Conjunctival keratoacanthoma

An 83-year-old man presented with a 1-month history of a rapidly enlarging conjunctival mass. On examination, slit lamp biomicroscopy revealed a leukoplakic tumour at the temporal limbus. The lesion was excised with cryotherapy application to the limbus and conjunctival margins. Histopathology revealed a keratoacanthoma (KA). KA typically occurs on sun-exposed areas of the skin. Conjunctival KA is very rare, and differentiation between conventional squamous cell carcinoma (SCCA) and KA can be challenging. The present case highlights the indication for excisional surgery in patients with conjunctival KA using the no touch technique, cryotherapy, amniotic membrane and the histopathological differentiation between KA and SCCA

Time trend of prevalence and susceptibility to nitrofurantoin of urinary MDR Escherichia coli from outpatients

Objectives:&nbsp;To assess the time trend of the prevalence of urinary MDR Escherichia coli in Belgian outpatients (2005 versus 2011-12), the antibiotic susceptibility of urinary MDR E. coli, and the time trend of non-susceptibility to nitrofurantoin, i.e. first-line treatment for uncomplicated urinary tract infections (UTIs), of urinary MDR E. coli (2005 versus&nbsp;2011-12). Methods:&nbsp;In this secondary analysis of a multicentre study, which collected a convenience sample of voluntary participating laboratories (15 and 8 in 2005 and 2011-12, respectively), we analysed antimicrobial susceptibilities (ampicillin, amoxicillin/clavulanate, cefalotin, ciprofloxacin, nitrofurantoin and trimethoprim/sulfamethoxazole) of urinary E. coli. MDR was defined as resistance to three or more of these agents. The prevalence of MDR E. coli and its non-susceptibility to nitrofurantoin was compared between 2005 and 2011-12 using a generalized estimating equation&nbsp;model. Results:&nbsp;MDR status could be determined for 9704 and 12512 urinary E. coli isolates from 7911 and 9441 patients in 2005 and 2011-12, respectively, with most patients being women (79% in both study periods). The prevalence of MDR increased from 28.4% (2758/9704) in 2005 to 34.3% (4286/12512) in 2011-12 (adjusted OR 1.305; 95% CI 1.220-1.397). Within the MDR isolates, the prevalence of nitrofurantoin non-susceptibility decreased from 23.2% (623/2684) in 2005 to 10.7% (455/4253) in 2011-12 (adjusted OR 0.424; 95% CI&nbsp;0.363-0.494). Conclusions:&nbsp;Despite a high prevalence of MDR E. coli in urinary samples from Belgian outpatients, nitrofurantoin could still be recommended as first-line empirical treatment in uncomplicated UTIs.</p

Periorbital Pyoderma Gangrenosum Associated With a Cocaine-Induced Midline Destructive Lesion: Case Report and Review of the Literature

A 72-year-old woman with a history of chronic cocaine use presented 9 months after a dog-bite with a large facial ulceration and absent sinonasal structures. Biopsies were negative for infectious, vasculitic, or neoplastic pathologies. The patient was lost to follow up for 15 months and returned with a significantly larger lesion despite abstinence from cocaine. Additional inflammatory and infectious workup was negative. Intravenous steroids were administered with clinical improvement. Therefore, she was diagnosed with pyoderma gangrenosum and cocaine-induced midline destructive lesion due to cocaine/levamisole. Pyoderma gangrenosum is a rare dermatologic condition that uncommonly involves the eye and ocular adnexa. Diagnosis involves clinical examination, response to steroids, exclusion of infectious or autoimmune conditions, and identifying potential triggers including cocaine/levamisole. This report highlights a rare presentation of periorbital pyoderma gangrenosum causing cicatricial ectropion associated with concomitant cocaine-induced midline destructive lesion and reviews important aspects of clinical manifestations, diagnosis, and management of pyoderma gangrenosum and cocaine/levamisole autoimmune phenomenon

Vitreous metastasis from cutaneous melanoma: diagnosis and management

ABSTRACT Purpose: To report the clinical findings, treatments, and outcomes in a series of patients with vitreous metastasis from cutaneous melanoma. Methods: This single-center, retrospective, interventional case series included patients with biopsy-confirmed vitreous metastasis from cutaneous melanoma diagnosed between 1997 and 2020. Standard 23- or 25-gauge pars plana vitrectomy was performed for diagnostic sampling. Sclerotomies were treated with double or triple freeze-thaw cryotherapy. Perioperative intravitreal injections of melphalan (32 µg/0.075 mL) were administered, when indicated. Visual acuity, intraocular pressure, and systemic and ocular treatment responses were reported. Results: Five eyes of five patients with unilateral vitreous metastasis from cutaneous melanoma were identified. The median age at diagnosis was 84 (range, 37-88) years. The median follow-up after ophthalmic diagnosis was 28 (8.5-36) months; one patient did not have a follow-up. The initial visual acuity ranged from 20/30 to hand motions. Baseline clinical findings included pigmented or non-pigmented cellular infiltration of the vitreous (5/5), anterior segment (4/5), and retina (3/5). Four patients had secondary glaucoma. Systemic therapy included checkpoint inhibitor immunotherapy (n=3, all with partial/complete response), systemic chemotherapy (n=2), surgical resection (n=3), and radiation (n=2). The median time from primary diagnosis to vitreous metastasis was 2 (2-15) years. One patient had an active systemic disease at the time of vitreous metastasis. The final visual acuity ranged from 20/40 to no light perception. Ophthalmic treatment included vitrectomy in all five patients, intravitreal administration of melphalan in three, and intravitreal administration of methotrexate in one. One patient required enucleation, and histopathology revealed extensive invasion by melanoma cells. Conclusions: Vitreous metastasis from cutaneous melanoma can present as a diffuse infiltration of pigmented or non-pigmented cells into the vitreous and may be misdiagnosed as uveitis. Diagnostic pars plana vitrectomy and periodic intravitreal chemotherapy may be indicated

Diagnosis of Ocular Surface Lesions Using Ultra–High-Resolution Optical Coherence Tomography

To assess the use of ultra–high-resolution (UHR) optical coherence tomography (OCT) in the diagnosis of ocular surface lesions. Prospective, noncomparative, interventional case series. Fifty-four eyes of 53 consecutive patients with biopsy-proven ocular surface lesions: 8 primary acquired melanosis lesions, 5 amelanotic melanoma lesions, 2 nevi, 19 ocular surface squamous neoplasia lesions, 1 histiocytosis lesion, 6 conjunctival lymphoma lesions, 2 conjunctival amyloidosis lesions, and 11 pterygia lesions. Ultra–high-resolution OCT imaging of the ocular surface lesions. Clinical course and photographs, UHR OCT image, and histopathologic findings. Ultra–high-resolution OCT images of all examined ocular surface lesions showed close correlation with the obtained histopathologic specimens. When clinical differential diagnosis of ocular surface lesions was broad, UHR OCT images provided optical signs indicating a more specific diagnosis and management. In cases of amelanotic melanoma, conjunctival amyloidosis, and primary histiocytosis and in 1 case of ocular surface squamous neoplasia, UHR OCT was instrumental in guiding the diagnosis. In those cases, UHR OCT suggested that the presumed clinical diagnosis was incorrect and favored a diagnosis that later was confirmed by histopathologic examination. Correlations between UHR OCT and histopathologic findings confirm that UHR OCT is an adjunctive diagnostic method that can provide a noninvasive means to help guide diagnosis and management of ocular surface lesions. The author(s) have no proprietary or commercial interest in any materials discussed in this article

In Vivo Characteristics of Corneal Endothelium/Descemet Membrane Complex for the Diagnosis of Corneal Graft Rejection

To evaluate the utility of endothelial/Descemet membrane complex (En/DM) characteristics in diagnosing corneal graft rejection. Diagnostic reliability study. One hundred thirty-nine eyes (96 corneal grafts post penetrating keratoplasty or Descemet stripping automated endothelial keratoplasty: 40 clear, 23 actively rejecting, 24 rejected, and 9 nonimmunologic failed grafts; along with 43 age-matched control eyes) were imaged using high-definition optical coherence tomography. Images were used to describe En/DM and measure central corneal thickness (CCT) and central En/DM thickness (DMT). En/DM rejection index (DRI) was computed to detect the relative En/DM thickening to the entire cornea. In actively rejecting grafts, DMT and DRI were significantly greater than controls and clear grafts (28, 17, and 17 μm and 1.5, 1 and 1, respectively; P < .001). Rejected grafts had the highest DMT and DRI compared to all groups (59 μm and 2.1; P < .001). DMT and DRI showed excellent accuracy, significantly better than that of CCT, in differentiating actively rejecting from clear grafts (100% and 96% sensitivity; 92.5% and 92.5% specificity), actively rejecting from rejected grafts (88% and 83% sensitivity; 91% and 83% specificity), and nonimmunologic failed from rejected grafts (100% and 100% sensitivity; 88% and 100% specificity). DMT correlated significantly with rejection severity (P < .001). In corneal grafts, in vivo relative thickening of the En/DM is diagnostic of graft rejection as measured by DMT and DRI. These indices have excellent accuracy, sensitivity, and specificity in detecting graft immunologic status, superior to CCT. DMT is a quantitative index that correlates accurately with the severity of rejection

Predictors of Ocular Surface Squamous Neoplasia Recurrence after Excisional Surgery

PURPOSE: To identify predictors of ocular surface squamous neoplasm (OSSN) recurrence after surgical resection. DESIGN: Retrospective case series. PARTICIPANTS: Three hundred and eighty nine consecutive patients who underwent excisional biopsy for OSSN lesions at the Bascom Palmer Eye Institute from January 1, 2001, to September 20, 2010 METHODS: Review of pathology records and patient charts. MAIN OUTCOME MEASURES: Identification of factors predictive of OSSN recurrence. RESULTS: Of 389 excised OSSN lesions, forty-four recurred during follow up. The 1 year recurrence rate was 10% and the 5 year recurrence rate was 21% with a mean time to recurrence in those with a recurrence of 2.5 years (standard deviation (SD) 3.4). Using the American Joint Committee on Cancer (AJCC) clinical staging system, T3 and T2 lesions portended a higher risk of recurrence compared to T1 (T2/T1: hazard ratio (HR) = 2.05, p=0.04; T3/T1: HR= 2.31, p=0.07). In addition, a location characteristic that increased the risk of tumor recurrence was tarsal involvement (AJCC T3 stage lesion) (HR=4.12, p = 0.007). Nasal location was associated with a decreased risk of tumor recurrence (HR=0.41, p=0.008). Pathologic characteristics significantly associated with tumor recurrence were the presence of positive margins (HR=2.73, p= 0.008) and higher grade lesions (carcinoma in situ and squamous cell carcinoma versus dysplasia) (HR=2.55, p=0.02). Treatment with adjuvant cryotherapy significantly decreased the risk of tumor recurrence (HR=0.51, p=0.03). In those patients with positive margins, the use of post-operative topical interferon therapy lowered the recurrence rate to a level similar to that of patients with negative margins. CONCLUSIONS: Certain patient and tumor factors are associated with a higher risk of OSSN recurrence after surgical excision, such as tarsal tumor location and positive surgical margins. Post-operative adjuvant therapy should be considered in patients with high risk OSSN characteristics

Parallel Gene Expression Changes in Sarcoidosis Involving the Lacrimal Gland, Orbital Tissue, or Blood

Sarcoidosis is a major cause of ocular or periocular inflammation. The pathogenesis of sarcoidosis is incompletely understood and diagnosis often requires a biopsy. To determine how gene expression in either orbital adipose tissue or the lacrimal gland affected by sarcoidosis compares with gene expression in other causes of orbital disease and how gene expression in tissue affected by sarcoidosis compares with gene expression in peripheral blood samples obtained from patients with sarcoidosis. In a multicenter, international, observational study, gene expression profiling of formalin-fixed biopsy specimens, using GeneChipp U133 Plus 2 microarrays (Affymetrix), was conducted between October 2012 and January 2014 on tissues biopsied from January 2000 through June 2013. Participants included 12 patients with orbital sarcoidosis (7 in adipose tissue; 5 affecting the lacrimal gland) as well as comparable tissue from 6 healthy individuals serving as controls or patients with thyroid eye disease, nonspecific orbital inflammation, or granulomatosis with polyangiitis. In addition, results were compared with gene expression in peripheral blood samples obtained from 12 historical individuals with sarcoidosis. Significantly differentially expressed transcripts defined as a minimum of a 1.5-fold increase or a comparable decrease and a false discovery rate of P < .05. Signals from 2449 probe sets (transcripts from approximately 1522 genes) were significantly increased in the orbital adipose tissue from patients with sarcoidosis. Signals from 4050 probe sets (approximately 2619 genes) were significantly decreased. Signals from 3069 probe sets (approximately 2001 genes) were significantly higher and 3320 (approximately 2283 genes) were significantly lower in the lacrimal gland for patients with sarcoidosis. Ninety-two probe sets (approximately 69 genes) had significantly elevated signals and 67 probe sets (approximately 56 genes) had significantly lower signals in both orbital tissues and in peripheral blood from patients with sarcoidosis. The transcription factors, interferon-response factor 1, interferon-response factor 2, and nuclear factor κB, were strongly implicated in the expression of messenger RNA upregulated in common in the 3 tissues. Gene expression in sarcoidosis involving the orbit or lacrimal gland can be distinguished from gene expression patterns in control tissue and overlaps with many transcripts upregulated or downregulated in the peripheral blood of patients with sarcoidosis. These observations suggest that common pathogenic mechanisms contribute to sarcoidosis in different sites. The observations support the hypothesis that a pattern of gene expression profiles could provide diagnostic information in patients with sarcoidosis

The Role of the Immune Response in the Pathogenesis of Thyroid Eye Disease: A Reassessment.

Although thyroid eye disease is a common complication of Graves' disease, the pathogenesis of the orbital disease is poorly understood. Most authorities implicate the immune response as an important causal factor. We sought to clarify pathogenesis by using gene expression microarray.An international consortium of ocular pathologists and orbital surgeons contributed formalin fixed orbital biopsies. RNA was extracted from orbital tissue from 20 healthy controls, 25 patients with thyroid eye disease (TED), 25 patients with nonspecific orbital inflammation (NSOI), 7 patients with sarcoidosis and 6 patients with granulomatosis with polyangiitis (GPA). Tissue was divided into a discovery set and a validation set. Gene expression was quantified using Affymetrix U133 Plus 2.0 microarrays which include 54,000 probe sets.Principal component analysis showed that gene expression from tissue from patients with TED more closely resembled gene expression from healthy control tissue in comparison to gene expression characteristic of sarcoidosis, NSOI, or granulomatosis with polyangiitis. Unsupervised cluster dendrograms further indicated the similarity between TED and healthy controls. Heat maps based on gene expression for cytokines, chemokines, or their receptors showed that these inflammatory markers were associated with NSOI, sarcoidosis, or GPA much more frequently than with TED.This is the first study to compare gene expression in TED to gene expression associated with other causes of exophthalmos. The juxtaposition shows that inflammatory markers are far less characteristic of TED relative to other orbital inflammatory diseases

Orbital pseudotumor can be a localized form of granulomatosis with polyangiitis as revealed by gene expression profiling

Biopsies and ANCA testing for limited forms of granulomatosis with polyangiitis (GPA) are frequently non-diagnostic. We characterized gene expression in GPA and other causes of orbital inflammation. We tested the hypothesis that a sub-set of patients with non-specific orbital inflammation (NSOI, also known as pseudotumor) mimics a limited form of GPA. Formalin-fixed, paraffin-embedded orbital biopsies were obtained from controls (n=20) and patients with GPA (n=6), NSOI (n=25), sarcoidosis (n=7), or thyroid eye disease (TED) (n=20) and were divided into discovery and validation sets. Transcripts in the tissues were quantified using Affymetrix U133 Plus 2.0 microarrays. Distinct gene expression profiles for controls and subjects with GPA, TED, or sarcoidosis were evident by principal coordinate analyses. Compared with healthy controls, 285 probe sets had elevated signals in subjects with GPA and 1472 were decreased (>1.5-fold difference, false discovery rate adjusted p<0.05). The immunoglobulin family of genes had the most dramatic increase in expression. Although gene expression in GPA could be readily distinguished from gene expression in TED, sarcoidosis, or controls, a comparison of gene expression in GPA versus NSOI found no statistically significant differences. Thus, forms of orbital inflammation can be distinguished based on gene expression. NSOI/pseudotumor is heterogeneous but often may be an unrecognized, localized form of GPA. •Some types of orbital inflammation are distinguishable by gene expression profiles.•Non-specific orbital inflammation can be subdivided by analysis of gene expression.•Some NSOI gene expression profiles are indistinguishable from those of GPA.•Limited GPA in the orbit requires gene expression profiling to be identified