DIFFERENT MODALITIES IN THE MANAGEMENT OF OCULAR SURFACE SQUAMOUS NEOPLASIA

Purpose: To study the different modalities in the management of Ocular Surface SquamousNeoplasia(OSSN).Method: A prospective study of 30 cases of OSSN was undertaken. Based on patient factors andtumour size and characteristics , 20 patients underwent surgical excision with cryotherapy and 10patients were managed conservatively with topical interferon therapy. Patients were followed up for aperiod of nine months.Results: OSSN is more common in males (80%) with mean age of 55 years (range 30-76 years).Histopathology report of excision biopsy showed 6 benign dysplasia, 8 carcinoma in situ and 6invasive squamous carcinoma. Postoperative topical interferon reduced the risk of recurrence.Of the patients who underwent interferon therapy, complete resolution was seen in 6 cases.Conclusion : Management of OSSN requires adequate excision and regular follow up to monitor anyrecurrence. Although surgical excision is still the gold standard for OSSN treatment, topicalinterferon has revolutionised the management of OSSN. Pre and Post operative adjunctive therapyshould be considered to prevent recurrence.

Histopathological spectrum of ocular surface squamous neoplasia: A retrospective study of 776 lesions

Background: Ocular surface squamous neoplasia (OSSN) comprises neoplasm arising from the ocular surface, which includes conjunctiva, cornea, and limbus and ranges from mild dysplasia to invasive squamous cell carcinoma. Purpose: The aim of this work was to study the spectrum of OSSN based on histopathological analysis. Materials and Methods: This was a retrospective cross-sectional study comprising 776 histopathologically diagnosed cases of OSSN from January 2004 to December 2014. Results: The mean age of presentation of OSSN was 45 years (median, 45 years; 2 to 87 years) with male preponderance (74%). The most common age group of presentation was 41–60 years (n = 299; 39%). The most common type of OSSN was invasive squamous cell carcinoma seen in 50% (n = 383) eyes followed by severe dysplasia/carcinoma in situ in 31% (n = 250) eyes. Tumor infiltration at base was seen in 16% (n = 124), positive margins in 32% (n = 248), scleral infiltration in 14% (n = 109), intraocular extension in 3% (n = 23), and orbital extension in 4% (n = 26) eyes. OSSN was associated with actinic keratosis in 21% (n = 165) cases. Conclusion: Based on histopathology, invasive squamous cell carcinoma is the most common form of OSSN in the Asian Indian population.

Ipsilateral presentation of ocular surface squamous neoplasia and conjunctival melanoma in xeroderma pigmentosum: A rare occurrence

A case of a 16-year-old male with xeroderma pigmentosum (XP) who presented with multiple pigmented and nonpigmented conjunctival lesions in both eyes is reported. He had a keratinized lesion at the limbus and a pigmented lesion in bulbar conjunctiva in the left eye and multiple pigmented bulbar conjunctival lesions and a keratinized limbal nodule in the right eye. Excision biopsy confirmed the diagnosis of ocular surface squamous neoplasia (OSSN) and conjunctival intraepithelial melanocytic neoplasia-2 (CIMN-2) in the right eye and OSSN and conjunctival melanoma in situ (CIMN-5) in the left eye. Two malignant conjunctival lesions occurring simultaneously in the same eye of a patient with XP have not been reported earlier.

Severe necrotising inflammatory skin reaction to topical 5-fluorouracil

I report two patients who developed a severe necrotising inflammatory skin reaction with ulceration and hemorrhagic crusting during the first cycle of chemotherapy with 1% 5-Fluorouracil eye drops for Ocular surface squamous neoplasia. The skin reaction subsided on stoppage of the drops and the use of a steroid ointment. 5 fluorouracil therapy was terminated and the patients were shifted to interferon therapy subsequently.

Primary limbal stem cell transplantation in the surgical management of extensive ocular surface squamous neoplasia involving the limbus

Purpose: To determine the role of primary limbal stem cell transplantation (LSCT) in managing extensive ocular surface squamous neoplasia (OSSN) with more than 3 quadrants of limbal involvement to prevent manifestations of limbal stem cell deficiency. Methods: A multi-center, comparative, and interventional clinical study of cases and historical controls was done. Patients with a limbal mass suggestive of OSSN involving more than 3 quadrants of limbus (> 9 clock hours) and no local, regional or systemic metastasis, who underwent primary surgical excision with or without adjuvant chemotherapy and had a minimum follow-up of 12 months were included in this study. Two historical controls underwent tumor excision with only amniotic membrane grafting. Three cases underwent tumor excision along with LSCT in the form of conjunctival limbal autograft (CLAG) or simple limbal epithelial transplant (SLET). Results: None of the eyes had any recurrences of OSSN during the follow-up period. Cases with primary LSCT with tumor excision showed better ocular surface stability in the long term. Conclusion: Concomitant LSCT either in the form of CLAG or SLET appears to provide better long-term outcomes and is advocated while excision of extensive OSSN involving the limbus.

Topical chemotherapy for giant ocular surface squamous neoplasia of the conjunctiva and cornea: Is surgery necessary?

Purpose: The purpose of this study is to report on the efficacy and safety of topical chemotherapy alone for giant ocular surface squamous neoplasia (OSSN). Methods: In this retrospective, interventional series, 10 eyes with giant OSSN underwent exfoliative biopsy to confirm the diagnosis followed by application of interferon alpha 2b (IFN ?2b) and/or 5 fluorouracil, 1% (5FU). Reported outcome measures were tumor response, visual acuity, recurrence, systemic metastasis, and treatment complications. Results: Ten patients (3 female, 7 male) had a mean age of 73 (median, 69; range 40–89) years. Mean tumor diameter was 13.1 (median, 12.3; range 8.2–19.4) mm. Five (50%) eyes were treated with IFN-?2b alone; 1 (10%) with 5-FU alone and 4 (40%) required both IFN-?2b and 5-FU. The mean duration of treatment was 3, 0.5, and 6.4 months for IFN-?2b alone, 5-FU alone, and both IFN-?2b and 5-FU respectively. Complete tumor response was observed in all 10 cases at mean follow-up of 12.8 (median, 11.5; range, 3–25) months. Complications noted were transient irritation and burning (n = 4), dry eyes (n = 2), and transient flu-like symptoms (n = 2). There was no evidence of chemotherapy-related symblepharon, stem cell deficiency, scleral thinning, or corneal opacity. There were no tumor recurrences, and no patient required surgical excision or cryotherapy. Conclusion: Topical chemotherapy was a safe and effective treatment, inducing complete regression in all cases of giant OSSN in this series. There were no sight-limiting complications.

Research progress of ocular surface squamous neoplasia / 国际眼科杂志(Guoji Yanke Zazhi)

· Ocular surface squamous neoplasia(OSSN) is a type of ocular surface tumor,which is difficult to diagnose because of its low incidence is low and it is easy to be confused with pterygium.In recent years,the improvement of various diagnostic techniques and the extensive application of interferon (IFN) to OSSN therapy have greatly reduced the recurrence rate,and the diagnostic and therapeutic methods of OSSN tend to be diversified.Understanding the current causes of OSSN and the ways of treatment can better guide the OSSN study.

The Effectiveness of Topical Chemotherapy for the Primary Treatment of Ocular Surface Squamous Neoplasia

PURPOSE: In the present study, the effectiveness of topical chemotherapy for the primary treatment of ocular surface squamous neoplasia (OSSN) was evaluated. METHODS: We enrolled 10 patients (10 eyes) diagnosed with OSSN who received both clinical examination and anterior segment optical coherence tomography (AS-OCT) imaging. The patients were administered topical 0.02% mitomycin-C (MMC) 4 times/day in the affected eye. The patients with MMC-resistant OSSN received topical 1% 5-fluorouracil (5-FU) 4 times/day. AS-OCT imaging was performed before and after the treatment. Clinical examination and AS-OCT were used to monitor the efficacy of topical chemotherapy, recurrence and side effects. RESULTS: The mean age of the 10 patients (8 males, 2 females) was 76.7 years. The proportion of complete remission resulting from topical treatment with MMC was 80.0% (8 eyes) and 20.0% (2 eyes) when 5-FU was changed to MMC. The average duration of complete remission was 4.3 weeks and the average duration of no recurrence was 17.5 months. The epithelial thickness of the lesions, measured using AS-OCT, significantly decreased from 315.0 µm (pretreatment) to 105.3 µm (after complete remission). Additionally, the epithelial lesion appeared normal after treatment. The most common side effect was conjunctival hyperemia (60.0%, 6 eyes), followed by ocular allergy (30.0%, 3 eyes), superficial punctate keratitis (30.0%, 3 eyes) and corneal erosion (20%, 2 eyes). No serious complications were reported. CONCLUSIONS: Topical chemotherapy is as effective and well tolerated as a primary treatment for OSSN. Additionally, AS-OCT is a useful noninvasive adjunctive tool in the diagnosis and management of OSSN.

Recombinant interferon alpha 2b for ocular surface squamous neoplasia: An efficient and cost‑effective treatment modality in Asian Indian patients.

Purpose: The purpose was to study the efficacy of interferon alpha 2b (INF α2b) in the treatment of ocular surface squamous neoplasia (OSSN) and analyze its cost‑effectiveness in India. Study Design: This was a retrospective study of thirty patients with OSSN treated with topical INF α2b (1 MIU/cc) ± perilesional INF α2b (5 MIU/cc). Results: The tumor involved cornea (n = 9, 30%), conjunctivo‑limbal‑corneal surface (n = 19, 63%), or bulbar conjunctiva (n = 2, 7%). The mean basal dimension of the tumor was 16 mm. The tumors belonged to Tis (n = 6, 20%) or T3 (n = 24, 80%) based on the American Joint Committee Classification, 7th edition. In the six patients with Tis, three cycles of topical INF α2b were used for immunoprevention. In the remaining 24 patients, INF α2b was advised for immunoreduction, but served as immunotherapy with 100% tumor regression in 22 (92%) cases, and resulted in 95% immunoreduction in 2 (6%) cases. Complete tumor regression by immunotherapy (n = 22) was achieved with a mean number of three topical INF α2b cycles and two perilesional injections. All these 22 patients received three additional topical INF α2b cycles after complete tumor regression. For immunoreduction (n = 2), both patients received six cycles of topical INF α2b which was three perilesional INF α2b injections. The mean total treatment cost per patient with INF α2b was INR 9164 ($US 137). Based on maximum basal diameter of tumor at presentation, the mean total treatment cost per patient with INF α2b was INR 4866 ($US 73) for eyes with microscopic evidence of tumor residue (n = 6), INR 9607 ($US 143) for tumors ≤10 mm (n = 13), and INR 10,985 ($US 164) for tumors >10 mm (n = 11), with two patients needing additional surgical excision for complete tumor control. Conclusion: INF α2b can be used for immunoreduction, immunotherapy, or immunoprevention of OSSN. INF α2b is a cost‑effective treatment modality for OSSN at an average total treatment cost of INR 9164 ($US 137) per patient.

Squamous Cell carcinoma (Moderately Differentiated) of Conjunctiva – A Rare Case in a Five Year Retrospective Study.

Worldwide squamous cell carcinoma (SCC) of the conjunctiva is a rare malignancy; however, it is reported to be the most common malignant tumour of the ocular surface. Its incidence varies between 0.02 and 3.5/100.000. We report a case of squamous cell carcinoma of conjunctiva presented with triangular pedunculated mass of left eye of 75 years old female. It is diagnosed on FNAC and confirmed on histopathological examination after excision. On analyzing the data of FNA done (19150) and biopsies received (23158) in 5 years in the department of pathology, we found only five cases of eye region came for FNA while 25 biopsies of eye region received and diagnosed rightly. Out of all these cases, this is the only case of squamous cell carcinoma of conjunctiva in this study. Incidence of SCC of conjunctiva in our retrospective study of data of total pathological biopsies received found to be 4.3/100000.

Management and Treatment of Ocular Surface Neoplasia.

Conjunctival squamous cell carcinoma (CSCC) is an invasive ocular surface neoplasia ranging from dysplasia to carcinoma in situ to invasive squamous cell carcinoma, which is identifi ed as premalignant and malignant epithelial lesions. Often, it is seen in males in tropical countries lying close to the equator where there is excessive exposure to sunlight. Clinical diagnosis requires close examination with a degree of high suspicion. Appropriate and defi nitive diagnosis of conjunctival squamous neoplasia by ocular pathologists and the need for future detailed clinicopathologic studies is recommended. Appropriate and defi nitive diagnosis requires histopathology. We describe a case of CSCC underlying dysplasia with intraepithelial squamous cell neoplasia, where the case was confi rmed by histopathological examination. Th e treatment modality involving surgery and medication and follow-up is described. Th ere was no evidence of recurrence, complication, or metastasis.

Topical 002% Mitomycin C for management of primary corneal-conjunctival intraepithelial neoplasia as primary therapy: A long term follow up

Background: The corneal-conjunctival intraepithelial neoplasia (CCIN) is an ocular surface neoplasia commonly found among populations exposed to strong UV light. Although surgical excision is mainstay treatment, topical Mitomycin-C (MMC) 0.02% has been tried as a sole therapeutic treatment of non- invasive Ocular Surface Squamous Neoplasia (OSSN). Aim: The aim of this study was to report the long term outcome of treatment of non invasive ocular surface squamous neoplasia with topical Mitomycin C (0.02%) as primary therapy. Materials and methods: Total six eyes of six patients with CCIN were treated with topical mitomycin C (0.02%) alone as a sole therapy. All patients received topical MMC (0.02%) four times daily as a cycle therapy of two week ON and two week OFF for 12 weeks. The patients were followed up to two years. Results: All patients showed total cure with no recurrence during 2 years follow up period. Ocular irritation and mild conjunctival hyperemia were observed in 4 eyes during treatment with MMC. There were no serious complications noted at the end of the follow-up period. Conclusion: We concluded that Topical Mitomycin C (0.02%) may be used as a sole therapeutic treatment of non invasive Ocular surface squamous neoplasia with close on going follow-up.

Ocular Surface Squamous Cell Carcinoma with Intraorbital Extension in a Patient with Long-Term Immunosuppression

PURPOSE: To report a case of ocular surface squamous cell carcinoma with intraorbital extension in a patient with renal transplantation and long-term immunosuppressive therapy. CASE SUMMARY: A 59-year-old Korean male presented with a whitish mass in the medial limbus and conjunctiva of the right eye. The patient had undergone renal transplantation 17 years prior due to lupus nephritis and was on systemic immunosuppression with daily prednisolone (10 mg), tacrolimus (5 mg), and mycophenolate sodium (720 mg). The complete excision of the mass was performed and mitomycin C application and amniotic membrane transplantation on the excised area were combined. Histopathological examination revealed the mass was squamous cell carcinoma. There were no abnormal findings on the orbit computed tomography (CT). The patient was additionally treated with topical interferon alpha 2b 6 months postoperatively. One year later, a mass recurred at the same site in the right eye. The complete excision of the mass, mitomycin C application, cryotherapy, and amniotic membrane transplantation were performed. Orbit CT showed a 1.9 cm-sized intraorbital mass involving the medial rectus of the right eye. The orbital exenteration was performed and the intraorbital mass was histologically proven to be squamous cell carcinoma. CONCLUSIONS: Ocular surface squamous neoplasia in patients with renal transplantation and long-term immunosuppressive therapy should be monitored closely for the possibility of orbital invasion.

Neoadjuvant chemotherapy for invasive squamous cell carcinoma of the conjunctiva: A case report.

A 40‑year‑old male presented with an orbital extension of conjunctival squamous cell carcinoma (SCC). The orbital mass was seen protruding outward from the left palpebral fissure overhanging the lower eyelid, completely obscuring the globe and lower lid. The patient gave a history of excision biopsy, which was histopathologically diagnosed as ocular surface squamous neoplasia. He also gave a history of tumor recurrence, which gradually progressed to assume the form of the presently visible orbital mass. Computed tomography of the orbits showed the mass extending into the left orbit causing superior displacement of the globe. After a negative locoregional and systemic metastatic screening, neoadjuvant intravenous systemic chemotherapy with cisplatin and 5‑fluorouracil were initiated in an attempt to reduce the size of the tumor. Three cycles of tri‑weekly chemotherapy resulted in a significant reduction of the orbital tumor size with the globe and the lower lid being visible, thus making a lid‑sparing orbital exenteration possible. The patient subsequently underwent an orbital exenteration and at 6‑month follow‑up, the patient was free from local and regional disease. To our knowledge, this is the first reported case where systemic neoadjuvant chemotherapy has been used to reduce the size of invasive SCC with orbital extension, thereby permitting a lid‑sparing orbital exenteration.

Limbal Squamous Cell Carcinoma in a Young Non‑Human Immunodeficiency Virus Patient and its Surgical Outcome: A Rare Case Report.

Ocular surface squamous neoplasia presents as a spectrum from simple dysplasia to carcinoma in situ to invasive squamous cell carcinoma (SCC) involving the conjunctiva as well as the cornea. SCCs are commonly seen in eye at the transitional zone of epithelium-the limbus and eyelid margin and usually seen in elderly patients or in young human immunodeficiency virus (HIV) positive patients. Limbal lesion spreads over the ocular surface and enters the fornices but rarely penetrates the globe. Wide total excision serves both therapeutic and diagnostic purpose. We report a rare case of 32 years old, non-HIV male patient who presented with complaints of painless, progressive mass in the right eye with mild visual blurring since 2 months. Slit lamp examination suggested the clinical diagnosis of limbal carcinoma for which a total excisional biopsy with fibrin glued conjunctival autograft was performed. Postoperatively with the confirmed diagnosis of SCC from histopathology, mitomycin - C 0.02% eye drops were prescribed for 4 weeks along with steroid- antibiotic combination in a tapering dose. Postoperatively no recurrence was seen, and good cosmetic improvement was noted.

Electron beam radiotherapy for the management of recurrent extensive ocular surface squamous neoplasia with orbital extension.

Recurrent extensive ocular surface squamous neoplasia (OSSN) with orbital invasion can be successfully managed with external radiotherapy using electrons resulting in eye and vision salvage. We report a case of right eye recurrent OSSN in an immunocompetent adult Indian male, with extensive orbital involvement. The patient had two previous surgical excisions with recurrent disease. At this stage, conventionally exenteration is considered the treatment modality. However, he was treated with 5040 cGy radiotherapy (15eV electrons) resulting in complete disease regression. At the end of 3 years follow‑up, the patient was disease free, maintained a vision of 20/25, with mild dry eye, well‑managed with topical lubricants. Extensive OSSN with orbital invasion does not always need exenteration. External beam electron radiotherapy provides a noninvasive cure with organ and vision salvage and should be considered in extensive OSSN not amenable to simple excision biopsies. Long‑term studies to evaluate the effect of radiation on such eyes are suggested.

Tumors of the ocular surface: A review.

Tumors of the Ocular Surface clinically manifest with a very wide spectrum and include several forms of epithelial, stromal, caruncular, and secondary tumors. As a group, these tumors are seen commonly in the clinical practice of a comprehensive ophthalmologist, cornea specialist, and an ocular oncologist. This review is aimed to discuss the common tumors of the ocular surface and emphasize on their clinical diagnosis and appropriate management.

Analysis of Clinical Features and Prognostic Factors of Ocular Surface Squamous Neoplasia

PURPOSE: To analyze the clinical features and prognostic factors of ocular surface squamous neoplasia (OSSN). METHODS: A total of 31 eyes of 31 patients with suspected OSSN who were treated with excision and biopsy were retrospectively reviewed. Clinical features such as patient symptoms, invasion type, morphologic feature and size of lesion were analyzed. All patients were treated with simple excision or mitomycin C combination therapy. Factors affecting recurrence were evaluated. RESULTS: The most common symptom, invasion type, morphological feature, lesion size and histological diagnosis were foreign body sensation (38.7%), combined conjunctiva and cornea type (71.0%), gelatinous type (74.2%), 5 - 10 mm in largest diameter (45.2%) and intraepithelial neoplasia (51.6%), respectively. Age, sex, morphological features, lesion size and histological diagnosis had no effect on recurrence. Mitomycin C combination therapy was significantly associated with decreased recurrence compared to simple excision (p < 0.05). CONCLUSIONS: In OSSN, intraepithelial neoplasia was the most common subtype. Mitomycin C combination therapy was effective in decreasing recurrence.