Ocular surface squamous neoplasia, a now medically treatable disease spectrum?

Abstract

Purpose : To highlight the role of medical therapy when treating ocular surface squamous neoplasia by evaluating the long-term recurrence of conjunctival-corneal intraepithelial neoplasia (CCIN) cases treated with combination interferon alfa-2b and retinoic acid (I/RA). For cases refractory to traditional interventions, we trialed topical cidofovir (CDV), theorizing a viral influence mitigating treatment resistance.

Methods : A retrospective interventional case series of 82 eyes from 82 patients with biopsy proven CCIN was conducted to highlight the effectiveness of combination I/RA. Recurrence was monitored through clinical assessment and slit-lamp biomicroscopy. A pilot study of 6 eyes from 6 patients with biopsy-proven CCIN was executed to demonstrate the activity of CDV upon treatment-refractory tumors.

Results : 79 of 82 eyes with CCIN diagnoses were treated with I/RA achieved tumor resolution (Figure 1). The median tumor-free follow-up achieved was ~109.8 months (Figure 2). For our pilot study, complete resolution of OSSN lesions was achieved in 5 of 6 eyes treated with topical CDV. Mean tumor-free follow-up after clinical resolution was ~14.9. High risk serotype HPV-16 was detected in one specimen utilizing a HPV PCR assay.

Conclusions : Findings from our two studies highlights the potential for long-term tumor-free ocular surfaces with medical therapy. A viral etiology driving treatment resistance cannot be excluded. Our therapeutic strategy avoids the potential sight-limiting outcomes associated with repeat surgery. Studies comparing primary medical and surgical therapeutic options are required.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

Figure 1. A – Pre-treatment image of a gentleman in his 70s with a left keratinized ocular surface squamous neoplasia (CCIN II) overlying his left nasal limbus and bulbar conjunctiva. B – Conjunctival appearance post-interferon and retinoic application at 4122 days’ follow-up. C – In-vivo confocal microscopy of left nasal limbus at 4122 days’ follow-up with no dysplastic changes noted.

 

Figure 2. Survival plot of patients treated with combination interferon alfa-2b and retinoic acid. The “red line” delineates the median tumor-free follow-up for our entire study’s patient cohort (3342 days; n=82), whilst the “blue line” highlights the median tumor-free follow-up for patients with >10 year’s tumor-free follow-up (4613 days; n=30). The “green line” identifies the 10-year tumor-free follow-up mark.