C L I N I C A L
A N D
E X P E R I M E N T A L
OPTOMETRY CLINICAL COMMUNICATION
Chronic red eye due to amelanotic conjuctival melanoma masquerading as pyogenic granuloma. More than meets the eye DOI:10.1111/cxo.12251
Clin Exp Optom 2015; 98: 283–285 Nikolaos Kopsachilis*† MD PhD Dimitrios Chatzibougias† MD Nikolaos Ziakas§ MD PhD Efstathios Detorakis|| MD PhD Michael Tsatsos*† MD PhD * Moorfields Eye Hospital, London, United Kingdom † Modern Eye Centre Thessaloniki, Greece § 1st Department of Ophthalmology, Aristotle University of Thessaloniki, Greece || Faculty of Medicine, University of Crete, Heraklion, Crete, Greece E-mail: [email protected]
Submitted: 8 April 2014 Revised: 21 September 2014 Accepted for publication: 28 October 2014 Red eye is a common ophthalmic morbidity often attributed to benign inflammatory ocular surface conditions, which can be managed at a primary ophthalmic care setting. Red eye usually refers to injection of the superficial blood vessels of the conjunctiva, sclera or episclera and may be caused by disorders of these or adjacent structures. Differential diagnosis includes a plethora of conditions that are easily diagnosed and treated by general ophthalmologists and therapeutically trained optometrists. Typical red eye conditions include conjunctivitis, blepharitis, iritis, keratitis, acute glaucoma, scleritis, pyogenic granuloma and episcleritis.1 Pyogenic granuloma is an inflammatory lesion of the conjunctiva that usually appears after surgery or even trauma to the conjunctiva. It presents as a fleshy, fast growing, red, pedunculated and vascular mass that bleeds easily. On the other hand, conjunctival malignant melanoma (CM) is a less common but potentially sight- and lifethreatening condition. We present an interesting case of a chronic red eye associated with an amelanotic malignant melanoma. CASE REPORT A 39-year-old Caucasian man was originally referred to our tertiary referral centre with a
three-month history of worsening left ocular irritation and redness. His previous ophthalmic history was unremarkable and his medical history included a road traffic accident that needed tibia reconstruction. He was not taking any regular medication. There was no family history of any malignancy and he was tobacco free for two years after 10 years of smoking. The patient was being managed at a general primary-care centre for presumed pyogenic granuloma of the left eye with dexamethasone 0.1 per cent eye drops four times per day without improvement. Notably he reported a gradual enlargement of the flesh-coloured lump on his temporal left conjunctiva. The dimensions of the nodule were measured by the primary-care ophthalmologist as 3.5 mm by 4 mm. Visual acuity (VA) was 6/6 in each eye. Intraocular pressure was 14 mmHg in each eye. Slitlamp examination showed a nonpigmented nodular lesion of his left temporal bulbar conjunctiva, 5.0 mm from the limbus. The lesion was 4.5 mm by 4.5 mm, had a fleshy albeit translucent appearance and was associated with two bulky feeder vessels (Figure 1A). The right eye appeared normal. Fundoscopy and gonioscopy of the left eye appeared normal with no evidence of pigmentation or neovascularisation of the angle and no evidence of choroidal lesions or masses. After referral to our tertiary referral centre, the patient was assessed and photographed and a detailed history was taken. Indeed, the original provisional diagnosis of pyogenic granuloma appeared plausible due to the appearance of the lesion (Figure 1A) and the fact that pyogenic granulomata are often associated with dilated episcleral vessels. The differential diagnosis of nodular scleritis was considered but as the patient had been pain free since the beginning of the episode and vascular dilation did not include the deep plexus as inspected in both daylight and slit-lamp, it
© 2015 The Authors Clinical and Experimental Optometry © 2015 Optometry Australia
was not considered a likely cause. Likewise, it was not an inflamed hamartoma, as it had increased considerably in size. A hamartoma would have been present from birth. The lesion’s sudden growth (patient noticing the growth and also significant increase in size measured at the slitlamp in our centre compared to the previously measured dimensions) raised the suspicion of malignancy and an excisional biopsy was scheduled. We considered epithelial or an amelanotic malignancy as likely culprits. We performed an uneventful excisional biopsy with mitomycin C (MMC) 0.04 per cent application for two minutes using a no-touch technique under sub-Tenon’s anaesthesia2 and cryotherapy (triple freeze thaw cycles). A clean set of instruments was used after resection of the tumour. After removal of the lesion en block, the specimen was marked with sutures, transferred to a piece of pencil-marked cardboard and sent to pathology in formalin.2 The patient was scheduled for review at two weeks and one month post-excisional biopsy and then every four months, where a thorough examination of the site was made, as well as careful palpation of the submandibular and preauricular lymph nodes. Full serology including liver function, urea, creatinine, glucose, full blood count, haematocrit and coagulation screening was performed to help rule out metastatic spread. Chest X-ray and liver ultrasonography were also unremarkable. The patient was screened for human immunodeficiency virus (HIV) and xeroderma pigmentosa given his relatively young age to have this condition. Histopathologic examination of the specimen revealed a diffuse infiltration of the mucosa by large epithelioid neoplastic cells. The tumor cells had large hyperchromatic nuclei, with often prominent eosinophilic nucleoli. Nests of naevoid cells were observed at the bottom of the lesion. The mitotic activity was low (two per mm2). Clinical and Experimental Optometry 98.3 May 2015
28 3
Amelanotic conjuctival melanoma masquerading as pyogenic granuloma Kopsachilis, Chatzibougias, Ziakas, Detorakis and Tsatsos
Figure 1. Photograph showing (A) a 39-year-old patient with a non-pigmented nodular lesion of his left temporal bulbar conjunctiva, 5.0 mm away from limbus. The lesion was 4.5 mm by 4.5 mm, had a fleshy and translucent appearance and was associated with two bulky feeder vessels. (B) Four weeks and (C) three months after excisional biopsy with mitomycin C 0.04 per cent and cryotherapy showed no evidence of recurrence.
Figure 2. Histopathologic examination of an excised non-pigmented nodular lesion of the bulbar conjunctiva. (A) The specimen shows infiltration of the mucosa by large epithelioid neoplastic cells. The tumour cells had large hyperchromatic nuclei, with often prominent eosinophilic nucleoli. Nests of naevoid cells were observed at the bottom of the lesion. The mitotic activity was low (two per mm2). Tumour thickness was 1.6 mm. There was no ulceration of the epithelium. The neoplastic cells expressed strongly S100 (B) and melan-A (C), which suggests a diagnosis of primary conjuctival melanoma. Ki-67 index was 15 per cent.
Tumour thickness was 1.6 mm. There was no ulceration of the epithelium. The neoplastic cells expressed strongly S100 and Melan A. Ki-67 index was 15 per cent (Figure 2). Based on the histological and immunohistochemical findings, a diagnosis of primary conjuctival melanoma (CM) was made. Ophthalmological review at four weeks and two, four and six months after surgery showed no signs of recurrence. DISUSSION Conjuctival melanoma is a rare ocular tumour that accounts for two to five per cent of ocular malignancies.3 It originates de novo in about five per cent of all cases, from pre-existing conjunctival primary acquired melanosis in 75 per cent and from naevi in 20 per cent.4 Conjuctival melanoma has a Clinical and Experimental Optometry 98.3 May 2015
28 4
recurrence rate as high as 62 per cent and often metastasises to the parotid, preauricular and submandibular lymph nodes. It can be lethal with a mortality ranging from 13 to 44 per cent over 10 years.5–7 Although occurring most commonly in the elderly, these lesions are also seen in young adults and can be associated with xeroderma pigmentosa and HIV infection.8,9 The incidence of primary acquired melanosis with atypia or with malignant melanoma of the conjunctiva has been estimated to be 0.052 cases per year per 100,000 population in Denmark.10 There is evidence that approximately 20 to 25 per cent of patients with conjuctival melanoma have a history or microscopic evidence of a benign conjunctival naevus.11 The age-standardised incidence of conjuctival melanoma in
Sweden is 0.74 cases per one million population in men and 0.45 cases per one million population in women.12 Typically, conjuctival melanoma occurs in Caucasian patients in their early 50s. It is rarely seen in people younger than 20 years. Conjuctival melanoma presents usually as a pigmented nodular lesion usually located at the limbus during the sixth or seventh decade of life. Pigmentation grade can vary and it can also present as an amelanotic lesion. The differential diagnoses include epithelial malignant neoplasm, pyogenic granuloma, hamartoma and nodular episcleritis.13
Adjuvant therapy Topical chemotherapy of conjunctival tumours offers a non-surgical treatment with less dependence on surgical margins. It can © 2015 The Authors
Clinical and Experimental Optometry © 2015 Optometry Australia
Amelanotic conjuctival melanoma masquerading as pyogenic granuloma Kopsachilis, Chatzibougias, Ziakas, Detorakis and Tsatsos
treat tumour extension onto the corneal epithelium and can easily be repeated. This approach also allows for high concentrations of chemotherapy to be delivered directly to the tumour. Topical MMC, interferon (IFN)-α2b or 5FU chemotherapy can be used both as a primary treatment and after excision and cryotherapy of the bulk of the tumour.14 Recurrence rates with positive margins can be up to 50 per cent.15 Different treatment options have been used for the management of positive surgical margins. These include surgical re-excision of the positive margins and the use of the chemotherapeutic agents MMC or IFN-α2b without further surgical excision. Advanced disease or multiple recurrences despite aggressive treatment may require removal of the eye or the entire orbital contents. Ophthalmological review every 4 months is essential to detect early recurrence.
CONCLUSIONS Conjuctival melanoma (especially amelanotic) is a rare ocular tumour that if not treated promptly can have devastating lifethreatening effects. We present an atypical presentation of an amelanotic conjuctival melanoma in an otherwise healthy 39-yearold man. Conjunctival melanoma may masquerade as a ‘red eye’ mimicking other benign ocular surface conditions, which may delay its diagnosis and effective management. A lesion that continues to grow despite optimal treatment should raise the suspicion of an ocular surface neoplasm and should be closely monitored and investigated.
7.
8.
9.
10.
11.
12.
13.
14.
15.
patients with conjunctival melanoma: experience at a cancer center over four decades. Ophthalmology 2001; 108: 2101–2105. Shields CL, Shields JA, Gündüz K, Cater J, Mercado GV, Gross N, Lally B. Conjunctival melanoma: risk factors for recurrence, exenteration, metastasis, and death in 150 consecutive patients. Arch Ophthalmol 2000; 118: 1497–1507. Gaasterland DE, Rodrigues MM, Moshell AN. Ocular involvement in xeroderma pigmentosum. Ophthalmology 1982; 89: 980–986. Waddell KM, Lewallen S, Lucas SB, Atenyi-Agaba C, Herrington CS, Liomba G. Carcinoma of the conjunctiva and HIV infection in Uganda and Malawi. Br J Ophthalmol 1996; 80: 503–508. Gerner N, Nørregaard JC, Jensen OA, Prause JU. Conjunctival naevi in Denmark 1960–1980. A 21-year follow-up study. Acta Ophthalmol Scand 1996; 74: 334–337. Damato B, Coupland SE. Management of conjunctival melanoma. Expert Rev Anticancer Ther 2009; 9: 1227–1239. Kujala E, Tuomaala S, Eskelin S, Kivelä T. Mortality after uveal and conjunctival melanoma: which tumour is more deadly? Acta Ophthalmol 2009; 87: 149–153. Lim L-A, Madigan MC, Conway RM. Conjunctival melanoma: a review of conceptual and treatment advances. Clin Ophthalmol 2013; 7: 521–531. Finger PT, Milner MS, McCormick SA. Topical chemotherapy for conjunctival melanoma. Br J Ophthalmol 1993; 77: 751–753. Tabin G, Levin S, Snibson G, Loughnan M, Taylor H. Late recurrences and the necessity for long-term follow-up in corneal and conjunctival intraepithelial neoplasia. Ophthalmology 1997; 104, 485–492.
REFERENCES 1. Cronau H, Kankanala RR, Mauger T. Diagnosis and management of red eye in primary care. Am Fam Physician 2010; 81: 137–144. 2. Tsatsos M, Karp CL. Modern management of ocular surface squamous neoplasia. Expert Rev Ophthalmol 2013; 8: 287–295. 3. Isager P, Engholm G, Overgaard J, Storm H. Uveal and conjunctival malignant melanoma in Denmark 1943–1997: observed and relative survival of patients followed through 2002. Ophthalmic Epidemiol 2006; 13: 85–96. 4. Folberg R, McLean IW, Zimmerman LE. Malignant melanoma of the conjunctiva. Hum Pathol 1985; 16: 136–143. 5. Werschnik C, Lommatzsch PK. Long-term follow-up of patients with conjunctival melanoma. Am J Clin Oncol 2002; 25: 248–255. 6. Esmaeli B, Wang X, Youssef A, Gershenwald JE. Patterns of regional and distant metastasis in
© 2015 The Authors Clinical and Experimental Optometry © 2015 Optometry Australia
Clinical and Experimental Optometry 98.3 May 2015
28 5
Copyright of Clinical & Experimental Optometry is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
A N D
E X P E R I M E N T A L
OPTOMETRY CLINICAL COMMUNICATION
Chronic red eye due to amelanotic conjuctival melanoma masquerading as pyogenic granuloma. More than meets the eye DOI:10.1111/cxo.12251
Clin Exp Optom 2015; 98: 283–285 Nikolaos Kopsachilis*† MD PhD Dimitrios Chatzibougias† MD Nikolaos Ziakas§ MD PhD Efstathios Detorakis|| MD PhD Michael Tsatsos*† MD PhD * Moorfields Eye Hospital, London, United Kingdom † Modern Eye Centre Thessaloniki, Greece § 1st Department of Ophthalmology, Aristotle University of Thessaloniki, Greece || Faculty of Medicine, University of Crete, Heraklion, Crete, Greece E-mail: [email protected]
Submitted: 8 April 2014 Revised: 21 September 2014 Accepted for publication: 28 October 2014 Red eye is a common ophthalmic morbidity often attributed to benign inflammatory ocular surface conditions, which can be managed at a primary ophthalmic care setting. Red eye usually refers to injection of the superficial blood vessels of the conjunctiva, sclera or episclera and may be caused by disorders of these or adjacent structures. Differential diagnosis includes a plethora of conditions that are easily diagnosed and treated by general ophthalmologists and therapeutically trained optometrists. Typical red eye conditions include conjunctivitis, blepharitis, iritis, keratitis, acute glaucoma, scleritis, pyogenic granuloma and episcleritis.1 Pyogenic granuloma is an inflammatory lesion of the conjunctiva that usually appears after surgery or even trauma to the conjunctiva. It presents as a fleshy, fast growing, red, pedunculated and vascular mass that bleeds easily. On the other hand, conjunctival malignant melanoma (CM) is a less common but potentially sight- and lifethreatening condition. We present an interesting case of a chronic red eye associated with an amelanotic malignant melanoma. CASE REPORT A 39-year-old Caucasian man was originally referred to our tertiary referral centre with a
three-month history of worsening left ocular irritation and redness. His previous ophthalmic history was unremarkable and his medical history included a road traffic accident that needed tibia reconstruction. He was not taking any regular medication. There was no family history of any malignancy and he was tobacco free for two years after 10 years of smoking. The patient was being managed at a general primary-care centre for presumed pyogenic granuloma of the left eye with dexamethasone 0.1 per cent eye drops four times per day without improvement. Notably he reported a gradual enlargement of the flesh-coloured lump on his temporal left conjunctiva. The dimensions of the nodule were measured by the primary-care ophthalmologist as 3.5 mm by 4 mm. Visual acuity (VA) was 6/6 in each eye. Intraocular pressure was 14 mmHg in each eye. Slitlamp examination showed a nonpigmented nodular lesion of his left temporal bulbar conjunctiva, 5.0 mm from the limbus. The lesion was 4.5 mm by 4.5 mm, had a fleshy albeit translucent appearance and was associated with two bulky feeder vessels (Figure 1A). The right eye appeared normal. Fundoscopy and gonioscopy of the left eye appeared normal with no evidence of pigmentation or neovascularisation of the angle and no evidence of choroidal lesions or masses. After referral to our tertiary referral centre, the patient was assessed and photographed and a detailed history was taken. Indeed, the original provisional diagnosis of pyogenic granuloma appeared plausible due to the appearance of the lesion (Figure 1A) and the fact that pyogenic granulomata are often associated with dilated episcleral vessels. The differential diagnosis of nodular scleritis was considered but as the patient had been pain free since the beginning of the episode and vascular dilation did not include the deep plexus as inspected in both daylight and slit-lamp, it
© 2015 The Authors Clinical and Experimental Optometry © 2015 Optometry Australia
was not considered a likely cause. Likewise, it was not an inflamed hamartoma, as it had increased considerably in size. A hamartoma would have been present from birth. The lesion’s sudden growth (patient noticing the growth and also significant increase in size measured at the slitlamp in our centre compared to the previously measured dimensions) raised the suspicion of malignancy and an excisional biopsy was scheduled. We considered epithelial or an amelanotic malignancy as likely culprits. We performed an uneventful excisional biopsy with mitomycin C (MMC) 0.04 per cent application for two minutes using a no-touch technique under sub-Tenon’s anaesthesia2 and cryotherapy (triple freeze thaw cycles). A clean set of instruments was used after resection of the tumour. After removal of the lesion en block, the specimen was marked with sutures, transferred to a piece of pencil-marked cardboard and sent to pathology in formalin.2 The patient was scheduled for review at two weeks and one month post-excisional biopsy and then every four months, where a thorough examination of the site was made, as well as careful palpation of the submandibular and preauricular lymph nodes. Full serology including liver function, urea, creatinine, glucose, full blood count, haematocrit and coagulation screening was performed to help rule out metastatic spread. Chest X-ray and liver ultrasonography were also unremarkable. The patient was screened for human immunodeficiency virus (HIV) and xeroderma pigmentosa given his relatively young age to have this condition. Histopathologic examination of the specimen revealed a diffuse infiltration of the mucosa by large epithelioid neoplastic cells. The tumor cells had large hyperchromatic nuclei, with often prominent eosinophilic nucleoli. Nests of naevoid cells were observed at the bottom of the lesion. The mitotic activity was low (two per mm2). Clinical and Experimental Optometry 98.3 May 2015
28 3
Amelanotic conjuctival melanoma masquerading as pyogenic granuloma Kopsachilis, Chatzibougias, Ziakas, Detorakis and Tsatsos
Figure 1. Photograph showing (A) a 39-year-old patient with a non-pigmented nodular lesion of his left temporal bulbar conjunctiva, 5.0 mm away from limbus. The lesion was 4.5 mm by 4.5 mm, had a fleshy and translucent appearance and was associated with two bulky feeder vessels. (B) Four weeks and (C) three months after excisional biopsy with mitomycin C 0.04 per cent and cryotherapy showed no evidence of recurrence.
Figure 2. Histopathologic examination of an excised non-pigmented nodular lesion of the bulbar conjunctiva. (A) The specimen shows infiltration of the mucosa by large epithelioid neoplastic cells. The tumour cells had large hyperchromatic nuclei, with often prominent eosinophilic nucleoli. Nests of naevoid cells were observed at the bottom of the lesion. The mitotic activity was low (two per mm2). Tumour thickness was 1.6 mm. There was no ulceration of the epithelium. The neoplastic cells expressed strongly S100 (B) and melan-A (C), which suggests a diagnosis of primary conjuctival melanoma. Ki-67 index was 15 per cent.
Tumour thickness was 1.6 mm. There was no ulceration of the epithelium. The neoplastic cells expressed strongly S100 and Melan A. Ki-67 index was 15 per cent (Figure 2). Based on the histological and immunohistochemical findings, a diagnosis of primary conjuctival melanoma (CM) was made. Ophthalmological review at four weeks and two, four and six months after surgery showed no signs of recurrence. DISUSSION Conjuctival melanoma is a rare ocular tumour that accounts for two to five per cent of ocular malignancies.3 It originates de novo in about five per cent of all cases, from pre-existing conjunctival primary acquired melanosis in 75 per cent and from naevi in 20 per cent.4 Conjuctival melanoma has a Clinical and Experimental Optometry 98.3 May 2015
28 4
recurrence rate as high as 62 per cent and often metastasises to the parotid, preauricular and submandibular lymph nodes. It can be lethal with a mortality ranging from 13 to 44 per cent over 10 years.5–7 Although occurring most commonly in the elderly, these lesions are also seen in young adults and can be associated with xeroderma pigmentosa and HIV infection.8,9 The incidence of primary acquired melanosis with atypia or with malignant melanoma of the conjunctiva has been estimated to be 0.052 cases per year per 100,000 population in Denmark.10 There is evidence that approximately 20 to 25 per cent of patients with conjuctival melanoma have a history or microscopic evidence of a benign conjunctival naevus.11 The age-standardised incidence of conjuctival melanoma in
Sweden is 0.74 cases per one million population in men and 0.45 cases per one million population in women.12 Typically, conjuctival melanoma occurs in Caucasian patients in their early 50s. It is rarely seen in people younger than 20 years. Conjuctival melanoma presents usually as a pigmented nodular lesion usually located at the limbus during the sixth or seventh decade of life. Pigmentation grade can vary and it can also present as an amelanotic lesion. The differential diagnoses include epithelial malignant neoplasm, pyogenic granuloma, hamartoma and nodular episcleritis.13
Adjuvant therapy Topical chemotherapy of conjunctival tumours offers a non-surgical treatment with less dependence on surgical margins. It can © 2015 The Authors
Clinical and Experimental Optometry © 2015 Optometry Australia
Amelanotic conjuctival melanoma masquerading as pyogenic granuloma Kopsachilis, Chatzibougias, Ziakas, Detorakis and Tsatsos
treat tumour extension onto the corneal epithelium and can easily be repeated. This approach also allows for high concentrations of chemotherapy to be delivered directly to the tumour. Topical MMC, interferon (IFN)-α2b or 5FU chemotherapy can be used both as a primary treatment and after excision and cryotherapy of the bulk of the tumour.14 Recurrence rates with positive margins can be up to 50 per cent.15 Different treatment options have been used for the management of positive surgical margins. These include surgical re-excision of the positive margins and the use of the chemotherapeutic agents MMC or IFN-α2b without further surgical excision. Advanced disease or multiple recurrences despite aggressive treatment may require removal of the eye or the entire orbital contents. Ophthalmological review every 4 months is essential to detect early recurrence.
CONCLUSIONS Conjuctival melanoma (especially amelanotic) is a rare ocular tumour that if not treated promptly can have devastating lifethreatening effects. We present an atypical presentation of an amelanotic conjuctival melanoma in an otherwise healthy 39-yearold man. Conjunctival melanoma may masquerade as a ‘red eye’ mimicking other benign ocular surface conditions, which may delay its diagnosis and effective management. A lesion that continues to grow despite optimal treatment should raise the suspicion of an ocular surface neoplasm and should be closely monitored and investigated.
7.
8.
9.
10.
11.
12.
13.
14.
15.
patients with conjunctival melanoma: experience at a cancer center over four decades. Ophthalmology 2001; 108: 2101–2105. Shields CL, Shields JA, Gündüz K, Cater J, Mercado GV, Gross N, Lally B. Conjunctival melanoma: risk factors for recurrence, exenteration, metastasis, and death in 150 consecutive patients. Arch Ophthalmol 2000; 118: 1497–1507. Gaasterland DE, Rodrigues MM, Moshell AN. Ocular involvement in xeroderma pigmentosum. Ophthalmology 1982; 89: 980–986. Waddell KM, Lewallen S, Lucas SB, Atenyi-Agaba C, Herrington CS, Liomba G. Carcinoma of the conjunctiva and HIV infection in Uganda and Malawi. Br J Ophthalmol 1996; 80: 503–508. Gerner N, Nørregaard JC, Jensen OA, Prause JU. Conjunctival naevi in Denmark 1960–1980. A 21-year follow-up study. Acta Ophthalmol Scand 1996; 74: 334–337. Damato B, Coupland SE. Management of conjunctival melanoma. Expert Rev Anticancer Ther 2009; 9: 1227–1239. Kujala E, Tuomaala S, Eskelin S, Kivelä T. Mortality after uveal and conjunctival melanoma: which tumour is more deadly? Acta Ophthalmol 2009; 87: 149–153. Lim L-A, Madigan MC, Conway RM. Conjunctival melanoma: a review of conceptual and treatment advances. Clin Ophthalmol 2013; 7: 521–531. Finger PT, Milner MS, McCormick SA. Topical chemotherapy for conjunctival melanoma. Br J Ophthalmol 1993; 77: 751–753. Tabin G, Levin S, Snibson G, Loughnan M, Taylor H. Late recurrences and the necessity for long-term follow-up in corneal and conjunctival intraepithelial neoplasia. Ophthalmology 1997; 104, 485–492.
REFERENCES 1. Cronau H, Kankanala RR, Mauger T. Diagnosis and management of red eye in primary care. Am Fam Physician 2010; 81: 137–144. 2. Tsatsos M, Karp CL. Modern management of ocular surface squamous neoplasia. Expert Rev Ophthalmol 2013; 8: 287–295. 3. Isager P, Engholm G, Overgaard J, Storm H. Uveal and conjunctival malignant melanoma in Denmark 1943–1997: observed and relative survival of patients followed through 2002. Ophthalmic Epidemiol 2006; 13: 85–96. 4. Folberg R, McLean IW, Zimmerman LE. Malignant melanoma of the conjunctiva. Hum Pathol 1985; 16: 136–143. 5. Werschnik C, Lommatzsch PK. Long-term follow-up of patients with conjunctival melanoma. Am J Clin Oncol 2002; 25: 248–255. 6. Esmaeli B, Wang X, Youssef A, Gershenwald JE. Patterns of regional and distant metastasis in
© 2015 The Authors Clinical and Experimental Optometry © 2015 Optometry Australia
Clinical and Experimental Optometry 98.3 May 2015
28 5
Copyright of Clinical & Experimental Optometry is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
