Corneal melt with systemic chemotherapy in eyelid sebaceous gland carcinoma: Chemo-toxicity or tumor-necrosis-induced inflammation

Dear Editor, The use of systemic neoadjuvant chemotherapy (NAC) is increasingly being explored in eyelid and adnexal tumors.[1,2] The aim of NAC is globe salvage and achieving tumor-free resection margins per-operatively. We report two cases of eyelid sebaceous gland carcinoma (SGC), where corneal melt was noted after NAC. The clinico-demographic details of both cases are summarized in Table 1. Both patients received three cycles of systemic intravenous cisplatin (80 mg/m2 on day 1) and 5-FU (1000 mg/m2 over 6 h on days 1–4), each cycle 3 weeks apart. There was a remarkable response to NAC. Corneal melt was noted after the second and third cycles, respectively, in cases 1 and 2. Corneal scraping and culture ruled out infective etiology and investigations performed to rule out systemic collagen vascular diseases were within normal limits. Ptosis resolved completely in case 2; however, in case 1, ptosis persisted despite remarkable tumor regression. There was no lagophthalmos in any of the two cases and hence exposure keratopathy was ruled out as a cause of exposure keratopathy and corneal ulceration. None of the patients had any history of receiving external beam radiotherapy (EBRT). 5-FU is a widely used chemotherapeutic agent. Ocular side effects reported with 5-FU include tearing (26.9%), blurred vision (11.5%), ocular irritation (5.8%), eyelid dermatitis (5.8%), punctal and canalicular stenosis (5.8%), blepharitis (3.8%), conjunctivitis (3.8%), keratitis (3.8%), and cicatricial ectropion (1.9%).[3] But there are no previous reports of corneal melt.Table 1: Clinico-demographic and treatment details of patients of eyelid SGC treated with NAC that developed corneal meltingBoth cases, in our study, had severe mechanical ptosis from large upper eyelid tumors [Fig. 1] that showed an excellent response to chemotherapy. Also, there were no systemic or ocular predisposing conditions for corneal ulceration. We hypothesize that corneal melting in both cases could be due to a combination of the effect of 5FU and the release of biomolecules from the rapidly regressing eyelid tumor. The cell death from chemotherapy is believed to be necrotic.[4] Massive cell necrosis may incite a local inflammatory response causing collateral damage to adjacent tissues. This is observed for cells that die by necrosis and sometimes for cells undergoing necroptosis.Figure 1: Clinical photograph of patients showing (a) a large upper eyelid sebaceous gland carcinoma (SGC) causing complete mechanical ptosis in case 1, (b) post-NAC (3 cycles) almost complete (>90%) tumor regression with persistent complete ptosis, (c) upper eyelid SGC extending from medial canthus to three-fourths of upper eyelid horizontally in case 2, (d) post-NAC (2 cycles) regressed mass with a paracentral corneal ulcer measuring 2 mm × 2 mmThe presence of severe mechanical ptosis brought the cornea into persistent close contact with the tumor. The inflammatory mediators produced within the regressing tumor permeated through the conjunctiva to the corneal surface augmenting the epitheliotoxicity of 5FU. In both cases the severity and location of corneal involvement correlated with the size and location of the eyelid tumor. There are other instances of tumor necrosis-induced inflammation in the ophthalmic literature. Cases of intraocular retinoblastoma may present with sterile orbital cellulitis hypothesized to be due to massive tumor necrosis. There are only two case series and a few case reports on the use of 5FU-based NAC in eyelid SGC.[2,5] None of these authors reported any corneal melt. But the fact that the use of NAC in eyelid SGC is sparse and cases reported with a combination of large upper eyelid SGC with severe mechanical ptosis and excellent tumor response to NAC are very few; make the observation of this sight-threatening complication in two of our patients worth noticing. To conclude, tumor necrosis-induced aseptic inflammation in large upper eyelid SGCs with severe ptosis may enhance corneal complications of 5FU-based NAC. Administration of copious lubricants and topical steroids while receiving NAC may possibly prevent this side effect. Future studies on tear proteonomics in cases of eyelid malignancy treated with NAC are recommended to confirm the proposed hypothesis. Permission Obtained from LAR. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship: Nil. Conflicts of interest: There are no conflicts of interest.