OSSN is primarily managed by complete excision using the traditional “no-touch” technique.17 In the past decade, the use of topical chemotherapy (mitomycin-C and 5-fluorouracil) and immunotherapy (topical or injection interferon alpha-2b) as alternatives to surgical resection of OSSN has been widely reported.18-20 Topical therapy for OSSN can achieve good tumour control, especially in eyes with small tumours and extensive corneal involvement.18-21 Topical chemotherapy and immunotherapy, however, have a longer course of treatment and is reliant on the patient’s capability to administer the drops in a timely and precise manner. In addition, a recent literature analysis by Siedlecki et al concluded that surgical excision is the best primary treatment for OSSN and the use of topical therapy is favoured only as an adjuvant treatment for cases with positive excision margins.21
The “no touch” technique in the surgical management of OSSN involves wide excision without any direct handling of the tumour mass and only manipulating the surrounding normal tissue.17 A 4-mm wide margin is ensured around the conjunctival component, followed by excision of the tumour base.17 Double freeze-thaw cryotherapy is then applied to the resected conjunctival edges.17 Conjunctival reconstruction is done using advancement or sliding flaps, or with the use of an amniotic membrane graft.17 For tumours with scleral involvement, lamellar sclerectomy is additionally performed.17 However, for deeper scleral invasion, deeper sclerectomy is generally avoided for fear of scleral thinning, necrosis and inadvertent perforation. The use of topical therapy is also limited in these eyes as they do not penetrate the sclera.1,16
For deeper scleral invasion in OSSN, radiotherapy has been known to achieve good success.7-16 An important prerequisite is the placement of the plaque over the sclera to cover the entire scleral base of the tumour adequately. The plaque is sutured directly onto the sclera and the duration of the treatment calculated based on the radiation dose, thickness of the scleral invasion and the type of radiation being used. In a report by Lommatzsch who treated 15 patients using strontium-90 (beta radiation) plaque brachytherapy, only 1 eye (7%) was noted to have a delayed recurrence 5 years after the radiation therapy for which enucleation was necessary.8 Of the 15 eyes, 11 eyes (73%) received radiation as a primary treatment after an incision biopsy to confirm the diagnosis.8
Lecuona described 69 eyes with OSSN that underwent primary surgical excision without lamellar sclerectomy.11 Histopathology revealed either carcinoma-in-situ (n = 28, 41%) or invasive squamous cell carcinoma (n = 41, 59%).11 Although the authors did not analyse the specimen for excision base positivity, margin positivity was noted in 39 eyes (57%).11 Regardless of the histopathology result, all patients received plaque radiotherapy with strontium-90.11 Recurrence was noted in 8 eyes (11%), and the authors ascribed it to inadequate radiation coverage.11 Cerezo et al and Kearsley et al also used strontium-90 both as primary therapy in eyes with OSSN and obtained excellent results.10,13 In all these series, histopathology after surgical excision did not guide the use of plaque radiotherapy. Similarly, a study from Liverpool recommended the use of radiation in all cases of invasive OSSN irrespective of surgical clearance.12 In their series, Ru-106 brachytherapy was used as a source of radiation and whenever the tumour location was inaccessible to plaque brachytherapy, proton beam radiotherapy was used.12 In contrast, Arepalli et al described the use of plaque brachytherapy only in those eyes where histopathology confirmed excision base positivity.16 In their case series consisting of 15 eyes with OSSN, all patients primarily underwent excision.16 On histopathology, in addition to the presence of deep scleral involvement in all 15 eyes, 3 eyes (20%) had tumour extension into the anterior chamber and Iodine-125 plaque brachytherapy was used to manage the residual tumour and intraocular extension.16 Of the 15 eyes, 4 developed recurrence at a site remote from the area of irradiation, and the overall eye salvage rate was 67%.16 The authors speculated that immunosuppression is an important underlying factor that could have led to remote progressive recurrence in these cases.16
In our series, we followed a histopathology-guided adjuvant treatment protocol. All eyes with OSSN primarily underwent excision biopsy. Adjuvant radiotherapy using Ru-106 plaque brachytherapy was used only when the excision base was positive for tumour cells on histopathology. In case of anterior chamber extension of OSSN, the authors preferred enucleation. It must be noted that in our series of 42 eyes, 39 eyes (93%) had scleral fixity noted clinically at the time of presentation. This is an important finding that can perhaps help in planning a primary plaque radiotherapy at the time of primary excision biopsy. In our series, of the 5 patients (12%) with tumour recurrence, 2 patients (40%) had hepatitis B infection. The recurrences were noted at a mean duration of 6 months post-plaque tretament and at a site distant from the original tumour, which perhaps indicates aggressive multifocal tumour that evolved over a period of time.
Ruthenium-106 is a source of beta radiation, and like strontium-90, it provides a sharply cut-off, precise, low-penetration radiotherapy which is relatively safe to the deeper and surrounding normal tissue.8-12 This results in fewer side effects as compared to Iodine-125 which is a source of gamma radiation.14-16 Gamma radiation has a deeper penetrability and hence carries a greater chance for cataract and secondary glaucoma, especially when the radiation plaque is placed directly over the cornea, exposing the lens and angle structures to a higher dose of radiation.14-16 While the most frequently reported symptoms with strontium-90 are dry eyes and conjunctival telangiectasias, scleral thinning has also been reported.11,13 In contrast, Kenawy et al did not observe any complications after Ru-106 application in 14 eyes with OSSN.12 However, in a recent single case report of use of Ru-06 plaque for OSSN with corneal endothelial extension, the authors noted sectoral cataract formation at a 4-year follow-up.22 In our series, we noted recurrent corneal epithelial defect in 2 eyes (5%), which was managed conservatively. None of the patients developed cataract or glaucoma at the final follow-up.
In conclusion, ruthenium-106 plaque brachytherapy achieves excellent tumour control in OSSN with scleral invasion. However, the indications for the use of plaque brachytherapy for OSSN differ widely, leading to wide variations in the tumour recurrence and eye salvage rates. Plaque brachytherapy in the management of OSSN must be guided by the histopathology and is best used as an adjuvant therapy for excision base positivity. More studies in this regard are necessary to define the absolute indications for plaque brachytherapy in OSSN.