Search

The authors describe two cases of corneal ocular surface squamous neoplasia (OSSN), presenting at our rural eyecare centre, which were initially misdiagnosed as viral epithelial keratitis and corneal pannus with focal limbal stem cell deficiency. Both the cases were refractory to initial treatment and corneal OSSN was suspected. Anterior segment-optical coherence tomography (AS-OCT) revealed a thickened, hyper-reflective epithelium with abrupt transition and an underlying cleavage plane, features typical of OSSN. Topical 1% 5-fluorouracil (5-FU) therapy was initiated and in two cycles (first case) to three cycles (second case), complete resolution was noted both clinically and on AS-OCT, with no significant side effects. Both patients are currently free of tumour at the 2-month follow-up period. The authors report the rare, atypical presentations of corneal OSSN, discuss the masquerades and highlight the role of primary topical 5-FU in managing corneal OSSN in limited resource settings., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

An atypical Advancing Wavelike Epitheliopathy case, consecutive to topical treatment for a 360º Conjunctival Intraepithelial Neoplasia, is presented. Mitomycin (0.2 mg/mL) and interferon (1 MUI/mL) drops were used. An atypical presentation, with migrating limbal focus, non clearly delimited in its hourly site through its evolution. Treated with flurometholone drops plus artificial tears, working to complete resolution., (Copyright © 2022 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

Significance: Ocular surface squamous neoplasias are superficial tumors of the cornea and conjunctiva that can be sight threatening if neglected. Therefore, accurate noninvasive diagnostic modalities are needed., Purpose: The purpose of this case series was to describe the hallmark features of ocular surface squamous neoplasia on high-resolution optical coherence tomography (HR-OCT) imaging and its use in the evaluation and management of superficial ocular tumors., Case Series: Five eyes of four patients with ocular surface squamous neoplasia are described. Whereas two eyes displayed the classic clinical features of ocular surface squamous neoplasia, three of the five eyes had more subtle atypical features. However, all shared features on HR-OCT of epithelial thickening and hyperreflectivity with abrupt transitions between normal and abnormal tissue, classic features of ocular surface squamous neoplasia. All lesions ultimately underwent incisional or excisional biopsy and were confirmed to be ocular surface squamous neoplasia on histopathology., Conclusions: Ocular surface squamous neoplasia may present as a classic tumor but can also have subtle features or masquerade. Accurate methods to diagnose and manage patients with ocular surface squamous neoplasia are necessary. With recent advancements in technology, HR-OCT has been demonstrated to accurately identify ocular surface squamous neoplasia with the repeatable optical findings of (1) epithelial thickening, (2) epithelial hyperreflectivity, and (3) abrupt transition zone between normal and abnormal tissue. This case series demonstrates how HR-OCT can help provide an optical biopsy to guide appropriate diagnosis and management of this neoplastic lesion., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2021 American Academy of Optometry.)

Purpose: To study the efficacy of interferon alfa-2b (IFN-a2b) on pigmented ocular surface squamous neoplasia (p-OSSN) and assess the resolution of the pigment to the treatment., Methods: A retrospective case series of 8 tumors in 7 patients., Results: The mean age at diagnosis of p-OSSN was 65 years (median, 61 years; range, 51-84 years), and all patients were men. The mean duration of symptoms was 2 months (median, 1 month; range, 1-4 months). One patient had 2 distinct lesions in the same eye. Tumor epicenter was located at the limbus (n = 5) or bulbar conjunctiva (n = 2). Complexion-associated melanosis was noted in all eyes. The mean basal dimension of the tumor was 8 mm (median, 7 mm; range, 5-12 mm). The mean % of tumor pigmentation was 47% (median, 30%; range, 10%-100%). The treatment details included topical IFN-a2b (n = 1) or a combination of topical and subconjunctival injection of IFN-a2b (n = 7). All patients with p-OSSN showed excellent response to IFN-a2b with complete tumor regression and resolution of tumor-associated pigment with a mean number of 2 subconjunctival IFN-a2b injections (median, 2; range, 0-3) and topical IFN-a2b for an average of 2 months (median, 2 months; range, 1-3 months). There was no change in the complexion-associated melanosis with IFN-a2b., Conclusions: IFN-a2b is very effective in the management of p-OSSN. There is a complete resolution of the pigment along with the tumor., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate the long-term follow-up of recurrent conjunctival and corneal intraepithelial neoplasia (CCIN) treated with combination topical interferon alfa-2b and retinoic acid (I/RA)., Methods: Our study represents a retrospective observational interventional series of 82 eyes from 82 patients from a single institution, reviewed for CCIN. All were administered topical interferon alfa-2b 1 million IU/mL QID and retinoic acid 0.01% every other day. Patients had been diagnosed by biopsy. A Kaplan-Meier survival analysis, Wilcoxon signed-rank test and a multivariate logistic regression were statistical tests used to correlate recurrence with patient and tumor variables., Results: 79 eyes assessed for CCIN diagnoses and treated with I/RA achieved tumor resolution. The median tumor-free follow-up was ~109.1 months with a median time to resolution being ~2.8 months. Our median treatment duration was ~11.3 months. The greatest difference in the mean total residual tumor size was identified between Months 0-1 [-7.63 mm 2 ]. The difference in mean total residual tumor size remained significant till 36-months. A statistically significant correlation with recurrence was identified for biopsy type [OR 0.138]. 6 patients experienced papillary conjunctivitis which resolved with dosage reduction., Conclusions: Combination I/RA was effective in treating CCIN lesions with few transient side effects. The combination of retinoids and interferons may represent a viable topical therapeutic agent with an extended tumor-free follow-up and a large proportion of our study's patients achieving >10 year's tumor-free follow-up. Our treatment duration is long, but by cost-comparing surgical against medical interventions, topical I/RA may serve as a safe and effective alternative., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A 54-year-old patient presented with a large, fleshy conjunctival lesion in the right eye that had been previously surgically removed in another centre. Diagnosis of Conjunctival intraepithelial neoplasia (CIN) was confirmed by conjunctival impression cytology. The tumor was treated with topical IFN-α-2β (1,000,000 IU/ (ml) adjuvant to surgery for chemoreduction purposes. One month after treatment, the lesion showed almost complete involution, therefore the treatment was continued up to 6 months, and the lesion showed full regression. The patient is currently under periodical follow-up by conjunctival impression cytology. We consider that topical IFN-α-2β can be used in CIN for chemoreduction and/ or curative purposes. We believe that conjunctival impression cytology is a useful and non-invasive method for diagnosis and follow-up in this condition., (©Romanian Society of Ophthalmology.)

Purpose: To compare the efficacy of topical 5-fluorouracil 1% (5FU) and interferon alfa-2b 1 MIU/mL (IFN) eye drops as primary treatment modalities for ocular surface squamous neoplasia (OSSN)., Design: Retrospective, comparative, interventional case series., Methods: Fifty-four patients who received 5FU and 48 patients who received IFN as primary therapy for OSSN were included. Primary outcome measures were the frequency of clinical resolution and time to OSSN recurrence by treatment modality. Secondary outcome was the frequency of side effects with each therapy., Results: The mean age of patients was 68 years. More Hispanics were treated with 5FU. In a univariable analysis, frequency of OSSN resolution was higher with 5FU (96.3%, n = 52) than with IFN (81.3%, n = 39), P = .01. In a multivariable analysis, treatment modality did not remain a significant predictor of resolution. In patients whose OSSN resolved, time to resolution was similar with both agents, (5FU mean 6.6 months, standard deviation (SD) 4.5 vs IFN mean 5.5 months, SD 2.9, P = .17). Of the 52 eyes whose OSSN resolved with 5FU, 11.5% of lesions (n = 6) recurred, whereas of the 39 eyes whose OSSN resolved with IFN, 5.1% of lesions (n = 2) recurred, P = .46. Kaplan-Meier survival curves of OSSN recurrence were similar between groups (log-rank = 0.16). One-year recurrence rates were 11.4% with 5FU and 4.5% with IFN. Eyelid edema (P = .04) and tearing (P = .02) were more significant with 5FU., Conclusions: This is the first direct comparison study between 5FU and IFN eye drops as primary treatment modalities for OSSN. Both modalities resulted in a high frequency of tumor resolution and low recurrence rates and are effective treatment options for OSSN., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Importance: Although the most recent American Joint Committee on cancer staging guidelines for ocular surface squamous neoplasia place a heightened emphasis on biopsy and histopathologic analysis, the interpretation and clinical relevance of these staging criteria are not always clear. We address limitations of using histopathologic analysis to predict clinical outcomes and suggest less-invasive assessments., Background: To investigate the impact of histopathologic depth of invasion on outcomes for tumours with the common presentation of multiple structure involvement., Design: Retrospective chart review at tertiary institution., Samples: Of 41 eyes with ocular surface squamous neoplasia between 2012 and 2017, 27 tumours involving multiple ocular structures clinically were included., Methods: Biopsied tumours were determined to be invasive beyond the basement membrane or non-invasive; non-biopsied tumours were clinically identified with unknown depth of invasion. Outcomes were compared using Fisher's exact or Student's t tests., Main Outcome Measures: Proportion of tumours cured, recurred and/or persisting., Results: Twelve tumours (44%) received primary excisional biopsy, 10 (37%) received chemotherapy without biopsy and 5 (19%) received chemotherapy and biopsy. Clinical diagnosis was correct in all biopsied cases. While there were no significant differences in outcomes between invasive vs non-invasive tumours or treatments, there was a trend toward larger basal diameter in recurrent tumours regardless of treatment., Conclusions and Relevance: When ocular surface squamous neoplasia tumours with similar clinical involvement were compared, histopathologic depth of invasion was not predictive of clinical outcomes. Future staging criteria may consider the potential of largest basal dimension for more accurate prognostication., (© 2018 Royal Australian and New Zealand College of Ophthalmologists.)

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 α2b) 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-α2b alone; 1 (10%) with 5-FU alone and 4 (40%) required both IFN-α2b and 5-FU. The mean duration of treatment was 3, 0.5, and 6.4 months for IFN-α2b alone, 5-FU alone, and both IFN-α2b 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.

Purpose: The mechanism by which ocular surface squamous neoplasia (OSSN) responds to topical interferon-alpha-2b (IFNα2b) is not known. We report the cases of 3 immunosuppressed patients whose tumors did not respond to topical IFNα2b therapy. The purpose of this series is to shed light on potential mechanisms of IFNα2b in OSSN., Methods: Retrospective case series of 3 immunosuppressed patients whose biopsy-proven OSSN did not respond to topical IFNα2b treatment., Results: Three white, immunosuppressed males (mean age 70 years, range 66-76) were diagnosed with OSSN. Topical IFNα2b 1 million units/mL was administered 4 times a day and used for a mean of 5 months (range 2-7 mo) without an adequate response. All patients were then switched to 5-fluorouracil. Successful eradication of OSSN was achieved in 2 cases, and improvement of OSSN in another. The latter patient was switched to mitomycin-C with subsequent resolution of OSSN., Conclusions: These cases suggest that an intact immune system may be an important link between IFNα2b therapy and tumor resolution. As such, topical IFNα2b may not be an optimal choice for patients with underlying immunosuppression. It may be more effective in this patient population to switch to a non-immune-modulating therapy such as 5-fluorouracil or mitomycin-C.

Purpose: To determine the efficacy of topical 5-fluorouracil 1% (5-FU) as a primary treatment of ocular surface squamous neoplasia (OSSN)., Design: Retrospective study., Participants: Topical 5-FU was used as primary therapy in 44 patients with OSSN., Methods: 5-Fluorouracil 1% administered topically 4 times daily for 1 week followed by a drug holiday of 3 weeks. Patients were identified through a pharmacy database. Patients were excluded if 5-FU was used as adjuvant therapy, if they did not complete therapy, or if they were still actively receiving treatment for OSSN at the time of last follow-up., Main Outcome Measures: The primary outcome measures were the frequency of complete resolution with topical 5-FU treatment and the rate of OSSN recurrence., Results: Of the 44 patients identified, 32 were men and 12 were women. The mean age was 68 years. Complete resolution of OSSN was noted in 82% of patients (36/44); 18% (8/44) were considered treatment nonresponders. Patients were treated with a median of 4 cycles (range, 2-9 cycles). Nasal location was the only risk factor identified for nonresponse to therapy (P = 0.04). The median follow-up after resolution was 10 months (range, 2-77 months). In the 36 patients who showed complete resolution, 4 experienced tumor recurrence. Recurrence rates at 1 and 2 years were 6% and 15%, respectively, using Kaplan-Meier survival analysis. At least 1 side effect from the medication was reported by 61% of patients (21/44), but only 1 patient discontinued the medication because of intolerance. The most common side effect was pain (n = 17; 39%), followed by tearing (n = 10; 23%), photophobia (n = 6; 14%), itching (n = 4; 9%), swelling (n = 2; 5%), and infection (n = 1; 2%). No long-term complications were reported., Conclusions: 5-Fluorouracil is effective and well tolerated as a primary treatment for OSSN, with 82% of tumors responding completely to therapy., (Copyright © 2016 American Academy of Ophthalmology. All rights reserved.)

Inflammatory myofibroblastic tumor (IMT) is a distinct mesenchymal neoplasm of myofibroblastic spindle cells associated with an inflammatory infiltrate formed by lymphocytes, eosinophils, and plasma cells in a myxoid or collagenous stroma. This tumor has a predilection for children and young adults and most commonly occurs in the lungs, retroperitoneum, abdomen, and pelvis. Ocular and orbital involvement is exceedingly rare. We describe a case of IMT in a 7-year-old girl involving the cornea, conjunctiva, and the anterior orbit treated with crizotinib, resulting in complete tumor remission., (Copyright © 2016 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Purpose: The objective of this study was to compare the cost associated with surgical versus interferon-alpha 2b (IFNα2b) treatment for ocular surface squamous neoplasia (OSSN)., Design: A matched, case-control study., Participants: A total of 98 patients with OSSN, 49 of whom were treated surgically and 49 of whom were treated medically., Methods: Patients with OSSN treated with IFNα2b were matched to patients treated with surgery on the basis of age and date of treatment initiation. Financial cost to the patient was calculated using 2 different methods (hospital billing and Medicare allowable charges) and compared between the 2 groups. These fees included physician fees (clinic, pathology, anesthesia, and surgery), facility fees (clinic, pathology, and operating room), and medication costs. Time invested by patients was calculated in terms of number of visits to the hospital and compared between the 2 groups. Parking costs, transportation, caregiver wages, and lost wages were not considered in our analysis., Main Outcome Measures: Number of clinic visits and cost of therapy as represented by both hospital charges and Medicare allowable charges., Results: When considering cost in terms of time, the medical group had an average of 2 more visits over 1 year compared with the surgical group. Cost as represented by hospital charges was higher in the surgical group (mean, $17 598; standard deviation [SD], $7624) when compared with the IFNα2b group (mean, $4986; SD, $2040). However, cost between the 2 groups was comparable when calculated on the basis of Medicare allowable charges (surgical group: mean, $3528; SD, $1610; medical group: mean, $2831; SD, $1082; P = 1.00). The highest cost in the surgical group was the excisional biopsy (hospital billing $17 598; Medicare allowable $3528), and the highest cost in the medical group was interferon ($1172 for drops, average 8.0 bottles; $370 for injections, average 5.4 injections)., Conclusions: Our data in this group of patients previously demonstrated equal efficacy of surgical versus medical treatment. In this article, we consider costs of therapy and found that medical treatment involved two more office visits, whereas surgical treatment could be more or equally costly depending on insurance coverage., (Copyright © 2016 American Academy of Ophthalmology. All rights reserved.)

Purpose: The aim of this study was to evaluate the efficacy and safety of topical interferon α-2b (IFNα2b) as a single therapy for primary ocular surface squamous neoplasia (OSSN)., Methods: Medical records of 24 eyes of 24 patients with primary OSSN were reviewed retrospectively. The diagnosis of OSSN was primarily based on the slit-lamp examination. All cases were treated with topical IFNα2b (1 million IU/mL) 4 times daily. The duration of treatment, tumor response, adverse effects, and number of vials of topical IFNα2b were noted. Complete response was defined as total disappearance of lesions., Results: The complete remission of the tumor was observed in 22 patients (91.6%). Two patients (8.3%) did not respond to the treatment. The mean age was 62.44 ± 13.65 years (range, 50-92 years). The mean follow-up period was 18.81 ± 3.81 months (range, 14-22 months). The median greatest linear dimension was 6 mm (range, 5.2-12 mm). In all successful remissions, the median time to lesion resolution was 3.25 months. Adverse effects of topical IFNα2b included spontaneous intratumoral bleeding after 3 weeks of topical therapy in 1 patient. No long-term complication or recurrence was found at the end of the follow-up period., Conclusions: Topical IFNα2b is effective and safe as a single therapy in the management of primary OSSN with minimal self-limited adverse effects. It may provide the least invasive way of treating OSSN.

Purpose: To report a case of ocular surface squamous neoplasia (OSSN) that resolved with topical Aloe vera eye drop treatment., Methods: A 64-year-old Hispanic woman with a lesion typical for OSSN in her left eye was followed up with multiple clinical examinations and ocular surface photographs to document changes over time with A. vera-based topical treatment., Results: The patient refused biopsy of her lesion and traditional treatments and, instead, initiated using A. vera eye drops 3 times daily. At follow-up visits, the lesion was noted to regress until it finally resolved 3 months after commencing treatment. No additional topical medications were used, and she has remained tumor free for 6 years., Conclusions: Ongoing research is warranted because A. vera may represent a new therapeutic class of medications for OSSN treatment.

Background: Ocular surface squamous neoplasia (OSSN) characterized by diffuse conjunctival or corneal spread is much less common than localized conjunctival disease. However, it is an important subcategory of the disease because of the difficulty it poses to treatment. It is rarely amenable to simple excision, and a purely surgical approach usually necessitates ocular surface reconstruction. Primary treatment with topical chemotherapy is an alternative, but its efficacy for these lesions is not well understood., Design: Retrospective case series., Participants: Thirty-eight eyes treated for diffuse OSSN, defined as a lesion extending over five or more limbal clock hours or by extensive central or paracentral corneal spread., Methods: Treatment utilized either topical 5-FU 1% or mitomycin-C (MMC) 0.04%., Main Outcome Measures: (i) Disease remission; (ii) complications., Results: Thirty-two patients were treated for a primary diffuse OSSN. Ten patients (31%) required further treatment for disease persistence or recurrence. Thirteen patients had previously undergone a single unsuccessful treatment course for diffuse OSSN. Administration of a second treatment course (whether MMC or 5FU) was successful in 46% (six) of patients. 5-FU 1% resulted in drug-related complications in seven of 12 cases, and included a single case of focal paracentral corneal stromal melt. MMC 0.04% resulted in transient drug related complications in 23 of 39 cases., Conclusion: Diffuse OSSN is often recalcitrant to initial treatment with either 5-FU 1% or MMC 0.04%, and a pragmatic and vigilant approach to this heterogenous disease is required. Compared to localized disease, diffuse disease often requires multiple treatment efforts., (© 2014 Royal Australian and New Zealand College of Ophthalmologists.)

Purpose: To investigate the effect of surgical wide excision and amniotic membrane transplantation with adjuvant mitomycin C 0.04% eye drops on recurrent conjunctival-corneal intraepithelial neoplasia (CCIN)., Methods: The authors applied amniotic membrane transplantation after total surgical excision of a tumor to a patient with recurrent conjunctival-corneal intraepithelial neoplasia. The tumor co-existed as a conjunctival lesion and corneal opacity. After one week, the patient received mitomycin C 0.04% eye drops four times a day for one month to prevent recurrence. Ocular complications and recurrence were evaluated under slit lamp microscopy for one year., Results: Corneal epithelium completely healed within one week after the surgery. Both conjunctival and corneal lesions were completely regressed and no recurrence has been found with follow-up to 24 months., Conclusions: Surgical wide excision and amniotic membrane transplantation with adjuvant topical MMC would be an effective treatment modality for treatment of recurrent CCIN.

Background: To report rates of recurrence and complications of localized ocular surface squamous neoplasia treated with 5-fluorouracil or mitomycin C as adjunctive treatment to surgical excision., Design: Long-term follow up of two prospective, non-comparative interventional case series., Participants: One hundred fifty-three eyes with histologically confirmed localized, non-invasive ocular surface squamous neoplasia. 89 eyes were treated with adjuvant 5-fluorouracil and 64 eyes were treated with adjuvant mitomycin C., Methods: Following surgical excision±cryotherapy patients received topical 5-fluorouracil 1% four times daily for two weeks or topical mitomycin C 0.04% four times daily for two to three 1-week cycles., Main Outcome Measures: Ocular surface squamous neoplasia recurrence, complications of therapy and compliance., Results: Median follow up was 33.6 (range 12-84) months and 57.9 (range 12-160) months in 5-fluorouracil and mitomycin C groups, respectively. There was one recurrence in the 5-fluorouracil group and no recurrences in the mitomycin C group. Side-effects occurred in 69% of 5-fluorouracil patients and 41% of mitomycin C patients. Five patients (6%) required intervention for treatment-related side-effects in the 5-fluorouracil group versus 11 (17%) in the mitomycin C group. No vision-threatening complications were noted., Conclusions: Long-term recurrence of localised ocular surface squamous neoplasia is rare when topical 5-fluorouracil or mitomycin C are used as adjunctive treatment to surgical excision. While side-effects are common, the majority are transient and rarely limit compliance., (© 2013 Royal Australian and New Zealand College of Ophthalmologists.)

Purpose: Treatment for ocular surface squamous neoplasia (OSSN) has historically been surgery, but nonsurgical interventions are increasingly used. Treatment with interferon is efficacious, but evidence is needed regarding recurrence and complication rates in comparison with surgery. The objective of this study is to compare the recurrence and complication rates of surgical treatment and interferon treatment for OSSN., Design: A matched, case-control study., Participants: Ninety-eight patients with OSSN, 49 of whom were treated with interferon (IFN) α2b therapy and 49 of whom were treated with surgical intervention., Methods: Patients with OSSN were treated with surgery versus IFNα2b therapy, either in topical or injection form. Median follow-up after lesion resolution was 21 months (range, 0-173 months) for the IFNα2b group and 24 months (range, 0.9-108 months) for the surgery group., Main Outcome Measures: The primary outcome measure for the study was the rate of recurrence of OSSN in each of the treatment groups. Recurrence rates were evaluated using Kaplan-Meier survival analysis., Results: Mean patient age and sex were similar between the groups. There was a trend toward higher clinical American Joint Committee on Cancer tumor grade in the IFNα2b group. Despite this, the number of recurrences was equal at 3 per group. The 1-year recurrence rate was 5% in the surgery group versus 3% in the IFNα2b group (P = 0.80). There was no statistically significant difference in the recurrence rate between the surgically and medically treated groups. Nonlimbal location was a risk factor for recurrence (hazard ratio, 8.96) in the entire study population. In patients who were treated successfully, the side effects of the 2 treatments were similar, with mild discomfort seen in the majority of patients in both groups. There was no limbal stem cell deficiency, symblepharon, or diplopia noted in either group. Two patients were excluded from the IFNα2b group because of intolerance to the medication., Conclusions: No difference in the recurrence rate of OSSN was found between surgical versus IFNα2b therapy., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the rate of recurrence and associated risk factors after the use of mitomycin C (MMC), interferon alpha-2b, or both for management of noninvasive ocular surface squamous neoplasia (OSSN)., Design: Retrospective, noncomparative, interventional case series., Methods: Clinical practice setting of 135 patients treated consecutively with topical MMC (0.4 mg/mL), interferon alpha-2b (1 million units/mL), or both for OSSN observed for clinical recurrence., Results: Clinical recurrences were diagnosed in 19 (14.1%) of 135 eyes after topical treatment. The mean time to recurrence was 17.2 months (range, 4 to 61 months), with 14 eyes (73.7%) recurring within a 2-year period. There was no greater risk of recurrence identified for variables including lesion size, lesion location, gender, age, treatment type, or treatment duration. Post hoc log-rank pairwise comparisons revealed that lesions initially treated using surgery alone had significantly reduced time to recurrence (21.1 ± 5.6 months) compared with previous topical treatment with MMC (with or without surgery; 29.6 ± 4.7 months; P = .04) and primary OSSN (23.2 ± 1.8 months; P = .09)., Conclusions: Topical MMC and interferon alpha-2b are an effective treatment method for a wide range of noninvasive OSSNs. Topical therapy avoids the morbidity of excisional surgery with equivalent or reduced recurrence rates and should be considered as primary therapy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We critically analyze available peer-reviewed literature, including clinical trials and case reports, on local ocular cancer treatments. Recent innovations in many areas of ocular oncology have introduced promising new therapies, but, for the most part, the optimal treatment of ocular malignancies remains elusive., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose of Review: Ocular surface squamous neoplasia (OSSN) is an umbrella term for a spectrum of epithelial dysplasias of the cornea, conjunctiva, and limbus. Treatment for OSSN has historically been surgery, but nonsurgical interventions have been increasingly adopted. Advantages of medical treatments include the ability to treat the entire ocular surface and prevention of surgical complications., Recent Findings: The primary medical treatments for OSSN include mitomycin C, 5-fluorouracil, and interferon α2b. Mitomycin C has been shown in studies to be highly effective but has short-term and long-term side-effects that may be intolerable. 5-Fluorouracil and interferon α2b have been found to be similar in efficacy to mitomycin, with interferon being extremely well tolerated in the majority of patients. Most recently, other chemotherapeutic agents have been tried for OSSN including antivascular endothelial growth factor agents and vitamin A. The data regarding these latter treatment strategies are still limited., Summary: An understanding of the recent literature, with respect to the efficacy, advantages, and disadvantages of the various therapies for OSSN will allow us to tailor treatment to each patient.

Objective: To evaluate the long-term recurrence rate of conjunctival and corneal intraepithelial neoplasia (CIN) treated with retinoic acid and topical interferon alfa-2b., Design: Retrospective, noncomparative, interventional case series., Participants: A total of 89 eyes of 89 patients from 1 institution who were treated between September 2003 and February 2010 for CIN lesions used topical interferon alfa 1 million IU/ml drops 4 times daily and retinoic acid 0.01% once every second day., Methods: Diagnosis was made by biopsy and impression cytology. Patients' notes and clinical photographs were reviewed, and data were analyzed. All eyes were monitored for the possibility of recurrence with a minimum of 1 year of follow-up from the time of documented clinical resolution., Main Outcome Measures: All eyes were monitored for the possibility of recurrence with a minimum of 1 year of follow-up from the time of documented clinical resolution., Results: Complete clinical resolution of the CIN lesions was achieved in 87 of the 89 eyes treated (97.75%). Two of the 89 eyes treated (2.25%) had only a partial response to treatment; of these 2 patients, 1 was taking cyclosporine for keratitis sicca. For the 87 eyes with complete response, resolution occurred after a mean of 1.69 months (range, 19 days to 6.5 months). Mean follow-up after clinical resolution (tumor-free period) was 51.5 months (range, 11-84 months). Four of the 87 patients with complete response developed a mild allergic papillary conjunctivitis that settled on halving the interferon dose to 0.5 million IU drops and reducing the frequency to 3 times daily. Side effects were limited to 1 case of epithelial microcysts and 1 case of marginal keratitis., Conclusions: In this group of patients observed with CIN lesions, combination treatment of topical retinoic acid and interferon alfa-2b was effective in treating lesions with minimal self-limited side effects with faster and greater resolution and a longer tumor-free period compared with studies using interferon alfa-2b alone. We hypothesize that topical all-trans retinoic acid and interferon alfa-2b may act synergistically. We believe that combination treatment of interferon alfa-2b and retinoic acid may offer a superior alternative to interferon alfa-2b alone in treating CIN., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the efficacy of topical interferon alfa-2b in the management of ocular surface squamous neoplasia (OSSN)., Methods: Clinically visible OSSN in 20 patients (23 tumors) was managed with topical interferon alfa-2b, 1 million IU/mL, 4 times daily. Tumor control and complications were evaluated according to American Joint Committee on Cancer classification., Results: Complete tumor resolution was achieved in 19 tumors (83%) following topical interferon alfa-2b treatment for a median period of 6 months (mean, 7 months; range, 1-12 months) and maintained for up to 24 months of follow-up. Of the 4 tumors with partial resolution (17%), tumor surface area was reduced 44% (median) during 4 months (median) without further response and alternative therapy was used. Based on American Joint Committee on Cancer classification, complete control was achieved in 2 of 3 Tis (67%), 17 of 20 T3 (85%), 19 of 23 N0 (83%), and 19 of 23 M0 (83%) category tumors. Tumors involving the cornea responded earlier compared with those without corneal involvement (P = .01). Initial tumor size did not correlate with time to response (P = .27). Recurrence was noted in 1 case (Tis, 4%) at 3 months. Adverse effects included conjunctival hyperemia (2 [10%]), follicular hypertrophy (2 [10%]), giant papillary conjunctivitis (1 [5%]), irritation (1 [5%]), corneal epithelial defect (1 [5%]), and flulike symptoms (1 [5%]); all resolved within 1 month of medication discontinuation., Conclusion: According to American Joint Committee on Cancer classification, complete control with topical interferon alfa-2b can be achieved in 67% of Tis, 85% of T3, and 83% of all OSSN.

Purpose: To report a novel diagnostic technique and a case series of conjunctival and corneal intraepithelial neoplasia (CCIN) diagnosed and followed up using prototype ultra high-resolution (UHR) optical coherence tomography (OCT)., Design: Prospective, noncomparative, interventional case series., Participants: Seven eyes of 7 consecutive patients with CCIN treated using topical interferon alfa-2b or 5-fluorouracil and 7 eyes of 6 consecutive patients with history of surgically excised pterygia., Intervention: Ultra high-resolution OCT imaging of the ocular surface at primary diagnosis of CCIN and during the follow-up period until resolution of the lesion. Ultra high-resolution OCT images of sites of excised pterygia also were captured and compared with images from resolved CCIN patients., Main Outcome Measures: Clinical course and photographs, UHR OCT images, and histopathologic findings., Results: Ultra high-resolution OCT was capable of providing a noninvasive optical biopsy of all examined CCIN lesions. Ultra high-resolution OCT images of the lesions disclosed a thickened hyperreflective epithelium and abrupt transition from normal to hyperreflective epithelium in all 7 cases. Ultra high-resolution OCT images showed excellent correlation with histopathologic specimens obtained at primary diagnosis of the cases that had incisional biopsies before treatment. All patients were treated medically and were followed up for clinical resolution. In 4 patients, at clinical resolution, UHR OCT images also showed normal epithelial configuration at the site of the treated lesions. In 3 patients, despite apparent clinical resolution, the UHR OCT was able to detect residual disease that was clinically invisible. Continuation of treatment resulted in complete resolution of the residual lesions on the UHR OCT images in all cases. Ultra high-resolution OCT images of patients with surgically excised pterygia demonstrated similar findings to resolved CCIN cases., Conclusions: Ultra high-resolution OCT is a novel noninvasive technique to diagnose and manage medically treated CCIN. Using UHR OCT to guide medical treatment could prevent the premature termination of topical treatment in the presence of subclinical disease. A larger sample size is needed for further validation of its sensitivity and specificity., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To analyze the outcome of excisional biopsy of ocular surface (conjunctival and corneal) squamous cell intraepithelial (in situ) neoplasia with and without the adjunctive use of intraoperative and postoperative mitomycin C., Methods: A retrospective case review was conducted on 34 consecutive patients with histopathologically proven ocular surface squamous cell intraepithelial neoplasia who were treated from January 1, 1980, to December 31, 2008, at University of Iowa Hospitals and Clinics. Eyes in which a minimum follow-up period of 3 months was available were included in the statistical analysis., Results: Of 34 eyes, 32 met the inclusion criteria. Adjunctive therapy was provided with mitomycin C in 17 eyes, including 13 that had only postoperative treatment and 4 that had only intraoperative treatment. The adjunctive use of mitomycin C was associated with a significantly reduced prevalence of recurrence (5.9% vs. 66.7%; P = 0.0005). When the surgical margins were positive, the use of adjunctive mitomycin C was associated with a reduced prevalence of tumor recurrence (12.5% vs. 55.6%), but this difference was not statistically significant (P = 0.13). When surgical margins were negative, the adjunctive use of mitomycin C was significantly associated with a reduced prevalence of recurrence (0% vs. 83.3%; P = 0.002)., Conclusions: The adjunctive use of mitomycin C is significantly associated with a reduction in the prevalence of postoperative recurrences of ocular surface squamous cell intraepithelial neoplasia and should be considered as an adjunctive therapy even when surgical margins are negative.

Purpose: To conduct a pilot study of pegylated interferon alpha 2b (PEGIFNalpha2b) for treatment of ocular surface squamous neoplasia (OSSN)., Methods: Three patients with histologically proven OSSN were studied prospectively. Patients were given subconjunctival/perilesional injections of 1 microg/kg of PEGIFNalpha2b (PEG Intron, Schering-Plough, Kenilworth, NJ) until the tumor resolved. Patients were followed clinically and photographically for evidence of tumor resolution and recurrence., Results: All patients had clinical resolution of the tumor. The mean time to resolution was 47 days. During the follow-up time after resolution of the lesion (mean 41 months), one patient had disease recurrence 7 months after clinical resolution. This was successfully treated with one further injection., Conclusion: PEGIFNalpha2b may be a viable medical alternative for the treatment of OSSN. Future studies will be needed to evaluate whether PEGIFNalpha2b is as effective as recombinant interferon alpha 2b.

Purpose: The aim of this work is to report the long-term results of using immunotherapy for the management of cornea and conjunctiva intraepithelial neoplasia and squamous cell carcinoma after surgical excision of the neoplasm., Methods: Ten eyes of 10 patients with cornea and conjunctiva intraepithelial neoplasia or squamous cell carcinoma had wide surgical excisions of the neoplasm after evaluation of the level of corneal involvement using ultrasound biomicroscopy. All eyes received topical cyclosporine A (0.05%) and topical mitomycin C (0.01%) 4 times daily for 12 weeks after surgery. All eyes were followed up every month for 6 months and then every 6 months for another 18 months., Results: All eyes showed total cure with no recurrence during the 2-year follow-up period. Epithelial toxicity (punctate keratopathy) occurred in 3 eyes, ocular irritation and mild conjunctival hyperemia in 5 eyes, and lid toxicity in 2 cases during the treatment with mitomycin C. There were no serious complications that necessitated stopping the treatment., Conclusion: During a 2-year follow-up period, the use of topical cyclosporine A (0.05%) combined with mitomycin C (0.01%) as an adjunctive treatment after surgical excision in cornea and conjunctiva intraepithelial neoplasia and squamous cell carcinoma was found to prevent tumor recurrence, especially in extensive lesions, when surgical excision cannot ensure a tumor-free margin.

Purpose: To evaluate the efficacy, recurrence rate, and long-term complications of topical mitomycin C (MMC) 0.02% for conjunctival-corneal intraepithelial neoplasia (CCIN)., Methods: A prospective, nonrandomized, noncontrolled study was conducted of patients with primary or recurrent CCIN treated with topical MMC 0.02%, four times per day, for 28 consecutive days. The main outcome measures were complete resolution of the neoplasia by slit-lamp examination and cytology 1 month after treatment, tumor recurrence, and long-term complications., Results: Between June 1999 and September 2005, 23 patients were included. Eighteen had primary CCIN (group 1) and 5 had recurrent CCIN (group 2). The mean follow-up was 46 months in group 1 and 54 months in group 2. All patients were treated with MMC 0.02% for 28 consecutive days. Complete resolution of the lesion was achieved in all patients after 1 month of treatment. Recurrence occurred in 1 patient (4.3%) after 24 months of treatment. Four patients developed corneal erosion (17.4%), 2 of them with primary CCIN and 2 with recurrent CCIN. Corneal erosion occurred 4 to 24 months after treatment and was treated successfully. The probability for corneal erosions by the log-rank test was equal for both groups (p = 0.1705)., Conclusions: The use of topical MMC 0.02% for 28 consecutive days to treat primary or recurrent CCIN was effective and showed a low recurrence rate. Corneal erosion occurred in 17.4% of cases and can occur as late as 24 months after treatment.

Objective: To describe the successful treatment and long-term outcomes of primary ocular surface squamous neoplasia (OSSN) with topical interferon alfa-2b or surgical excision., Design: Retrospective, comparative, interventional case series., Participants: Twenty-nine consecutive patients with OSSN never before treated., Intervention: Patients with primary OSSN chose topical interferon alfa-2b or excision with wide surgical margins, with crossover to surgery in those interferon-treated patients whose OSSN failed to regress within 2 months after beginning therapy., Main Outcome Measures: Successful resolution of clinical disease at 2 months after topical interferon treatment and time to recurrence after either topical interferon or surgical excision., Results: Of 29 patients with primary OSSN, 15 elected topical interferon and 14 chose surgical excision. Two patients in the interferon group subsequently underwent surgical excision for apparent lack of response to interferon. No patient in either group developed a recurrence during the study period (disease-free follow-up: interferon group, mean, 35.6 months [95% confidence interval, 21.9-49.3]; surgery group, mean, 35.6 months [22.9-48.3])., Conclusions: Both topical interferon alfa-2b and aggressive surgical excision appear to be effective for primary OSSN.

Objective: To evaluate the long-term recurrence rate (>1 year) of conjunctival and corneal intraepithelial neoplasia (CIN) treated with topical interferon alfa-2b., Design: Retrospective, noncomparative, interventional case series., Participants: Twenty-eight eyes of 26 patients from 2 institutions, treated between April 1997 and June 2005, with CIN lesions utilized topical interferon alfa-2b drops 4 times daily until clinical resolution was achieved., Methods: Patients' charts and clinical photographs were reviewed, and data were analyzed., Main Outcome Measures: All eyes were monitored for the possibility of recurrence with a minimum of 1-year follow-up from the time of documented clinical resolution., Results: Complete clinical resolution of the CIN lesions was achieved in 27 of the 28 eyes treated (96.4%). One of the 28 eyes treated (3.6%) had only a partial response to treatment. For the 27 eyes with complete response, resolution occurred after a median of 2.0 months (range, 10 days-15 months). Eyes were treated for a median of 3.2 months (range, 1-15). Median follow-up after clinical resolution (tumor-free period) was 42.4 months (range, 14-89). One eye of the 27 analyzed (3.7%) experienced a recurrence. Side effects of treatment were limited to mild conjunctival hyperemia and follicular conjunctivitis in 3 patients (12%). In all cases, there was total resolution of the side effects within 1 month after cessation of the medication., Conclusions: In this group of patients with CIN lesions observed for >1 year, topical interferon alfa-2b was effective in treating lesions with minimal self-limited side effects.

Purpose: To examine if the cells of human ocular surface neoplasms express sonic hedgehog (Shh) and the effects of topical mitomycin C on its expression., Methods: Conjunctival tissues obtained from two normal subjects, two patients with squamous cell carcinoma of the ocular surface (conjunctiva), and one patient with ocular epithelial dysplasia were used in this study. Histological sections were processed for light microscopic immunohistochemical analysis for Shh., Results: Faint immunoreactivity for Shh was detected in basal epithelial cells of limbus, bulbar, and palpebral conjunctival epithelial cells. On the other hand, squamous cell carcinoma cells markedly expressed Shh with positive staining for Patched 1(Ptc), the cell surface receptor of Shh. Similar marked expression of Shh was detected in the patient with ocular epithelial dysplasia, and this Shh expression was almost eliminated following topical mitomycin C treatment. A cell culture experiment was conducted to examine the effect of mitomycin C on Shh expression in a cultured squamous cell carcinoma cell line., Conclusions: Conjunctival epithelium constitutively expresses a low level of Shh, and its expression increases during malignant conversion of epithelial cells. Reduction of Shh expression might be involved in the therapeutic efficacy of topical mitomycin C for ocular surface epithelial neoplasms.

Objective: To assess the efficacy and safety of mitomycin C in the treatment of ocular surface squamous neoplasia., Design: Prospective, randomized, controlled, masked, single-center trial., Participants: Forty-eight consecutive patients with biopsy-proven noninvasive ocular surface squamous neoplasia., Intervention: Mitomycin C (0.4 mg/ml) or a placebo was administered as 1 drop 4 times a day for 3 weeks, with crossover of drops if there was no regression within 6 weeks., Main Outcome Measures: Successful treatment was measured as complete resolution of the neoplasia by slit-lamp examination within 6 to 8 weeks of treatment, with a secondary end point of histological resolution by 6 weeks., Results: None of 20 in the placebo group resolved clinically, whereas 24 of 26 in the mitomycin group resolved, giving a relative resolution rate of mitomycin versus placebo of 40.87 (95% confidence interval [CI], 1.01-1656.8). There were no complications. There was no statistical treatment effect on histological resolution, with a resolution rate of mitomycin versus placebo of 1.37 (95% CI, 0.34-5.42)., Conclusions: Mitomycin C (0.4 mg/ml) eyedrops used 4 times a day for 3 weeks is an effective agent to cause early clinical resolution of noninvasive ocular surface squamous neoplasia.

Aims: The aim of this study was to report on the effectiveness and tumor side effects of topical interferon (INF) alpha 2-beta in a case of conjunctiva-cornea intraepithelial neoplasia (CIN) of a patient that rejected any surgical procedure., Methods: This study is a case report description., Results: An 81-year-old man with a history of neoplasies of the colon and prostate and anticoagulant treatment was referred for treatment of an ocular surface neoplasia on his left eye. Pathognomonic signs of CIN were present. The patient rejected surgical procedures. A regimen of topical INF alpha 2-beta 4 times daily was administered. An increase in tumor volume of 25% was observable 15 days after the beginning of therapy. No subjective discomfort was reported. The treatment continued with follow-ups every 15 days. The progressive regression was remarkable. Complete regression of the CIN was observable after 60 days of therapy. No other side-effects were detected., Conclusions: Topical INF alpha 2-beta is a valid choice for the treatment of CIN in patients for whom surgery is not possible. The increase of tumor volume at the beginning of therapy does not require the suspension of treatment.

Purpose: To report a case of extensive conjunctiva-cornea intraepithelial neoplasia (CIN) treated topically with mitomycin C (MMC) and interferon (INF)-alpha2beta without surgical resection., Methods: Case report., Results: : An 82-year-old woman showed an extensive gelatinous red mass in the bulbar conjunctiva with invasion into the caruncle, inferior fornix, and tarsal conjunctiva and extending for 270 degrees of the corneal surface. A diagnosis of CIN was made by surgical biopsy. Surgical excision with safety margins carried the risk of limbal stem cell depletion. A conservative treatment strategy was used with 2 cycles of topical MMC (0.02%), followed by INF-alpha2beta eye drops at a dose of 1 million IU/mL, 4 times a day until tumor disappearance. Total resolution was noted after 75 days of treatment with INF, with no clinical evidence of limbal stem cell deficiency. After 1 year of monitoring, no signs of CIN recurrences were observed., Conclusion: MMC (0.02%), followed by INF-alpha2beta (1 million IU/mL) 4 times a day, is an effective treatment against highly extensive CIN, in cases where surgical resection with safety margins is unfeasible.

Purpose: To determine the efficiency of topical cyclosporine-A (CSA) combined with mitomycin C (MMC) as an adjunctive treatment in diffuse conjunctival and corneal squamous cell carcinoma (CCSC)., Design: Interventional case reports., Methods: Two patients who had positive margins following surgical excision of CCSC were treated by topical CSA (0.05%) four times a day for 12 weeks, and topical MMC (0.01%) four times a day was combined with CSA at the second, fourth, and sixth weeks of the treatment. We controlled the tumor recurrence, vision, and ocular surface healing during the follow-up., Results: There was no tumor recurrence during the follow up of 18 months. Limbal vascularization regressed considerably and the vision improved without any ocular surface problems in both patients., Conclusions: As an adjunctive treatment, topical CSA (0.05%) combined with MMC (0.01%), may prevent tumor recurrence and provide excellent ocular surface healing in diffuse CCSC.

Surgical excision with cryotherapy is a well-established treatment option for malignant melanoma or primary acquired melanosis (PAM) with atypia of the conjunctiva and cornea. Topical chemotherapeutic agents such as mitomycin C (MMC) however, are increasingly finding use in clinical practice. A search was performed of Medline and Pubmed databases for English language articles from 1980 to the present in this field. Relevant studies were reviewed with regards to treatment regimen, rates of recurrence and metastasis, side effect profile and length of follow up. A total of 22 and 16 unique cases of biopsy proven PAM with atypia and malignant melanoma, respectively, treated with topical MMC were identified. Topical MMC was well tolerated and shows considerable promise, particularly in the treatment of diffuse PAM with atypia. However, long-term data are lacking and further studies are required.

We review the use of three topical medications for the therapy of ocular surface tumors: mitomycin C, 5-fluorouracil, and interferon alpha-2B. One hundred sixty patients with histologically or cytologically proven epithelial and melanocytic tumors were identified in the literature. Side effects occurred most often with mitomycin C, followed by 5-fluorouracil, and interferon alpha-2B. Patients most frequently experienced transient keratitis, redness, and irritation. Topical agents were used as both primary and adjuvant therapy. Rates of tumor regression for CIN and squamous cell carcinoma ranged from 80 to 96%, and 70% of pigmented tumors regressed after an average follow-up of 27 months.

Three cases of corneal-conjunctival intraepithelial neoplasia treated differently with mitomycin C based on clinical presentation are reported. The selected patients were followed at the Department of Ophthalmology of the Casa de Saúde Santo Inácio. According to the clinical appearance of the lesions, 0.04% mitomycin C was employed in three different ways: 1) postoperative chemoablation; 2) preoperative chemoreduction; and 3) isolated chemoablation. Regression of the neoplastic lesion was observed in all cases with no recurrence detected during a follow-up time ranging from 18 to 29 months. Conjunctival hyperemia was the single side effect. The use of mitomycin C seems to be efficient and safe for the treatment of corneal-conjunctival intraepithelial neoplasia under several approaches.

Case Report: A 78-year-old man was referred for evaluation of a limbic lesion in his left eye. This had a gelatinous appearance and an extension of 240 degrees . The lesion was clinically diagnosed to be a conjunctival and corneal intraepithelial neoplasia (CIN). Topical treatment with interferon alpha2b (INFalpha2b) four times daily was started and continued until the lesion had completely resolved at 4 months., Discussion: Topical INFalpha2b alone may be a safe and effective treatment of CIN instead of the other classic alternatives such as surgical excision with cryotherapy, which could induce the development of severe limbic deficiency in cases with extensive disease.