Sentinel lymph node biopsy (SLNB)

The role of SLNB in ocular SC is controversial. Application of SLNB has been found to be positive in ocular SC.17,39 The rate of regional lymph node metastasis is reported to be as high as 10%–28% in ocular SC.20,27,40 However, 2 other retrospective studies demonstrated low rates of regional metastasis at 1.3% and 4.4%.1,4 The large-scale absence of definitive records of patients’ lymph node status in these studies may explain the statistical diversity. These researchers recommend SLNB or at least strict regional lymph node surveillance for patients with tumors of T2b or worse or 10 mm or more in their greatest dimension.4,27

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However, the Multicenter Selective Lymphadenectomy Trial II found disease-specific survival to be similar at 73 months in patients who underwent complete lymphadenectomy immediately after positive SLNB compared to those who did not.41 Thus, additional rigorous studies are required to verify the utility of SLNB, and an ongoing clinical trial will possibly provide some insights.42

Mohs micrographic surgery (MMS)

MMS consists of the removal and extemporaneous analysis of every skin stratum until disease-free margins are identified. The advent of MMS has given ophthalmologists a reliable method for intraoperative assessment of surgical margins while ensuring maximal preservation of healthy tissue.17Based on MMS appropriate use criteria, MMS is deemed appropriate for SC in all locations, except the inner, outer canthus and cases with orbital involvement. According to a series of retrospective studies from 2001 to 2017, which is reviewed and summarized as below (Table 2), MMS is associated with lower local recurrence rates (6.4%–11%) than wide local excision (11%–36%).16,43

(To view a larger version of Table 2, click here.)

Overall, MMS has been associated with very good outcomes for tumor control and should be considered for all patients with ocular SC.49 The rarity of this tumor precludes large-scale comparative studies, but the existing studies may have provided some clues. Circumstances may be different in the UK, where MMS is not frequently undertaken in ophthalmic/oculoplastic services.

Wide local excision (WLE)

If tissue-sparing techniques are not available, wide surgical excision with margins of normal-appearing tissue at least 5 mm are preferred.7,17 Scheduled map biopsies at the time of WLE may improve the reliability of complete excision. Within the past 15 years, the local recurrence rate after WLE has slightly declined (11%–36%) for ocular SC. This may be due to the increased clinical awareness of SC, leading to an overall earlier stage at diagnosis.7,16,50,51 Among patients who underwent excision with 5 mm surgical margins and paraffin section pathologic analysis, involvement of both eyelids, topical treatments at other clinics, multicentric origin, diffuse pattern, stage T3a, large tumor size, and a nonlobular pattern significantly influenced local recurrence and metastasis.7,16,28,45,50,51 In general, recurrent disease is treated with surgical re-excision. It must be mentioned that in any patient with corneal involvement, incisional cataract surgery should be avoided because disruption of the Bowman membrane may seed carcinomatous cells into the eye.26

Well-designed reconstruction with a flap from neighboring tissue needs to be performed after WLE to restore eyelid function and aesthetics. Despite traditional 2-staged reconstructive surgical methods, a single-staged procedure has also shown optimal outcomes.38,52

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Radiation therapy

Radiation therapy, especially brachytherapy, has been proven as an efficient treatment of ocular SC, facilitating functional and cosmetic preservation of the eyelid with good local control and acceptable toxicity. However, the tumor is generally regarded as resistant to radiation therapy, and high recurrence rates have been reported.10,17,53 Radiation is only employed as adjuvant treatment for locally advanced (stage T3a or higher) or high-risk (pagetoid spread) periorbital SC,49,54,55 perineural invasion, nodal metastasis, or palliative treatment.55,56

To date, numerous case series and case reports have demonstrated a response to radiation therapy in patients who were either poor surgical candidates or who refused surgical treatment. In a study of 13 patients with T3 SC, the local recurrence rate was lower among those who received adjuvant radiotherapy (28%) than among those who did not (83.3%).57 Complications from radiotherapy can be quite extensive and include chronic dry eye, conjunctival keratinization, blepharitis, trichiasis, exposure keratopathy, cataract, optic neuropathy, retinopathy, and even permanent loss of visual acuity.49,56 The risk should be minimized with appropriate shielding and balanced against the obvious morbidity of orbital exenteration.

Cryotherapy and topical chemotherapy

Cryotherapy and topical chemotherapy (mitomycin C) have a certain effect on ocular SC with pagetoid spread to the conjunctiva or cornea.58 For elderly patients who prefer more conservative approaches, they seem to be feasible choices.

In a retrospective case series identifying predictors of ocular surface squamous neoplasm recurrence after surgical resection, the addition of cryotherapy to the margins and scleral bed has been shown to dramatically reduce recurrence rates,59 which may be significant in ocular SC. The side effects of cryotherapy include permanent loss of visual acuity, corneal ulceration, and chronic dry eye. The use of this method is somewhat controversial and is largely surgeon dependent at this point.49 Topical chemotherapy has been used as adjuvant therapy for residual SC in situ. Topical mitomycin C 0.04% 4 times a day for 1 week on and 1 week off has induced clinical tumor regression after 3 cycles in 1 patient and 4 cycles in 2 patients.27,58 This pilot study58 demonstrated complete clearing of intraepithelial pagetoid invasion after topical application of mitomycin C.