canthal ligament, and the lateral horn of the levator aponeurosis is cut. In all cases the skin crease is reformed by including tarsus in the closure.

1.6.3 Botulinum Toxin

In early active TAO, when medical treatment is still ongoing and/or while waiting for the thyroid function to stabilise, lid surgery for upper lid retraction is inadvisable, except in severe cases of corneal exposure. This is because both the shortand long-term results of surgery performed at this active stage of the disease are extremely variable and associated with a high failure rate, and as a result often require several further corrective operations. During this time, temporary lid lowering may be required to alleviate symptoms of exposure if topical treatment and nocturnal taping is ineffective. This can be achieved with botulinum toxin.

Patient selection: ocular discomfort is very often a complaint of patients with upper scleral show associated with early TAO. This is due to inflammation as well as exposure from incomplete blinking by day and incomplete lid closure at night (lagophthalmos). They are also distressed by their appearance. Conventional treatment with topical lubrication and taping the lids/ creating moisture chambers at night may be ineffective. Patients may also be allergic to certain topical treatments. Even after the acute phase is over, patients may decline conventional surgery. In all these cases, the injection of botulinum toxin in the upper lid will give patients temporary relief of their symptoms [21, 73]. They must be made aware that this is only a temporary measure.

Method: botulinum toxin can be injected through the cutaneous or conjunctival route. The cutaneous route, high through the upper lid with the patient looking down, leads directly to the levator palpebrae superioris muscle in the superior orbit. Between 2.5 and 5 U of Botox (c.10–20 U of Dysport) are injected. It is usual to start with a low dose and top up if required. For the conjunctival approach, a few drops of topical anaesthetic drops are instilled into the upper fornix before everting the upper lid. Again starting with the lower dosage, between 2.5 and 5 U of Botox (c. 10–20 U of Dysport) are injected sub-conjunctivally 5 mm above the upper border of the tarsal plate, and

this can be topped up as required. By this route, the toxin will affect Muller’s muscle and possibly, by diffusion, some of the lower fibres of levator palpebrae superioris.

Within 2 or 3 days, most, if not all, patients experience some improvement in the amount of lid retraction, but the amount varies and includes ptosis. Some also experience transient diplopia. Both ptosis and diplopia can last up to 3 or 4 weeks, depending on the amount of toxin injected and the state of the levator and rectus muscles prior to the injection. The sub-conjunctival approach may cause less diplopia as the bolus of toxin is further away from the superior rectus than that injected directly through the skin into the levator muscle. It is also easier to administer.

Ptosis induction for corneal protection: botulinum toxin produces a temporary ptosis of the levator muscle which can last several weeks. A protective ptosis may be required, for example, in patients with indolent corneal ulcers. The amount of toxin required to produce a sufficiently effective ptosis will depend on the state of the levator and its aponeurosis. It will also affect superior rectus function, particularly if injected through the skin. This in turn will temporarily disturb the normal Bells’ phenomenon, which is necessary for nocturnal corneal protection. Generally, in a noninflamed or fibrotic levator palpebrae muscle (unlike in TAO), up to 5 U of Botox injected by the conjunctival approach (c. 20 U Dysport) will result in total ptosis within 2 days and will last several weeks.

1.7 Lid Tumours

1.7.1 Mohs’ Micrographic Surgery

When removing a well defined cutaneous basal cell carcinoma (BCC) or squamous cell carcinoma (SCC), orthodox teaching suggests that a rim of up to half a centimetre of clinically normal looking skin be taken as part of the excision to ensure clearance; 9–10 mm margins are necessary for complete removal of morpheaform BCCs and tumours larger than 2 cm in diameter [14]. Traditional histological examination of excised tumour involves vertical sections, which “bread-loaf” the specimen and its few extra millimetres of “normal” tissues to account for microscopic

extensions. This method not only sacrifices normal tissue but also examines histologically only a small percentage of the tumour area. Mohs’ micrographic surgery (MMS) allows for a much higher percentage of the tumour margin to be microscopically examined and better preserves unaffected tissue.

The essence of MMS is to minimise normal tissue loss while ensuring histological clearance. As a result, it aims to keep to a minimum the size and depth of defects following tumour excision, thus simplifying reconstruction of the defects. The history of its development is worth telling as it is an example (not unlike Ridley and the intraocular lens) of a good idea ahead of its time, which was finally adopted as a gold standard when some of its logistics had been simplified.

Mohs was a general surgeon at the University of Wisconsin and pioneered a form of tumour excision in the 1930s. He found that injecting a 20% zinc chloride solution into a tumour induced necrosis in both tumour and the immediately surrounding normal tissue. He also noted that microscopic examination of this necrotic tissue showed well-preserved tumour and cell histology, the same as when the tissue has been excised and immersed in a fixative solution. This fixed tissue technique formed the basis for a method by which cancers could be excised under complete microscopic control [50, 51].

A zinc chloride paste, rather than an injection, was developed. When applied to the patient’s lesion, it allowed in vivo tissue fixation and microscopic excision. This fixed-tissue chemosurgery provided very high cure rates. However, the zinc chloride application was uncomfortable and obtaining histological clearance was very time consuming. Additionally, the surgeon had to wait for sloughing of any remaining fixed tissue postoperatively before reconstruction could be performed. Furthermore, when the defects were left to heal by secondary intention, some led to cosmetically unacceptable results. The combination of these factors led to minimal adoption of this method by others.

In 1953, whilst filming his technique, an involved margin led to a delay. Mohs processed the last few layers using horizontal frozen sections, without fixative, in order to speed up the process. This worked so well that he continued to apply this method and the fresh tissue technique was established. By the late 1960s, it became evident that the fresh tissue technique obtained close to a 0% recurrence rate for basal

and squamous cell carcinomas excised in this way. Wide acceptance of the fresh-tissue technique increased substantially after the publication of Tromovitch and Stegman’s series in 1974 and Mohs’ series in 1976, forty years after the original idea was formulated [70]. The fresh-tissue technique has the additional advantage of being less painful than the fixed tissue method and allowing faster reconstruction. This method is now the most commonly performed approach to Mohs’ surgery.

Fresh tissue technique method: after marking the tumour margins with a pen, the area is infiltrated with vasoconstrictive local anaesthetic. Sometimes the central “core” tumour is debulked with a curette. The tumour is then carefully orientated and either tattooed (e.g. with methylene blue) or marked (e.g. with sutures, or superficial incisions). Following this, the tissue is excised with the scalpel angled at 45° to the skin to bevel the edge, to facilitate histological processing using a small border (1–3 mm). The excision is continued circumferentially around the tumour at a 45° angle and under the skin parallel to the surface so that the deep margin is excised horizontally. Using the same method of orientation as above, a map of the defect is drawn and the excised disc of tissue is divided and the edges of the specimen are colourcoded with tissue dyes (Fig. 1.19). Horizontal “en face” frozen sections of 5–7 mm thickness are shaved off the entire surface of the base of each section of the disc using a cryostat. The sections are then stained with hematoxylin-eosin and the Mohs’ surgeon, who also serves as the histopathologist, examines the slides (Fig. 1.20). Any residual neoplasm is marked on the map in red ink. The surgeon can then precisely remove additional tissue where residual tumour is identified. In this manner, uninvolved tissue is preserved because only the areas with residual tumour are removed. The patient is then sent on for reconstruction of the defect.

Patient selection: Mohs’ surgery lends itself to tumours that grow continuously, with root-like extensions not evident clinically. In these situations, the traditional excision of removing clinically evident tumour will fail either to remove it adequately or require a large volume of macroscopically normal tissue to be sacrificed to ensure clearance. The bulk of Mohs’ surgery is performed on BCCs and SCCs and the technique is especially helpful where better cosmetic results are

desired (especially on the face). In the US and Australia, access to a Mohs’ surgeon is almost universal. In Europe, and the rest of the world, this is not the case and selection criteria need to be applied. Mohs’ surgery is therefore reserved for certain cases including the following: recurrent or incompletely excised BCC or SCC; primary BCC or SCC with indistinct borders; lesions located in high-risk areas such as the medial canthus; tumours with aggressive clinical behaviour (e.g. rapidly growing); large tumours (>15mm diameter); tumours with an aggressive histological subtype (e.g. morpheaform BCC, perineural invasion or poorly differentiated); tumours arising in sites of previous radiation therapy; tumours arising in immuno-sup- pressed patients, high risk hereditary or genetic predisposition (e.g. Gorlin’s syndrome patients); tumours in young patients.

In general, complications from MMS are few and usually minor. Similar to other skin defect repairs, the most common complications include post-operative haematoma formation, wound dehiscence, flap necrosis, graft failure, infection, contact dermatitis to antibiotic ointments or dressing materials, excessive

Fig. 1.20 H and E stained “en face” frozen sections

granulation formation, keloid and/or hypertrophic scar formation, hyper-pigmentation and/or hypo-pigmenta- tion, and recurrence of the tumour.

MMS is a minimally invasive technique which has several major advantages. By using a microscopically controlled method of tumour excision, it minimises the healthy tissue sacrifice upon which traditional methods rely, thus leaving smaller defects requiring repair.

Another benefit is that it is the same person who excises the tumour, orientates the tissue specimen and examines its entire periphery, repeating the process until tumour free margins are confirmed, tracing and eradicating areas of tumour that are invisible to the naked eye. It has proved to be a highly effective means of treating common skin cancers and has an unrivalled low recurrence rate. Five-year recurrence free rates have been reported as high as 100% for primary BCCs and over 92% for recurrent BCCs [47, 48]. MMS has also been reported to have a low recurrence rate for SCC at under 4% [46]. Although these two tumours numerically make up the vast bulk of periocular skin malignancies, MMS has also been successfully applied to other periocular tumours [4]. Lastly, when other standard methods have been unsuccessful, MMS surgery offers another chance for cure.

However MMS still has a number of disadvantages over standard techniques. It is potentially much more time consuming in relation to direct excision, which is especially true if several stages are required. MMS is performed by specially trained dermatologists who are not universally available. Both these features make the procedure relatively expensive. Although MMS is the most efficacious manner to eradicate periocular BCCs and SCCs when looking at long term cure rate, there is a growing debate when considering parameters other than long-term cure rate [5, 75]. MMS’s main indication is in the treatment of skin tumours that primarily spread by direct extension, that is, tumours that grow contiguously. The use of MMS for the treatment of certain tumours, such as sebaceous gland carcinoma, where there is multi-focality and discontinuous growth patterns, or malignant melanoma with its in-transit metastasis, is controversial as it may fail to adequately treat the full extent of the tumour. Similarly, in very large tumours, for example, with deep penetration into bone, or with extensive perineural invasion or requiring adjuvant treatment, surgical excision will not offer a cure although it will improve patient comfort. Access to MMS may be limited owing to the specialist dermatologist being located at too far a distance from the patient. In these cases, MMS would not be the first choice of treatment.

Optimal functional and aesthetic results are achieved when the dermatologist who excises the tumour works seamlessly with the reconstructive surgeon. Mohs’ surgeons are in the majority dermatologists and they have

assertively increased their own repertoire of experience with flaps and grafts in the past two decades: this has, on occasion, resulted in territorial battles and likely decreased referrals from surgical specialists who would otherwise consider referral of these patients [5]. All the above factors feed into the patient’s decision as to whether MMS is an appropriate technique or a tolerable procedure for them.

1.7.2 Lamella Sparing Tumour Excision

It is traditional for a tumour to be removed by making a full thickness lid resection when the tumour is within 4 mm of the margin. As is often the case with BCCs, particularly the nodular ones with distinct edges, the deep surface of the tumour has not breached or has barely reached the superficial fibres of the orbicularis muscle. If that is so, there would appear to be little reason to remove the posterior lamellar portion of a full thickness excision. Anterior lamellar excision, with fast paraffin histological control, is a useful procedure as it preserves unaffected posterior lamellar tissue. It reduces the amount of reconstruction required and unnecessary morbidity to the patient.

Patient selection: patients with all the following criteria are ideal for this lamella sparing procedure – nodular BCC with distinct margins, less than 15 mm in diameter, primary lesion, not encroaching the horizontal part of the lid margin (i.e. not posterior to the lash line).

Method: After marking a 3-mm margin of apparently clear skin around the tumour, the area is infiltrated with vasoconstrictive local anaesthetic (1:80,000 adrenaline) at the level of orbicularis, to create a natural plane. A chalazion clamp is a useful instrument to stabilise the lid margin, while the marked area is excised with a blade (Fig. 1.21). Haemostasis is achieved with bipolar cautery. The area is padded for 24 h. As the defects are often small, the surgical site is left to heal by secondary intention. The patient is shown how to grease the defect with antibiotic ointment twice daily until a dry crust is formed. This is a combination of serous ooze from the wound and antibiotic cream. This crust loosens and falls off once the wound has epithelialised under it. If the margin defect is repaired surgically, stitches are removed after 5–7