Treatment of conjunctival and corneal intraepithelial neoplasia with topical interferon α-2b

doi:10.1016/S0161-6420(01)00577-2

Ophthalmology

Volume 108, Issue 6, June 2001, Pages 1093-1098

https://doi.org/10.1016/S0161-6420(01)00577-2 Get rights and content

Abstract

Objective

To evaluate the role of topical interferon alfa-2b (IFNα2b) in the treatment of conjunctival and corneal intraepithelial neoplasia (CIN).

Design

Noncomparative case series.

Participants

Five patients with histologically proven CIN or recurrences of proven CIN were studied prospectively.

Intervention

After histologic confirmation, patients were given topical recombinant IFNα2b (INTRON A, Schering Plough, Kenilworth, NJ) 1 million IU/ml four times a day. Patients were continued on interferon until complete resolution of the tumor had occurred.

Main outcome measures

Patients were followed clinically and photographically for evidence of tumor resolution.

Results

All patients had complete resolution of the CIN lesion on IFNα2b. The mean time to clinical resolution was 11.6 weeks (range, 4–22 weeks). The mean follow-up was 17.6 months (range, 7–28 months). One patient had a clinical recurrence of his corneal CIN 1 year after tumor resolution. This patient was retreated, resulting in clinical resolution within 6 weeks, and has been tumor free for 8 months of follow-up.

Section snippets

Patients and methods

Approval for the study was obtained from the University of Miami School of Medicine Medical Science Subcommittee for the Protection of Human Subjects. Patients with histologically proven biopsy specimens of CIN or recurrent CIN (cases that were originally histologically proven CIN) were offered entrance into the study. After obtaining informed consent, patients were initiated on 1 million IU/ml of recombinant IFNα2b (INTRON A, Schering Plough, Kenilworth, NJ) four times a day. The patients were

Results

The case series has been summarized in Table 1.

Discussion

The traditional treatment for CIN is surgical excision, usually with adjunctive cryotherapy. Unless an intraoperative frozen-section technique11, 22 is used, residual tumor may remain, which can lead to recurrence rates of more than 50%.9, 10 Furthermore, extensive surgical excision for recurrent or large ocular surface tumors can lead to limbal stem cell deficiency and other ocular surface complications. Also, in glaucoma patients with filtering blebs or in patients who might need future

References (27)

G.A. Lee et al.
Ocular surface squamous neoplasia
Surv Ophthalmol
(1995)
R. Newton et al.
Effect of ambient solar ultraviolet radiation on incidence of squamous-cell carcinoma of the eye
Lancet
(1996)
G.A. Lee et al.
Risk factors in the development of ocular surface epithelial dysplasia
Ophthalmology
(1994)
S.A. Lauer et al.
Human papillomavirus type 18 in conjunctival intraepithelial neoplasia
Am J Ophthalmol
(1990)
G. Tabin et al.
Late recurrences and the necessity for long-term follow-up in corneal and conjunctival intraepithelial neoplasia
Ophthalmology
(1997)
J.C. Erie et al.
Conjunctival and corneal intraepithelial and invasive neoplasia
Ophthalmology
(1986)
J. Frucht-Pery et al.
Mitomycin C therapy for corneal intraepithelial neoplasia
Am J Ophthalmol
(1994)
R.P. Yeatts et al.
Topical 5-fluorouracil in treating epithelial neoplasia of the conjunctiva and cornea
Ophthalmology
(1995)
F.R. Hu et al.
Interferon treatment for corneolimbal squamous dysplasia
Am J Ophthalmol
(1998)
R.R. Vann et al.
Perilesional and topical interferon alfa-2b for conjunctival and corneal neoplasia
Ophthalmology
(1999)

B.A. Schechter

Conjunctival intraepithelial neoplasia

Ophthalmology

(1999)

B. Berman et al.

Dermatologic uses of interferons

Dermatol Clin

(1995)

H.E. Grossniklaus et al.

Conjunctival lesions in adults. A clinical and histopathologic review

Cornea

(1987)

Cited by (129)

Use of interferon alpha 2b to manage conjunctival primary acquired melanosis and conjunctival melanoma
2022, Survey of Ophthalmology
Primary acquired melanosis (PAM) is acquired conjunctival pigmentation that can give rise to conjunctival melanoma (CM), a malignant tumor of the bulbar and palpebral conjunctiva or the caruncle. Surgical excision is the treatment of choice for this neoplasm. Topical chemotherapy is also used for patients with PAM with atypia or CM and, in patients with recurrent or extensive disease, this may be an important option. Of the several chemotherapeutic drugs used, topical interferon alpha 2b (IFN-α2b) has become popular because of its low toxicity. Clinical evidence from case reports and case series supports the efficacy of IFN-α2b as the preferred adjuvant treatment for PAM and CM. In addition, topical IFN-α2b has been successfully applied to melanocytic tumors refractory to other treatments, such as cryotherapy and topical mitomycin C. In patients with locally advanced CM, the combination of IFN-α2b and systemic immunotherapy may serve as an alternative to exenteration. Given the low frequency of CM, long-term multicenter studies are needed to demonstrate the efficacy of IFN-α2b for preventing local recurrence and distant metastasis.
Corneal melt in conjunctival intraepithelial neoplasia
2020, American Journal of Ophthalmology Case Reports
Citation Excerpt :
One of the dreaded complications is corneal perforation due to extensive progression of corneal melt. IFN alpha-2b eye drops have several side effects such as ocular discomfort, photophobia, punctate epithelial keratitis, conjunctival hyperemia, and follicular conjunctivitis.3,6–8 Most of these side effects are self-limited and abate by one month after cessation of treatment.
Report a case of corneal melt in a patient with conjunctival intraepithelial neoplasia (CIN) treated with topical interferon (IFN) alpha-2B.
An 89-year-old man presented with gelatinous paralimbal lesions of the left eye extending onto the cornea with corneal neovascularization extending 5–6 clock hours. Nasally there was mild absence of the terminal vascular loops of the limbal palisades of Vogt and conjunctivalization. Diffuse punctate epithelial erosions were noted. The corneal graft displayed subepithelial and stromal edema. Anterior segment optical coherence tomography detected hyperreflectivity, sectional thickened epithelium, and abrupt transitions from normal to abnormal tissue. The patient was treated with excision of the corneal and conjunctival lesions with cryotherapy to the conjunctival borders. Excisional biopsy revealed CIN Grade 3 and carcinoma in situ of the cornea. Topical IFN alpha-2B four times daily was initiated postoperatively. Two months later, a central epithelial defect developed. The cornea progressively thinned and corneal melt ensued. The patient had several risk factors for corneal melt including neurotrophic cornea, early limbal stem cell deficiency, history of cryotherapy, keratoconjunctivitis sicca, and chronic use of glaucoma medications and steroid medications.
Interferon alpha-2B is an effective first line treatment for CIN with few side effects. It's side effects include punctate epithelial erosions, conjunctival hyperemia, and follicular conjunctivitis. We report a case of pre-existing keratoconjunctivitis sicca, early limbal stem cell deficiency, neurotrophic cornea, and newly diagnosed CIN Grade 3; it was treated with surgical excision, cryotherapy, and topical IFN alpha-2b with development of corneal melt 2 months later. Caution should be taken when using interferon alpha -2b in patients with pre-existing keratoconjunctivitis sicca, neurotrophic cornea, or limbal stem cell deficiency as it could exacerbate these conditions resulting in corneal melt.
Changes in in vivo confocal microscopic findings of ocular surface squamous neoplasia during treatment with topical interferon alfa-2b
2018, Ocular Surface
To evaluate in vivo confocal microscopy (IVCM) findings of ocular surface squamous neoplasia (OSSN) during treatment with topical interferon alfa-2b (IFN alfa-2b).
In this prospective interventional case series, 20 eyes from 20 patients with OSSN were treated with topical IFN alfa-2b 3 million IU/mL four times a day. Treatment was continued for 2 or 3 months after clinical resolution. IVCM was done at baseline, on a monthly basis, and at the end of treatment. Confocal images were evaluated in conjunction with clinical findings during treatment. Limbal dendritic cell (DC) density within the involved areas was calculated manually in confocal images.
Topical therapy resulted in clinical resolution of neoplasia in 80% of eyes. Main features of OSSN on IVCM were hyper-reflectivity of epithelium, demarcation line between neoplastic and normal epithelium, and pleomorphic cells. These findings became less prominent in response to IFN alfa-2b therapy. However, some degree of residual epithelial hyper-reflectivity could be detected in 9 (56.2%) subjects who responded to therapy at time of treatment cessation. Limbal DCs density within involved areas was significantly increased at month 1 follow-up compared to baseline only in responders (P < .0001). There was a trend toward higher limbal DCs density in responders to topical IFN alfa-2b than non-responders (208.6 ± 53.5 vs. 153.1 ± 48.2 cell/mm², respectively; P = .08) at month 1 follow-up.
IVCM is proposed as an adjunctive tool for monitoring OSSN during topical treatment. IVCM documents epithelial cell response as well as limbal DC density increase during topical IFN therapy.
Interferon alpha-2a as alternative treatment for conjunctival squamous cell carcinoma
2017, Archivos de la Sociedad Espanola de Oftalmologia
Paciente varón de 35 años con antecedente de infección por VIH, caracterizado por tumoración de crecimiento progresivo en conjuntiva bulbar de ojo izquierdo correspondiente a un carcinoma conjuntival de células escamosas que responde a tratamiento con interferón alfa-2a.
A nivel conjuntival, el interferón alfa-2b tópico ha sido utilizado como tratamiento inmunomodulador, con el que se observó remisión completa de las neoplasias epiteliales; sin embargo, no se ha publicado el uso del interferón alfa-2a para el tratamiento de carcinoma conjuntival de células escamosas, el cual difiere del intererón alfa-2b en un solo aminoácido.
A 35 year-old male patient with a history of HIV infection characterized by progressive tumour growth in bulbar conjunctiva of the left eye, corresponding to conjunctival squamous cell carcinoma that responded to treatment with interferon alpha-2a.
Interferon alpha-2b has been used at conjunctival level as a topical immunomodulator treatment, with complete remission of epithelial neoplasms being observed. However, there have not been any previous publications on the use of interferon alpha-2a, which differs from interferon alpha-2b in a single amino acid, for the treatment of conjunctival squamous cell carcinoma.
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
2023, BMC Ophthalmology
Local ocular safety of the subconjunctival injection of cetuximab in rabbits
2023, BMC Ophthalmology

View all citing articles on Scopus

^☆: Funding was provided in part by Research to Prevent Blindness, Inc., New York, New York.

¹: The authors have no financial interest related to the article.

View full text

Treatment of conjunctival and corneal intraepithelial neoplasia with topical interferon α-2b1☆,

Abstract

Objective

Design

Participants

Intervention

Main outcome measures

Results

Section snippets

Patients and methods

Results

Discussion

Surv Ophthalmol

Lancet

Ophthalmology

Am J Ophthalmol

Ophthalmology

Ophthalmology

Am J Ophthalmol

Ophthalmology

Am J Ophthalmol

Ophthalmology

Ophthalmology

Dermatol Clin

Conjunctival lesions in adults. A clinical and histopathologic review

Cornea

Treatment of conjunctival and corneal intraepithelial neoplasia with topical interferon α-2b¹☆,