The development of optical coherence tomography (OCT) technology has helped to usher in a new era of in vivo diagnostic imaging of the eye. The utilization of OCT for imaging of the anterior segment and ocular surface has evolved from time-domain devices to spectral-domain devices with greater penetrance and resolution, providing novel images of anterior segment pathology to assist in diagnosis and management of disease. Ocular surface squamous neoplasia (OSSN) is one such pathology that has proven demonstrable by certain anterior segment OCT machines, specifically the newer devices capable of performing ultra high-resolution OCT (UHR-OCT). Distinctive features of OSSN on high resolution OCT allow for diagnosis and differentiation from other ocular surface pathologies. Subtle findings on these images help to characterize the OSSN lesions beyond what is apparent with the clinical examination, providing guidance for clinical management. The purpose of this review is to examine the published literature on the utilization of UHR-OCT for the diagnosis and management of OSSN, as well as to report novel uses of this technology and potential directions for its future development.
Purpose To determine the efficacy of topical 5-fluorouracil 1% (5FU) as a primary treatment of ocular surface squamous neoplasia (OSSN). Design Retrospective study. Participants Topical 5FU was used as primary therapy in 44 patients with OSSN. Methods 5FU 1% administered topically four times a day for a week followed by a drug holiday of 3 weeks. Patients were identified through pharmacy database. Patients were excluded if 5FU was used as adjuvant therapy, did not complete therapy, or were still in active treatment for their OSSN at the time of last follow up. Main outcome measure The primary outcome measures were the frequency of complete resolution with topical 5FU treatment and the rate of OSSN recurrence. Results Of the 44 patients identified, 32 were males and 12 were females. The mean age was 68 years. Complete resolution of OSSN was noted in 82% (36/44) patients; and, 18% (8/44) were considered treatment non-responders. Patients were treated a median of 4 cycles (range 2-9). 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). In the 36 patients with complete resolution, 4 had tumor recurrence. Recurrence rates at 1 and 2 years were 6% and 15% respectively using Kaplan-Meier survival analysis. At least one side effect from the medication was reported by 61% (21/44) of patients, but only 1 patient discontinued the medication due to 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. Conclusion 5-fluorouracil is efficacious and well tolerated as a primary treatment for OSSN, with 82% of tumors completely responding to therapy.
Key Points• POAML (specifically Ann Arbor stage I disease) has an excellent clinical outcome, with only a few patients succumbing to lymphoma.• POAML patients face a continuous risk of distant relapse, including in the central nervous system, and transformation to aggressive lymphoma.While primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (POAML) is the most common orbital tumor, there are large gaps in knowledge of its natural history. We conducted a retrospective analysis of the largest reported cohort, consisting of 182 patients with POAML, diagnosed or treated at our institution to analyze long-term outcome, response to treatment, and incidence and localization of relapse and transformation. The majority of patients (80%) presented with stage I disease. Overall, 84% of treated patients achieved a complete response after first-line therapy. In patients with stage I disease treated with radiation therapy (RT), doses ‡30.6 Gy were associated with a significantly better complete response rate (P 5 .04) and progression-free survival (PFS) at 5 and 10 years (P < .0001). Median overall survival and PFS for all patients were 250 months (95% confidence interval [CI], 222 [upper limit not reached]) and 134 months (95% CI, 87-198), respectively. Kaplan-Meier estimates for the PFS at 1, 5, and 10 years were 91.5% (95% CI, 86.1% to 94.9%), 68.5% (95% CI, 60.4% to 75.6%), and 50.9% (95% CI, 40.5% to 61.6%), respectively. In univariate analysis, age >60 years, radiation dose, bilateral ocular involvement at presentation, and advanced stage were significantly correlated with shorter PFS (P 5 .006, P 5 .0001, P 5 .002, and P 5 .0001, respectively). Multivariate analysis showed that age >60 years (hazard ratio [HR] 2.44) and RT<30.6Gy (HR54.17) were the only factors correlated with shorter PFS (P 5 .01 and P 5 .0003, respectively). We demonstrate that POAMLs harbor a persistent and ongoing risk of relapse, including in the central nervous system, and transformation to aggressive lymphoma (4%), requiring long-term follow-up. (Blood. 2017;129(3):324-332)
Purpose Coexistence of an ocular surface disease can mask the typical features of ocular surface squamous neoplasia (OSSN). The purpose of this study was to evaluate high resolution optical coherence tomography (HR-OCT) as an adjunct in the detection and differentiation of OSSN within coexisting ocular surface pathologies. Methods Retrospective study of 16 patients with ocular surface disease and lesions suspicious for OSSN that were evaluated with HR-OCT. HR-OCT images of the lesions were taken to look for evidence of OSSN. Biopsies were performed in all cases, and the HR-OCT findings were compared to the histological results. Results Of the 16 patients with OSSN and a coexisting ocular surface disease, 12 were found to have OSSN by HR-OCT and all were subsequently confirmed by biopsy. Two patients had OSSN with rosacea, one with pingueculum, two within pterygia, one with Salzmann’ nodular degeneration, six with limbal stem cell deficiency (LSCD)/scarring. In all 12 cases HR-OCT images revealed classical findings of hyper-reflective, thickened epithelium and an abrupt transition from normal to abnormal epithelium. OSSN was ruled out by HR-OCT in four cases (2 Salzmann’s, 1 mucous membrane pemphigoid, and 1 LSCD). Negative findings were confirmed by biopsy. HR-OCT was used to follow resolution of the OSSN in positive cases, and it detected recurrence in 1 case. Conclusions While histopathology is the gold standard in the diagnosis of OSSN, HR-OCT can be used to noninvasively detect the presence of OSSN in patients with coexisting ocular conditions.
Purpose: The aim of this paper was to describe 2 cases of ocular surface squamous neoplasia (OSSN) of the conjunctiva with intracorneal and intraocular extension following intraocular surgery. Methods: We conducted a clinical pathological retrospective case series. Results: Case 1 underwent cataract surgery in the setting of an unnoticed adjacent OSSN. An excisional biopsy with cryotherapy and intraoperative mitomycin C was subsequently performed, confirming OSSN. The patient had two recurrences treated topically with resolution. While the conjunctiva remained clear, a corneal haze emanating from the cataract incision site was noted. Penetrating keratoplasty (PK) for this haze revealed midstromal infiltrative carcinoma. Case 2 had a history of herpes simplex keratitis that ultimately required corneal grafts. Fifteen years later, he developed an OSSN treated with excisional biopsy and had clear margins. Eight months later, he presented with a recurrence of his OSSN and was treated briefly with topical interferon for 4 weeks; however, he developed an infectious keratitis with a corneal perforation requiring another PK. Four months after PK, low-grade inflammation was noted. Cytology of the anterior chamber aspirate revealed neoplastic squamous cells. Another PK was then performed. Pathology confirmed extensive intraocular neoplasia. Limited exenteration was performed. Conclusion: Patients with a history of OSSN may be at increased risk of neoplastic intraocular extension following intraocular surgery.
Interface fungal keratitis and endophthalmitis due to infected donor corneal tissue is difficult to treat, and both recipients of grafts originating from the same donor are at risk of developing this challenging condition.
Purpose To identify the frequency of human papilloma virus (HPV) in ocular surface squamous neoplasia (OSSN), and evaluate differences in clinical features and treatment response of HPV positive versus negative tumors. Design Retrospective case series. Participants 27 patients with OSSN Methods OSSN specimens were analyzed for the presence of HPV. Clinical features and response to interferon were retrospectively determined and linked to the presence (versus absence) of HPV. Main Outcome Measures Clinical characteristics of OSSN by HPV status. Results Twenty one of 27 tumors (78%) were HPV positive. HPV genotypes identified included HPV 16 in 10 (48%), HPV 31 in 5, HPV 33 in 1, HPV 35 in 2, HPV 51 in 2, and a novel HPV in 3 (total 23 as one tumor had 3 genotypes identified). Tumors found in the superior limbus were more likely to be HPV positive (48% vs 0%, Fisher exact P = 0.06). HPV 16 positive tumors were larger (68mm2 vs 34 mm2, Mann Whitney U P = 0.08) and were more likely to have a papillomatous morphology (50% vs 12%, Fisher exact P = 0.07) compared to HPV 16 negative tumors. HPV status was not found to associate with response to interferon therapy (Fisher exact P = 1.0). Metrics found to associate with a non-favorable response to interferon were male gender and tumors located in the superior conjunctivae. Conclusions HPV presence in OSSN appears more common in lesions located in the non-exposed, superior limbus. HPV presence does not seem to be required for a favorable response to interferon therapy.
The Corneal Nerve Analysis tool is a reproducible diagnostic software technique for the analysis of the SCNP with confocal microscopy. Older age, DM, and higher level of HbA1c were associated with a significant reduction in SCNP parameters.
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