AS-OCT Guided Treatment Of Diffuse Conjunctival Squamous Cell Carcinoma With Resection, Amniotic Membrane Graft And Topical Mitomycin C

Figures & data

Figure 1 Case 1 (MMC group); a 32-year-old male with OSSN of the left eye (A–C): slit-lamp photographs: (A) preoperative; shows a diffuse gelatinous lesion on the temporal conjunctiva with extensive corneal involvement. (B) One week postoperative; the conjunctiva was edematous and reconstructed with AMG (C) 2-year follow-up shows a complete resolution of the lesion. (D,E) AS-OCT images: (D) preoperative shows a thickened, hyper-reflective epithelium (red arrow) and abrupt transitions between normal and abnormal epithelium. (E) 2-year follow-up; in the area of the previous lesion shows back to a normal thin epithelial thickness and appearance (red arrow). (F,G) Histopathological specimen [H&E, low power (F) & high power (G)]; sections reveal squamous cell proliferation forming sheets & solid nests extending from the surface epithelium down to the subepithelial level. The squamous cells are atypical showing large nuclei, multiple eosinophilic nucleoli with frequent mitosis and atypical forms. The intercellular bridges between the squamous cells are readily seen. There are many individually keratinized cells with small pearl-like structures. This is consistent with invasive squamous cell carcinoma, moderately differentiated.

Figure 2 Case 2 (MMC group); a 56-year-old male with OSSN of the left eye, A–C: slit-lamp photographs: (A) preoperative shows a diffuse papillary lesion on the temporal conjunctiva with conjunctival fornices extension. (B) 1-week post-operative shows congested ocular surface which was reconstructed with AMG. (C) 2-year follow-up shows a complete resolution of the lesion. (D, E) AS-OCT images: (D) preoperative shows a thickened and hyper-reflective epithelium (red arrow). (E) 2-year follow-up; in the area of the previous lesion shows back to a normal thin epithelial thickness and appearance (red arrow). (F–I) Histopathological specimen [H&E, low power (F, G) & high power (H, I)]; sections reveal fibrovascular tissue with many congested blood vessels lined by stratified squamous epithelium. In some areas, there is atypia throughout the full thickness of epithelium with individual tumor cells and nests extending into underlying stroma. The tumor cells (yellow arrow) show eosinophilic cytoplasm, intercellular bridges and atypical nuclei with prominent nucleoli and coarse chromatin. Frequent mitotic figures, including atypical mitoses, are also seen. This is consistent with invasive squamous cell carcinoma; moderately differentiated and adjacent area shows moderate to severe dysplasia and intraepithelial neoplasia (carcinoma-in-situ).

Table 1 Summary Of Demographic And Clinical Results

Variable	Result (Mean±SD) Or Total (%)
Age (years):
MMC group No MMC group	57.4±12.6 60.4±3.8
Gender, male & female (%):
MMC group	11 (73.3%) & 4 (26.7%)
No MMC group	6 (66.7%) & 3 (33.3%)
Follow-up period (months):	27.1±4.1 (range, 19–31)
Extent of the limbal involvement (clock hours):
MMC group	7.0±0.7
No MMC group	7.25±0.6
Operative time(minutes):
MMC group	38.6±2.7
No MMC group	39.8±3.2
Conjunctival defects(mm^2):*
MMC group	63.6±19.3
No MMC group	92.4±17.3
BCVA preoperative & 2-year follow-up (log MAR):
MMC group	0.3±0.25 & 0.25±0.17
No MMC group	0.32±0.18 & 0.27±0.17
The conjunctival epithelial thickness preoperative & 2-year follow-up (μm):*
MMC group	267±24.2 & 56.7±11.6
No MMC group	256±19.1 & 60.4±9.6
Number of MMC treatment cycle (cycles)	2.1±0.85
Recurrence, total (%)
MMC group	Zero (0%)
No MMC group	1(11%)

Note: *A significant different at P value <0.05.

Abbreviations: SD, standard deviation; MMC, mitomycin C; CSCC, conjunctival squamous cell carcinoma.

Table 2 Previous Reports On Treatment For Diffuse CSCC

Author(s)/Year	Surgical Technique	Recurrence (%)	Number Of Eyes	Follow-Up Months
Shield et al^Citation6/2002	Topical mitomycin C 0.04% four times daily for 7 days followed by 7 days off (repeated until completely regressed using slit-lamp biomicroscopy)	0%	10 extensive CSCC	6–50
Frucht-Pery et al^Citation37/2002	(Topical MMC, 0.02% or 0.04%, four times daily for 14 days per course/2-3 courses) Histologic evaluation was done 1 month after the final treatment	0%	5 incompletely excised CSCC.	18 - 37
Khokhar et al^Citation38/2002	Excision+cryotherapy+0.02% MMC at the time of surgery.	0%	5 recurrent OSSN	More than 12
Shields et al^Citation13/2005	Chemoreduction: MMC (0.04% four times a day/week on –week off per cycle/2–3 cycles until no further regression or patient intolerance or toxicity)+ surgical resection of the residua (2 weeks after cessation of MMC)	0%	3 extensive thick CSCC	N/A
Gupta, Muecke^Citation5/2010	Primary topical MMC (0.04% four times a day/week on –week off per cycle/2–3 cycles)	● 10% (one case) with partial Regression ● 20% (two) with recurrence.	10 diffuse CSCC	5.8–119.8
Kim et al^Citation24/2012	Topical and/or intralesional IFN‑α2b	● Complete control in 72% ● Reduction in size in 28%	18 giant OSSN	Median follow-up of 11
Palamar et al^Citation45/2014	Excision+AMG secured by suture	0% (good cosmetic and functional)	10 OSSN	13–75
Albert et al^Citation22/2015	Excision+cryotherapy±AMG	7% (3/43; all from +ve margin group)	28 incomplete excision OSSN	18.4–44.3
Joag et al^Citation28/2016	Primary topical 5FU	11% (4 patients)	44 OSSN	2–77
Bello et al^Citation23/2016	A surgical excision without safety margins+IFNα2b.	0%	Case study of giant OSSN	24
Hanada et al^Citation21/2017	Excision +0.04% MMC treatment for the exposed sclera+AMG	25%	8	36–78
Joag et al^Citation28/2016	5-Fluorouracil 1% 4 times daily for 1 week followed by a drug holiday of 3 weeks	18%	44 OSSN	The median follow-up 10 months (range, 2–77 months)
Parrozzani et al^Citation45/2017	1% 5-FU four times a day for 4 weeks Adjunctive courses were administered after 1 month of chemotherapy-free interval.	17% (effective treatment for patients affected by preinvasive OSSN and for a limited proportion (50%) of invasive OSSN).	41	Mean follow-up was 105±32 months (range 60–171 months)
Chaugule et al^Citation35/2018	IFN α2b and/or 5 1% 5FU. Exfoliative biopsy to confirm the diagnosis	0%	10 giant OSSN	3–25
Meel et al^Citation44/2018.	Immunoreduction(intraorbital IFα2b of 3 injections at week interval)+ A wide surgical excision and cryotherapy and intraoperative 0.04% MMC +Topical interferon (1 million IU/mL – four times a day) drops 3 months after surgery.	0%	Case report of locally advanced orbito-conjunctival	24 months
Current study	Modified excision+AMG+MMC (0.04% four times a day/week on –week off per cycle)/(repeated until completely regressed clinically using slit-lamp biomicroscopy and AS-OCT)	0%	15 diffuse CSCC	19 –31

Abbreviations: OSSN, ocular surface squamous cell neoplasia; CSCC, conjunctival squamous cell carcinoma; AMT, amniotic membrane transplant; MMC, mitomycin C; IFNα2b, interferon alpha 2b; 5FU, 5 fluorouracil; AS-OCT, anterior segment optical coherent tomography.

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Data Availability Statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request without end date.