even lower (14%).¹⁴,¹⁵ It is the length of the anagen phase that determines the length of the eyelashes. Any process that leads to prolongation of the anagen phase will eventually result in trichomegaly.¹⁵,¹⁸ A clear mechanistic distinction should be made here between trichomegaly and hypertrichosis, because as was mentioned earlier, the term hypertrichosis may also be associated with an actual increase in hair follicle density or number. This may result from a decrease in hair shedding because of a relative decline in the percentage of follicles in the telogen phase compared with the anagen phase. Therefore, in hypertrichosis, both mechanisms may be at play (prolongation of the anagen phase and an increase in the anagen-telogen ratio).¹⁸ Vellus to terminal hair follicle differentiation is another mechanism that is used to explain hypertrichosis elsewhere in the body but may not play a significant pathogenetic role in the eyelids where lanugo/vellus hairs are absent except on the anterior surface of the eyelid skin and in the caruncle.¹³,¹⁸,²¹,²²

The trigger factors that initiate the above-mentioned underlying etiopathogenetic mechanisms remain obscure. Although several hormones and chemical mediators are known to be involved in the body hair growth cycle including androgens, growth hormone, insulin, glucocorticoids, and prolactin, these growth factors are region specific, and as far as is known, there is no concrete evidence to support a similar role of any of the above hormones in the eyelids.¹⁸,²³,²⁴

The list of conditions causing trichomegaly is extensive and may be congenital, acquired, or drug-induced. Congenital trichomegaly may be isolated or associated with systemic syndromes. Isolated (also called familial or benign trichomegaly) is transmitted in an autosomal recessive fashion due to a homozygous mutation in the FGF5 gene.²⁵ Another congenital condition (hypertrichosis lanuginosa, werewolf syndrome), which is transmitted in an autosomal dominant or X-linked dominant fashion, is associated with generalized hypertrichosis throughout the body including hair follicle growth that covers the entire anterior surface of the upper and lower eyelids, eyelashes, and eyebrow hairs and results from a genetic defect that results in the persistence of fine lanugo hairs after birth.¹¹,¹⁸

Trichomegaly is a constant feature of Cornelia de Lange syndrome or Brachmann-de Lange syndrome²⁶ and Oliver-McFarlane syndrome.²⁷ Other inconstant syndromic associations where trichomegaly may be observed but may not be a key feature of the syndrome include conerod dystrophy, tetralogy of Fallot, Macinnes syndrome, Hermansky-Pudlak syndrome, Aghaei-Dastgheib syndrome, Laurence-Moon syndrome, phylloid hypomelanosis, and congenital heart disease.³,¹⁰,²⁸,²⁹,³⁰,³¹,³² Of note is that more than 100 syndromes are associated with hypertrichosis all over the body, any of which, at least theoretically, may also show trichomegaly as an associated finding.¹⁰,¹⁸