Scleral Melt after Cryotherapy for Conjunctival Melanoma Susan M. Tucker, MD, 1 Jeffrey]. Hurwitz, MD, 1 Charles J. Pavlin, MD, 2 David J. Howarth, MD,3 Nicholas Nianiaris, MDl
c.
Background: The authors report a patient with a cryotherapy-induced scleral melt after combined excision and cryotherapy of a conjunctival melanoma arising within primary acquired melanosis with atypia. Findings: In a 65-year-old white man, a severe scleral melt developed within 1 month of complete excision of a superficial conjunctival melanoma combined with doublefreeze-thaw nitrous oxide cryotherapy to the scleral bed and surrounding conjunctival margins. Ultrasound biomicroscopy showed the degree of scleral thinning. Conclusions: Although many complications associated with cryotherapy have been described in the literature, there are no reports of a scleral melt. Scleral melt is a potential complication of cryotherapy that can occur despite taking precautions and should be monitored in the first few weeks after cryotherapy to the scleral bed of excised conjunctival tumors. Ophthalmology 1993;100:574-577
Since the first report describing the combination of cryotherapy with surgical excision of superficial conjunctival melanomas by Jakobiec and associates 1 in 1980, doublefreeze-thaw cryotherapy as an adjunct to surgery has become well established. 2-9 Whereas Liesegang and Campbell lO found a 60% recurrence rate for focal nodular conjunctival melanoma with surgery alone, Jakobiec and associates6 reported that combined surgery and cryotherapy for focal melanoma with or without primary acquired melanosis resulted in only 3 patients (10%) of 30 developing recurrence, with an average follow-up of 3.5 years. Two of these three patients received a second treatment and were free of disease at 9 and 12 months. Although effective, cryotherapy can be associated with complications that include tarsal floppiness, ptosis, symblepharon,
Originally received: June 25, 1992. Revision accepted: October 23, 1992. I Oculoplastics Service, Department of Ophthalmology, University of Toronto and Mount Sinai Hospital, Toronto. 2 Princess Margaret Hospital, University of Toronto, Toronto. 3 Department of Pathology, Mount Sinai Hospital, Toronto.
The authors have no proprietary interest in the ultrasound biomicroscope. Reprint requests to Jeffrey J. Hurwitz, MD, Department of Ophthalmology, Mount Sinai Hospital, 600 University Ave, Suite 408, Toronto, Ontario, Canada M5G IX5.
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scarring of the substantia propria, descemetocele, anterior uveitis, hypotony, and even phthisis bulbi. 2,5,6,8,9,11 We report a patient with a cryotherapy-induced scleral melt after combined excision and cryotherapy of a conjunctival malignant melanoma arising within primary acquired melanosis with atypia. A scleral melt is a significant complication that should be monitored during the first few weeks after cryotherapy to the scleral bed of excised conjunctival tumors.
Case Report A 65-year-old man was referred for assessment of a right medial conjunctival mass that developed within an area oflongstanding melanosis. The mass had increased in size over a 9-month period. Biopsy ofthis mass showed a conjunctival malignant melanoma of epithelioid cell type arising within primary acquired melanosis with atypia. There was evidence that the underlying premalignant process had not been completely extirpated; therefore, the patient was referred to us for further treatment. Results of examination after the biopsy showed a mobile 2.5 X O.5-mm pigmented nodule ofthe conjunctiva at the plica with associated ocular melanosis which extended inferiorly into the palpebral aperture and superiorly (Fig 1). There was no preauricular or submandibular lymphadenopathy. Results of the general examination and systemic workup including investigations for inflammatory, collagen, vascular, and autoimmune disorders were normal.
Tucker et al . Scleral Melt after Cryotherapy
Left, Figure 1. Photograph of the right eye after the initial biopsy shows a pigmented nodule at the plica with associated melanosis. Right, Figure 2. Photograph of right eye shows severe scleral thinning inferonasally.
Because of its superficial nature, the lesion was treated with simple excision and nitrous oxide cryotherapy. After subconjunctival injection of2 ml of2% xylocaine without epinephrine, a 2.3 X 0.7-cm elliptical area of pigmented conjunctiva with a 2.0-mm margin of apparently healthy conjunctiva was excised. Tenon's fascia was left intact over bare sclera, and this bed as well as the surrounding conjunctival margins received doublefreeze-thaw cryotherapy with nitrous oxide using a retinal cryoprobe. A temperature of - 30°C for 5 seconds was applied for each application, and probe imprints were not overlapped. A thermocouple was not used to monitor the core temperature achieved at each treatment site. The procedure appeared unremarkable with no apparent complications, and the patient was discharged with an antibiotic ointment to apply twice daily to the right eye for 7 days. Results of histopathologic examination of the specimen showed residual primary acquired melanosis of the conjunctiva with severe atypical melanocytic hyperplasia. The surgical margins were negative, and there was no evidence of extension to the sclera. The patient's course was unremarkable until 1 month later when he noticed a progressive bluish discoloration of his right medial conjunctiva. However, the patient only became alarmed when associated severe right ocular pain, redness, and bifrontal headache subsequently developed. He was examined at this point and found to have a decrease in corrected visual acuity in the right eye from 20/25 to 20/60. A large, bulging, pear-shaped area of extreme scleral thinning 11 mm in length came within 2 mm of the limbus and 5 mm of the right caruncle (Fig 2). There also was an extended area of mild thinning superior to this. There was inflammation of the surrounding episclera, sclera, and anterior chamber; however, the cornea and anterior segment were otherwise unremarkable. The intraocular pressure was 10 mmHg in the right eye and 16 mmHg in the left. To document the extent and severity of the scleral melt, ultrasound biomicroscopy was done using a 62-MHz transducer. The ultrasound biomicroscope is a new imaging tool which allows subsurface imaging of the intact eye at microscopic resolution. 12•13 This imaging showed an area of scleral thinning commencing close to the angle and gradually decreasing in thickness (Fig 3). The thinnest area measured only 90 ~m in thickness using a sound speed of 1640 m/second in sclera. We believe that the initial asymptomatic scleral melting process had developed a secondary inflammatory component that led to further melting. The patient
was therefore treated with prednisone (30 mg daily) along with steroid drops hourly, homatropine drops twice daily, and erythromycin ointment at night, with resolution of ocular pain, scleral inflammation, and no progression of thinning clinically or by ultrasound biomicroscopy. The systemic and topical steroids were gradually tapered over 4 months and then discontinued. Results of repeat examination 3 months after stopping the steroids showed a corrected visual acuity in the right eye of 20/30. Vascularization and healing of the thinned sclera were evident. With no further progression of scleral thinning, surgical scleral reinforcement was not required.
Discussion It is generally agreed that the most significant factor in
assessing prognosis and risk for metastatic spread with conjunctival melanomas is lesion depth of more than 0.8 mm. 14- 17 Other adverse prognostic factors such as extent of involvement (multifocal/multicentric versus unifocal) and primary acquired melanosis sine pigmento (microscopic but not clinically detectable primary acquired melanosis)18 stress the importance of treating possible residual invasive cells at the surgical margin. It is equally important to extirpate primary acquired melanosis with atypia because patients in high-risk groups (those with epithelioid melanocytes and pagetoid spread of melanocytes to the more superficial epithelial levels) have a 75% to 90% chance of developing malignant melanomas. 19 Because surgical .margins are frequently microscopically positive on permanent histopathology, adjunctive radiotherapy or cryotherapy to the scleral bed and surrounding areas of flat pigmentation at the time of surgery have been described. 1-9 This can limit extensive conjunctivectomy and even avoid exenteration in certain situations. Many ophthalmologists prefer adjunctive cryotherapy over radiation therapy because of the well-known significant ocular side effects of radiation therapy.
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Figure 3. Ultrasound biomicroscope cross-section through the sclera adjacent to the angle. The scleral margins (broad arrows) can be differentiated from overlying and underlying tissue by the change in reflectivity. The sclera can be seen to gradually decrease in thickness as one moves away from the region of the scleral spur (narrow arrow), measuring only 90 /lm at its thinnest section.
Adjunctive cryotherapy for the surgical removal of conjunctival melanomas was first described in 1980 by lakobiec and associates. I Subsequent ultrastructural studies proved melanocytes were more sensitive to cryoinsult than surrounding squamous cells, and indeed, melanocytes are destroyed at -10°C compared with -30°C required for squamous cells.? Cryotherapy works by a combination of mechanical cell injury, ischemic necrosis, and an immunologic response to releasing tumor antigens. 2o The double-freeze-thaw technique has ~esu1ted in the optimal balance between cellular destructIon and ocular side effects. II ,20 In our patient, Tenon's fascia was left intact, the cryotherapy temperature did not exceed -30°C with the nitrous oxide cryoprobe, and probe imprints were not overlapped. Despite these precautions, a scleral melt developed in the treated area with resulting extreme scleral thinning which was accelerated by a delayed secondary inflammatory component. It is possible that our application of cryotherapy was too heavy, and this may possibly ~e avoided by aiming for higher temperatures of apprOXImately -10° to -15°C which are known to be adequate for destroying melanocytes, monitoring core temperature with thermocouple, limiting application time to 3 to 5 seconds, and using a wider-based cryoprobe than the retinal probe for a more even distribution of temperature across the treated area. Weare not aware of any other reports of scleral melting after cryotherapy. Scleral thinning is a potential complication that can occur despite taking precautions, and should be monitored, especially in the first few weeks after cryotherapy.
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References \. Jakobiec FA, Brownstein S, Wilkinson RD, et al. Combined surgery and cryotherapy for diffuse malignant melanoma of the conjunctiva. Arch Ophthalmol 1980;98: 1390-6. 2. Lommatzsch PK, Lommatzsch RE, Kirsch I, Fuhrmann P. Therapeutic outcome of patients suffering from malignant melanomas of the conjunctiva. Br J Ophthalmol 1990;74: 615-19. 3. Divine RD, Anderson RL. Nitrous oxide cryotherapy for intraepithelial epithelioma of the conjunctiva. Arch Ophthalmol 1983; 10 1:782-6. 4. Jakobiec FA, Brownstein S, Wilkinson RD, Katzin HM. Adjuvant cryotherapy for focal nodular melanoma of the conjunctiva. Arch Ophthalmol 1982; 100: 115-8. 5. Jakobiec FA, Brownstein S, Albert W, et al. The role of cryotherapy in the management of conjunctival melanoma. Ophthalmology 1982;89:502-15. 6. Jakobiec FA, Rini FJ, Fraunfelder FT, Brownstein S. Cryotherapy for conjunctival primary acquired melanosis and malignant melanoma. Experience with 62 cases. Ophthalmology 1988;95: 1058-70. 7. Jakobiec FA, Iwamoto T. Cryotherapy for intraepithelial conjunctival melanocytic proliferations. Ultrastructural effects. Arch Ophthalmol 1983;101:904-12. 8. Brownstein S, Jakobiec FA, Wilkinson RD, et al. Cryotherapy for precancerous melanosis (atypical melanocytic hyperplasia) of the conjunctiva. Arch Ophthalmol 1981 ;99: 1224-3\. 9. Peksayar G, Soytiirk MK, Demiryont M. Long-term results of cryotherapy on malignant epithelial tumors of the conjunctiva. Am J Ophthalmo! 1989;107:337-40.
Tucker et al . Scleral Melt after Cryotherapy 10. Liesegang TJ, Campbell RJ. Mayo Clinic experience with conjunctival melanomas. Arch Ophthalmol 1980;98: 1385-9. I I . Wingfield DL, Fraunfelder FT. Possible complications secondary to cryotherapy. Ophthalmic -Surg 1979;10(8):47-55. 12. Pavlin CJ, Sherar MD, Foster FS. Subsurface ultrasound microscopic imaging of the intact eye. Ophthalmology 1990;97:244-50. 13. Pavlin CJ, Harasiewicz K, Sherar MD, Foster FS. Clinical use of ultrasound biomicroscopy. Ophthalmology 1991 ;98: 287-95. 14. Silvers DN, Jakobiec FA, Freeman TR, et al. Melanoma of the conjunctiva: a clinicopathologic study. In: Jakobiec FA, ed. Ocular and Adnexal Tumors. Birmingham, AL: Aesculapius 1978;583-99.
15. Breslow A. Thickness cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg 1970; 172:902-8. 16. Folberg R, McLean IW, Zimmerman LE. Conjunctival melanosis and melanoma. Ophthalmology 1984;91:673-8. 17. Folberg R, McLean IW, Zimmerman LE. Malignant melanoma of the conjunctiva. Hum Pathol 1985;16:136-43. 18. Griffith WR, Green WR, Weinstein GW. Conjunctival malignant melanoma originating in acquired melanosis sine pigmento. Am J Ophthalmol 1971;72:595-9. 19. Folberg R, McLean IW, Zimmerman LE. Primary acquired melanosis of the conjunctiva. Hum Pathol 1985;16:12935. 20. Wilkes TD, Fraunfelder FT. Principles of cryosurgery. Ophthalmic Surg 1979; 10(8):21-30.
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