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Recent Advances in Ophthalmic Plastic Surgery: Part 1—Eyelid

Honavar, Santosh G. MD, FACS,*; Manjandavida, Fairooz P. MD

The Asia-Pacific Journal of Ophthalmology: September/October 2013 - Volume 2 - Issue 5 - p 328–340
doi: 10.1097/APO.0000000000000003
Annual Review
Free
Editor's Choice

Purpose The objective of this study was to provide an update of the current literature in ophthalmic and facial plastic surgery, specifically related to disorders of the eyelid.

Design This was a review of published literature from January 2012 to June 2013

Methods The authors conducted a PubMed literature search of English-language articles published between January 2012 and June 2013 using the following search terms: eyelid, congenital, acquired, infection, inflammation, trauma, tumor, ptosis, entropion, ectropion, lagophthalmos, botulinum toxin, fillers, blepharoplasty, and miscellaneous topics related to the disorders of the eyelid. The authors included original articles, review articles, and case reports with relevant new information that is of potential clinical use to a comprehensive ophthalmologist as well as to the subspecialist.

Results Current literature on the disorders of the eyelid is replete with useful clinical information of relevance to a practicing ophthalmologist. Major advances have been reported in understanding of the surgical anatomy and its applications, ptosis, entropion, ectropion, lagophthalmos, infection, inflammation, trauma, and tumors.

Conclusions There seems to be tremendous excitement in revisiting the anatomy and pathology and modifying the management protocols and surgical procedures to achieve optimal results, as the subspecialty continues to advance at a brisk pace.

From the *Department of Ophthalmic and Facial Plastic Surgery and Ocular Oncology, Centre for Sight, Hyderabad, India; and †Department of OphthalmicPlastic Surgery, Orbit and Ocular Oncology, C-MER (Shenzhen) Dennis Lam Eye Hospital, Shenzhen, China.

Received for publication June 27, 2013; accepted August 24, 2013.

The authors have no funding or conflicts of interest to declare.

Reprints: Santosh G. Honavar, MD, FACS, Department of Ophthalmic and Facial Plastic Surgery and Ocular Oncology, Centre for Sight, Road No. 2, Banjara Hills, Hyderabad 500034, India. E-mail: santosh.honavar@gmail.com.

Congenital and acquired deformities and disorders of the eyelid continue to provide a fertile ground for research and innovation. The review aims to provide relevant highlights from the literature published between January 2012 and June 2013. We conducted a literature search of English-language articles published in the period under review using the search terms eyelid, congenital, acquired, infection, inflammation, trauma, tumor, ptosis, entropion, ectropion, lagophthalmos, botulinum toxin, fillers, blepharoplasty, and miscellaneous topics related to the disorders of the eyelid. We included original articles, review articles, editorials, and case reports with relevant new information; categorized the information; and organized it into clinically relevant subsets as follows.

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TRICHIASIS

Worldwide, there are estimated to be more than 40 million people with active trachoma and a further 8 million with trachomatous trichiasis.1 More than half of patients with trachomatous trichiasis have only mild entropion, thus needing management for trichiasis alone.1 In a cross-sectional study of 2556 patients (4310 eyes), Rajak and associates1 found an inverse association between epilation and central corneal opacity. The results suggest that, among patients who have mild entropion or mild trichiasis and in those who decline or are unable to access surgery, the provision of good-quality epilation forceps and home epilation training may be beneficial in preventing vision loss.2

The Surgery for Trichiasis, Antibiotics to Prevent Recurrence trial was a randomized, single-masked, clinical trial conducted in southern Ethiopia, a region where trachoma is hyperendemic.3 A total of 1452 patients who underwent trichiasis surgery were randomly assigned at a 2:1 ratio to either a single dose of oral azithromycin (1 g) or topical tetracycline (twice per day for 6 weeks) following surgery. The azithromycin group had a 22% reduction in recurrence of trichiasis 3 years after surgery compared with the tetracycline group.3 A single dose of azithromycin after surgery remains an integral component of the World Health Organization’s strategy for the elimination of trachoma by the year 2020.3

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ENTROPION AND ECTROPION

Entropion and ectropion constitute a major portion of patient referrals to an oculoplasty clinic.4 Involutional eyelid malposition is being recognized as a common etiology. Jyothi and associates4 evaluated the effect of axial globe length and other biometry parameters on age-related lower eyelid malposition and found that axial globe length directly correlates with the ectropion group having a longer axial length as compared with the entropion group. Essentially, the axial length influences eyelid vector forces and is therefore linked to whether involutional changes manifest as entropion or ectropion.

Tarsal kink is a rare congenital eyelid anomaly manifesting with severe entropion, which may lead to corneal opacity and consequent amblyopia. Demirel et al5 have described an effective modified temporary eyelid margin suture for tarsal kink correction. They passed a double-armed 6-0 Prolene suture through the lower section of the gray line of the upper eyelid and the upper section of gray line of the lower eyelid at 3-mm distance from the lateral commissure of each eye, tying off the suture just above the lash line.5 The authors’ aim was to provide better mechanical traction on the tarsal plate by drawing the upper eyelid down to the lower eyelid as much as possible.5 The authors had called the procedure modified temporary eyelid margin suture.5 The patient recovered completely from the tarsal kink, without recurrence.

Yagci and Palamar6 reported a technique of tarsal margin rotation with extended posterior lamellar advancement for cicatricial entropion. A full-thickness posterior tarsal incision was made approximately 3 mm above the lash line, corresponding to the Arlt line, from the lateral canthus to just lateral to the upper punctum.6 Dissection on the anterior tarsal surface was followed by back cuts to the lash line through the inferior portion of the tarsus to enable the rotation of posterior lamellae.6 Then the inferior portion of the tarsus was rotated 180 degrees, and the remaining superior portion of the posterior lamellae was advanced a few millimeters past the new eyelid margin.6 The pivot line of these newly formed anterior lamellae was enhanced with horizontal mattress sutures.6 There was no recurrence in their set of 27 eyelids in managing cicatricial entropion and accompanying multiple eyelash problems of the upper eyelid due to trachoma.6

Involutional lower eyelid entropion is caused by lower eyelid laxity, weakness of the retractors, and lamellar dissociation with overriding of the preseptal orbicularis.7 Roberts and associates7 reported a series of 42 patients presenting with involutional entropion in the absence of lateral canthal tendon dehiscence who underwent horizontal eyelid shortening with elongated diamond-shaped full-thickness eyelid excision at the junction of the lateral third and the central third of the eyelid (as opposed to the classic Bick procedure involving lateral wedge resection) combined with lower eyelid retractor plication, with 92% success in entropion correction.7

Cicatricial lower eyelid entropion is usually due to shortening of the posterior tarsoconjunctival lamella or fornix, causing inward rotation due to vertical contracture.8 The choice of surgical procedure for the management of a lower eyelid cicatricial entropion is dictated by the severity and extent of entropion, degree of eyelid retraction, fornix and tarsal involvement and keratinization, eyelid margin distortion, underlying disease progression, and systemic status.8 Surgical approaches may be broadly classified into 4 categories: (1) eyelid margin rotation or eversion, (2) posterior lamella expansion and increasing posterior lamella height, (3) gray-line splitting of anterior and posterior lamellae and anterior lamella recession or posterior lamella advancement, and (4) excisional procedures with excision of the anterior lamella and lash line.8 It may be challenging to correct cicatricial lower eyelid entropion, particularly with predominant tarsoconjunctival contraction, eyelid margin distortion, and trichiasis where anterior lamella excision or further eyelid retraction is not desired. Malhotra et al8 report the outcomes of using a lower eyelid gray-line split, retractor recession with lateral-horn lysis, and anterior lamella repositioning technique, without a mucosal graft, for lower eyelid cicatricial entropion with surgical success in two-thirds of patients. The causes of cicatricial entropion in their series of 19 patients (21 eyelids) included ocular cicatricial pemphigoid (6 eyelids), Stevens-Johnson syndrome (3 eyelids), previous eyelid reconstruction (2 eyelids), socket scarring (2 eyelids), thermal burn (1 eyelid), chemical burn (3 eyelids), postradiotherapy (1 eyelid), and meibomian gland dysfunction (1 eyelid).

Barrett and Meyer9 have described a Quick Strip technique, a hybrid procedure that combines features of the classic Bick procedure and lateral tarsal strip for the correction of lower eyelid malpositions due to horizontal laxity, both for ectropion and entropion. Similar to the Bick procedure, a triangular portion of the tissue is removed, although unlike the classic Bick, this is initiated following a cantholysis rather than by excision of a wedge of tissue from an intact eyelid margin, and the triangular excision is more laterally oriented.9 The lateral tarsal strip is also initiated following a cantholysis; however, the subsequent excision is technically easier than fashioning a classic tarsal strip with fewer steps, its main virtue.9 Also similar to the lateral tarsal strip, the Quick Strip reattaches the eyelid to periosteum inside the lateral orbital rim, thus minimizing the risk of recurrence or lateral canthal rounding (a common criticism of the Bick procedure), and any lateral canthal malposition may be corrected based on the vertical placement of the suture inside the rim.9 Complete resolution of eyelid malposition was achieved in 92.4% eyelids with no significant complication, proving it effective and safe.9

Lower-eyelid tarsal ectropion involves the entire lower eyelid caused by possible disinsertion of the lower eyelid retractors.10 Singa et al10 describe a procedure to treat lower-eyelid tarsal ectropion using a lateral canthal tendon tuck with adjunctive resection of conjunctiva and Müller muscle of the lower eyelid using the Putterman ptosis clamp with complete correction in 6, partial correction but not needing resurgery in 2, and symptomatic relief in all the 8 patients.

Lateral tarsal strip being a workhorse surgical procedure to address lower eyelid malposition due to horizontal eyelid laxity, a panel of 7 experts set up by the International Council of Ophthalmology adapted a previously published tool for assessing lateral tarsal strip surgery by using a modified Dreyfus scale of skill acquisition (novice, beginner, advanced beginner, competent) and by developing behavioral anchors explicitly defined for each level in each step of the surgical procedure.11 The International Council of Ophthalmology-Ophthalmology Surgical Competency Assessment Rubric for Lateral Tarsal Strip Surgery can be used globally to assess lateral tarsal strip surgical skill among trainees.11

Lateral canthal dystopia can lead to lower eyelid malposition, abnormal lateral eyelid fissure appearance, and lagophthalmos. In most cases, the lateral canthus can be repaired with a standard lateral canthopexy or canthoplasty.12 In a few cases, especially when recurrent, the surgical repair may require additional lateral canthal reinforcement.12 Numerous reinforcement techniques have been described for lateral canthal dystopia, including inferior retinacular lateral canthoplasty and lateral rim drill hole fixation with sutures.12 Dailey and Chavez described the use of an acellular cadaveric dermal matrix in the form of a lateral canthal Y-shaped graft with deep soft tissue suture lateral canthal anchoring.12

Cutis laxa is a rare condition, characterized by progressive loose hanging skin folds, which can cause a “bloodhound-like” facies. It can be inherited or acquired (cutis laxa acquisita), as a paraneoplastic process in multiple myeloma.13 Ophthalmologic findings in cutis laxa acquisita include dermatochalasis, ptosis, mild lower eyelid ectropion, and subconjunctival fat prolapse.13 Slingerland et al13 reported a patient with marked lower eyelid ectropion in cutis laxa acquisita with multiple myeloma. Following initiation of systemic treatment for multiple myeloma, ectropion was corrected with a large elliptical excision of palpebral conjunctiva and lower eyelid retractors, combined with a lateral tarsal strip procedure.13 Recurrence of ectropion was successfully managed by combining the components of the original surgery with lower eyelid blepharoplasty.13

Floppy eyelid syndrome is characterized by lax, rubbery eyelids, which can easily be everted and associated with chronic papillary conjunctivitis of the upper palpebral conjunctiva, generally seen in middle-aged patients.14 Nuruddin14 highlighted the occurrence of floppy eyelid syndrome by birth in a nonobese child with Down syndrome and stressed the need to look for it in routine ophthalmic evaluation in such patients.

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GIANT FORNIX SYNDROME

First described by Rose in 2004, giant fornix syndrome (GFS) is often misdiagnosed, mistreated, and underrecognized.15,16 Giant fornix syndrome can lead to chronic relapsing conjunctivitis in the elderly.15,16 Deep conjunctival fornices in affected patients can be a site for prolonged sequestration of bacteria causing recurrent infections.15,16 Patients older than 60 years with repeated bouts of copious purulent discharge, punctate epitheliopathy, conjunctival injection, limbal vascularization, and superior sulcus deformity with a concomitant levator dehiscence should be evaluated for GFS.15,16 Particularly, patients with unilateral symptoms in the absence of nasolacrimal duct obstruction should raise suspicion of GFS.15,16 Turaka and associates15 analyzed 5 patients with GFS and concluded that removing the infected debris from the superior fornix and reconstruction of the upper eyelid may prevent the recurrent chronic persistent infection. Nabavi and associates16 have described a simple new surgical technique addressing the anatomical problem of a redundant conjunctiva and fornix by resecting excess fornicial tissue using a Putterman clamp. By removing redundant fornicial conjunctiva, they demonstrated that there is a restoration of the normal fornicial anatomy and resolution of symptoms.16

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EYELID RECONSTRUCTION

Repair of the eyelid margin remains one of the basic techniques in eyelid reconstruction. Precise apposition of the tarsal plates and meticulous alignment of the eyelid margins are essential to ensure a seamless repair and avoid notching. Traditional techniques of direct eyelid closure include a layered repair of the anterior and posterior lamella and 1 to 3 marginal sutures to align the eyelid margin.17 Willey and Caesar17 describe a diagonal suture technique, which they have used in 652 eyelids over 9 years with only 9 instances of notching, all in patients with concurrent infection. Their technique involves placement of a tarsal suture incorporating a substantial amount of tissue in order to have a secure wound closure. The key diagonal tarsal suture enters the tarsus anteriorly approximately 2 mm inferior to the eyelid margin, extends diagonally across the tarsus, and exits just inside the conjunctival border at the apex of posterior aspect of the tarsus.17

Direct closure of surgically induced eyelid colobomas is limited by the lack of tissue laxity, and in such situations, liberal lateral cantholysis has been the standard approach. Lateral cantholysis may lead to a visible scar and recruits tissue devoid of eyelashes.18 Perry and associates18 have described an internal cantholysis from the conjunctival aspect to reconstruct not just small- and moderate-sized defects, but also substantially larger defects (range, 14–25 mm; average, 20.8 mm), which would otherwise have needed flaps and eyelid sharing procedures. Complications such as lateral canthal dystopia, horizontal disparity, and notch are acceptable in light of the morbidity of other therapeutic options, such as semicircular flap or shared eyelid flap procedures.18

Kang and associates19 have used levator aponeurosis as a sandwich flap, over which they have used a free skin graft to reconstruct large defects of the upper eyelid. Yoon and McCulley20 have modified the traditional Cutler-Beard procedure to reconstruct the upper eyelid to use a secondary tarsoconjunctival graft in lieu of bilaminar transposition, thus avoiding potential complications of entropion and eyelid retraction.

The traditional Hughes tarsoconjunctival flap to reconstruct large defects of the lower eyelid has also seen modification this year with Beare and associates21 reporting their technique of early division of the posterior lamina and allowing laissez-faire granulation (healing by secondary intention) of the anterior lamina. Peter and Kumar22 have used nonlayered Permacol to reconstruct the posterior lamina in combination with an advancement skin flap to reconstruct large defects of the lower eyelid. Permacol is a relatively new biomaterial made from acellular cross-linked porcine dermal collagen with a structural architecture very similar to that of human dermis.22 Used as a scaffold, it eventually becomes vascularized and remodeled to reconstruct the eyelid.22 It is resistant to degradation by collagenase and is devoid of any material likely to elicit an allergic reaction.22 Decellularized bioengineered porcine-derived membrane (Tarsys) has been successfully used as a spacer to reconstruct the retracted lower eyelid following extensive surgery and radiotherapy for a malignant tumor.23

Yazici and associates24 have used a bilobed flap to reconstruct inferior and lateral periocular defects. Bilobed flap is a random pattern transposition flap that may be successfully used in combination with posterior lamellar and canthal reconstruction techniques.24

Full-thickness skin grafts in the periocular region have traditionally been dressed with a sutured bolster to minimize the risk of postoperative graft ischemia, hematoma, and contraction.25 Bush et al25 report a high success rate for periocular skin grafts without the use of a bolstered dressing. The use of a bolster increases operating time and postoperative care and is possibly less acceptable to the patient.25 They suggest that in most cases the use of a bolster is not necessary for periocular skin grafts.25

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LAGOPHTHALMOS

Lagophthalmos is commonly caused by facial nerve paralysis. Other causes of lagophthalmos are related to cicatricial changes of the eyelids due to chemical/thermal injury or disorders such as Stevens-Johnson syndrome, neurogenic eyelid retraction, exophthalmos in thyroid eye disease, and proptosis of any etiology.26 Gaudiani and associates26 have reported lagophthalmos in a series of 5 patients with anorexia nervosa. Severe starvation, resulting in orbital fat atrophy, is the primary cause of the mechanical-anatomic abnormality between the globes and eyelids that leads to clinical lagophthalmos and ocular surface drying.26 Progeria and progeria-like syndromes are conditions characterized by features of accelerated aging including a classic facies and loss of subcutaneous fat and tight skin, resulting in lagophthalmos and exposure keratitis.27 Kwong and associates27 have used hyaluronic acid gel filler to reduce upper eyelid sulcus hollowing and increase the weight of the upper eyelid in such a case with success.

The main purpose when treating lagophthalmos is to prevent exposure keratitis and reestablish eyelid function. Intensive lubrication is the mainstay treatment especially in early stages.28,29 Medical treatment can include the use of botulinum toxin to induce a protective ptosis.28,29 Surgical procedures include tarsorrhaphy and upper eyelid reanimation techniques including eyelid loading with gold weights and palpebral springs.28,29 Gire and associates28 have successfully used Prosthetic Replacement of the Ocular Surface Ecosystem device that provides a liquid bandage to protect the cornea from eyelid interaction and dessication in addition to improving vision in all their 4 patients. The use of botulinum toxin chemodenervation has been reinforced by Yücel et al.29 In patients with peripheral facial paralysis and lagophthalmos, protective ptosis created by 7.5 units of botulinum neurotoxin type A injection into the levator muscle was found to be a reliable and effective technique for the protection of the ocular surface and treatment of existing corneal complications.29 Bladen et al30 have compared the traditional eyelid loading with gold weight with denser and thus thinner platinum and have found platinum as safe and effective, with better cosmesis.

The association of meibomian gland dysfunction and facial palsy has been a subject of recent research.31 Shah and associates31 hypothesized that the inability to blink adequately after facial palsy leads to stasis of the meibomian gland secretions, resulting in poor lubrication and subsequent corneal irritation. Their study indicated a strong relationship between the two, leading to the recommendation that clinical optimization of meibomian gland function may benefit facial palsy patients.31

Call and colleagues32 objectively quantified the meibomian gland dysfunction using “meibograde” derived from infrared meibography. The progression of meibomian gland disease and associated meibography changes occur in a stepwise fashion.32 This begins first with glandular shortening and distortion (dilatation and irregularity of the gland initially, later followed by atrophy) and eventually leads to total gland dropout.32 In an attempt to improve quantification of the meibography images, the authors added these factors to the meiboscore (percentage of surface area of the eyelid showing gland dropout) and termed the result meibograde.32 In their grading variation, the authors first evaluated the lid for gland dropout. Any eyelid receiving a point for gland dropout also received at least the corresponding value in the gland shortening and distortion categories. The 3 category values were then summed, and the resulting meibograde for each lid was given a total value of 0 to 9.32 The meibograde scale allows for finer tuning of image grading and is a more comprehensive system in the evaluation of meibomian gland morphology. Fourteen upper and 18 lower eyelids affected by facial nerve palsies of various durations were examined using meibography. They concluded that facial nerve palsy with consequent weakness of the orbicularis oculi may be associated with morphological changes in the lower eyelid and may induce meibomian gland dysfunction.32

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PTOSIS

Recognition of coexisting refractive error and amblyopia and appropriate management are essential in the comprehensive management of a child with congenital ptosis.33 Griepentrog and associates33 found that 1 in 7 patients with ptosis manifested amblyopia in their population-based study conducted over 40 years in a cohort of 107 patients. Occlusion of the visual axis was the leading cause of amblyopia in this report.33 This finding is in contrast to large referral-based retrospective studies of congenital ptosis in which the leading causes of amblyopia were strabismus or significant refractive error.33 Early intervention in congenital ptosis may help minimize the incidence of amblyopia.33

Ocular torticollis refers to abnormal head position secondary to ophthalmic conditions, driven by a conscious or unconscious effort to maintain a clear visual axis and preserve binocularity.34 Bohnsack and colleagues34 have identified a set of patients with bilateral severe ptosis with ocular torticollis with developmental delay. Whereas amblyopia can be assessed objectively, a delay in motor development is difficult to ascertain in the ophthalmologist’s office and would require direct questioning of parents.34 The authors have found that early intervention for ptosis in such patients is beneficial and propose symptomatic ocular torticollis as an indication for early ptosis repair.34

Temporizing tarsofrontal sling is the surgery of choice in children younger than 3 years where cooperation may be limited for accurate assessment of levator function, with an intent to reassess and revise at about 5 to 6 years of age. Primary permanent tarsofrontal sling is generally performed in patients with poor levator function. While several suture materials are used for temporary tarsonfrontal sling, fascia lata is considered the criterion standard for permanent sling.35 However, fascia lata, once integrated with the tissues, is neither adjustable nor easily reversible, if need be in the event of an overcorrection or an undercorrection.35 Kim and associates35 have found that postoperative eyelid height may be predicted more accurately by compensating for anesthesia-induced lagophthalmos and adjusting the palpebral fissure to be larger than ultimately desired for patients with more severe ptosis (>4 mm).

Quest for an ideal sling material continues. MacVie et al36 used 2-0 Prolene in 27 patients (37 eyelids) and found 72.9% success (defined as upper eyelid clear of the pupil and palpebral aperture asymmetry of ≤2 mm) at a mean follow-up period of 71 months. In a study comparing Nylon suture and polytetrafluroethylene in 49 patients (79 eyelids), Hayashi et al37 found 62% recurrence with the Nylon suture, whereas polytetrafluroethylene provided stable correction but with a 7% rate of complications (granuloma and infection).

Over the years, silicone has become one of the synthetic materials of choice for tarsofrontal sling. Epitarsal migration is the most common cause for regression in silicone sling.38 Buttanri and associates38 compared surgical results of eyes in which silicone had not been sutured to the tarsal plate (group 1) with those sutured with monofilament polypropylene suture (group 2) and those sutured with polybutylate-coated braided polyester suture (group 3) and found failure in 9 (50%) of 18 cases in group 1, in 5 (20.8%) of 24 cases in group 2, and in 5 (13%) of 38 cases in group 3 during the follow-up period after adequate eyelid elevation had been achieved just after the surgery. The difference between surgical success rates in group 1 and group 2 (p = 0.047) and group 1 and group 3 (P = 0.003) was statistically significant. However, the difference between group 2 and group 3 did not reach statistical significance, indicating that tarsal fixation of silicone may help minimize the risk of sling failure, whereas the type of material used for tarsal fixation may not matter.38

Fay and Santiago have reported using a custom-fit Levine palpebral spring (conventionally used in lagophthalmos) fashioned from 0.012-inch nickel alloy wire in a patient with myogenic ptosis to lift the eyelid.39 The spring is placed in the upper and lower eyelids and orbit.39 As in the Levine technique, one arm is anchored to upper eyelid tarsus, and the other arm is anchored to orbital periosteum. By moving the inferior branch to the inferior orbit and the superior branch to superior tarsus, the spring can be loaded by compression as the upper eyelid approaches the inferior orbit.39 The spring itself is much like the Levine spring, with the major modification in placement than design.39 Successful use of the Levine palpebral spring requires normal levator function. In this current procedure, levator function should be poor or nil. Conversely, success here absolutely requires intact orbicularis function, whereas complete orbicularis paralysis is the indication for Levine palpebral spring placement.

There is renewed interest in using the frontalis muscle itself for a sling, with or without a muscle flap.40 Where a frontalis muscle flap is used, creation of a pulley in the levator aponeurosis may help minimize eyelid stand-off especially in deep set eyes.41 Despite the surgical technique performed, good results in terms of functionality, contour, and aesthetics were observed.41 In the eyes that underwent frontalis muscle flap without the levator pulley, there were 2 cases with moderate anteriorization of eyelid margin in extreme upgaze, and all patients showed eyelash ptosis that persisted 1 year after surgery, but improved after 5 years.41 In the eyes that underwent frontalis muscle flap with the levator pulley, no upgaze anteriorization of eyelid margin was observed, and 3 patients had eyelash ptosis of lesser extent than the fellow eye, improving after 1-year follow-up. Frontalis muscle flap with the levator pulley showed more long-term stability in eyelid height.

Attempts continue to improvise surgical procedures for mild and moderate ptosis to achieve predictable results. Carruth and Meyer42 used a modified Müller muscle-conjunctival resection procedure with no traction sutures, a double-opposing mattress suture, and single external knot in a series of 29 patients (42 eyelids) with mild acquired ptosis and greater than 10-mm levator function.42 Eyelids with 2 mm of ptosis and 2-mm phenylephrine response underwent 8-mm excision, with variations based on degree of ptosis relative to desired height. Specifically, ptosis less than 2 mm or overcorrection with phenylephrine resulted in excision less than 8 mm, whereas ptosis greater than 2 mm or undercorrection with phenylephrine prompted an increase in excision in linear fashion up to 10 mm.42 The results were impressive—eyelid symmetry to within 0.5 mm was achieved in 27 (93%) of 29 patients overall and in 13 (100%) of 13 bilateral cases. Symmetry to within 1 mm was found in all 29 patients (100%).42

The Fasanella-Servat procedure, favored for its simplicity and predictability in patients with mild ptosis and good levator function but with negative phenylephrine test, has been modified by Samimi and associates, essentially to address the issues of contour abnormality and suture keratopathy.43 They have used a modified contour mullerectomy clamp with screw fixation for accurate excision and exteriorized suture to minimize the risk of corneal complications.43 Two-millimeter tarsal excision for every millimeter of ptosis was found to provide predictable outcome.43

Malhotra and Salam44 have described the predictability of posterior approach white line (which represents the posterior border of the levator aponeurosis) advancement in patients undergoing surgery under general anesthesia. Their technique differs in several ways from the conventional posterior approach levator advancement surgeries. They do not dissect the septum to expose the anterior surface of levator and simply pass the sutures through the posterior white surface of the aponeurosis and reattach it to the tarsus. Their initial incision is just above the superior border of the tarsus as opposed to below, avoiding any excision of tarsus. There is no excision of Müller or conjunctiva, and the Müller conjunctiva composite flap is simply replaced without the need for resuturing. Nineteen of 20 patients in their series achieved desirable eyelid height and symmetry (≤1 mm), whereas one of them manifested 2-mm asymmetry.44

Local anesthesia is preferred for ptosis surgery because of the inherent advantage of intraoperative eyelid height adjustment. Aghai et al45 have confirmed that local anesthesia of the eyelid with 1 mL bupivacaine plus epinephrine causes a temporary increase in ptosis within the first few minutes with minimal effect on levator muscle function measurements and thus may be suitable for intraoperative adjustment.

The effect of Hering’s dependency on the outcome of ptosis surgery was studied by Cetinkaya and Kersten.46 They have found that bilateral ptosis with documented Hering’s dependency yielded better results when both eyes were operated in the same session, rather than delaying surgery for the second eyelid.46 They suspected that ocular dominance probably has a significant impact on Hering’s dependency and postoperative outcome after unilateral operations.46 Shah and associates47 reported that involuntary asymmetric eyebrow elevation and ocular dominance are significantly associated. The assessment of ocular dominance should therefore be included in the preoperative and postoperative evaluation of patients with asymmetric brow elevation.47

Astigmatic changes have been shown to occur after ptosis repair due to the altered vector forces on the underlying cornea from the repositioned upper eyelid. The astigmatic change is usually transient, but it may affect a patient’s vision for at least the first few months after surgery.48 Sussenbach and associates48 present a case of a patient who underwent ptosis repair and subsequently developed postoperative decline in best corrected visual acuity due to previously undiagnosed keratoconus. The patient’s irregular astigmatism seems to have been masked by the ptotic upper eyelid, which may have acted similar to a stenopaic slit. Correction of the upper eyelid ptosis unveiled previously asymptomatic irregular astigmatism including vertical coma, leading to alteration in the optical wavefront and resultant image degradation.48

Ptosis is a well-known complication following anterior segment surgery.49 However, its precise etiology remains elusive.49 In view of the frequency with which ophthalmologists perform anterior segment procedures such as cataract surgery, postoperative ptosis represents a significant concern for all ocular surgeons. Identifying the underlying mechanism is imperative, not only to identify those patients at greatest risk, but also to perhaps provide novel surgical approaches to the management of this complication. There are currently 2 widely held views on the pathogenesis of persistent postoperative ptosis, namely, the speculum and bridle suture theories.49 However, both suggested explanations fail to address important anatomical and epidemiological features of this condition. Until now, the majority of published literature describing persistent postoperative ptosis following anterior segment surgery has largely concentrated on dehiscence of the levator aponeurosis as the common mechanism underlying this postoperative complication.49 However, numerous studies have failed to show any correlation between preoperative or postoperative skin crease positions in such patients. Mehat and associates49 propose an alternative mechanism for the development of ptosis following anterior segment surgery, namely, horizontal stretch of the upper eyelid induced by the use of the speculum. This mechanism also provides a plausible explanation for less commonly described oculoplastic complications, such as lower eyelid malpositions, following anterior segment surgery.49

Complications following aponeurotic ptosis repair include incorrect eyelid height, eyelid contour abnormality, asymmetrical skin crease, and upper eyelid show.50 Entropion as a complication of ptosis surgery following aponeurosis advancement has been described very rarely. Shafi and associates50 report 2 such cases to highlight the importance of taking special care when advancing the aponeurosis, in cases where the tarsus is thin, as it may result in vertical buckling of the tarsus.

The results of ptosis surgery are said to improve with the surgeon’s experience. Anderson,51 after performing thousands of ptosis corrections, has provided pearls of wisdom and professes in his recent editorial that a ptosis surgeon must perform predictable procedures and should not go to the dark side. Beard has said, “Ptosis will always remain an art rather than a science, and therefore ptosis surgeons will always have a job.” Oculoplasty fellows, however, may find it soothing to note that there are indeed some science, standardization, and predictability in the modern-day ptosis surgery, and whereas experience does generally help tide over difficult situations with ease, a novice can deliver comparable results as well by following standard thumb rules.52 In a study by Mehta and Perry52 involving 170 patients (248 surgeries), there was no significant difference in mean postoperative marginal reflex distance, mean anesthesia time, complication rate, or reoperation rate between either conjunctival mullerectomy with or without tarsectomy or external levator advancement ptosis repair performed by trainee versus staff surgeons.

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BLEPHAROPHIMOSIS

Blepharophimosis-ptosis-epicanthus inversus syndrome is an uncommon congenital disorder characterized by a narrowed horizontal palpebral aperture, blepharoptosis, epicanthus inversus, and telecanthus.53 None of the existing methods of addressing the epicanthal fold are free from criticism because of the complexity of the flap creation, prolonged operating time, or postoperative scarring.53 Sa and associates describe an alternate technique for medial epicanthoplasty using the skin redraping method in patients with blepharophimosis-ptosis-epicanthus inversus syndrome, which has a simple flap design, less scarring, and the effective repair of epicanthus inversus and telecanthus.53 The authors found the technique effective in eliminating the epicanthal fold, reducing the inner intercanthal distance, increasing the horizontal palpebral fissure length, and achieving minimal scar.53

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OCULAR MYOPATHY

Common causes of ocular myopathy include chronic progressive external ophthalmoplegia, myotonic dystrophy, and oculopharyngeal dystrophy.54 The overlapping clinical features of these conditions include progressive ophthalmoplegia, bilateral ptosis, and orbicularis weakness.54 The ptosis associated with these ocular myopathies is frequently a cause of visual disability and distress when the visual axis becomes occluded by the upper eyelid.54 Traditionally, there has been a reluctance to undertake surgery with this group of patients, owing to the possibility of postoperative corneal exposure, secondary to lagophthalmos and a poor Bell phenomenon.54 Doherty and associates54 performed levator resection, brow suspension, anterior lamellar repositioning, or lower eyelid elevation and upper eyelid lowering surgery in 29 such patients. Palpebral aperture was significantly increased in all the patients, more significantly following brow suspension compared with levator resection.54 The patients’ feedback was positive. Postoperative complications included corneal exposure and ulceration, ptosis recurrence, arched brow, and sling infection, all of which were successfully treated.54 Their results demonstrate subjective and objective benefit following surgery in patients with ocular myopathy, although intensive postoperative monitoring may be necessary to recognize and manage complications.54 The use of prophylactic lower eyelid elevation followed by correction of ptosis (which “shifts” the palpebral fissure upward to expose the pupillary axis while maintaining the vertical fissure height at the preoperative extent to minimize the risk of corneal exposure) seems a promising modality in such cases.54

Involvement of extraocular muscles is common in mitochondrial cytopathies with symptoms of chronic progressive external ophthalmoplegia and associated syndromes.55 In peripheral skeletal muscle biopsies, most commonly from the quadriceps or deltoid, excess numbers of cytochrome oxidase–negative fibers and/or “ragged-red” fibers for age are usually diagnostic features for mitochondrial cytopathy.55 The orbicularis oculi has been proposed as an ideal muscle for investigation of mitochondrial cytopathy.55 McKelvie and associates55 confirmed the marked type II fiber (fast myosin heavy chain) predominance in orbicularis oculi but also noted a different proportion and distribution of mitochondria in these fibers with occasional pseudo–ragged-red fibers with prominent subsarcolemmal and cytoplasmic aggregation of mitochondria. Cytochrome oxidase–negative fibers and true ragged-red fibers were found at all ages older than 40 years at levels that approach those used for diagnosis of mitochondrial cytopathy in peripheral or limb skeletal muscles. Based on the results, they urge caution in the use of orbicularis oculi biopsy for diagnosis of mitochondrial cytopathy and advise concomitant biopsy of limb skeletal muscle and/or supplementary genetic studies.5

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BLEPHAROPLASTY

Blepharoplasty is the most commonly performed aesthetic surgery worldwide. It has evolved over the years to yield consistent results. Further understanding of the eyelid anatomy has contributed to surgical refinements. Different theories have been proposed to explain the causative factor of Asian double eyelid, with the 2 main possible factors being the insertion of the terminal branch of the levator aponeurosis and thickness of the upper eyelid tissues.56 Kakizaki and associates56 performed an experimental anatomical study to address this issue and found that the thickness of orbicularis oculi muscle or the way it folds (bending shape) and the thickness of the skin at the skin crease are major causative factors in Asian double-eyelid formation. Other factors, such as levator extension, skin and subcutaneous tissue thickness, inferior drooping of fat tissue, and the fusional site between the levator aponeurosis and orbital septum, were not shown as significant causative factors in forming the Asian double eyelid.56 These findings may have implications on the techniques for Asian blepharoplasty.

There is new understanding about the role of sparing orbicularis oculi in blepharoplasty for better cosmetic and functional outcome in selected patients.57 Lee and colleagues57 support their recommendation with their histopathologic study of aging changes in the orbicularis oculi muscle. It is well known that gradual loss of elastic fibers and skin relaxation cause the aging process, but whether changes in the orbicularis oculi muscle may contribute to the aging of the upper eyelid is not known. The aim of their study was to use histopathologic examination to investigate whether the orbicularis oculi contributes to upper eyelid aging at all by comparing specimens from younger patients undergoing cosmetic blepharoplasty with those from older patients undergoing functional blepharoplasty. Their study revealed that the entire orbicularis oculi muscle layer remained morphologically intact with aging, thus supporting their contention that it can be spared in blepharoplasty.57

Concepts of deflation in the face in addition to descent have shifted focus from excising tissue to reinflating.58 This premise is also true in the upper eyelid, but evaluation in this area has not been assessed critically.58 A youthful female eyelid has several distinct features, which have gone largely unmentioned. The key female features are tight skin, a medial concavity, and lateral convexity with fullness without hooding.58 In 3 dimensions, this medial slope concavity rising to a laterally full convexity is a sigmoid shape.58 A sigmoid shape by definition refers to a curve in 2 directions forming the letter “S.” It can be noted best on oblique views, which may detect subtle shadows and contour changes. With age, the weakening in the orbital septum allows for a herniation of medial fat, whereas ptosis and atrophy of the lateral eyelid-brow fat pad complex create a deflation laterally.58 The medial fullness and flattening laterally are the opposite of a youthful eyelid. A retrospective chart review of 142 female patients who underwent sigmoid blepharoplasty was conducted by Fezza.58 To recreate a youthful eyelid in 3 dimensions, the medial eyelid concavity was achieved by removing a strip of medial orbicularis oculi muscle along with selective medial fat removal. Excess skin and hooding were removed, and fat grafts from the medial eyelid were placed laterally below the muscle to achieve a fullness and tight skin. The sigmoid blepharoplasty restored a youthful eyelid appearance by recreating a concave medial eyelid and fuller lateral eyelid as assessed by photographs and chart records by 2 nurse observers and the surgeon himself/herself; however, there is no objective quantification of the same.58 There has been a trend toward adoption of these techniques, but that more objective studies are warranted to further characterize the results. Putting the procedure in perspective, Glasgold and Glasgold59 have commented that the surgeon selectively spares orbicularis and injects autologus harvested fat in small parcels (with high surface area-to-volume ratio to have a better adipocyte take) to the entire superior orbital rim to achieve a natural fuller effect. Massry60 has used the concept of volume augmentation with success in revision surgeries.

The orbitoglabellar groove is an involutional periorbital hollow present over the superonasal orbital rim.61 The depression can be reduced with native eyelid fat transposition during upper blepharoplasty in a similar way that lower blepharoplasty with fat repositioning effaces the nasojugal groove.61 Yoo et al61 have used this simple technique in 11 patients with good results.

Assessment of the digital photographs by Prado and associates62 by using angular measurements obtained before and after upper blepharoplasty showed changes in the position of the eyebrow. Alterations were highly apparent in the lateral portion of the eyebrow and occur bilaterally.62 The matrix used to determine the extent of skin-muscle excision is not specified by the authors. The measurement technique used by the authors to document the change in eyebrow position, however, seems objective. They suggest that the patient for upper eyelid blepharoplasty must be preoperatively counseled about the possibility of brow descent and be considered for concurrent brow fixation along with blepharoplasty if there is an apparent sag.62

There is some more objective evidence now to favor the functional benefit of blepharoplasty. Rogers et al63 have documented significant improvement in contrast sensitivity in patients who have undergone upper eyelid blepharoplasty. Putterman64 has devised a blepharoplasty clamp to assess and demonstrate the effect of functional blepharoplasty.

An aesthetic lower eyelid rejuvenation involves assessment of the eyelid, adjacent cheek, and the interface of the 2 structures as a continuum and on effacement of the depressions inherent to their transition—the nasojugal and orbitomalar grooves.65 Traditional lower blepharoplasty has consisted of the excision of variable amounts of skin, muscle, and fat with subsequent redraping of tissue.65 The new paradigm shift focuses on the preservation of tissue (primarily fat) by native fat redistribution (fat repositioning) or augmentation by autologous fat grafting to restore a natural and youthful appearance.65 Massry and Hartstein65 present their results of combined transconjunctival fat repositioning lower blepharoplasty, with orbicularis muscle suspension through a canthal/infraciliary skin incision. This “lift-and-fill” technique, which simultaneously preserves eyelid volume and enhances eyelid support, has improved lower eyelid appearance and contour in their series of 54 patients.65

Festoons are redundant folds of loose skin, muscle, fat, and interstitial edema that extend from beyond the lateral cheek often past the midpupillary line or even from canthus to canthus.66 Orbicularis weakness or attenuation may play a central role in the development of festoons.66 It is hypothesized that festoons are a laxity within the roof of the prezygomatic space and that they develop because of laxity of the orbicularis retaining ligament, which forms the upper border of the festoon, whereas the stronger zymgomaticocutaneous ligament forms the lower border of the festoon.66 Einan-Lifshitz and Hartstein66 suggest that direct excision of the festoons can provide a successful, reliable, and safe outcome. Krakauer and associates67 have used subperiosteal midface lift, lower-eyelid tarsal strips, and orbicularis muscle-skin flaps, to avoid possible scarring from direct excision and have achieved an excellent outcome.

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BROWPEXY AND FOREHEAD ELEVATION

Lifting or stabilizing the temporal brow can be an essential adjunct to both aesthetic and functional upper blepharoplasty surgery.68 Traditional brow lifting typically involves large or multiple incisions behind or at the hairline.68 The external browpexy is a minimally invasive, quick, and simple temporal brow suspension that can be added to blepharoplasty to enhance results.68 With the patient sitting upright, the appropriate location for brow fixation is marked. This is typically at, or close to, the junction of the body and tail of the brow (junction of middle and outer third). The brow is then manually elevated at this point to identify the desired height for fixation. A marking pen is placed over the brow at its elevated height, and the brow is released. After the brow descends to its native position, the forehead skin is marked where the pen is positioned. This is the fixation point of the brow intraoperatively. An arched incision is drawn, 8 mm in length, contouring to the brow at the upper row of hairs or slightly within the brow cilia, where the initial elevation point was demarcated. An incision is made through the skin and subcutaneous tissue in the predetermined area with the scalpel blade beveled in the direction of the brow hairs. The orbicularis muscle is grasped with a toothed forceps and elevated. A surgical scissors is used to make a cut through the muscle directed perpendicular to the frontal bone to expose the periosteum. A 4-0 Prolene suture is passed at the intended site of fixation in the periosteum, through brow fat, and frontalis/orbicularis muscle interdigitation and tied to ensure adequate brow elevation. The wound is closed in layers. Massry68 has shown that the procedure yielded excellent brow lift with high patient satisfaction over a 6-month average follow-up.

Direct brow lift involves the excision of an ellipse of skin, subcutaneous tissue, and muscle immediately superior to each brow with direct closure, enabling the surgeon to elevate the brow and define the superior brow contour.69 Forehead paresthesia after brow lift is well documented with rates as high as 41%.69 Barker et al69 have demonstrated a wide range of variation in the exit points of the supraorbital neurovascular bundle, including within the 2 sides of the same individual. The data suggest that deep dissection should not be performed within 3 cm of the midline to prevent iatrogenic damage to the supraorbital nerve.69

Endoscopic forehead surgery has grown since its introduction in the 1990s and is now accepted by many as an excellent choice for forehead lift.70 Endotine and Ultratine are both biodegradable devices and polymers of polylactic acid and polyglycolic acid. These polymers degrade by hydrolysis and enzymatic activity and have a range of mechanical and physical properties that can be engineered appropriately to suit a particular application.70 In the case of Endotine, the ratio is 82:18 polylactic acid to polyglycolic acid.70 However, the Ultratine device consists of a similar blend, but absorbs more rapidly, losing its biological strength after 2 to 3 months.70 In recent years, surgeons have experienced inflammatory cysts with the implantation of the Ultratine device.70 Servat and Black70 found a statistically significant difference between Endotine and Ultratine and the appearance of enlarging retention cysts (6.91% vs 0%).

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FILLERS

The use of dermal filler for soft tissue augmentation has become increasingly popular in aesthetic practices. Although generally regarded to be a safe modality of treatment, dermal fillers can be associated with significant morbidity. Published literature this year reports several complications of fillers. Malik and associates71 report a patient with polyalkylimide glabellar filler injected 10 years ago, migrated to the temporal area to clinically simulate an arteriovenous malformation. Griepentrog et al,72 in a cadaver study, demonstrated that the location of a significant portion of hyaluronic acid gel following injection to the infraorbital hollows differed from the intended injection plane. Soft tissue structures including fat compartment septa and the orbicularis oculi muscle appear to influence the resting position of hyaluronic acid gel.71 Careful attention should be used to avoid overfilling the thin soft tissue layers of the medial infraorbital hollows or tear trough.71 Kashkouli et al73 illustrated the issue of hyaluronic acid gel filler migration from the area of tear trough deformity to involve the inferior oblique muscle and cause diplopia. It completely resolved following hyaluronidase injection.73 In contrast, migrated calcium hydroxyapatite (Radiesse) can pose problems.74 Vrcek and associates74 have used saline injection and erbium laser treatment to resolve migrated Radiesse. Park et al75 have reported a series of 12 patients with arterial embolization following filler injection. Seven, 2, and 3 patients had ophthalmic, central retinal, and branch retinal artery occlusions, respectively. Injected materials included autologous fat (7 cases), hyaluronic acid (4 cases), and collagen (1 case), and injection sites were the glabellar region (7 cases), nasolabial fold (4 cases), or both (1 case). Injected autologous fat was associated with worse final best corrected visual acuity than the other materials. All patients with ophthalmic artery occlusion had ocular pain and no improvement in best corrected visual acuity. Severe visual loss and orbital infarction have been reported following periorbital aesthetic poly-L-lactic acid injection.76 It is recommended that ophthalmic examination and brain magnetic resonance imaging should be performed in patients with ocular pain after filler injections.76 It is important to minimize the risk of migration of fillers by understanding the anatomy and soft tissue barriers and boundaries, identifying and keeping to the intended anatomical plane, confirming the plane as the injection progresses, and avoiding an overfill or vigorous massage.71–76

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BLEPHAROSPASM

The cause of blepharospasm is unknown in most of the patients. If neuroimaging is obtained, it seldom reveals a structural lesion. Gilbert et al77 have reported a patient with pontine capillary telangiectasia resulting in blepharospasm. Choe and Gausas78 reported a case of occult small cell carcinoma lung with paraneoplastic blepharospasm and levator apraxia related to anti-Hu (type 1 antineuronal) antibodies. Although rare, systemic associations should be considered in atypical cases of blepharospasm.78

Botulinum toxin chemodenervation is the current standard of care for benign essential blepharospasm and hemifacial spasm. Lee and colleagues79 assessed the change in quality of life and function following treatment with botulinum toxin using the Glasgow Benefit Inventor and Blepharospasm Disability Index scores and reported that there is significant patient-reported improvements in quality of life and functional ability with a strong positive correlation between both scores. Chundury et al80 studied the subjective outcomes and preferences in patients with benign essential blepharospasm (treated with both onabotulinum toxin A [BoTox] and incobotulinum toxin A [Xeomin]) and found that patients who prefer Xeomin over BoTox had a statistically significant shorter treatment interval. In addition, those who preferred Xeomin thought it was more effective, whereas those patients who preferred BoTox thought it had a longer duration.80

The treatment of hemifacial spasm with higher doses of botulinum toxin can create disfiguring and undesirable weakness in the lower face during active facial movements.81 The use of 1- to 2-mL asymmetric hyaluronic acid gel filler injections to the lower face provides a refinement allowing for a lowered neurotoxin dose.81 By asymmetric injection, fillers can create an improvement in lower face symmetry by usual bulk filler effect. In addition and unique to hemifacial spasm, slightly greater soft tissue mass-weight created by the filler can serve to have a ballasting effect stabilizing the involuntary lower face movement. Because unilateral neurogenic facial weakness is associated with the involved side, facial movement is particularly susceptible to the mass effect of the filler.81 The conventional filler effect also further reduces asymmetric nasolabial folds and marionette lines.81 Fifteen of 18 patients with lower facial spasms found the filler toxin combination an improvement over toxin alone.81

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EYELID TUMORS

Capillary Hemangioma of Infancy

Capillary hemangioma of infancy is the most common eyelid tumor in children. It appears shortly after birth and usually begins to involute spontaneously in early childhood. Treatment is necessary because of vision loss secondary to amblyopia induced by astigmatism, ptosis, or globe displacement. Therapeutic options include intralesional, topical, or systemic corticosteroids and systemic propranolol as first line of treatment, and interferon, vincristine, cyclophosphamide, topical imiquimod, focal laser photocoagulation, and surgical excision as secondary therapeutic options.82 Vassallo et al82 report results of their prospective study including 14 patients with capillary hemangioma of infancy. They found that oral propranolol in the dose of 2 mg/kg of body weight for 4 months was adequate to resolve the tumor in 10 children younger than 12 months, whereas 2 children older than 5 years also showed treatment benefit.82 Hypotension and allergy prompted withdrawal of 2 children from the protocol.

Xue and Hildebrand83 found the beneficial role of topical timolol maleate 0.5% gel in resolving superficial capillary hemangioma of infancy. The efficacy of cutaneously applied timolol maleate may be attributed to several factors.83 The barrier function of skin does not appear to be fully developed until the age of 1 year. The lipophilic nature of timolol maleate would be expected to enhance transcutaneous absorption.83 Moreover, timolol is approximately 10 times more potent than propranolol as a β-blocker in head-to-head comparisons.83 Chambers and associates84 evaluated the efficacy of timolol maleate 0.25% gel for the treatment of cutaneous capillary hemangioma of infancy and reported sustained success in non–vision-threatening lesions with a superficial component. Role of anti–vascular endothelial growth factor drugs in the management of capillary hemangioma of infancy is currently being explored. Davies and associates85 documented potential benefits of anti–vascular endothelial growth factor agents in a rat model.

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Xanthogranuloma

London and associates86 reported 2 cases of adult-onset asthma associated with periocular xanthogranuloma and found that positron emission tomography–computed tomography is beneficial in diagnosing systemic involvement, and oral steroids are a durable first-line treatment.

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Sweat Gland Tumors

Cutaneous sweat gland neoplasms are classified into 4 broad categories: (1) eccrine and apocrine (mixed origin), (2) eccrine, (3) apocrine, and (4) composite/mixed cutaneous adnexal tumors.87,88 Apocrine adenomas are rare benign tumors of the eyelid in contradistinction to apocrine hidrocystomas (cyst of Moll), which are common and favor the medial and lateral canthal margins.87,88 Palpebral margin location is characteristic of apocrine origin because the Moll gland ducts empty in the cilial follicular infundibulum.87 These are nodular, large, and slow growing and are usually found in the lower eyelid.87 Apocrine hydrocystoma can be bilateral and multifocal as reported by Smith et al.88 Valenzuela and associates89 have reported primary apocrine adenocarcinoma of the eyelid that mimicked a chalazion. They stress the need for aggressive multimodal therapy in such cases. Hoguet and associates90 described 16 patients with mucinous sweat gland carcinoma, a rare and generally clinically unsuspected lesion, which presents with vascularized, focally cystic, nonulcerated eyelid margin lesion. Mucin-producing sweat gland carcinoma pathologically represents a continuum, from an in situ lesion to a classic, invasive mucinous carcinoma.90 Immunohistochemical evidence of neuroendocrine differentiation can be observed in all lesions and does not appear to have a prognostic significance, arguing against the utility of immunohistochemical subtyping of mucinous sweat gland carcinomas.90

Shah and colleagues91 reported a case of Merkel cell carcinoma that presented with multiple left lower eyelid conjunctival nodules, intense conjunctival erythema, and ipsilateral cervical lymphadenopathy. An incisional biopsy helped diagnose Merkel cell carcinoma with a positron emission tomography scan showing distant metastatic disease. The combination of a presentation of conjunctival nodules and erythema, location in the lower eyelid and the conjunctiva, and the presence of metastatic disease on diagnosis make this an unusual case.91

Benign papillomas of the eyelid are very common lesions that can be excised for cosmetic or functional indications. However, significant morbidity can occur after excision of extensive lesions involving the eyelid margin and lash line. Lee and Nelson92 have shown the efficacy of intralesional interferon α2b in the treatment of an extensive eyelid margin and lash line squamous papilloma.

Cutaneous horn is a skin lesion composed of compacted keratin. The hyperkeratotic activity in the base lesion results in an unusually cohesive keratinized material and the formation of a protruding keratin horn.93 Various types of associated lesions can be found at the base of the keratin mound, which may be benign, premalignant, or malignant.93 Tambe and associates93 studied 25 specimens of cutaneous horns. Of the base lesions, 8% were malignant, 28% were premalignant, and the remaining 64% were benign. Analysis of the findings on clinical presentation revealed no clinical indicators to correlate with the final histology, thus emphasizing the role of complete excision of the cutaneous horn with a lucent margin and preferably cryotherapy to the excision base.93

Actinic keratoses are epidermal dysplasias or carcinomas in situ derived from neoplastic keratinocytes and occur after prolonged sun exposure.94 They may progress to invasive squamous cell carcinoma (SCC), the risk of progression being as high as 8% per year.94 It is not possible to determine clinically which lesions will progress to SCC, and hence, treatment of all lesions is generally advisable. A wide spectrum of management strategies includes ablative treatments such as laser and cryotherapy, photodynamic therapy, surgical excision, and topical treatments such as 5-fluorouracil and topical nonsteroidal anti-inflammatory drugs.94,95 The treatments most commonly used in ophthalmology are excision and cryotherapy.94,95 Batra and associates94 have used 3% topical diclofenac gel in 2.5% hyaluronan gel to manage periocular actinic keratosis with modest success. The use of 5% 5-fluorouracil has been described in the treatment of noninvasive squamous neoplasia. Couch and Custer95 used it to successfully manage periocular actinic keratosis and SCC in situ.

Basal cell carcinoma (BCC) is the most common malignancy of the eyelid in the West. Basal cell carcinoma is typically found in the lower eyelids or medial canthus. Clinically and histopathologically, the most common variants are the noduloulcerative, micronodular, superficial, and infiltrating. Pigmented BCC is rare. Kirzhner and Jakobiec96 studied the clinicopathologic and immunohistochemical characteristics of BCC and concluded that clinical pigmentation was imparted by varying densities and distributions of melanocytes with arborizing dendrites, which were present in all BCCs. Melanophages within the stroma and basaloid cell melanization also contributed to pigmentation. No behavioral or biologic differences in pigmented BCC were documented compared with clinically nonpigmented lesions.96

Mutation in the patched 1 gene (PTCH1) has been implicated in BCC. Vismodegib, an inhibitor of smoothened, which is activated upon binding of hedgehog to Ptc, has been shown to significantly decrease BCC tumor size or produce complete resolution, especially in cases of basal cell nevus syndrome.97 Yin and associates97 described successful outcomes after vismodegib treatment in a patient with basal cell nevus syndrome with numerous bulky lesions of the eyelid and periocular region. Such targeted therapy may be appropriate for patients who are not good candidates for surgery.

Standard management options for BCC include Mohs micrographic-controlled or en face frozen section–controlled surgical excision with subsequent paraffin sections, cryotherapy, radiotherapy, and medical treatment.98 Kvannli and associates99 looked at the percentage of cases of BCC in which further resections were needed beyond the boundaries of the initial excision for complete tumor clearance, using the en face frozen section technique.98 They showed that a significant percentage of lesions needed further resection after the initial frozen section edge checks to achieve clear margins.98 One hundred twenty BCCs had a full-thickness eyelid “wedge” resection, of which 45% needed more than the standard 2 frozen sections taken to achieve clear margins. Eighty-four BCCs were removed using ring resection, of which 35.7% needed more than the standard initial resections (peripheral annulus and deep disc) to achieve clear margins, thus emphasizing the role for a good clinical judgment of the extent of the tumor. On the contrary, the suboptimal nature of the initial resections underlines the inadequacy of clinical judgment and the critical role of histological control. The results were similar for SCCs.98

Orthovoltage external beam radiotherapy is another option for BCCs that are difficult to operate and reconstruct such as those located in the medial canthal area. Krema and associates99 found 94% cure rate in a series of 90 such patients. Orbital exenteration was needed in 5.5% of 506 patients in a large series of BCCs managed at the Orbital Unit of the University of Naples, Italy.100 The need for exenteration for BCC may be significantly higher when the lesion involves a medial canthal location; initial management does not include margin-controlled excision, or pathologic analysis reveals an infiltrative subtype.100

Sebaceoma is a benign sebaceous tumor that has been well characterized in the dermatologic literature and may have systemic implications. Yonekawa and associates101 reported the first fully documented case of sebaceoma occurring in the eyelid. The lesion, they speculated, may have originated from an alveolus of a meibomian gland near the eyelid margin.101

A population-based prospective study from the United Kingdom confirmed sebaceous gland carcinoma (SGC) as a rare cancer in the West.102 Masquerade syndromes result in significant diagnostic delays and increase the risk of pagetoid tumor spread.102 There is considerable variation in the pathological features and surgical management in the United Kingdom, and ocular reconstruction and radical surgery are often required due to delayed presentation.102 The estimated annual incidence was 0.41 cases per million population at a median age of 70 years.102 The location was upper eyelid (54%), lower eyelid (20%), multicentric (14%), and caruncle (12%).102 Most common misdiagnoses included chalazion (42%), BCC (30%), and blepharoconjunctivitis (16%), with median delay in diagnosis of 10 months.102 Pagetoid spread was present in 39%. Misdiagnosis of chalazion and pagetoid tumor spread was associated with a significant diagnostic delay.102 Primary surgical management involved excision with reconstruction (49%), primary exenteration (10%), and Mohs surgery (8%). Only 2% developed metastasis.102

The previously published studies on treatment outcomes and biologic behavior of SGC have not classified the tumors on the basis of size, thickness, or extent at presentation, and thus it is not known whether tumor size is predictive of metastatic behavior. Esmaeli and associates103 studied 50 consecutive cases of SGC and concluded that T category in the seventh edition of the American Joint Committee on Cancer TNM staging system for eyelid carcinoma correlates with outcomes in patients with SGC of the eyelid. No tumors smaller than 12 mm in greatest dimension were associated with distant metastasis or death. T category was significantly associated with disease-specific survival, and disease-specific survival was poorer among patients with T category of T3a or worse. On the basis of their findings, they recommended sentinel lymph node biopsy (SLNB) or at least strict regional lymph node surveillance for patients with eyelid sebaceous carcinoma with tumors of T category T2b or worse or 10 mm or more in greatest dimension.103 Thirteen cases of orbital extension of SGC were reported from India.104 Ten of them had regional lymph node involvement at the time of presentation, all of them to the parotid and 2 of them to level 2 cervical nodes. All of them underwent orbital exenteration, 10 of them had regional lymph node excision, and 7 received postoperative external beam radiotherapy.104 Seven patients had local recurrence, 2 of 7 in the group who received radiotherapy, and 4 of 6 in the group who did not. The authors concluded that orbital exenteration with margin clearance and postoperative external beam radiotherapy may benefit patients with orbital extension of SGC.104

Two-millimeter punch biopsy is a swift and practical diagnostic tool in the outpatient setting. Carneiro and associates105 studied its role in diagnosing malignant eyelid tumors in 50 patients. The indicators of efficacy in the identification of malignancy by 2-mm punch biopsy were sensitivity 88%, specificity 100%, positive predictive value 100%, and negative predictive value 64%. Accuracy was 90% for malignancy and 80% for histological type.105 A positive result with 2-mm punch biopsy is a safe indication for surgical excision of the tumor, whereas a negative result does not necessarily rule out malignancy. In cases of high clinical suspicion, a second biopsy should be taken from a different part of the tumor to rule out malignancy.105

As the quest to minimize the incidence of regional lymph node metastasis intensifies, SLNB is gaining increasing popularity. The SLNB is based on the concept that a tumor preferentially drains to the first relay lymph node.106–108 Radiolabeling of this node makes it possible to obtain a specific biopsy with less morbidity than with extensive lymphadenectomy.106–108 Maalouf and colleagues108 reported it positive in 2 of 17 eyelid and conjunctival tumors. One case of initially negative SLNB recurred after 6 months. Chak et al107 reported 5 cases of periocular invasive SCC, all with positive SLNB in the absence of other signs or evidence of regional or systemic metastasis. The preauricular lymph node was identified as the sentinel lymph node on lymphoscintigraphy in all 5 patients. With a positive sentinel lymph node, the results of SLNB changed the clinical staging and influenced subsequent treatment recommendations for each patient.107 Pfeiffer performed a meta-analysis of 31 publications in the last decade.106 The use of SLNB has evolved greatly in the past decade, and positive SLNB has been reported for melanoma, Merkel cell carcinoma, SGC, and SCC.106–108 Current indications for SLNB are the presence cutaneous eyelid melanomas 1 mm thick or greater, those with more than 1 mitotic figures per high-power field, and/or those with histological ulceration; sebaceous carcinomas 10 mm in width or greater; and Merkel cell carcinomas of any size.106–108 The frequency of false-negative biopsy results seems to be decreasing as more experience is gained with the technical nuances of the procedure and with the complex lymphatic drainage of the head and neck region. Given the emerging data published on feasibility and reported cases of microscopically positive SLNB identified in patients with otherwise normal examination of the regional lymph nodes and normal imaging studies, it seems appropriate to continue to further evaluate SLNB for selected eyelid tumors.106–108

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CONCLUSIONS

Recent advances in the understanding, diagnosis, management, and outcome of the deformities and diseases of the eyelid are extremely encouraging. The utopian goal of an oculoplasty surgeon is to achieve optimal results with minimal intervention. It is important for the practicing oculoplasty surgeons to be familiar with the current literature and adopt the preferred practice standards into their respective practices. Annual reviews such as this aim to provide an overview of the published literature and stimulate the interested subspecialist to explore further.

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REFERENCES

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Keywords:

eyelid; congenital; acquired; infection; inflammation; trauma; tumor; ptosis; entropion; ectropion; lagophthalmos; botulinum toxin; fillers; blepharoplasty

© 2013 by Asia Pacific Academy of Ophthalmology