AIOS – Ocular Pathology Award
Dr. Rath Suryasnata, R07510, Dr. Ruchi Mittal, Dr. Swati Singh
SuryasnataRath, MS., FRCS 1
Swati Singh, MD.1
ArnavGhosh, B Optom.1
Ruchi Mittal MD.2
1 Ophthalmic Plastics, Orbit and Ocular oncology services
L V Prasad Eye Institute, Bhubaneswar, India
2 Dalmia Ophthalmic Pathology Service,
L V Prasad Eye Institute, Bhubaneswar, India
Support provided by Hyderabad Eye Research Foundation, Hyderabad, India and the Operation Eyesight Universal Institute of Eye Cancer. The funders had no role in the preparation, review or approval of the manuscript.
No conflicting relationship exists for any author.
Correspondence:
DrSuryasnataRath, MS FRCS
Ophthalmic Plastic Surgery, Orbit and Ocular Oncology,
L V Prasad Eye Institute, Bhubaneswar, India
Tel: 91-674-3987999
Fax: 91-674-3987130
Email:drsuryasnata@gmail.com
Keywords:
OSSN, TD ASOCT, Hyper-reflectivity
Abstract
Purpose: To evaluate the role of time domain-anterior segment optical coherence tomography (TD-ASOCT) in the diagnosis and management of ocular surface squamous neoplasia (OSSN) by clinico-pathological correlation and serial imaging. Design: Prospective non-comparative interventional series
Participants: Ten eyes of 10 consecutive patients with OSSN, 2 with pterygia and one patient with pinguecula.
Methods: TD-ASOCT (Visante OCT 3.0; Carl Zeiss Meditec, Dublin, CA) was performed in 10 consecutive patients with clinical suspicion of unilateral OSSN, pterygium and pinguecula and the site of optical section marked with India ink (Camelin). After surgical excision the histopathological sections at the predetermined marked points were correlated with TD-ASOCT images. Three patients needed interferon alfa-2B (IFN)/mitomycin C (MMC) and underwent serial imaging to monitor treatment response.
Main Outcome measures: TD-ASOCT images, histopathology, clinical course and outcome of OSSN.
Results: The mean age of the group was 49 + 16 (range 25-85) years, 11 were male and median follow-up was 6 (1-18) months.TD-ASOCT imaging characteristics included an abrupt transition, epithelial hyper-reflectivity with or without thickening, clear plane of separation and basal membrane. Based on the imaging characteristics, OSSN were classified into 4 types. A hyper-reflective thickened epithelial lesion with a clear plane of separation (type I) was seen in 3 and without a clear plane (type II) in 3 patients. A hyper-reflective non-thickened epithelial lesion (type III) was seen in 1 patient and hyper-reflective epithelium with clear plane and hyper-reflective basal membrane (type IV) was seen in 3 patients. All invasive OSSN had no clear plane of separation. Based on clinico-pathological correlation the basal hyper-reflective membrane may represent the thickened basement membrane. TD-ASOCT in pterygia and pinguecula showed an intact epithelium with normal thickness/reflectivity and underlying hyper-reflectivity. Overall there was good correlation between TD-ASOCT and histopathology in OSSN and benign lesions. Serial TD-ASOCT in patients on IFN/MMC showed progressive, gradual and consistent decrease in thickening, hyper-reflectivity over time.
Conclusion: Commercially available TD-ASOCT is non-invasive and useful in diagnosis of OSSN and may be used to detect invasive disease. Serial imaging in OSSN on immunotherapy/chemotherapy helps in surveillance and titration of treatment duration.
Ocular surface squamous neoplasia (OSSN) has clinical variants characterized by elevated, papillomatous and leukoplakic lesions usually straddling the corneal
limbus.1-5 Atypical variants like corneal OSSN pose a diagnostic challenge.1 To this day histopathology remains the gold standard for definitive diagnosis in atypical and extensive lesions. Noninvasive techniques like impression cytology, ultrasound bio-microscopy, anterior segment optical coherence tomography(ASOCT) and confocal microscopy have been reported to be effective in diagnosis and management of OSSN.6-8Impression cytology detects OSSN in 77-80% but fails to provide details pertaining to the depth of the infiltration.6 Ultrasound biomicroscopy and confocal microscopy provide details of cellular differentiation but have limited application as they are contact-techniques and need relatively longer time for image capture.6
Ultra high resolution optical coherence tomography (UHR OCT) has an axial resolution of 3 microns with scanning speed of 26000 axial scans per second.6Shousha et al have reported UHR OCT as a novel, noninvasive technique to diagnose and manage conjunctival intra epithelial neoplasia (CIN).6Thomas and colleagues have reviewed the literature on utility of UHR OCT in management and differentiation of OSSN from other ocular surface lesions like pannus, pterygium and corneal degenerations.9Though UHR OCT machines are commercially available – Bioptigen SD OCT (Bioptigen Inc., Research Technology Park, NC) and Copernicus HR SOCT (Optopol Technologies SA, Zawiercie, Poland) – much of the published literature on UHR OCT in OSSN are based on custom-built machines.6,8,9 Accessibility of most ophthalmologists to UHR OCT is limited owing to its cost and the fact that custom-built machines are primarily used for research purposes. Our primary objective was to correlate the imaging characteristics of OSSN on time domain anterior segment optical coherence tomography (TD-ASOCT) with histopathology (gold standard) and possibly derive imaging characteristics that can differentiate between conjunctival intra-epithelial neoplastic lesions, invasive OSSN and benign ocular surface lesions. The secondary objective was to evaluate if serial TD-ASOCT can be of help in surveillance of OSSN treated with immunotherapy and/or chemotherapy.
METHODS
All cases of clinically diagnosed OSSN who presented to the oncology service of L V Prasad Eye Institute, Bhubaneswar, India between July 2014 and December 2015 were included in this study. The study was approved by the institutional ethics committee (2014-28-IM-6) and adhered to the tenets of the Declaration of Helsinki. Surface of the lesion was marked at multiple points with India ink (Camelin) before surgery. The built-in high resolution corneal scan protocol of the TD-ASOCT (Visante OCT 3.0; Carl Zeiss Meditec, Dublin, CA) was used.The pre-marked points were scanned using high resolution standard anterior segment single-scan protocol.All patients of OSSN were counselled about the options of treatment including complete tumour excision with margin clearance and cryotherapy to the conjunctival edges, chemotherapy with mitomycin C (MMC) and/or immunotherapy with interferon alpha2B (IFN) therapy. In those who chose surgery, a standard excision was performed and the margins were sent separately for histopathological examination. This was followed by double-freeze-thaw cryotherapy to the conjunctival edges and an amniotic membrane graft to cover the defect. Excised tissue was anatomically oriented on Whatmans’ filter paper, carefully marked and sent for histopathological examination, where grossing and processing was performed, conforming to the markings.A thorough histopathological evaluation was performed by an experienced ophthalmic pathologist (RM). TD-ASOCT characteristics were correlated with histopathological sections.
Those patients who opted for immunotherapy and/or chemotherapy (IFN or MMC) underwent TD-ASOCT before initiation of treatment and at regular monthly intervals to look for signs of resolution. To enable differentiation from benign degenerative conditions TD-ASOCT was performed before surgery in 2 cases of pterygia and a pinguecula.
Results
Thirteen cases were included in this study. There were 11 males and the mean age of the group was 49+16 (range 25-85) years. There were 10 cases of OSSN, 2 pterygia and one case of pinguecula in this group. AJCC TNM Staging showed T3N0M0 in 8 and T2N0M0 in 2 patients (table 1). Median follow-up for the group was 6 (range1-18) months. Morphological variants of OSSN included 3 cases each of nodular, leukoplakic and papillomatous types and a single case with a gelatinous appearance. There was one case of multifocal OSSN involving the left bulbar and upper tarsal conjunctiva. Diffuse OSSN was seen in 2 patients and these were treated with topical and subconjunctival IFN and MMC.
TD-ASOCT characteristics
Imaging characteristics found on optical sections of TD-ASOCT included an abrupt transition, hyper-reflectivity, epithelial thickening, clear plane of separation, a basal hyper-reflectivity and back shadowing. Based on the presence/absence of these characteristics (table 2) OSSN were divided into 4 types.
Type I – Hyper-reflective Thickening with clear plane
Three patients with a clinical diagnosis of OSSN had a clear plane of separation between hyper-reflective thickened epithelium and underlying tissue. This clear plane of separation was seen across optical sections on TD-ASOCT.
Case – A 42 year old male presented with a progressive limbal lesion in his left eye of 6 months duration. Slit lamp examination showed a gelatinous conjunctival mass straddling the temporal limbus (figure 1A) with no intrinsic vascularity. A few feeder vessels were present. TD-ASOCT images showed an abrupt transition to a thickened hyper-reflective epithelial lesion with clear plane of separation (arrow; figure 1B) from underlying tissue. Focal areas showed shadow effect. Histopathological examination showed irregularly thickened epithelium with surface maturation and almost full thickness replacement by atypical squamous cells with hyperchromatic nuclei (star; figure 1C) consistent with severe dysplasia. Eighteen months after excision the left eye had a conjunctival scar with no local recurrence. TD-ASOCT sections showed normal conjunctival epithelium with hyper reflectivity in sub-epithelial layer possibly secondary to the scar.
Type II -Hyper-reflective Thickening without clear plane
Three patients showed hyper-reflectivity with obscuration of underlying tissues. No clear plane of separation could be seen. Histopathology showed invasive squamous carcinoma in all of them.
Case – A 51 year old farmer had a raised conjunctival mass of 8 months duration in left eye. Slit lamp examination of the left eye showed a large papillomatous mass extending from 7-11’0 clock of the nasal bulbar conjunctiva (figure 1D) straddling the limbus and encroaching the cornea. Presence of large nasal feeder vessels and intrinsic vascularity led to a clinical diagnosis of OSSN. TD-ASOCT images through the lesion showed an abrupt transition to a hyper-reflective epithelial lesion without an underlying clear plane (figure 1E). Multiple hypo-reflective foci were present (asterisk; figure 1E) and there was obscuration of underlying tissue due to the shadow effect. Complete excision with 4mm of healthy conjunctival margin and double-freeze-thaw cryotherapy to edges was performed. On histopathology the epithelium showed surface keratinization, marked acanthosis and papillomatosis, and an abrupt transition with adjacent uninvolved epithelium, (figure 1F); deeper part of the lesion showed invasive cell masses (Inset: 1F). Foci of hypo-reflectivity on TD-ASOCT corresponded to the edematous inflamed fibrovascularstromatolites on histopathology sections. Final visit at 4 months after excision showed loco-regional control with normalization of the ocular surface on clinical examination and TD-ASOCT.
Type III – Hyper-reflectivity without thickening
A single case showed hyper-reflectivity without thickening. A 30 year old female presented with decreased vision in the left eye. She had ipsilateral cataract and diminished amplitude on visual evoked potential. Slit lamp examination showed a keratinized partially pigmented lesion involving the limbus from 3-7’0 clock (figure 1G) with no intrinsic vascularity. TD-ASOCT images showed a hyper-reflective epithelial lesion without thickening (arrowhead; figure 1H). Significant shadowing effect precluded delineation of underlying layers. A complete excision of the lesion was done. Histopathology showed moderate to severe dysplasia of epithelium, and actinic stromal changes with no evidence of stromal invasion(figure 1I).
TD-ASOCT for Pterygium
TD-ASOCT was performed in a 36 year old female with a nasal pterygium (figure 1J) in the left eye. The intact epithelium appeared hypo-reflective (figure 1K) and with an underlying hyper-reflectivity. TD-ASOCT characteristics of OSSN like abrupt transition, epithelial hyper-reflectivity were absent. Histopathology of the excised tissue showed an intact epithelium (figure 1L) with normal maturational sequence of epithelial cells. Surface of the epithelium showed deposits of the India ink used to mark the lesion(white star; figure 1L).
Type IV – Hyper-reflectivity with clear plane and basal membrane
Three patients had an abrupt transition to a hyper-reflective thickened epithelium with a clear plane and an overlying intensely hyper-reflective basal membrane.
Case – A 65 year old female presented with a conjunctival lesion of 6 months duration. On examination she was found to have large papillomatous lesion at the superior corneo-scleral limbus from 9-3’O clock (figure 2A) in left eye. Large feeder vessels were seen and intrinsic vascularity was present. The upper eyelid showed a papillomatous lesion (largest dimension 24mm) involving the entire length of the upper tarsal conjunctiva (figure 2B). A clinical diagnosis of multifocal OSSN of the bulbar and tarsal conjunctiva was made. TD-ASOCT of the bulbar lesion showed an abrupt transition to a hyper-reflective epithelial lesion with clear plane of separation from underlying tissue. There was an intensely hyper-reflective basal layer (arrow; figure 2C) above the clear plane. TD-ASOCT of the upper eyelid lesion showed epithelial hyper-reflectivity with clear plane (arrowhead; figure 2D) and an overlying basal membrane. Primary management consisted of complete excision of the bulbar OSSN. Histopathology showed full thickness replacement of epithelium by atypical squamous cells with absence of stromal invasion consistent with carcinoma-in-situ. The epithelial basement membrane and superficial stromal collagen appeared thickened and edematous (black star; figure 2E) with plump stromal cells, which is hypothesized to cause hyper-reflectivity in the basal layer. She received 2 injections subconjunctival IFN in the superior fornix (1Million units/ml X 6 cycles) at one month interval and topical IFN 4 times a day for one month. Repeat TD-ASOCT showed a poor response. Subsequently she received 4 cycles of topical MMC (0.04%) in which one cycle consisted of MMC given 4 times a day for 4 days in a week for 4 weeks. Serial TD-ASOCT was done for surveillance of the eyelid lesion. The lesion responded dramatically with progressive decrease in thickness on TD-ASOCT (figure 2F) and disappearance of the hyper-reflective basal layer. A small residual lesion was excised. Eighteen months after treatment she had loco-regional control with normalization of the bulbar and palpebral conjunctiva.
TD-ASOCT for Surveillance
Two cases of diffuse OSSN (cases 12 and 13; Table 1) were treated primarily with IFN/MMC therapy. Both patients received 6 cycles of IFN (subconjunctival injection; 1million units/ml) followed by 4 cycles of topical interferon (1million units/ml) given at regular intervals of one month. One patient (case 13; Table 1) needed 1 cycle of topical MMC (0.04%) for small residual OSSN. Serial TD-ASOCT was done to document response and showed progressive and consistent decrease in the thickness of the lesion (Figure 3&4).
Case – A 43 year old male presented with a conjunctival lesion (figure 3A-C) straddling the limbus from 1-7’O clock in right eye. After 3 months of subconjunctival injection and topical IFN,TD-ASOCT showed a decrease in the thickness of hyper-reflective epithelium (figure 3D-F). While clinical restoration of the normal architecture was achieved at 5 months, TD-ASOCT showed residual hyper-reflectivity necessitating prolonged topical interferon therapy. Fourteen months after initiation of IFN, TD-ASOCT showed restoration of the normal architecture in all sectors except the nasal limbus(figure 3G-I).
Discussion
Custom designed UHR OCT has been reported to have an adjuvant diagnostic role in differentiating OSSN from benign simulating lesions.6, 8We found the commercially available TD-ASOCT showed excellent correlation with histopathology (gold standard) in OSSN and benign conditions of the ocular surface. In addition to the abrupt transition, hyper-reflective thickened epithelium described earlier, the presence/absence of a clear plane of separation and the thickened hyper-reflective basal layer were unique on TD-ASOCT and may have a role in differentiating conjunctival intra epithelial neoplasia (CIN) from invasive squamous carcinoma. Finally TD-ASOCT was useful in surveillance of OSSN on topical/subconjunctival IFN and/or topical MMC therapy.
OSSN is a clinical diagnosis except in atypical cases where feeder vessels, intrinsic vasculature, keratin and staining with Rose-Bengal are absent. Biopsy is the gold standard for diagnosis of OSSN. The advent of medical management has ushered in the use of non-invasive imaging modalities both for the diagnosis and surveillance of OSSN.6-11 ASOCT is a non-invasive diagnostic imaging tool and gives in-vivo optical sections of the ocular surface. Typical UHR OCT imaging characteristics of OSSN include an abrupt transition from normal epithelium to hyper-reflective thickened epithelium.8The hyper-reflectivity is postulated to be because of the hyper-cellularity and/or an increased nuclear cytoplasmic ratio of the dysplastic epithelial cells. Commercially available TD-ASOCT used in our series can be used to delineate the typical imaging characteristics in OSSN. Our experience with TD-ASOCT describes two unique features in OSSN – presence/absence of a clear plane of separation and a hyper-reflective basal layer. Correlation of the imaging and histopathological characteristics in our series showed that an abrupt transition to a hyper-reflective thickened epithelium with a clear plane of separation was likely to be seen in CIN. We postulate this clear plane of separation corresponds to the intact basement membrane in CIN. Interestingly absence of the clear plane of separation in all the 3 cases of invasive squamous carcinoma, strengthens our hypothesis. Second was the hyper-reflective basal layer above clear plane of separation in 3 patients of CIN. This could either be the thickened basement membrane/thickened basal layer of dysplastic cells with denser nuclei or the thickened stromal connective tissue. Normal conjunctiva did not have this hyper-reflective basal layer. Another feature was the presence of hypo-reflective foci on TD-ASOCT. These were found to correspond with stromal edematous cores in papillomatous lesions. We believe the above unique characteristics on TD-ASOCT may aid in differentiating CIN from invasive disease.
UHR OCT has been found to be of benefit in differentiating OSSN from benign surface lesions like pterygia.8 Kieval and associates prospectively studied 17 cases each of OSSN and pterygia.8 Hyper-reflectivity in a pterygium was always sub-epithelial and the intact epithelium appeared dark on optical sections. Measurement of the epithelial thickness in OSSN and pterygia showed a statistically significant difference. Based on this they concluded that UHROCT showing an epithelial thickness of >142 microns were likely to be OSSN with 94% sensitivity and 100% specificity.8 In our study TD-ASOCT could delineate the intact epithelium which was seen as dark layer and the sub-epithelial hyper-reflectivity in pterygia.
Persistence of epithelial thickening and/or hyper-reflectivity beyond clinical resolution has been documented in OSSN. UHR OCT seems to have a role in surveillance of OSSN on interferon/MMC/5-fluorouracil treatment. In our study TD-ASOCT was useful to document the response to IFN therapy. In a case of multifocal OSSN involving the eyelid and bulbar conjunctiva, sequential TD-ASOCT showed gradual and consistent decrease in thickness of the epithelium. In addition the hyper-reflective basal layer seen in earlier scans disappeared with restoration of the normal architecture. In another case of diffuse OSSN (case 13; Table 1) managed with IFN and MMC, sequential TD-ASOCT could document residual disease (figure 3H). In our experience documenting response to treatment with TD-ASOCT helped in patient compliance as they observed the interval change over time.
We acknowledge the limitations of our study. First, the small numbers of patients in our study are at best exploratory on the role of TD-ASOCT in routine diagnosis and management of OSSN. However wider application in large cohorts is imperative and necessary. Second, TD-ASOCT has lower resolution (18 microns) and this limits finer details that can be discerned with UHR OCT. Third, OSSN variants like leukoplakic and thick invasive types have significant shadow effect precluding the imaging details. Finally, we realize that while TD-ASOCT aided optical sections may point towards CIN there may be micro-invasive or invasive disease lurking elsewhere. This limitation exists even for histopathology and improved versions of ASOCT with wider scan-width, higher resolution and faster capture may be of help in the future.
In conclusion, despite the limitations, our study shows for the first time the promising role of commercially available TD-ASOCT in diagnosis of OSSN. Most ophthalmologists across the world have access to TD-ASOCT. Imaging characteristics like the clear plane of separation and the hyper-reflective basal layer could aid differentiation of CIN from invasive disease.Finally sequential TD-ASOCT in patients on IFN/MMC was found to be useful in titrating treatment duration.
Acknowledgement:We gratefully acknowledge the support of Triveni Earthmovers for part funding of this research.
References
- Basti S, Macsai MS. Ocular surface squamous neoplasia: a review. Cornea 2003;22:687-704.
- Schechter BA, Koreishi AF, Karp CL, et al. Long-term follow-up of conjunctival and corneal intraepithelial neoplasia treated with topical interferon alfa-2b. Ophthalmology 2008;115:1291– 6
- Vann RR, Karp CL. Perilesional and topical interferon alfa-2b for conjunctival and corneal neoplasia. Ophthalmology 1999;106:91–7.
- Frucht-Pery J, Rozenman Y. Mitomycin C therapy for corneal intraepithelial neoplasia. Am J Ophthalmol 1994;117:164–8.
- Schechter BA, Koreishi AF, Karp CL, et Long-term follow-up of conjunctival and corneal intraepithelial neoplasia treated with topical interferon alfa-2b. Ophthalmology 2008;115:1291– 6.
- Shousha MA, Karp CL, Perez VL, et al. Diagnosis and management of conjunctival and corneal intraepithelial neoplasia using ultra high resolution optical coherence tomography. Ophthalmology 2011;118:1531-7.
- Duchateau N, Hugol D, D’Hermies F, et al. Contribution of invivo confocal microscopy to limbaltumor evaluation [inFrench]. J FrOphtalmol 05;28:810–6.
- Kieval JZ, Karp CL, Shousha MA, et al. Ultra-high resolution optical coherence tomography for differentiation of ocular surface squamous neoplasia and pterygia. Ophthalmology 2012;119:481-6.
- Thomas BJ, Galor A, Nanji AA, et al. Ultra high-resolution anterior segment optical coherence tomography in the diagnosis and management of ocular surface squamous neoplasia. Ocul Surf. 2014;12:46-58.
- Shah SU, Kaliki S, Kim HJ, et al. Topical interferon alfa-2b for management of ocular surface squamous neoplasia in 23 cases: outcomes based on American Joint Committee on Cancer classification. Arch Ophthalmol 2012;130:159-64.
- Nanji AA, Sayyad FZ, Galor A et al. High-resolution optical coherence tomography as an adjunctive tool in the diagnosis of corneal and conjunctivalpathology.Ocul Surf. 2015;13:226-35.
Legends for Figures
Figure 1A-C: A 42-year-old male presented with a left limbalconjunctival gelatinous lesion involving the temporal limbus. TD-ASOCT images showan abrupt transition to a thickened hyper-reflective epithelial lesion with clear plane of separation (type I; arrow) from the underlying tissue. Focal areas showed shadow effect. Histopathological examination (H&E, X100) showed irregularly thickened epithelium with surface maturation. More than two-thirds of the epithelium (black star) showed replacement by atypical squamous cells with hyper chromatic nucleiconsistent with severe dysplasia.
D-F: A 51-year-male had a left conjunctival mass. Slit lamp examination shows a large papillomatous mass extending from 7 to 11’0 clock of the nasal bulbar conjunctiva and encroaching the cornea. TD-ASOCT shows an abrupt transition to a hyper-reflective epithelial lesion without an underlying clear plane (type II). Multiple hypo-reflective foci (asterix) are seen that correspond to the loose edematous stromal connective tissueon histopathology. Obscuration of underlying tissue was seen due to the shadow effect. Histopathological examination (H&E, X100) showed markedly thickened epithelium with papillomatosis and full thickness atypia. Inset shows invasive tumour masses.
G-I: A 30-year-female had a keratinized partially pigmented lesion involving the limbus from 3 to 7’0 clock with no intrinsic vascularity on slit-lamp photograph. TD-ASOCT images show a hyper-reflective epithelial lesion without thickening (type-III; arrowhead). Significant shadowing effect precluded delineation of underlying layers. Histopathology (H&E, X100) showed severe epithelial dysplasia without invasiveness. Actinicdegeneration of stroma is noted.
J-L: A 36-year-female underwent excision for a left nasal pterygium. TD-ASOCT shows an intact epithelium which appeared dark (hypo-reflective)with an underlying hyper-reflectivity. Typical TD-ASOCT characteristics of OSSN like abrupt transition, epithelial hyper-reflectivity were absent. Histopathology (H&E, X100) shows stratified squamous to stratified columnar epithelium with goblet cells, with absence of epithelial atypia. Surface of the epithelium shows deposits of the India ink (white star; Camelin) reminiscent of the marking done.
Figure 2 A-F: A 65-year-female presented with a left conjunctival lesion. Slit-lamp photograph shows a large papillomatous lesion at the superior corneo-scleral limbus from 9-3’O clock. Large feeder vessels and intrinsic vascularity are present. The ipsilateralupper eyelid shows velvety texture involving the length of the upper tarsal conjunctiva. TD-ASOCT of the bulbar lesion shows an abrupt transition to a hyper-reflective epithelial lesion with clear plane of separation from underlying tissue. There was an intensely hyper-reflective basal layer (type IV, arrow) above the clear plane. TD-ASOCT of the upper eyelid lesion showed epithelial hyper-reflectivity with clear plane and an overlying basal membrane (arrowhead). Histopathology (H&E, X100) showed full thickness epithelial atypia with hyperchromasia involving full-thickness epithelium consistent with of carcinoma-in-situ. The epithelial basement membrane and superficial stromal collagen appeared thickened and edematous (black star; figure 2E) with plump stromal cells. Six months after treatment with monthly cycles of topical and subconjunctival interferon alpha2B for 2 months and monthly topical MMC for 4 months shows good response with decrease in thickness on TD-ASOCT and disappearance of the hyper-reflective basal layer.
Figure 3 A-I: A 43-year-male presented with a conjunctival lesion involving the limbus from 1-7’O clock in right eye. TD-ASOCT shows thickened epithelial hyper-reflectivity with clear plane of separation at nasal and inferior limbus. The patient was treated with monthly cycles of subconjunctival and topical interferon alpha 2B (1million units/ml). Slit-lamp photographs and TD-ASOCT after 2 months (D-F) and 8 months (G-I) shows dramatic improvement. Serial TD-ASOCT shows progressive decrease in thickness of the OSSN.It must be noted that TD-ASOCT at 8 months shows residual thickened epithelial hyper-reflectivity at nasal limbus (H) versus restoration of normal architecture at inferior limbus (I).
Figure 4A-F: A 66-year-old female presented with papillaomatousconjunctival lesion involving 7 clock hours with of the inferior limbus in left eye. The lesion involved the nasal bulbar and the inferior forniceal conjunctiva. TD-ASOCT showed thickened epithelial hyper-reflectivity with clear plane of separation (type I). Monthly cycles of subconjunctival and topical interferon alpha 2B (1million units/ml) were given for 6 months followed by one cycle of topical mitomycin C (0.04%). Slit-lamp photographs and TD-ASOCT 3 and 8 months after initiation of treatment show clinical response and decrease in thickness respectively.
| Case No | Clinical Diagnosis
(AJCC TNM Stage) |
Time Domain-Anterior Segment OCT | Final Histopathological Diagnosis | |||||||
| Maximal Thickness
(microns) |
Epithelial
thickening |
Abrupt
Transition |
Hyper-
reflectivity |
Clear
plane |
Basal
membrane |
Back
Shadowing |
OSSN Type
|
|||
| 1 | OSSN
(T3NOMO) |
1200 | Present | Present | Epithelial | Present | Absent | Present, focal | Type I | Severe Dysplasia |
| 2 | OSSN
(T3NOMO) |
2550 | Present | Present | Epithelial | Absent | Absent | Present | Type II | Invasive SCC |
| 3 | OSSN
(T3NOMO) |
1070 | Present | Present | Epithelial | Present | Present | Absent | Type IV | Carcinoma-in-situ |
| 4 | OSSN
(T2NOMO) |
870 | Present | Present | Epithelial | Absent | Absent | Present | Type II | Invasive SCC |
| 5 | OSSN
(T3NOMO) |
880 | Absent | Present | Epithelial | Absent | Absent | Present | Type III | Severe Dysplasia |
| 6 | OSSN
(T3NOMO) |
150 | Present | Present | Epithelial | Absent | Absent | Absent | Type II | Invasive SCC |
| 7 | OSSN
(T2NOMO) |
1380 | Present | Present | Epithelial | Present | Present | Present,
focal |
Type IV | Severe Dysplasia |
| 8 | Pterygium | NA | Absent | Absent | Sub-epithelial | Absent | Absent | Absent | NA | Pterygium |
| 9 | Pterygium | NA | Absent | Absent | Sub-epithelial | Absent | Absent | Absent | NA | Pterygium |
| 10 | Pinguecula | NA | Absent | Absent | Sub-epithelial | Absent | Absent | Absent | NA | Pinguecula |
| 11 | Multifocal OSSN
(T3NOMO) |
580 | Present | Present | Epithelial | Present | Present | Absent | Type IV | Bulbar – Carcinoma-in-situ
Eyelid – Carcinoma-in-situ |
| 12 | Diffuse OSSN
(T3NOMO) |
630 | Present | Present | Epithelial | Present | Absent | Absent |
Type I |
NA |
| 13 | Diffuse OSSN
(T3NOMO) |
780 | Present | Present | Epithelial | Present | Absent | Absent |
Type I |
NA |
Table 1: Demography, clinical and histopathological diagnosis, treatment and outcome of OSSN
| Case No | Clinical Diagnosis
(AJCC TNM Stage) |
Time Domain-Anterior Segment OCT | Final Histopathological Diagnosis | |||||||
| Maximal Thickness
(microns) |
Epithelial
thickening |
Abrupt
Transition |
Hyper-
reflectivity |
Clear
plane |
Basal
membrane |
Back
Shadowing |
OSSN Type
|
|||
| 1 | OSSN
(T3NOMO) |
1200 | Present | Present | Epithelial | Present | Absent | Present, focal | Type I | Severe Dysplasia |
| 2 | OSSN
(T3NOMO) |
2550 | Present | Present | Epithelial | Absent | Absent | Present | Type II | Invasive SCC |
| 3 | OSSN
(T3NOMO) |
1070 | Present | Present | Epithelial | Present | Present | Absent | Type IV | Carcinoma-in-situ |
| 4 | OSSN
(T2NOMO) |
870 | Present | Present | Epithelial | Absent | Absent | Present | Type II | Invasive SCC |
| 5 | OSSN
(T3NOMO) |
880 | Absent | Present | Epithelial | Absent | Absent | Present | Type III | Severe Dysplasia |
| 6 | OSSN
(T3NOMO) |
150 | Present | Present | Epithelial | Absent | Absent | Absent | Type II | Invasive SCC |
| 7 | OSSN
(T2NOMO) |
1380 | Present | Present | Epithelial | Present | Present | Present,
focal |
Type IV | Severe Dysplasia |
| 8 | Pterygium | NA | Absent | Absent | Sub-epithelial | Absent | Absent | Absent | NA | Pterygium |
| 9 | Pterygium | NA | Absent | Absent | Sub-epithelial | Absent | Absent | Absent | NA | Pterygium |
| 10 | Pinguecula | NA | Absent | Absent | Sub-epithelial | Absent | Absent | Absent | NA | Pinguecula |
| 11 | Multifocal OSSN
(T3NOMO) |
580 | Present | Present | Epithelial | Present | Present | Absent | Type IV | Bulbar – Carcinoma-in-situ
Eyelid – Carcinoma-in-situ |
| 12 | Diffuse OSSN
(T3NOMO) |
630 | Present | Present | Epithelial | Present | Absent | Absent |
Type I |
NA |
| 13 | Diffuse OSSN
(T3NOMO) |
780 | Present | Present | Epithelial | Present | Absent | Absent |
Type I |
NA |