Topical Interferon Alpha-2b Research Articles

Chemoimmunotherapy-Resistant Ocular Surface Squamous Neoplasia Managed With I-125 Brachytherapy

Purpose: The purpose of this study was to report the management of chemoimmunotherapy-resistant ocular surface squamous neoplasia (OSSN) with iodine-125 (I-125) brachytherapy. Methods: A 36-year-old man presented to the clinic with biopsy-proven OSSN that covered ∼70% of the corneal surface and extended to the 6 o'clock position of the inferior limbus of the OS. The visual acuity was 20/20 in the OD and 20/40 in the affected OS. He was treated with topical interferon alpha-2b 1 MIU/mL (4 times daily [QID] for 6 weeks) and then 4 cycles of topical 5-fluorouracil 1% (QID, 1 week on, 3 weeks off) with an incomplete response. He switched to topical mitomycin C 0.04% (QID, 1 week on, 2 weeks off) for 2 cycles and received a subconjunctival injection 25 mg (0.5 mL of a 50-mg/mL solution) of 5-fluorouracil. The tumor persisted. The patient was ultimately cured with placement of an 18-mm I-125 brachytherapy plaque for 97 hours (50 Gy). Results: Because of extensive corneal involvement and risks associated with surgery, an 18-mm I-125 brachytherapy plaque was placed over the cornea and limbus. The treatment led to full resolution of the tumor within 1 month of treatment and recovery of 20/20 vision in the affected eye. Thirty-two months after treatment, the patient developed a visually significant posterior subcapsular cataract OS and underwent successful phacoemulsification surgery, returning to 20/20 vision. He has remained tumor-free for over 55 months. Conclusions: This case highlights the efficacy and safety of I-125 brachytherapy as an alternative for intraepithelial OSSN unresponsive to conventional chemoimmunotherapy, particularly when extensive surgical excision poses significant risks.

Efficacy of topical 5-Fluorouracil in the management of ocular surface squamous neoplasia: a study of 101 eyes.

To study the efficacy and side-effect profile of topical 5-Fluorouracil (5-FU) in the treatment of ocular surface squamous neoplasia (OSSN). Retrospective study of 101 eyes of 100 patients treated with 5-FU with one week on and 3weeks off regimen. Of the 100 patients (101 eyes), the mean age at diagnosis of OSSN was 49 (median, 52years; range, 11-87years). History of prior intervention was noted in 6 (6%) eyes. Tumor epicenter included bulbar conjunctiva (n = 54; 53%), limbus (n = 27; 27%), and cornea (n = 20;20%). Mean number of cycles of topical 5-FU administered was 3 (median, 3; range, 1-8). Complete tumor regression was achieved with topical 5-FU in 89 (88%) eyes with a mean number of 2 cycles (median, 2; range, 1-6) of 5-FU. The remaining 12 (12%) lesions underwent additional treatment including excisional biopsy (n = 7), extended enucleation (n = 3), and topical Interferon alpha 2b (n = 2) for complete tumor control. Over a mean follow-up period of 6months (median, 5months; range, 1-36months) following treatment, tumor recurrence was noted in 2 (2%) patients, and side-effects were noted in 7 (7%) eyes including conjunctival hyperemia (n = 1), punctal stenosis (n = 1), sterile keratitis (n = 4), and limbal stem cell deficiency (n = 1). Topical 5-FU is an effective non-invasive therapy for OSSN with a minimal side-effect profile.

Corneal ocular surface squamous neoplasia: Case series and review of literature.

The authors present a retrospective analysis of three cases of isolated corneal ocular surface squamous neoplasia (C-OSSN) without limbal or conjunctival involvement and review the clinical and anterior segment optical coherence tomography (AS-OCT) features, along with treatment outcomes. The mean age at presentation was 51 years (range: 32-64 years). The mean tumor diameter was 5 mm (range: 3-6.5 mm). All lesions were placoid with <1 mm thickness. One case had surface keratin. AS-OCT revealed hyperreflective epithelium with abrupt transition in all cases, with mean thickness of 118 μm (range: 60-162 μm). One patient underwent alcohol-assisted keratoepitheliectomy (AKE) and two patients received topical Interferon alpha-2B followed by AKE. Histopathology revealed mild squamous dysplasia in all. No tumor residue or recurrence was noted at a mean follow-up period of 2 years (range: 1-4 years). Isolated C-OSSN is rare. AS-OCT serves as a useful noninvasive tool for supporting the diagnosis of AKE yielding long-term favorable outcomes.

Adjuvant Topical Interferon Alpha 2b for the Treatment of Monkeypox Ocular Manifestations.

The aim of this study was to report a case of ocular Mpox that responded favorably to treatment with topical interferon and oral doxycycline. This is a case report of a previously healthy 24-year-old woman who developed a pustular rash, headache, fever, arthralgia, sore throat, and asthenia 3 weeks before attending to our clinic. Her main complaint at the moment of the visit was pain, photophobia, foreign body sensation, blurred vision, red eye, and discharge on the left eye. The slit-lamp examination of the left eye showed severe conjunctival hyperemia associated with tarsal follicles, 360 degrees ciliary injection, diffuse corneal epithelial edema with white linear epithelial infiltrates, pigmented and nonpigmented keratic precipitates, and two 1-mm peripheral corneal ulcers with white infiltrates, associated with positive fluorescein staining. Anterior chamber cellularity and flare were mildly present. Mpox with ocular manifestations diagnosis was confirmed by real-time quantitative reverse transcription polymerase chain reaction assay (qRT-PCR) testing; samples were taken from corneal, conjunctival, and nasopharynx swab as well as a skin scab. Topical interferon alpha 2b 1 MIU/mL every 6 hours for 1 month and oral doxycycline 100 mg BID were administered along with other medications with consequent decrease of inflammation and malaise symptoms 1 week later, associated with uncorrected visual acuity improvement. Alternative and efficacious treatment options for Mpox ocular manifestations are needed to prevent further disease progression and sequelae in countries with no access to the gold-standard therapy. Topical interferon alpha 2b and oral doxycycline have shown adequate response as shown with this patient.

Safety and efficacy of topical interferon alpha 2B and mitomycin C for localized conjunctival intraepithelial neoplasia: long-term report of their pharmacological safety and efficacy

PurposeOcular surface squamous neoplasia (OSSN) comprises a wide spectrum of squamous tumors, from which corneal/conjunctival intraepithelial neoplasia (CIN) is the most common one. The classic treatment is complete excision, but recurrence rates are high. Antineoplastic drugs such as mitomycin C (MMC) and interferon alpha 2b (IFNα2b) have been used as adjuvants or as primary treatment. To evaluate the efficacy and safety of topical IFNα2b and MMC in patients with CIN, a phase IIb double-blind clinical trial was performed.MethodsPatients diagnosed with localized CIN were evaluated by slit lamp and impression cytology and were randomly given MMC 0.04% or INF2b (1 million IU/mL) 4 times daily until neoplasia resolution. Time of resolution and frequency of adverse effects were analyzed to determine the pharmacological efficacy and safety of both medications.ResultsSeventeen patients were included. Nine patients were treated with MMC and 8 with IFNα2b. All patients responded to treatment. The resolution time in days was 59.11 ± 24.02 in patients treated with MMC and 143.50 ± 47.181 in those treated with IFNα2b (p < 0.001). In the MMC group, one recurrence was reported (11%). There were no recurrences at 2 years of follow-up in the IFNα2b group. Regarding adverse effects, one or more mild adverse reaction occurred in 77% of patients managed with MMC and in 50% of patients managed with IFNα2b (p > 0.05). No serious adverse effects were reported.ConclusionsTopical chemotherapy with MMC and IFNα2b demonstrate pharmacological safety and efficacy. Therefore, these drugs could be considered as primary therapies for localized CIN .

Medical treatment for ocular surface squamous neoplasia.

Ocular surface squamous neoplasia (OSSN) is the most common non-melanocytic tumour of the ocular surface. Surgical excision with wide margins using the "no-touch" method was originally the most popular treatment for OSSN. However, in the past two decades, the use of topical medications for OSSN treatment has gained a reputation amongst ophthalmologists for being an effective alternative to surgical excision. Furthermore, technological advancements, such asthose seen in high-resolution optical coherence tomography (HR-OCT) for the anterior segment, have facilitated the diagnosis and monitoring of OSSN. When selecting a topical agent, interferon alpha-2b (IFNα-2b) and 5-fluorouracil (5-FU) are two of the gentlest medications used for OSSN and are often considered first line therapies due to their high-resolution rates and mild side effect profiles. Mitomycin C (MMC), on the other hand, has a highly toxic profile; therefore, while effective, in our hands it is considered as a second-line treatment for OSSN if the other modalities fail. In addition, newer and less studied agents, such as immune checkpoint inhibitors, retinoic acid, aloe vera, and anti-vascular endothelial growth factor have anti-neoplastic properties and have shown potential for the treatment of OSSN. We enclose an updated literature review of medical treatments for OSSN.

Topical cyclosporine A and interferon alpha-2b as adjuvants to surgery to decrease pterygium recurrence.

Pterygium is very common in India and is usually removed by limbal conjunctival autograft transplantation (LCAT), which, despite being the first-line therapy, is still associated with recurrences of up to 18%. To compare the safety and efficacy of topical cyclosporine A (CsA) and interferon (IFN) alpha-2b in the prevention of postoperative recurrence of pterygium. A total of 40 patients with primary pterygium were randomized into two equal groups, Group C and Group I. Both the groups underwent LCAT, with Group C kept on topical cyclosporine 0.05% (CsA) 4 times daily and Group I on topical IFN alpha 2b 0.2 million IU 4 times daily postoperatively for 3 months. Pre- and posttreatment best-corrected visual acuity (BCVA), recurrence, and complications were assessed at day 1, week 1, 1 month, and 3 months. The mean preoperative BCVA of 0.51 ± 0.18 and 0.51 ± 0.23 improved to 0.13 ± 0.13 and 0.13 ± 0.13 in Group C and Group I, respectively, after 3 months of treatment (P < 0.0001). Recurrence was seen in 2 cases in Group C and in 1 case in Group I at 3 months. No significant complications occurred in either of the groups. Topical CsA and IFN Alpha-2b are newer efficacious adjuvants with LCAT for prevention of postoperative pterygium recurrence.

Topical interferon alpha-2b is a proper alternative for management of adenoviral keratitis: A case report

Topical interferon alpha-2b is a proper alternative for management of adenoviral keratitis: A case report

Real-life data of adjuvant IFN-α2b and MMC in conjunctival melanocytic lesions

PurposeWe herein compare topical interferon alpha 2b (IFN-α2b) to topical mitomycin C (MMC) in the adjuvant management after excision of primary acquired melanosis with atypia (PAM) and melanoma of the conjunctiva/cornea (CM).MethodsWe included 25 tumors from 25 patients (six with PAM and 19 with CM). After surgical excision, four patients started with adjuvant IFN-α2b (two in combination with radiotherapy), 19 with MMC, and two with radiotherapy alone. Five patients were switched from initial MMC/radiotherapy to IFN-α2b during follow-up. Efficacy was assessed via time to tumor recurrence and initial therapy response.ResultsWith initial IFN-α2b, three patients (3/4, two with additional radiotherapy) showed complete remission (follow-up: 1478–1750 days) and one recurrence (1/4) was noted after 492 days. With initial MMC, no recurrence was recorded in 15 of the 19 patients (follow-up: 99–4732 days). Five patients were switched from MMC or radiotherapy to IFN-α2b: two patients showed complete remission (2/5), while another two (2/5) experienced recurrences and remained without recurrence after repeated courses of IFN-α2b (follow-up: 1798 and 1973 days). Only one patient showed incomplete response. Adverse effects were recorded in five patients, all received MMC.ConclusionTopical IFN-α2b (arguably together with radiotherapy) may be a viable alternative to MMC in PAM and CM. We observed fewer side effects at similar response rates. However, when response to MMC was poor, IFN-α2b may also be of limited utility.

Efficacy and safety of topical 5-fluorouracil in conjunctival intraepithelial neoplasia refractory to interferon alpha-2b.

To report the efficacy and safety of 5-fluorouracil as the second line of treatment for two cases of conjunctival intraepithelial neoplasia refractive to topical interferon alpha-2b. In the first case, a 77-year-old woman was evaluated because of a fleshy vascularized lesion in the temporal conjunctiva on her right eye with leukoplakia of the corneal epithelium from 10- to 5-o'clock limbus. In the second case, an 81-year-old man, a nodular lesion in the temporal conjunctiva on his RE, with corneal adjacent opalescence, one millimeter in extent, was observed. Both patients were initially treated with excisional surgery, the samples being reported as conjunctival intraepithelial neoplasia with high-grade dysplasia. Co-adjuvant treatment with topical interferon alpha-2b 1 mIU/mL was indicated 4 times/day uninterruptedly. In the first case, there was no response despite 8 months of treatment, while in the second, the corneal lesion progressed in an arboriform pattern after 4 months of topical chemotherapy. In the absence of efficacy, the treatment was then changed to topical 5-fluorouracil (1%), 4 times/day for 7 days with a time-lapse of 21 days off, which constitutes a course. Two and four courses of treatment with 5-fluorouracil 1% were completed in both cases in the absence of important side effects. After the first course, both patients showed complete remission of the lesions. No clinical signs of relapse were noted after 1 year of follow-up. The treatment with 5-fluorouracil is a good option as the second line of treatment for conjunctival intraepithelial neoplasia who are low-responders to interferon alpha-2b, with fewer side effects than other currently available alternatives.

Topical interferon Alpha-2b in refractory limbal vernal keratoconjunctivitis: a case report

Purpose: To report our experience of managing a steroid resistant limbal vernal keratoconjunctivitis (VKC) by topical interferon alpha-2b (IFN- 2b) eye drops. Methods: Case report Results: A 20-year-old man was referred to our cornea clinic with the chief complaints of itching and photophobia in eyes and foreign body sensation, redness, and ptosis in a both eyes. He had a 10-year history of gradually enlarging limbal gelatinous masses on both eyes, which according to the other signs and impression cytology (IC) was diagnosed as a VKC. As the disease in his left eye was more severe and persistent with maximum topical steroid usage, we started the topical IFN- 2b eye drops, that a rapid therapeutic response was observed. After three months of using the topical IFN- 2b all ocular surface inflammation and other symptoms rapidly disappeared and we continued this drug till another 3 months, at 12-months follow-up, there was no recurrence of the limbal papillary hypertrophic lesions and other signs and symptoms of VKC. Conclusion: In a refractory VKC, topical IFN- 2b can be used and enhance remission in such complex cases and can resolve patient’s complains rapidly.

Clinicopathological profile, management and clinical outcomes in recurrent cases of ocular surface squamous neoplasia at a tertiary care centre.

This study was taken up to look into the various causes of recurrence, clinicopathological profile and final outcomes in recurrent cases of ocular surface squamous neoplasia (OSSN). A prospective cohort study was conducted and total 18 patients were recruited. All patients were subjected to detailed history, comprehensive eye examination and imaging studies. A treatment plan was formulated based on the size and extent of the lesion. The primary outcome measure was complete response to treatment with no evidence of recurrence after12months and secondary outcome measure was complication associated with each treatment modality. The common cause of recurrence in our study was misdiagnosis of the lesion as in 15 cases it was diagnosed as pterygium and in 03 cases it was actinic keratosis. Excision Biopsy with adjunctive cryotherapy was the preferred treatment modality followed by topical interferon-alpha 2b drop-in our study. We could achieve good outcomes in terms of complete response to the treatment in 16 cases. The complication associated with this treatment was minimal in our study as few patients complained redness and irritation which subsided after application of topical lubricants. There was no sign of recurrence even at 12months of follow-up in all 18 cases. The current study provided clinicopathological characteristics and treatment outcomes in recurrent cases of OSSN. In our study, adopting appropriate treatment strategy, regular follow-up to assess the response to treatment and change over to new treatment plan in cases with inadequate response helped in achieving good outcomes in recurrent cases of OSSN.

Case Report: Conjunctival Intraepithelial Neoplasia

Conjunctival intraepithelial neoplasia (CIN) is a dysplastic lesion of the conjunctiva and is the most common tumor of the ocular surface. CIN typically presents as a fleshy, gelatinous lesion that is typically located at the limbus. Risk factors include ultraviolet light exposure, immunocompromised state, history of smoking and human papilloma virus (HPV). Case Report: We present a case of CIN in a 76 year-old African American patient whose only complaint was of dry eye symptoms. Anterior segment examination revealed a gelatinous, vascularized lesion on the bulbar conjunctiva of the right eye. Excisional biopsy revealed a diagnosis of CIN with positive margins. The patient was treated with topical interferon alpha 2b drops. Conclusion: CIN is a neoplastic disorder that has a relatively favorable prognosis with treatment which includes both topical and surgical management. Careful anterior segment examination is crucial in detecting these lesions with prompt referral for treatment. CE Notification: This article is available as a COPE accredited CE course. You may take this course for 1-hour credit. Read the article and take the qualifying test to earn your credit. Click here to Enroll (https://www.crojournal.com/conjunctival-intraepithelial-neoplasia)

Functional impact of titin (TTN) mutations in ocular surface squamous neoplasia

Mutations in the titin (TTN) gene are among the most common genomic aberrations in ocular surface squamous neoplasia (OSSN), the most common cancer of the external eye. Further, TTN mutations are associated with resistance to standard therapy with topical interferon alpha-2b (IFN-α2b). However, it remains unclear how TTN mutations drive OSSN pathogenesis and treatment resistance. TTN encodes the largest protein in the human body and its best understood function is as a myofibril scaffold in striated muscle. However, recent evidence indicates that TTN has additional functions in non-muscle cells and in cancer. Here, we performed a disorder-based bioinformatics analysis which revealed that intrinsically disordered protein regions are abundant in TTN and provide mechanistic insights into its function as a nuclear protein in epithelial cells. Specific mutations found in OSSN are predicted to affect its intrinsically disordered protein regions (IDPRs), promoting chromosomal instability, oncogenesis, and altered response to IFN-α2b treatment.

Ocular surface squamous neoplasia resistant to topical interferon alpha 2b in a patient with follicular lymphoma

Ocular surface squamous neoplasia resistant to topical interferon alpha 2b in a patient with follicular lymphoma

Recombinant Interferon Alpha-2b as Primary Treatment for Ocular Surface Squamous Neoplasia.

Purpose:To investigate the effects of topical and perilesional interferon alpha-2b as primary treatment for ocular surface squamous neoplasia (OSSN).Methods:In this prospective interventional case series, topical interferon alpha-2b (3 MIU/mL) was used as the initial treatment of OSSN, with perilesional interferon alpha-2b (3 MIU/mL) added based on clinical response. The primary outcome was complete tumor resolution. Spearman's rank correlation test was used to investigate the association of complete tumor resolution and time to resolution with baseline tumor characteristics and the American Joint Committee on Cancer (AJCC) classification for OSSN.Results:Ninety-two patients (92 OSSN tumors) were included in the study. The total follow-up duration was 13.57 ± 2.14 months (median: 12, range: 3–23). The median basal tumor diameter was 4 mm (mean: 4.13 ± 1.37). Complete tumor resolution was achieved in 89 cases (96.73%), with a median time to complete tumor resolution of 5 months (mean: 4.64 ± 1.92). Complete tumor resolution was 57 of 57 in T1 (100%), 8 of 9 in T2 (88.88%), and 21 of 23 in T3 (91.30%). There were statistically significant correlations between AJCC classification and complete tumor resolution (Spearman's r = −0.22, P = 0.03) and maximal basal tumor diameter and the time to complete resolution (Spearman's r = 0.35, P = 0.001). There were no recurrences during the study follow-up period.Conclusion:Topical interferon alpha-2b is effective and well tolerated as a primary treatment for OSSN, with a high rate of tumors responding completely to therapy.

Tuberculosis Uveitis Associated With Ocular Surface Squamous Neoplasia in an Otherwise Healthy Patient

We describe a 34-year-old woman with isolated tuberculosis (TB) uveitis who had unsuccessful resolution of her ocular surface squamous neoplasia after multiple shave excisions with a positive purified protein derivative (PPD) test and interferon-gamma (IFN-γ) release assays (IGRAs) proven tuberculosis. She was managed with wide local excision of the lesion. Histopathology confirmed conjunctival intraepithelial neoplasia (CIN) grade II. Topical interferon alpha-2b (4 times daily) and anti-tuberculous therapy was planned for her, and there was no sign of recurrence of the lesion at six months follow-up.

Topical Interferon Alpha 2b in the Treatment of Refractory Diabetic Macular Edema

PurposeTo report the efficacy of topical interferon alpha 2b in the treatment of refractory diabetic macular edema.MethodsIn this retrospective interventional case series, five eyes of three individuals with diabetic macular edema resistant to multiple intravitreal injections of anti-vascular endothelial growth factor drugs and macular photocoagulation were included.ResultsAll studied eyes had undergone multiple intravitreal injections including bevacizumab, combination of bevacizumab and triamcinolone and aflibercept, and macular laser photocoagulation before being included in this study. Two intravitreal ranibizumab injections had also been performed in both eyes of one patient. Two eyes had undergone pars plana vitrectomy, one for diabetic macular edema and the other for rhegmatogenous retinal detachment. After a discussion regarding the experimental topical interferon alpha 2b treatment, all patients agreed to start interferon alpha 2b drops four times a day. One month after the treatment, optical coherence tomography demonstrated a significant improvement in macular structure and thickness which was stable or improved at the three-month follow-up visit. Visual acuity in all eyes was stable or improved throughout the three-month follow-up period. Conjunctival injection and follicular conjunctivitis were the side effects of topical interferon alpha 2b and were treated with lubrication and steroids.ConclusionThis case series demonstrated the potential efficacy of interferon alpha 2b in the treatment of refractory diabetic macular edema. It might be an option in patients with contraindications for intravitreal injections.

Conjunctival papillomatosis in children treated with co-adjuvant topical interferon alpha-2b

A series of paediatric patients is presented in whom topical interferon alpha-2b was used as a co-adjuvant treatment for conjunctival papilloma. This condition is frequently associated with human papillomavirus infection. There is little information on the pediatric population with the use of interferon for the treatment of these lesions. In this case series, adjuvant treatment with topical interferon alpha-2b in paediatric patients showed no recurrence and good tolerance.

Usefulness of Topical Interferon Alpha-2b Eye Drop as an Adjunctive Therapy Following Surgical Resection in Ocular Surface Squamous Neoplasia.

To report the clinical course of patients with ocular surface squamous neoplasia treated with topical interferon α-2b (IFNα-2b) after local excision of the tumor. This study enrolled four consecutive Japanese patients comprising one eye with conjunctival carcinoma in situ, and three eyes with squamous cell carcinoma (SCC) diagnosed histopathologically. All of them initially visited Hokkaido University Hospital in 2016. After resecting the tumor tissues, topical IFNα-2b eye drops were given to the eye four times a day. This study retrospectively analyzed the ophthalmological and imaging findings before and after the surgery, based on the patients' medical records. The mean follow-up duration was 37.8 months. All cases were males, and the mean age was 62.3 years. The tumor was located in the bulbar conjunctiva in three cases. Local pedunculated rotation flap, and free conjunctival flap were performed in one and two patients, respectively. In one case with SCC, the tumor involved the lower palpebral conjunctiva, already invading into the orbit at the first visit. The patient underwent extended resection of the lower lid, and reconstruction of the posterior lobe of the eyelid with Hughes flap. Cataract surgery was successfully conducted 18 months after tumor resection. All patients remain well without local recurrence or distant metastasis. Topical IFNα-2b treatment contributed to suppression of tumor recurrence and improvement of quality of vision in patients after local resection of ocular surface squamous neoplasia.