- Email: [email protected]
Anterior Segment Optical Coherence Tomography of Conjunctival Nevus
Anterior Segment Optical Coherence Tomography of Conjunctival Nevus Carol L. Shields, MD, Irina Belinsky, MD, Massi Romanelli-Gobbi, BM, Juan Mica Guzman, MS, Douglas Mazzuca, Jr., BS, W. Ross Green, BS, Carlos Bianciotto, MD, Jerry A. Shields, MD Purpose: To evaluate conjunctival nevi using anterior segment optical coherence tomography (AS-OCT). Design: Retrospective interventional case series. Participants: There were 22 eyes of 21 patients with conjunctival nevus imaged with AS-OCT for evaluation and detection of cysts within conjunctival nevi. Intervention: Anterior segment OCT. Main Outcome Measures: Evaluation and detection of intralesional cysts. Results: All margins of the nevus, including the deep margin, could be visualized on AS-OCT with high resolution of the anterior margin in 100% of cases, posterior margin in 82% of cases, and lateral margin in 86% of cases. The nevus was optically dense with homogeneous pattern in all cases. Some degree of deep optical shadowing, mostly from pigmented nevi, was noted in 86%. Intrinsic cysts within the nevus were detected by slit-lamp biomicroscopy in 18 cases (82%) and by AS-OCT in 17 cases (77%). In comparison with histopathologic findings, AS-OCT detected intrinsic cysts with a sensitivity of 80%, specificity of 100%, positive predictive value (PPV) of 100%, and negative predictive value (NPV) of 60%. Slit-lamp biomicroscopy (by experienced observers) compared with histopathology revealed detection of cysts with a sensitivity of 100%, a specificity of 100%, a PPV of 100%, and an NPV of 100%. Conclusions: Anterior segment OCT provides high-resolution imaging of conjunctival nevi with the ability to demonstrate all margins and to provide information on the presence of intralesional cysts, which are important in the diagnosis. The main drawback is optical shadowing of deeper structures from pigment within nevi. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2011;118:915–919 © 2011 by the American Academy of Ophthalmology.
Melanocytic nevus is the most common tumor of the conjunctiva.1 In an analysis of 1643 melanocytic and nonmelanocytic conjunctival tumors, 454 (28%) proved to be nevi.1,2 When assessing only melanocytic conjunctival tumors, the nevus represented 52% of all cases.2,3 In the pediatric population, conjunctival nevus is even more prevalent, representing 64% of 262 pediatric conjunctival tumors in one series.4 The typical clinical features of conjunctival nevus include onset in childhood, pigmentation (84%), location within 1 mm of the limbus in the nasal or temporal bulbar region (90%), and presence of intralesional (intrinsic) cysts (65%), most measuring less than 100 m in diameter.5 Intrinsic cysts are rarely found with simulators of nevus, such as racial melanosis, primary acquired melanosis, and melanoma. Levecq et al6 observed clinically visible intrinsic cysts in 57% of 255 conjunctiva nevi and observed that the presence of cysts was one of the factors predicting surgical excision of the mass, usually by patient preference. On the basis of our experience, intrinsic cysts within nevi are important because they generally infer a benign lesion rather than malignant melanoma.7 Cysts are often tiny and only visible with slit-lamp biomicroscopy. Smaller cysts can remain clinically undetectable and are beyond the resolution of most imaging modalities, including standard ultrasonography, ultrasound biomicroscopy, magnetic resonance imaging, and computed tomography. This report © 2011 by the American Academy of Ophthalmology Published by Elsevier Inc.
explores the role of anterior segment optical coherence tomography (AS-OCT) in the detection of intrinsic cysts within conjunctival nevi.
Materials and Methods The clinical records were reviewed of all patients on the Ocular Oncology Service at Wills Eye Institute, Philadelphia, Pennsylvania, with the diagnosis of conjunctival nevus and imaged with AS-OCT between June 2, 2008 and November 2, 2009. Anterior segment OCT (Visante OCT 3.0; Carl Zeiss Meditec, Dublin, CA) is a high-resolution, non-contact imaging technique that uses an illumination laser source of 1310 nm superluminescent light emission device to penetrate tissue. High-resolution scans can be obtained adjustable in 1-degree increments (10⫻3 mm) with 512 A scans per line sampling. Optical resolution is 18 m in the axial and 60 m in the transverse meridians. Institutional review board permission was obtained. Clinical data were collected regarding demographic patient features at the initial examination, including age, race (African American, Hispanic, Asian, Caucasian), and gender (female, male). Clinical features of the nevus included the amount of intrinsic pigment (dark, intermediate, light, no pigment), nevus thickness (millimeters), basal diameter (millimeters), quadrant location of tumor epicenter (superior, inferior, lateral, medial, diffuse), proximity of nevus to the limbus (millimeters), configuration (flat, dome), feeder vessels (present, absent), intrinsic vessels (present, absent), and intrinsic cysts (present, absent). ISSN 0161-6420/11/$–see front matter doi:10.1016/j.ophtha.2010.09.016
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Ophthalmology Volume 118, Number 5, May 2011 Table 1. Clinical Features of Conjunctival Nevus in 22 Eyes of 21 Patients Feature
No. (%) nⴝ22 Eyes
Intrinsic pigment Dark Moderate Light No pigment Estimated percent pigmentation Mean (median, range) Nevus thickness (mm) Mean (median, range) Nevus basal diameter (mm) Mean (median, range) Quadrant location Superior Inferior Lateral Medial Multiple quadrants involved Distance from limbus (mm) Mean (median, range) Nevus configuration Flat Dome Associated features Feeder vessel Intrinsic vessels Intrinsic cysts
3 (14) 6 (27) 5 (23) 8 (36) 30.9 (10, 0–100) 1.84 (1.5, 0.5–4.0) 7.25 (5.5, 1.5–22.0) 1 (5) 1 (5) 11 (50) 8 (35) 1 (5) 1.0 (0, 0–5.0)
6 (27) 16 (73) 14 (64) 17 (77) 18 (82)
Anterior segment OCT images were evaluated on the basis of intrinsic characteristics of the nevus, including overall optical features (hollow, solid), intrinsic pattern (homogeneous, heterogeneous), nevus thickness (millimeters), basal diameter (millimeters), configuration (flat, dome), and intrinsic cysts (present, absent). Anterior segment OCT images were evaluated for visibility of all tumor margins (good, fair, poor), quality of image (excellent, intermediate, poor), posterior tumor shadowing (present, absent), and degree of posterior tumor shadowing (trace, mild, moderate, severe). For those nevi managed with surgical excision, histopathologic correlation of intrinsic cysts with clinical and AS-OCT was made. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the detection of intrinsic cysts using AS-OCT versus slit-lamp biomicroscopy, AS-OCT versus histopathology, and slit-lamp biomicroscopy versus histopathology.
Results There were 22 eyes of 21 patients with conjunctival nevus evaluated by AS-OCT. The mean patient age at presentation was 23 years (median 15 years, range 3– 61 years). There were 11 male (52%) and 10 female (47%) patients. There were 18 Caucasian patients (85%), 1 African American patient (5%), 1 Hispanic patient (5%), and 1 Asian patient (5%). The clinical features of the nevi are listed in Table 1. The mean nevus thickness was 1.84 mm, and the mean basal diameter was 7.25 mm. Most nevi were located in the medial (n⫽8, 35%) or lateral (n⫽11, 50%) locations with a median distance to the limbus of 0 mm. Intrinsic cysts were found by slit-lamp examination in 18 patients (82%).
Table 2. Anterior Segment Optical Coherence Tomography Features in 22 Eyes of 21 Patients with Conjunctival Nevus Feature Optical features of nevus Hollow Solid Optical intrinsic pattern Homogeneous Heterogeneous Nevus thickness (mm) Mean (median, range) Nevus basal diameter (mm) Mean (median, range) Nevus configuration Flat Dome Visibility of nevus margin Good Fair None All nevus margins visualized Yes No Additional findings Posterior nevus shadowing Intrinsic cysts Posterior nevus shadowing (n⫽19) Trace Mild Moderate Severe
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No. (%) nⴝ22 Eyes 0 (0) 22 (100) 22 (100) 0 (0) 0.7 (0.55,0.1–1.7) 5.0 (4.0,0.3–20.0)
Anterior margin 22 (100) 0 (0) 0 (0)
3 (14) 19 (86) Posterior margin 18 (82) 4 (18) 0 (0)
Lateral margin 19 (86) 3 (14) 0 (0)
22 (100) 0 (0) 19 (86) 17 (77) If pigmented (n⫽12) 5 (42) 2 (17) 1 (8) 4 (33)
If non-pigmented (n⫽7) 5 (71) 2 (29) 0 (0) 0 (0)
Shields et al 䡠 AS-OCT Conjunctival Nevus
Figure 1. Clinical, AS-OCT, and histopathology of cystic conjunctival nevi. Pigmented nevus (A) in the superior bulbar conjunctiva in a 45-year-old man with minimally visible intrinsic cysts. Anterior segment OCT (B) shows homogeneous conjunctival thickening with multiple small intrinsic cysts and confirmation of a multicystic nevus on histopathology (C). Lightly pigmented nevus (D) with prominent feeder and intrinsic vessels in a 15-year-old male. Anterior segment OCT (E) demonstrates numerous intrinsic cysts within a homogeneously thickened mass, confirmed as multicystic conjunctival nevus on histopathology (F). Pigmented nevus (G) with giant intrinsic cysts in a 56-year-old woman. Anterior segment OCT (H) documented multiple large intrinsic cysts expanding the conjunctival mass, confirmed as multicystic conjunctival nevus on histopathology (I). AS-OCT ⫽ anterior segment optical coherence tomography.
With the use of AS-OCT, all 22 lesions appeared homogeneously solid (Table 2). Intrinsic cysts were detected in 17 patients (77%) (Fig 1). Good resolution was found with the nevus anterior margin (n⫽22, 100%) and posterior margin (n⫽18, 82%). Each margin of the nevus, including the deep margin in contact with sclera, could be visualized on AS-OCT in all 22 cases (100%). The overall image quality was judged excellent in 21 cases (95%), intermediate in 1 case (5%), and poor in no case (0%). Some degree of optical shadowing posterior to the nevus was found in 19 cases (86%), more often with pigmented tumors than nonpigmented tumors. The degree of shadowing in the 12 pigmented tumors was trace in 5 (42%), mild in 2 (17%), moderate in 1 (8%), and severe in 4 (33%). Of the 7 nonpigmented tumors, optical shadowing was judged trace in 5 (71%) and mild in 2 (29%) with no more advanced shadowing. Thirteen (59%) of the 22 nevi underwent excision and were histopathologically confirmed as compound nevus in 6 (46%), subepithelial nevus in 5 (39%), and combined nevus in 2 (15%). Intrinsic cysts were present in 10 lesions (77%) and absent in 3 lesions (23%) (Table 3). When compared with histopathology, AS-OCT detected intrinsic cysts in conjunctival nevi with a sensitivity of 80%, a specificity of 100%, a PPV of 100%, and an NPV of 60% (Table 4). When compared with histopathology, clinical examination by slit-lamp biomicroscopy detected intrinsic cysts in conjunctival nevi with a sensitivity of 100%, a specificity of 100%, a PPV of 100%, and an NPV of 100%. When compared with
clinical examination, AS-OCT detected intrinsic cysts in conjunctival nevi with a sensitivity of 94%, a specificity of 100%, a PPV of 100%, and an NPV of 80%.
Discussion Anterior segment OCT is a high-resolution, non-contact imaging modality using superluminescent long wavelength light at 1310 nm to image human tissue. This technology Table 3. Histopathology of 13 Excised Conjunctival Nevi Finding Diagnosis Compound nevus Subepithelial nevus Combined nevus Intrinsic cysts Yes No
No. (%) nⴝ13 Eyes 6 (46) 5 (39) 2 (15) 10 (77) 3 (23)
Combined nevus means combination of compound and subepithelial nevi.
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Ophthalmology Volume 118, Number 5, May 2011 Table 4. Detection of Intrinsic Cysts within Conjunctival Nevus Using Slit-Lamp Biomicroscopy, Anterior Segment Optical Coherence Tomography, and Histopathology Feature Intrinsic cysts Present
No. (%) Patients with Feature AS-OCT n⫽22 eyes 17 (77)
Slit-lamp biomicroscopy n⫽22 eyes 18 (82)
AS-OCT/slit-lamp biomicroscopy n⫽22 eyes Present/present Present/absent
Absent
Present
5 (23)
Slit-lamp biomicroscopy n⫽13 eyes 10 (77)
4 (18)
Histopathology n⫽13 eyes 10 (77)
Absent
3 (23)
3 (23)
Present
AS-OCT n⫽13 eyes 8 (62)
Histopathology n⫽13 eyes 10 (77)
Absent
5 (38)
3 (23)
Absent/absent Absent/present Slit-lamp biomicroscopy/histopathology n⫽13 eyes Present/present Present/absent Absent/absent Absent/present AS-OCT/histopathology n⫽13 eyes Present/present Present/absent Absent/absent Absent/present
17 (100) 0 (0) 4 (80) 1 (20)
10 (100) 0 (0) 3 (100) 0 (0)
8 (100) 0 (0) 3 (60) 2 (40)
AS-OCT ⫽ anterior segment optical coherence tomography.
has numerous applications in human disease, including investigation of cerebral blood flow and stroke, musculoskeletal, and dermatologic conditions, and in the field of oncology, particularly malignancies of the esophagus, gastric region, bladder, lung, and colon. Initial ophthalmic use of OCT was limited to the posterior segment of the eye with imaging of the retina for degenerative and vascular diseases, superficial imaging of the choroid, and imaging of intraocular tumors. Newer modifications of OCT have allowed imaging of the anterior segment of the eye with applications for corneal topography, assessment of angle structure in glaucoma, refractive surgery evaluation, and precise localization of intraocular lens placement and related posterior capsular opacification.8 –14 There is little information on the use of AS-OCT for tumors of the anterior segment.15–17 Pavlin and associates17 used AS-OCT to image 18 eyes with iris and iridociliary tumors, mostly iris nevus, iris melanoma, and iris pigment epithelial cysts. They found AS-OCT suitable for imaging small nonpigmented lesions. However, large lesions and pigmented lesions were incompletely imaged with AS-OCT and better depicted with ultrasound biomicroscopy. This report investigated the use of AS-OCT for imaging specifically conjunctival nevi. Anterior segment OCT provided clear images of all nevus margins. The basal margin of the nevus showed a clear separation from the underlying sclera and without scleral invasion in all cases. The optical quality of the nevus was homogeneous and solid in every case. Imaging was ideal for nonpigmented nevi with little shadowing artifact. Darkly pigmented nevi displayed more optical shadowing with slightly reduced imaging of the basal margin. Intralesional cysts were clearly visualized in 77% of cases, and all margins of the cyst could be seen in each case. In the published literature, there is scant information on AS-OCT for conjunctival tumors. Buchwald et al18 studied
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13 conjunctival lesions with AS-OCT, including pterygium, primary acquired melanosis, and 4 patients with nevus.18 They showed images of homogeneous optical reflectivity and the presence of tiny cysts in 2 cases. They concluded that AS-OCT was more capable of showing intrinsic cysts compared with ultrasound biomicroscopy. Lin et al19 indicated that in pigmented nevus, the visibility of cysts might be clinically camouflaged by pigment but imaged with ultrasound biomicroscopy, emphasizing the importance of this in establishing the diagnosis.19 In conclusion, in this analysis, visibility of the intrinsic cysts with histopathology showed high correlation with clinical examination (by experienced clinicians) and by AS-OCT. This preliminary report shows evidence that ASOCT may provide important data regarding the configuration of conjunctival lesions, tumor boundaries, and internal structures. This information may contribute to establishing the clinical diagnosis of a benign conjunctival nevus and assist in defining the extent of the tumor. Further research into imaging of conjunctival lesions with AS-OCT may allow characterization of classic features to better aid in establishing a clinical diagnosis and detecting early malignant transformation.
References 1. Shields CL, Demirci H, Karatza E, Shields JA. Clinical survey of 1643 melanocytic and nonmelanocytic conjunctival tumors. Ophthalmology 2004;111:1747–54. 2. Shields CL, Shields JA. Tumors of the conjunctiva and cornea. Surv Ophthalmol 2004;49:3–24. 3. Novais GA, Fernandes BF, Belfort RN, et al. Incidence of melanocytic lesions of the conjunctiva in a review of 10675 opthalmic specimens. Int J Surg Pathol 2010;18:60 –3.
Shields et al 䡠 AS-OCT Conjunctival Nevus 4. Shields CL, Shields JA. Conjunctival tumors in children. Curr Opin Ophthalmol 2007;18:351– 60. 5. Shields CL, Fasiudden A, Mashayekhi A, Shields JA. Conjunctival nevi: clinical features and natural course in 410 consecutive patients. Arch Ophthalmol 2004;122:167–75. 6. Levecq L, De Potter P, Jamart J. Conjunctival nevi: clinical features and therapeutic outcomes. Ophthalmology 2010;117: 35– 40. 7. Shields JA, Shields CL. Eyelid, Conjunctival and Orbital Tumors: Atlas and Textbook. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008:308 – 47. 8. Izatt JA, Hee MR, Swanson EA, et al. Micrometer-scale resolution imaging of the anterior eye in vivo with optical coherence tomography. Arch Ophthalmol 1994;112:1584 –9. 9. Koop N, Brinkmann R, Lankenau E, et al. Optical coherence tomography of cornea and anterior eye segment [in German]. Ophthalmologe 1997;94:481– 6. 10. Huang D, Li Y, Radhakrishnan S. Optical coherence tomography of the anterior segment of the eye. Ophthalmol Clin North Am 2004;17:1– 6. 11. Radhakrishnan S, Rollins AM, Roth JE, et al. Real-time optical coherence tomography of the anterior segment at 1310 nm. Arch Ophthalmol 2001;119:1179 – 85. 12. Wolffsohn JS, Davies LN. Advances in anterior segment imaging. Curr Opin Ophthalmol 2007;18:32– 8.
13. Konstantopoulos A, Hossain P, Anderson DF. Recent advances in ophthalmic anterior segment imaging: a new era for ophthalmic diagnosis? Br J Ophthalmol 2007;91:551–7. 14. Ramos JL, Li Y, Huang D. Clinical and research applications of anterior segment optical coherence tomography—a review. Clin Experiment Ophthalmol 2009;37:81–9. 15. Bakri SJ, Singh AD, Lowder CY, et al. Imaging of iris lesions with high-speed optical coherence tomography. Ophthalmic Surg Lasers Imaging 2007;38:27–34. 16. Siahmed K, Berges O, Desjardins L, et al. Anterior segment tumor imaging: advantages of ultrasound (10, 20 and 50 MHz) and optical coherence tomography [in French]. J Fr Ophtalmol 2004;27:169 –73. 17. Pavlin CJ, Vasquez LM, Lee R, et al. Anterior segment optical coherence tomography and ultrasound biomicroscopy in the imaging of anterior segment tumors. Am J Ophthalmol 2009; 147:214 –9. 18. Buchwald HJ, Muller A, Kampmeier J, Lang GK. Optical coherence tomography versus ultrasound biomicroscopy of conjunctival and eyelid lesions [in German]. Klin Monbl Augenheilkd 2003;220:822–9. 19. Lin HC, Shen SC, Huang SF, Tsai RJ. Ultrasound biomicroscopy in pigmented conjunctival cystic nevi. Cornea 2004;23: 97–9.
Footnotes and Financial Disclosures Originally received: July 16, 2010. Final revision: September 16, 2010. Accepted: September 17, 2010. Available online: December 13, 2010.
Manuscript no. 2010-981.
Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Support provided by the Mellon Charitable Giving from the Martha W. Rogers Charitable Trust, Philadelphia, Pennsylvania (CLS), and the Eye Tumor Research Foundation, Philadelphia, Pennsylvania (CLS). Carol L. Shields, MD, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Correspondence: Carol L. Shields, MD, Ocular Oncology Service, Suite 1440, Wills Eye Institute, 840 Walnut Street, Philadelphia, PA 19107. E-mail: [email protected].
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Melanocytic nevus is the most common tumor of the conjunctiva.1 In an analysis of 1643 melanocytic and nonmelanocytic conjunctival tumors, 454 (28%) proved to be nevi.1,2 When assessing only melanocytic conjunctival tumors, the nevus represented 52% of all cases.2,3 In the pediatric population, conjunctival nevus is even more prevalent, representing 64% of 262 pediatric conjunctival tumors in one series.4 The typical clinical features of conjunctival nevus include onset in childhood, pigmentation (84%), location within 1 mm of the limbus in the nasal or temporal bulbar region (90%), and presence of intralesional (intrinsic) cysts (65%), most measuring less than 100 m in diameter.5 Intrinsic cysts are rarely found with simulators of nevus, such as racial melanosis, primary acquired melanosis, and melanoma. Levecq et al6 observed clinically visible intrinsic cysts in 57% of 255 conjunctiva nevi and observed that the presence of cysts was one of the factors predicting surgical excision of the mass, usually by patient preference. On the basis of our experience, intrinsic cysts within nevi are important because they generally infer a benign lesion rather than malignant melanoma.7 Cysts are often tiny and only visible with slit-lamp biomicroscopy. Smaller cysts can remain clinically undetectable and are beyond the resolution of most imaging modalities, including standard ultrasonography, ultrasound biomicroscopy, magnetic resonance imaging, and computed tomography. This report © 2011 by the American Academy of Ophthalmology Published by Elsevier Inc.
explores the role of anterior segment optical coherence tomography (AS-OCT) in the detection of intrinsic cysts within conjunctival nevi.
Materials and Methods The clinical records were reviewed of all patients on the Ocular Oncology Service at Wills Eye Institute, Philadelphia, Pennsylvania, with the diagnosis of conjunctival nevus and imaged with AS-OCT between June 2, 2008 and November 2, 2009. Anterior segment OCT (Visante OCT 3.0; Carl Zeiss Meditec, Dublin, CA) is a high-resolution, non-contact imaging technique that uses an illumination laser source of 1310 nm superluminescent light emission device to penetrate tissue. High-resolution scans can be obtained adjustable in 1-degree increments (10⫻3 mm) with 512 A scans per line sampling. Optical resolution is 18 m in the axial and 60 m in the transverse meridians. Institutional review board permission was obtained. Clinical data were collected regarding demographic patient features at the initial examination, including age, race (African American, Hispanic, Asian, Caucasian), and gender (female, male). Clinical features of the nevus included the amount of intrinsic pigment (dark, intermediate, light, no pigment), nevus thickness (millimeters), basal diameter (millimeters), quadrant location of tumor epicenter (superior, inferior, lateral, medial, diffuse), proximity of nevus to the limbus (millimeters), configuration (flat, dome), feeder vessels (present, absent), intrinsic vessels (present, absent), and intrinsic cysts (present, absent). ISSN 0161-6420/11/$–see front matter doi:10.1016/j.ophtha.2010.09.016
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Ophthalmology Volume 118, Number 5, May 2011 Table 1. Clinical Features of Conjunctival Nevus in 22 Eyes of 21 Patients Feature
No. (%) nⴝ22 Eyes
Intrinsic pigment Dark Moderate Light No pigment Estimated percent pigmentation Mean (median, range) Nevus thickness (mm) Mean (median, range) Nevus basal diameter (mm) Mean (median, range) Quadrant location Superior Inferior Lateral Medial Multiple quadrants involved Distance from limbus (mm) Mean (median, range) Nevus configuration Flat Dome Associated features Feeder vessel Intrinsic vessels Intrinsic cysts
3 (14) 6 (27) 5 (23) 8 (36) 30.9 (10, 0–100) 1.84 (1.5, 0.5–4.0) 7.25 (5.5, 1.5–22.0) 1 (5) 1 (5) 11 (50) 8 (35) 1 (5) 1.0 (0, 0–5.0)
6 (27) 16 (73) 14 (64) 17 (77) 18 (82)
Anterior segment OCT images were evaluated on the basis of intrinsic characteristics of the nevus, including overall optical features (hollow, solid), intrinsic pattern (homogeneous, heterogeneous), nevus thickness (millimeters), basal diameter (millimeters), configuration (flat, dome), and intrinsic cysts (present, absent). Anterior segment OCT images were evaluated for visibility of all tumor margins (good, fair, poor), quality of image (excellent, intermediate, poor), posterior tumor shadowing (present, absent), and degree of posterior tumor shadowing (trace, mild, moderate, severe). For those nevi managed with surgical excision, histopathologic correlation of intrinsic cysts with clinical and AS-OCT was made. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the detection of intrinsic cysts using AS-OCT versus slit-lamp biomicroscopy, AS-OCT versus histopathology, and slit-lamp biomicroscopy versus histopathology.
Results There were 22 eyes of 21 patients with conjunctival nevus evaluated by AS-OCT. The mean patient age at presentation was 23 years (median 15 years, range 3– 61 years). There were 11 male (52%) and 10 female (47%) patients. There were 18 Caucasian patients (85%), 1 African American patient (5%), 1 Hispanic patient (5%), and 1 Asian patient (5%). The clinical features of the nevi are listed in Table 1. The mean nevus thickness was 1.84 mm, and the mean basal diameter was 7.25 mm. Most nevi were located in the medial (n⫽8, 35%) or lateral (n⫽11, 50%) locations with a median distance to the limbus of 0 mm. Intrinsic cysts were found by slit-lamp examination in 18 patients (82%).
Table 2. Anterior Segment Optical Coherence Tomography Features in 22 Eyes of 21 Patients with Conjunctival Nevus Feature Optical features of nevus Hollow Solid Optical intrinsic pattern Homogeneous Heterogeneous Nevus thickness (mm) Mean (median, range) Nevus basal diameter (mm) Mean (median, range) Nevus configuration Flat Dome Visibility of nevus margin Good Fair None All nevus margins visualized Yes No Additional findings Posterior nevus shadowing Intrinsic cysts Posterior nevus shadowing (n⫽19) Trace Mild Moderate Severe
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No. (%) nⴝ22 Eyes 0 (0) 22 (100) 22 (100) 0 (0) 0.7 (0.55,0.1–1.7) 5.0 (4.0,0.3–20.0)
Anterior margin 22 (100) 0 (0) 0 (0)
3 (14) 19 (86) Posterior margin 18 (82) 4 (18) 0 (0)
Lateral margin 19 (86) 3 (14) 0 (0)
22 (100) 0 (0) 19 (86) 17 (77) If pigmented (n⫽12) 5 (42) 2 (17) 1 (8) 4 (33)
If non-pigmented (n⫽7) 5 (71) 2 (29) 0 (0) 0 (0)
Shields et al 䡠 AS-OCT Conjunctival Nevus
Figure 1. Clinical, AS-OCT, and histopathology of cystic conjunctival nevi. Pigmented nevus (A) in the superior bulbar conjunctiva in a 45-year-old man with minimally visible intrinsic cysts. Anterior segment OCT (B) shows homogeneous conjunctival thickening with multiple small intrinsic cysts and confirmation of a multicystic nevus on histopathology (C). Lightly pigmented nevus (D) with prominent feeder and intrinsic vessels in a 15-year-old male. Anterior segment OCT (E) demonstrates numerous intrinsic cysts within a homogeneously thickened mass, confirmed as multicystic conjunctival nevus on histopathology (F). Pigmented nevus (G) with giant intrinsic cysts in a 56-year-old woman. Anterior segment OCT (H) documented multiple large intrinsic cysts expanding the conjunctival mass, confirmed as multicystic conjunctival nevus on histopathology (I). AS-OCT ⫽ anterior segment optical coherence tomography.
With the use of AS-OCT, all 22 lesions appeared homogeneously solid (Table 2). Intrinsic cysts were detected in 17 patients (77%) (Fig 1). Good resolution was found with the nevus anterior margin (n⫽22, 100%) and posterior margin (n⫽18, 82%). Each margin of the nevus, including the deep margin in contact with sclera, could be visualized on AS-OCT in all 22 cases (100%). The overall image quality was judged excellent in 21 cases (95%), intermediate in 1 case (5%), and poor in no case (0%). Some degree of optical shadowing posterior to the nevus was found in 19 cases (86%), more often with pigmented tumors than nonpigmented tumors. The degree of shadowing in the 12 pigmented tumors was trace in 5 (42%), mild in 2 (17%), moderate in 1 (8%), and severe in 4 (33%). Of the 7 nonpigmented tumors, optical shadowing was judged trace in 5 (71%) and mild in 2 (29%) with no more advanced shadowing. Thirteen (59%) of the 22 nevi underwent excision and were histopathologically confirmed as compound nevus in 6 (46%), subepithelial nevus in 5 (39%), and combined nevus in 2 (15%). Intrinsic cysts were present in 10 lesions (77%) and absent in 3 lesions (23%) (Table 3). When compared with histopathology, AS-OCT detected intrinsic cysts in conjunctival nevi with a sensitivity of 80%, a specificity of 100%, a PPV of 100%, and an NPV of 60% (Table 4). When compared with histopathology, clinical examination by slit-lamp biomicroscopy detected intrinsic cysts in conjunctival nevi with a sensitivity of 100%, a specificity of 100%, a PPV of 100%, and an NPV of 100%. When compared with
clinical examination, AS-OCT detected intrinsic cysts in conjunctival nevi with a sensitivity of 94%, a specificity of 100%, a PPV of 100%, and an NPV of 80%.
Discussion Anterior segment OCT is a high-resolution, non-contact imaging modality using superluminescent long wavelength light at 1310 nm to image human tissue. This technology Table 3. Histopathology of 13 Excised Conjunctival Nevi Finding Diagnosis Compound nevus Subepithelial nevus Combined nevus Intrinsic cysts Yes No
No. (%) nⴝ13 Eyes 6 (46) 5 (39) 2 (15) 10 (77) 3 (23)
Combined nevus means combination of compound and subepithelial nevi.
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Ophthalmology Volume 118, Number 5, May 2011 Table 4. Detection of Intrinsic Cysts within Conjunctival Nevus Using Slit-Lamp Biomicroscopy, Anterior Segment Optical Coherence Tomography, and Histopathology Feature Intrinsic cysts Present
No. (%) Patients with Feature AS-OCT n⫽22 eyes 17 (77)
Slit-lamp biomicroscopy n⫽22 eyes 18 (82)
AS-OCT/slit-lamp biomicroscopy n⫽22 eyes Present/present Present/absent
Absent
Present
5 (23)
Slit-lamp biomicroscopy n⫽13 eyes 10 (77)
4 (18)
Histopathology n⫽13 eyes 10 (77)
Absent
3 (23)
3 (23)
Present
AS-OCT n⫽13 eyes 8 (62)
Histopathology n⫽13 eyes 10 (77)
Absent
5 (38)
3 (23)
Absent/absent Absent/present Slit-lamp biomicroscopy/histopathology n⫽13 eyes Present/present Present/absent Absent/absent Absent/present AS-OCT/histopathology n⫽13 eyes Present/present Present/absent Absent/absent Absent/present
17 (100) 0 (0) 4 (80) 1 (20)
10 (100) 0 (0) 3 (100) 0 (0)
8 (100) 0 (0) 3 (60) 2 (40)
AS-OCT ⫽ anterior segment optical coherence tomography.
has numerous applications in human disease, including investigation of cerebral blood flow and stroke, musculoskeletal, and dermatologic conditions, and in the field of oncology, particularly malignancies of the esophagus, gastric region, bladder, lung, and colon. Initial ophthalmic use of OCT was limited to the posterior segment of the eye with imaging of the retina for degenerative and vascular diseases, superficial imaging of the choroid, and imaging of intraocular tumors. Newer modifications of OCT have allowed imaging of the anterior segment of the eye with applications for corneal topography, assessment of angle structure in glaucoma, refractive surgery evaluation, and precise localization of intraocular lens placement and related posterior capsular opacification.8 –14 There is little information on the use of AS-OCT for tumors of the anterior segment.15–17 Pavlin and associates17 used AS-OCT to image 18 eyes with iris and iridociliary tumors, mostly iris nevus, iris melanoma, and iris pigment epithelial cysts. They found AS-OCT suitable for imaging small nonpigmented lesions. However, large lesions and pigmented lesions were incompletely imaged with AS-OCT and better depicted with ultrasound biomicroscopy. This report investigated the use of AS-OCT for imaging specifically conjunctival nevi. Anterior segment OCT provided clear images of all nevus margins. The basal margin of the nevus showed a clear separation from the underlying sclera and without scleral invasion in all cases. The optical quality of the nevus was homogeneous and solid in every case. Imaging was ideal for nonpigmented nevi with little shadowing artifact. Darkly pigmented nevi displayed more optical shadowing with slightly reduced imaging of the basal margin. Intralesional cysts were clearly visualized in 77% of cases, and all margins of the cyst could be seen in each case. In the published literature, there is scant information on AS-OCT for conjunctival tumors. Buchwald et al18 studied
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13 conjunctival lesions with AS-OCT, including pterygium, primary acquired melanosis, and 4 patients with nevus.18 They showed images of homogeneous optical reflectivity and the presence of tiny cysts in 2 cases. They concluded that AS-OCT was more capable of showing intrinsic cysts compared with ultrasound biomicroscopy. Lin et al19 indicated that in pigmented nevus, the visibility of cysts might be clinically camouflaged by pigment but imaged with ultrasound biomicroscopy, emphasizing the importance of this in establishing the diagnosis.19 In conclusion, in this analysis, visibility of the intrinsic cysts with histopathology showed high correlation with clinical examination (by experienced clinicians) and by AS-OCT. This preliminary report shows evidence that ASOCT may provide important data regarding the configuration of conjunctival lesions, tumor boundaries, and internal structures. This information may contribute to establishing the clinical diagnosis of a benign conjunctival nevus and assist in defining the extent of the tumor. Further research into imaging of conjunctival lesions with AS-OCT may allow characterization of classic features to better aid in establishing a clinical diagnosis and detecting early malignant transformation.
References 1. Shields CL, Demirci H, Karatza E, Shields JA. Clinical survey of 1643 melanocytic and nonmelanocytic conjunctival tumors. Ophthalmology 2004;111:1747–54. 2. Shields CL, Shields JA. Tumors of the conjunctiva and cornea. Surv Ophthalmol 2004;49:3–24. 3. Novais GA, Fernandes BF, Belfort RN, et al. Incidence of melanocytic lesions of the conjunctiva in a review of 10675 opthalmic specimens. Int J Surg Pathol 2010;18:60 –3.
Shields et al 䡠 AS-OCT Conjunctival Nevus 4. Shields CL, Shields JA. Conjunctival tumors in children. Curr Opin Ophthalmol 2007;18:351– 60. 5. Shields CL, Fasiudden A, Mashayekhi A, Shields JA. Conjunctival nevi: clinical features and natural course in 410 consecutive patients. Arch Ophthalmol 2004;122:167–75. 6. Levecq L, De Potter P, Jamart J. Conjunctival nevi: clinical features and therapeutic outcomes. Ophthalmology 2010;117: 35– 40. 7. Shields JA, Shields CL. Eyelid, Conjunctival and Orbital Tumors: Atlas and Textbook. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008:308 – 47. 8. Izatt JA, Hee MR, Swanson EA, et al. Micrometer-scale resolution imaging of the anterior eye in vivo with optical coherence tomography. Arch Ophthalmol 1994;112:1584 –9. 9. Koop N, Brinkmann R, Lankenau E, et al. Optical coherence tomography of cornea and anterior eye segment [in German]. Ophthalmologe 1997;94:481– 6. 10. Huang D, Li Y, Radhakrishnan S. Optical coherence tomography of the anterior segment of the eye. Ophthalmol Clin North Am 2004;17:1– 6. 11. Radhakrishnan S, Rollins AM, Roth JE, et al. Real-time optical coherence tomography of the anterior segment at 1310 nm. Arch Ophthalmol 2001;119:1179 – 85. 12. Wolffsohn JS, Davies LN. Advances in anterior segment imaging. Curr Opin Ophthalmol 2007;18:32– 8.
13. Konstantopoulos A, Hossain P, Anderson DF. Recent advances in ophthalmic anterior segment imaging: a new era for ophthalmic diagnosis? Br J Ophthalmol 2007;91:551–7. 14. Ramos JL, Li Y, Huang D. Clinical and research applications of anterior segment optical coherence tomography—a review. Clin Experiment Ophthalmol 2009;37:81–9. 15. Bakri SJ, Singh AD, Lowder CY, et al. Imaging of iris lesions with high-speed optical coherence tomography. Ophthalmic Surg Lasers Imaging 2007;38:27–34. 16. Siahmed K, Berges O, Desjardins L, et al. Anterior segment tumor imaging: advantages of ultrasound (10, 20 and 50 MHz) and optical coherence tomography [in French]. J Fr Ophtalmol 2004;27:169 –73. 17. Pavlin CJ, Vasquez LM, Lee R, et al. Anterior segment optical coherence tomography and ultrasound biomicroscopy in the imaging of anterior segment tumors. Am J Ophthalmol 2009; 147:214 –9. 18. Buchwald HJ, Muller A, Kampmeier J, Lang GK. Optical coherence tomography versus ultrasound biomicroscopy of conjunctival and eyelid lesions [in German]. Klin Monbl Augenheilkd 2003;220:822–9. 19. Lin HC, Shen SC, Huang SF, Tsai RJ. Ultrasound biomicroscopy in pigmented conjunctival cystic nevi. Cornea 2004;23: 97–9.
Footnotes and Financial Disclosures Originally received: July 16, 2010. Final revision: September 16, 2010. Accepted: September 17, 2010. Available online: December 13, 2010.
Manuscript no. 2010-981.
Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Support provided by the Mellon Charitable Giving from the Martha W. Rogers Charitable Trust, Philadelphia, Pennsylvania (CLS), and the Eye Tumor Research Foundation, Philadelphia, Pennsylvania (CLS). Carol L. Shields, MD, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Correspondence: Carol L. Shields, MD, Ocular Oncology Service, Suite 1440, Wills Eye Institute, 840 Walnut Street, Philadelphia, PA 19107. E-mail: [email protected].
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