Ability of novice clinicians to interpret high-resolution optical coherence tomography for ocular surface lesions.

OBJECTIVE: To assess the ability of novice clinicians to use a commercially available high-resolution anterior segment optical coherence tomography (HR-OCT) device to diagnose various lesions of the ocular surface and cornea. METHODS: Cross-sectional study. Twenty-six black-and-white HR-OCT images were projected, and clinicians were asked to determine whether the lesions represented ocular surface squamous neoplasia (OSSN) or another ocular surface pathology. A 20-minute instructional lecture was given on HR-OCT interpretation, and the same 26 images were shown. The clinicians were asked to repeat their assessment of the lesions. Thirty-four novice clinicians at the Bascom Palmer Eye Institute, Miami, FL, participated. A commercially available device (RTVue, Optovue, Fremont, Calif.) was specifically chosen for this study. RESULTS: The mean frequency of correct identification of the 26 lesions was 70% (standard deviation [SD] 15%) before instruction; after a short lecture, the frequency of correct identification improved to 84% (SD 9%, p = 0.002). Novice clinicians were more accurate in correctly determining that a lesion was not an OSSN (ruling it out as a diagnosis) than in determining that a lesion was an OSSN (p = 0.001). Some lesions (both OSSN and not OSSN), however, were more difficult to interpret than others. CONCLUSION: This study demonstrated that all levels of novice clinicians can quickly improve diagnostic accuracy with a commercially available HR-OCT after a short training session.

Candida Endophthalmitis After Descemet Stripping Automated Endothelial Keratoplasty With Grafts From Both Eyes of a Donor With Possible Systemic Candidiasis.

PURPOSE: To report 2 cases with late postoperative Candida albicans interface keratitis and endophthalmitis after Descemet stripping automated endothelial keratoplasty (DSAEK) with corneal grafts originating from a single donor with a history of presumed pulmonary candidiasis. METHODS: Two patients underwent uncomplicated DSAEK by 2 corneal surgeons at different surgery centers but with tissue from the same donor and were referred to the Bascom Palmer Eye Institute with multifocal infiltrates at the graft-host cornea interface 6 to 8 weeks later, and anterior chamber cultures that were positive for the same genetic strain of C. albicans. Immediate explantation of DSAEK lenticules and daily intracameral and instrastromal voriconazole and amphotericin injections failed to control the infection. Thus, both patients underwent therapeutic penetrating keratoplasty with intraocular lens explantation, pars plana vitrectomy, and serial postoperative intraocular antifungal injection. RESULTS: Both patients are doing well at 2 years postoperatively with best-corrected vision of 20/20 and 20/30+ with rigid gas permeable lenses. One patient required repeat optical penetrating keratoplasty and glaucoma tube implantation 1 year after the original surgery. Literature review reveals that donor lenticule explantation and intraocular antifungals are often inadequate to control fungal interface keratitis, and a therapeutic graft is commonly needed. CONCLUSIONS: 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.

Sub-basal Corneal Nerve Plexus Analysis Using a New Software Technology.

PURPOSE: To study sub-basal corneal nerve plexus (SCNP) parameters by in vivo corneal confocal microscopy using a new software technology and examine the effect of demographics and diabetes mellitus (DM) on corneal nerves morphology. METHODS: A Confoscan 4 (Nidek Technologies) was used in this cross-sectional study to image the SCNP in 84 right eyes at the Miami Veterans Affairs eye clinic. Images were analyzed using a new semiautomated nerve analysis software program (The Corneal Nerve Analysis tool) which evaluated 9 parameters including nerve fibers length (NFL) and nerve fibers length density (NFLD). The main outcome measure was the examination of SCNP morphology by demographics, comorbidities, and HbA1c level. RESULTS: Interoperator and intraoperator reproducibility were good for the 9 parameters studied (Intraclass Correlations [ICCs] 0.73-0.97). Image variability between two images within the same scan was good for all parameters (ICC 0.66-0.80). Older individuals had lower SCNP parameters with NFL and NFLD negatively correlating with age (r=-0.471, and -0.461, respectively, P<0.01 for all). Patients with diabetes had lower mean NFLD 10987.6 µm/mm (±3,284.6) and NFL 1,289.5 µm/frame (±387.2) compared with patients without diabetes (mean NFLD 15077.1 µm/mm [±4,261.3] and NFL 1750.0 µm/frame [±540.7]) (P<0.05 for all). HbA1c levels in patients with diabetes were inversely correlated with NFL and NFLD (r= -0.568, and -0.569, respectively, P<0.05 for all). CONCLUSIONS: 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.

Intracorneal and Intraocular Invasion of Ocular Surface Squamous Neoplasia after Intraocular Surgery: Report of Two Cases and Review of the Literature.

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.

Role of high resolution optical coherence tomography in diagnosing ocular surface squamous neoplasia with coexisting ocular surface diseases.

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.

Long-term course of patients with primary ocular adnexal MALT lymphoma: a large single-institution cohort study.

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 = .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 = .006, P = .0001, P = .002, and P = .0001, respectively). Multivariate analysis showed that age >60 years (hazard ratio [HR] 2.44) and RT<30.6Gy (HR=4.17) were the only factors correlated with shorter PFS (P = .01 and P = .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.

Topical 5-Fluorouracil 1% as Primary Treatment for Ocular Surface Squamous Neoplasia.

PURPOSE: To determine the efficacy of topical 5-fluorouracil 1% (5-FU) as a primary treatment of ocular surface squamous neoplasia (OSSN). DESIGN: Retrospective study. PARTICIPANTS: Topical 5-FU was used as primary therapy in 44 patients with OSSN. METHODS: 5-Fluorouracil 1% administered topically 4 times daily for 1 week followed by a drug holiday of 3 weeks. Patients were identified through a pharmacy database. Patients were excluded if 5-FU was used as adjuvant therapy, if they did not complete therapy, or if they were still actively receiving treatment for OSSN at the time of last follow-up. MAIN OUTCOME MEASURES: The primary outcome measures were the frequency of complete resolution with topical 5-FU treatment and the rate of OSSN recurrence. RESULTS: Of the 44 patients identified, 32 were men and 12 were women. The mean age was 68 years. Complete resolution of OSSN was noted in 82% of patients (36/44); 18% (8/44) were considered treatment nonresponders. Patients were treated with a median of 4 cycles (range, 2-9 cycles). 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 months). In the 36 patients who showed complete resolution, 4 experienced tumor recurrence. Recurrence rates at 1 and 2 years were 6% and 15%, respectively, using Kaplan-Meier survival analysis. At least 1 side effect from the medication was reported by 61% of patients (21/44), but only 1 patient discontinued the medication because of 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. CONCLUSIONS: 5-Fluorouracil is effective and well tolerated as a primary treatment for OSSN, with 82% of tumors responding completely to therapy.

High-Resolution Optical Coherence Tomography Findings of Lisch Epithelial Corneal Dystrophy.

PURPOSE: To describe a case of Lisch epithelial corneal dystrophy (LECD) and present its unique characteristics on high-resolution optical coherence tomography (HR-OCT). METHODS: A 78-year-old man with whorled corneal epithelial opacities in the right eye was referred for the evaluation of ocular surface squamous neoplasia. Clinical evaluation, photographs, and HR-OCT images of the cornea involved were obtained and scrapings of the affected cornea were sent for histopathologic analysis. RESULTS: Clinically, the patient presented with an opalescent whirling epithelium in a linear pattern encroaching on the visual axis. HR-OCT showed normal thickness epithelial hyperreflectivity of involved cornea without stromal involvement, along with sharply demarcated borders of unaffected tissue. Histopathologic findings demonstrated vacuolated periodic acid-Schiff (PAS) positive cells throughout the epithelial layers consistent with LECD. CONCLUSIONS: HR-OCT was able to provide useful information to rule out ocular surface squamous neoplasia and confirm the clinical impression of LECD at the time of clinical examination. HR-OCT shows promise as an adjunctive diagnostic tool for ocular surface lesions and pathologies.

Human Papilloma Virus Infection Does Not Predict Response to Interferon Therapy in Ocular Surface Squamous Neoplasia.

PURPOSE: To identify the frequency of human papilloma virus (HPV) in ocular surface squamous neoplasia (OSSN) and to evaluate differences in clinical features and treatment response of tumors with positive versus negative HPV results. DESIGN: Retrospective case series. PARTICIPANTS: Twenty-seven patients with OSSN. METHODS: Ocular surface squamous neoplasia specimens were analyzed for the presence of HPV. Clinical features and response to interferon were determined retrospectively 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%) demonstrated positive HPV results. The HPV genotypes identified included HPV-16 in 10 tumors (48%), HPV-31 in 5 tumors, HPV-33 in 1 tumor, HPV-35 in 2 tumors, HPV-51 in 2 tumors, and a novel HPV in 3 tumors (total of 23 tumors because 1 tumor had 3 identified genotypes). Tumors found in the superior limbus were more likely to show positive HPV results (48% vs. 0%; P=0.06, Fisher exact test). Tumors with positive HPV-16 results were larger (68 vs. 34 mm2; P=0.08, Mann-Whitney U test) and were more likely to have papillomatous morphologic features (50% vs. 12%; P=0.07, Fisher exact test) compared with tumors showing negative results for HPV-16. Human papilloma virus status was not found to be associated with response to interferon therapy (P=1.0, Fisher exact test). Metrics found to be associated with a nonfavorable response to interferon were male gender and tumors located in the superior conjunctivae. CONCLUSIONS: The presence of HPV in OSSN seems to be more common in lesions located in the nonexposed, superior limbus. Human papilloma virus presence does not seem to be required for a favorable response to interferon therapy.

Delayed expulsive choroidal hemorrhage after penetrating keratoplasty.

The authors report a case of a late-onset spontaneous choroidal hemorrhage in a patient with a corneal transplant that resulted in rupture of the keratoplasty wound and expulsion of ocular contents. This case is important because it highlights the predisposing factors of a delayed-onset choroidal hemorrhage including anticoagulant therapy, advanced age, glaucoma, and hypertension.

Conjunctival Intraepithelial Neoplasia with Mucoepidermoid Differentiation: A Case Report of a Subtle Lesion.

OBJECTIVE: To describe the clinical presentation, diagnostic imaging, and treatment options of conjunctival intraepithelial neoplasia (CIN) with mucoepidermoid differentiation, an in situ stage of mucoepidermoid carcinoma of the conjunctiva (MCC). RESULTS: We report the case of an 86-year-old man presenting with a subtle limbal lesion that had only mild erythema and elevation. Based on a few atypical clinical features and an abnormal ultrahigh-resolution optical coherence tomography (UHR OCT), an incisional biopsy was performed revealing CIN with mucoepidermoid differentiation. Treatment involved aggressive surgical excision. No evidence of recurrence was noted in the 5 years of follow-up. CONCLUSION: MCC is an aggressive tumor that has a tendency to be invasive and recur after treatment. Therefore, early diagnosis and treatment is critical. CIN with mucoepidermoid differentiation may represent the earliest stage of MCC. It can present subtly, with a clinical resemblance to benign and less aggressive ocular surface lesions. Imaging with UHR OCT may be helpful to detect early neoplasia. A high level of suspicion must be maintained when evaluating potential ocular surface tumors.

Ultra high-resolution anterior segment optical coherence tomography in the diagnosis and management of ocular surface squamous neoplasia.

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.