Hyaluronic Acid Gel Biodegradation After Intrapalpebral and Intraorbital Injection in Experimental Study.

PURPOSE: Amid the increasing clinical application of hyaluronic acid (HA) fillers in the ocular adnexa is a paucity of histological data concerning the fate of the injected material. The current study documents the in vivo biodegradation of HA deposited in the eyelid and orbit. METHODS: The study included 22 chinchilla rabbits. The right upper eyelid of 12 rabbits received a single 0.2 ml Restylane (Galderma, Uppsala, Sweden) subcutaneous injection. In 10 different rabbits, the right orbit was injected with 1.0 ml Restylane SubQ (Galderma, Uppsala, Sweden) in the extraconal space. The rabbits in the eyelid group were euthanized at 2 weeks, 1 month, 2, 4, 6, and 9 months, while the rabbits in the orbit group were euthanized at 1 month, 3, 6, 12, and 18 months. Histological analysis was performed on the harvested samples. RESULTS: In the eyelid, the HA assumed a sponge-like structure that diminished gradually over time. At 9 months, the injected HA partially persisted, mainly in the peripheral areas of injection. A similar histologic pattern was observed in the injected orbits, with slow changes persisting at the eighteenth month. In both cohorts, clear signs of collagen deposition and pseudocapsule formation were observed around HA droplets, with no signs inflammation. CONCLUSIONS: HA injected subcutaneously into the eyelid and orbit of rabbits undergoes slow and gradual biodegradation, with HA persisting to no less than 9 months in the eyelid and 18 months in orbit. Neocollagen synthesis and lack of hyaluronidase activity could explain the unexpectedly prolonged HA persistence.

Chemokine Expression in Murine RPE/Choroid in Response to Systemic Viral Infection and Elevated Levels of Circulating Interferon-γ.

Purpose: To examine how circulating immune mediators in vivo may affect gene and protein expression at the RPE/choroid interface. Methods: Young mice were systemically infected with lymphocytic choriomeningitis virus (LCMV) or continuously infused with IFN-γ. RPE/choroid was isolated and analyzed with whole-transcriptome gene expression microarrays. Selected gene expression findings were validated at the protein level. Results: Both the systemic immune activation from virus infection and the sterile systemically increased level of IFN-γ resulted in increased expression of chemokine ligands, chemokine receptors, and early complement components in isolates of RPE/choroid. These findings were largely absent from LCMV-infected mice deficient in either the interferon α/ß receptor or IFN-γ. Conclusions: Together, these findings demonstrate that acute systemic immune activation results in a local response at the RPE/choroid interface that may include chemokine-dependent recruitment of inflammatory cells and engagement of the complement system. This may represent a link between the systemic low-grade inflammation and the retinal pathology observed in several multifactorial entities such as aging, AMD, and diabetes.

Bilateral diffuse uveal melanocytic proliferation: Case report and literature review.

Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare paraneoplastic intraocular disease that causes progressive visual loss in patients driven by an IgG factor associated with an underlying malignancy. Characteristic ocular findings include exudative retinal detachment, rapid cataract formation and uveal melanocytic tumours. The awareness and documentation of BDUMP has increased during the past decade, and the increasing amount of data collected demonstrates the effect of treatment with plasmapheresis and the value of diagnostic tools in BDUMP such as genetic and immunologic investigations. The literature of BDUMP has not been reviewed since 2003, and there is a growing need for an updated review on diagnosis and management of BDUMP. We review the literature and report a case of BDUMP with a white ciliary body tumour, iris rubeosis, increased iris pigmentation and cataract.

MicroRNA Expression Profile in Conjunctival Melanoma.

PURPOSE: Conjunctival melanoma (CM) is a rare disease associated with considerable mortality. As opposed to cutaneous melanoma, the epigenetic mechanisms involved in the development of CM and other mucosal melanomas (MMs) are unclear. The purpose of this study was to identify tumor-specific and prognostic microRNA (miRNA) in CM and to compare the miRNA profile with that of MM. METHODS: Using microarray analysis (Affymetrix) we determined the miRNA expression profile in 40 CMs compared with 7 normal conjunctival samples. Changes in miRNA expression were associated with T stage, local recurrence, metastasis, and mortality. Furthermore, the expression of six fresh frozen tissue samples of CM was compared with that of four laryngeal and sinonasal MM. RESULTS: Our analysis revealed 24 upregulated and 1 downregulated miRNA in CM; several of these miRNAs have key functions in the pathogenesis and progression of cutaneous melanoma. Additionally, we identified seven upregulated miRNAs specific for stage-T1 and stage-T2 CM, whose expression was associated with increased tumor thickness (P = 0.007), and two upregulated miRNAs (miR-3687 and miR-3916) associated with an increased risk of local recurrence. No stage T3-specific miRNAs were identified. CONCLUSIONS: We identified differentially expressed and potentially prognostic miRNAs in CM. Furthermore, the miRNA expression pattern of CM resembled that in MM. The identification of these differentially expressed miRNAs provides an entry point for future functional studies of miRNAs as prognostic or therapeutic targets in CM and highlights the resemblance between CM, MM, and cutaneous melanoma.

Mucosal malignant melanoma - a clinical, oncological, pathological and genetic survey.

Mucosal melanomas constitute 1.3% of all melanomas and they may develop in any mucosal membrane. Conjunctival melanomas (0.5/million/year) and melanomas in the sinonasal cavity (0.5/million/year) are the most common, followed by anorectal melanomas (0.4/million/year) and melanomas in the oral cavity (0.2/million/year). Anorectal melanoma occurs slightly more often in females, whereas oral melanoma has a male predilection. Mucosal melanoma most commonly develops in a patient's sixth or seventh decade of life, and no differences between races have been found except for sinonasal melanoma and conjunctival melanoma, which are very rare in Black people. The symptoms are not tumour-specific and are related to the organ system affected, and the disease is most often diagnosed at an advanced clinical stage. The diagnosis of a primary tumour is difficult, and metastatic cutaneous melanoma and choroidal melanoma must be excluded. Mutations in KIT are frequently found, while BRAF and NRAS mutations are rarely found - except in conjunctival melanomas that carry BRAF mutations. Mutations in the TERT promotor region are also found in mucosal melanomas. Complete surgical resection with free margins is the treatment of choice. The prognosis is poor, with the 5-year survival rate ranging from 0% (gastric melanoma) to 80% (conjunctival melanoma).

BRAF mutations in conjunctival melanoma: investigation of incidence, clinicopathological features, prognosis and paired premalignant lesions.

PURPOSE: To investigate incidence, clinicopathological features and prognosis of BRAF-mutated conjunctival melanoma in Denmark. Furthermore, to determine BRAF mutations in paired premalignant lesions and evaluate immunohistochemical BRAF V600E oncoprotein detection. METHODS: Data from 139 patients with conjunctival melanoma (1960-2012) were collected. Archived conjunctival melanoma samples and premalignant lesions were analysed for BRAF mutations using droplet digital polymerase chain reaction (PCR). Results were associated with clinicopathological features and compared with BRAF V600E oncoprotein stainings. RESULTS: The overall incidence of conjunctival melanoma (0.5 cases/1 000 000/year) increased during the study period with 0.13 cases/1 000 000/10 years. The increase comprised a higher proportion of patients aged >65 years, epibulbar tumours and tumours developed from a primary acquired melanosis with atypia. BRAF mutations were identified in 39 of 111 (35%) cases. The rate ratio of BRAF-mutated versus BRAF-wild-type melanoma did not change over time. BRAF mutations were associated with T1 stage (p = 0.007), young age (p = 0.001), male gender (p = 0.02), sun-exposed location (p = 0.01), mixed/non-pigmented tumour colour (p = 0.02) and nevus origin (p = 0.005), but did not associate with prognosis. BRAF status in conjunctival melanoma and paired premalignant lesions corresponded in 19 of 20 cases. Immunohistochemistry detected BRAF V600E mutations with a sensitivity of 0.94 and a specificity of 1.00 in newer conjunctival melanoma samples (2000-2012, n = 47). CONCLUSION: The incidence of conjunctival melanoma increased in Denmark over 50 years. The proportion of BRAF-mutated conjunctival melanoma was constant. BRAF mutations were identified as early events in conjunctival melanoma, associated with a distinct clinicopathological profile, similar to BRAF-mutated cutaneous melanoma. Immunohistochemical detection of BRAF can be used to assess BRAF V600E mutations.

Conjunctival Lymphoma--An International Multicenter Retrospective Study.

IMPORTANCE: To date, the clinical features of the various subtypes of conjunctival lymphoma (CL) have not been previously evaluated in a large cohort. OBJECTIVE: To characterize subtype-specific clinical features of CL and their effect on patient outcome. DESIGN, SETTING, AND PARTICIPANTS: A retrospective multicenter study was performed. Patient data were collected from January 1, 1980, through December 31, 2010. The dates of the analysis were May 15, 2015, to August 20, 2015. The median follow-up period was 43 months. Seven eye cancer centers were involved in the study. In total, 268 patients with CL were identified, 5 of whom were excluded because of missing clinical data. MAIN OUTCOMES AND MEASURES: Overall survival, disease-specific survival, and progression-free survival were the primary end points. RESULTS: Two hundred sixty-three patients with CL were included in the study. Their mean age was 61.3 years, and 55.1% (145 of 263) were female. All lymphomas were of B-cell type. The most frequent subtype was extranodal marginal zone lymphoma (EMZL) (68.4% [180 of 263]), followed by follicular lymphoma (FL) (16.3% [43 of 263]), mantle cell lymphoma (MCL) (6.8% [18 of 263]), and diffuse large B-cell lymphoma (DLBCL) (4.6% [12 of 263). Conjunctival lymphoma commonly manifested in elderly individuals (age range, 60-70 years old), with EMZL having a female predilection (57.8% [104 of 180]) and MCL having a marked male predominance (77.8% [14 of 18]). Unlike EMZL and FL, DLBCL and MCL were frequently secondary diseases (41.7% [5 of 12] and 88.9% [16 of 18], respectively), with MCL showing a frequent occurrence of stage IVE lymphoma (61.1% [11 of 18]) and bilateral manifestation (77.8% [14 of 18]). Localized disease (stage IE or IIE) was commonly treated with external beam radiation therapy (EBRT) with or without chemotherapy, while widespread lymphoma (stage IIIE or IVE) and MCL of any stage were managed with chemotherapy with or without EBRT. Diffuse large B-cell lymphoma and MCL had a poor prognosis, with 5-year disease-specific survival of 55.0% and 9.0%, respectively, in contrast to EMZL (97.0%) and FL (82.0%). Further survival predictors included age (EMZL), sex (FL), and Ann Arbor staging classification (EMZL and FL). The American Joint Committee on Cancer TNM staging showed limited prognostic usefulness, only being able to predict survival for patients with DLBCL. CONCLUSIONS AND RELEVANCE: Conjunctival lymphoma consists of mainly 4 subtypes of B-cell non-Hodgkin lymphoma: EMZL, FL, MCL, and DLBCL. Mantle cell lymphoma is characterized by a particularly high frequency of secondary disease of stage IVE and bilateral manifestation. The histological subtype is the main outcome predictor, with MCL and DLBCL having a markedly poorer prognosis than EMZL and FL.

Aquaporin-1 Expression in Retinal Pigment Epithelial Cells Overlying Retinal Drusen.

PURPOSE: In the outer retina, age-related macular degeneration (AMD) results in reduced hydraulic conductivity in Bruch's membrane, possibly leading to altered water transport in retinal pigment epithelial (RPE) cells. We hypothesize that RPE cells may express aquaporin-1 (AQP1) to compensate for these changes. Therefore, we wanted to investigate the expression of AQP1 in RPE cells of human eyes with age-related maculopathy (ARM) and AMD, and eyes with tumour-associated drusen. METHODS: Nine human eyes with ARM, 6 eyes with AMD and 9 eyes with choroidal malignant melanoma were examined for immunoreactivity to AQP1. AQP1 labelling in the RPE cells was evaluated for each drusen and grouped according to size and AQP1 labelling. AQP1 labelling in the RPE outside drusen was also evaluated. RESULTS: AQP1 labelling was observed in the apical membrane of the RPE cells situated above drusen in all three groups. There was a significant association between AQP1 labelling and drusen size (p < 0.001), and AQP1 labelling was more frequently observed in large drusen. CONCLUSION: AQP1 was expressed in RPE cells covering drusen but not in RPE cells outside drusen. We suggest that AQP1 expression is upregulated in the cell membranes of RPE cells above drusen in order to alleviate the increased need for fluid transport across the growing drusen.

Morphological features in eyes with endophthalmitis after cataract surgery - histopathology and optical coherence tomography assessment.

PURPOSE: To assess the ocular damage that occurs in eyes with postoperative endophthalmitis after cataract surgery (PE) based on optical coherence tomography (OCT) retinal scans of PE eyes and histological specimens of eyes removed due to PE. METHODS: Case-control study and case series. Fifty-one patients who had previously developed PE were clinically examined with OCT scans of the retina of both eyes. Histological specimens of 10 removed PE eyes were studied. RESULTS: The OCT scans showed that PE eyes had a statistically significantly higher frequency of hyperdense elements on the internal limiting membrane (ILM) of the retina (14 eyes versus 3 eyes, p = 0.015) and a higher degree of retinal atrophy temporal to the fovea (13 eyes versus 1 eye, p = 0.013) compared to fellow eyes. The histopathological analyses showed the formation of epiretinal membranes, derangement of all retinal layers with a reduced number of nuclei in the nuclear layers, loss of photoreceptor outer segments and massive retinal gliosis. CONCLUSIONS: Optical coherence tomography scans of the retina and histopathology analyses provide insights in the pathological process occurring in PE.

Comparative morphology of the snake spectacle using light and transmission electron microscopy.

OBJECTIVE: To determine the interspecific variation in the morphology of the snake spectacle. ANIMALS STUDIED: About 43 snakes of 14 different species, belonging to three different families: Boidae, Colubridae, and Pythonidae. PROCEDURE: The spectacles were examined by light and transmission electron microscopy. The thickness of the stromal layer was measured and the location of the blood vessels was noted. The shape of the transition zone located at the rim of the spectacle and the presence of pigment herein were also recorded. RESULTS: The spectacles of all species examined consisted of three layers. The outer epithelium was made of basal cells with overlaying keratin layers, the stroma comprised layers of organized collagen fibrils, and the inner epithelium was a layer of squamous cells with microvilli. Blood vessels were found in the stroma of all spectacles: in boas and pythons in the middle layers of the stroma and in colubrids adjacent to the inner epithelium. Boas and pythons were endowed with the thickest stromal layers (81-132 µm) compared to colubrids (9-95 µm). Boas and pythons had a convex transition zone, while the transition zone of the colubrids exhibited a steady increase in spectacle thickness toward the hinge region. The transition zone contained pigment in boas and pythons. CONCLUSION: The overall morphology of the spectacle was similar among the major families of snakes. However, the location of blood vessels and appearance of transition zone differed, as did the overall thickness of the spectacle.

Proteomic Analysis of the Vitreous following Experimental Retinal Detachment in Rabbits.

Purpose. The pathogenesis of rhegmatogenous retinal detachment (RRD) remains incompletely understood, with no clinically effective treatment for potentially severe complications such as photoreceptor cell death and proliferative vitreoretinopathy. Here we investigate the protein profile of the vitreous following experimental retinal detachment using a comparative proteomic based approach. Materials and Methods. Retinal detachment was created in the right eyes of six New Zealand red pigmented rabbits. Sham surgery was undertaken in five other rabbits that were used as controls. After seven days the eyes were enucleated and the vitreous was removed. The vitreous samples were evaluated with two-dimensional polyacrylamide gel electrophoresis and the differentially expressed proteins were identified with tandem mass spectrometry. Results. Ten protein spots were found to be at least twofold differentially expressed when comparing the vitreous samples of the sham and retinal detachment surgery groups. Protein spots that were upregulated in the vitreous following retinal detachment were identified as albumin fragments, and those downregulated were found to be peroxiredoxin 2, collagen-Iα1 fragment, and α-1-antiproteinase F. Conclusions. Proteomic investigation of the rabbit vitreous has identified a set of proteins that help further our understanding of the pathogenesis of rhegmatogenous retinal detachment and its complications.

Breast carcinoma metastasis to the lacrimal gland: Two case reports.

A 77-year-old female, with proptosis, reduced eye motility and diplopia which had developed over two to three months and a 69-year-old female with proptosis, oedema of the eyelid, reduced motility and ptosis, which had developed over three weeks, are presented in the present study. Computed tomography scans revealed irregular lacrimal gland tumours in the two patients. The two patients had history of breast cancer. The first breast cancer metastasis in the lacrimal gland demonstrated a cribriform growth pattern containing ductal elements. The epithelial tumour cells stained positive for cytokeratin (1-8, 10, 14-16, 18 and 19), oestrogen receptor, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA) and gross cystic disease fluid protein 15 (GCDFP-15). The second metastatic tumour was positive for EMA and estrogen receptor, but variably positive for CEA and GCDFP-15. The metastasis in the lacrimal gland was a pleomorphic tumour. The tumour cells were positive for EMA and variably positive for oestrogen and CEA. Metastases to the lacrimal gland are extremely rare, and metastases to the lacrimal gland should be considered in the diagnoses of lacrimal gland tumours. The present study aimed to describe two such cases and draw attention to breast carcinomas as a differential diagnosis and the most frequent cause of lacrimal gland metastasis.

Long term follow-up of persistent choroidal folds and hyperopic shift after complete removal of a retrobulbar mass.

BACKGROUND: Hyperopic shift and chorioretinal folds are common findings with intraorbital masses compressing the posterior pole of the globe. These signs usually regress after complete tumour excision. To the best of our knowledge this is the first reported case, where optical coherence tomography was used to document persistent chorioretinal folds after complete excision of a retrobulbar mass. CASE PRESENTATION: A 47-year-old Caucasian woman was referred to our department with long-documented hyperopic shift and gradually decreasing vision in her left eye. Optical coherence tomography showed chorioretinal folds. Magnetic resonance imaging revealed a retrobulbar mass which caused flattening of the posterior pole of the globe. The tumour was successfully removed, and was confirmed to be a cavernous haemangioma on histological assessment. 3 years after surgery the patient still has a similar amount of hyperopia and chorioretinal folds. CONCLUSION: Choroidal folds and hyperopic shift may persist after complete tumour removal. Long term follow-up is advised to rule out recurrence of the intraorbital mass.

A Retrospective Review of Conjunctival Melanoma Presentation, Treatment, and Outcome and an Investigation of Features Associated With BRAF Mutations.

IMPORTANCE: Large studies investigating clinical presentation and treatment in primary conjunctival melanoma (CM) are rare. Clinicopathological characteristics of BRAF-mutated CM have not been studied thoroughly. OBJECTIVES: To determine the associations of clinicopathological tumor features and treatment with local recurrence, metastasis, and mortality and to determine the association of BRAF mutations with these features. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study at the Eye Pathology Institute, Copenhagen, Denmark. Participants included 139 patients with primary CM in Denmark from January 1, 1960, to December 31, 2012. For BRAF analysis, all patients with available formalin-fixed, paraffin-embedded tumor samples from January 1, 1994, to December 31, 2012, were included. MAIN OUTCOMES AND MEASURES: BRAF mutations, local recurrence, regional and distant metastasis, melanoma-related mortality, and all-cause mortality were examined. RESULTS: A poor prognosis of tumors involving the extrabulbar conjunctiva and adjacent tissue structures was confirmed in multivariable Cox proportional hazards regression models. Patients undergoing incisional biopsy more frequently developed metastasis (hazard ratio [HR], 2.46; 95% CI, 1.08-5.58; P = .03). Excision without adjuvant treatment was associated with local recurrence (HR, 1.97; 95% CI, 0.11-3.48; P = .02), metastatic disease (HR, 2.51; 95% CI, 1.07-5.91; P = .03), and all-cause mortality (HR, 1.80; 95% CI, 1.05-3.08; P = .03). BRAF mutations were identified in 19 of 47 primary CMs (40.4%) and were more frequent in younger patients (P = .005), less frequent in the extrabulbar conjunctiva (P = .05), more frequently classified as T1 tumors (P = .03), and rarely manifested with primary acquired melanosis (P = .001) or with a uniformly pigmented lesion (P = .006). Distant metastases developed in 6 of 19 BRAF-mutated CMs (31.6%) as opposed to 1 of 28 BRAF wild-type CMs (3.6%). No definitive association with distant metastasis was seen in multivariable Cox proportional hazards regression models. CONCLUSIONS AND RELEVANCE: Incisional biopsy and excision without adjuvant therapy were associated with a poor outcome in patients with CM. Extrabulbar location was also associated with a poor outcome in multivariable analysis. BRAF-mutated CMs were frequent in younger patients and were rare in tumors involving the extrabulbar conjunctiva. Despite a more favorable location, BRAF-mutated tumors may be associated with more frequent distant metastasis.

Morphologic differences observed by scanning electron microscopy according to the reason for pseudophakic IOL explantation.

PURPOSE: To compare variations in surface morphology, as studied by scanning electron microscopy (SEM), of explanted intraocular lenses (IOLs) concerning the cause leading to the explantation surgery. METHODS: In this prospective multicenter study, explanted IOLs were analyzed by SEM and energy-dispersive X-ray spectroscopy. The IOLs were explanted in the centers of the research group from 2006 to 2012. The primary procedure was phacoemulsification in all cases. RESULTS: The study evaluated 40 IOLs. The main causes for explantation were IOL dislocation, refractive error, and IOL opacification. Those explanted due to dislocation demonstrated calcifications in 8 lenses (50%), salt precipitates in 6 cases (37.5%), and erythrocytes and fibrosis/fibroblasts in 2 cases (12.5%). In the refractive error cases, the SEM showed proteins in 5 cases (45.5%) and salt precipitates in 4 lenses (36.4%). In IOL opacification, the findings were calcifications in 2 of the 3 lenses (66.6%) and proteins in 2 lenses (66.6%). CONCLUSIONS: A marked variation in surface changes was observed by SEM. Findings did not correlate with cause for explantation. Scanning electron microscopy is a useful tool that provides exclusive information regarding the IOL biotolerance and its interactions with surrounding tissues.

Malignant lymphoma of the conjunctiva.

Conjunctival lymphomas constitute 25% of all ocular adnexal lymphomas. The majority are B-cell non-Hodgkin lymphomas (NHLs) (98%), whereas conjunctival T-cell NHLs are rare (2%). The most frequent subtype of conjunctival B-cell lymphoma is extranodal marginal zone lymphoma (EMZL; 81%), followed by follicular lymphoma (8%), diffuse large B-cell lymphoma (3%), and mantle cell lymphoma (3%). Extranodal marginal zone lymphoma occurs slightly more often in women and, along with follicular lymphoma, presents late in the seventh decade of life, whereas diffuse large B-cell lymphoma and especially mantle cell lymphoma have a predilection for the male gender and typically present in the eighth decade. Extranodal marginal zone lymphoma and follicular lymphoma present most frequently in the forniceal and bulbar conjunctiva. Conjunctival diffuse large B-cell lymphoma, mantle cell lymphoma and T-cell NHLs are characterized by a short duration of symptoms before the first ophthalmologic consultation. External beam radiotherapy is the treatment of choice for extranodal marginal zone lymphoma and follicular lymphoma, whereas diffuse large B-cell lymphoma, mantle cell lymphoma, and T-cell NHLs are mainly treated with chemotherapy. Conjunctival T-cell NHLs are associated with a particularly poor prognosis, with 50% of patients having progression or recurrence during a 1-year follow-up period.

Squamous cell dysplasia and carcinoma of the conjunctiva. A nationwide, retrospective, epidemiological study of Danish patients.

PURPOSE: To investigate the epidemiology of squamous cell dysplasia and carcinoma of the conjunctiva in Denmark. METHODS: Review of the histopathological case reports at the Eye Pathology Institute (EPI), University of Copenhagen, and the National Danish Pathology Bank from 1980 to 2011. Information regarding distribution of age and sex, localization, earlier pathology, comorbidity and recurrence of the condition was registered. The Cause of Death Registry at Statens Serum Institut was used to obtain information regarding cause of death. RESULTS: A total of 143 cases were identified. Ninety-five (61%) had epithelial dysplasia, 19 (13%) had carcinoma in situ, and 29 (20%) had squamous cell carcinoma. A significantly higher proportion of men were found. The median age at diagnosis was 65 years. The risk of recurrence was 10.0% [95% confidence interval (CI): 5.0-15.0] after 1 year and 17.2% (95% CI: 10.8-23.7) after 5 years. The lesions were most often localized to the corneal limbus. In our records, one patient had a lymph node metastasis and the disease necessitated enucleation in two patients. No patients had died from squamous cell carcinoma of the conjunctiva. CONCLUSION: Overall, our data are in agreement with the results of previous studies in Northern, high-latitude countries. There is a low incidence rate; the lesions are predominantly seen in men in their seventh decade and localized to the corneal limbus. The risk of recurrence is high, and the benign lesions have potential to progress to frank carcinoma.

Ocular adnexal diffuse large B-cell lymphoma: a multicenter international study.

IMPORTANCE: The clinical features of diffuse large B-cell lymphoma (DLBCL) subtype of ocular adnexal lymphoma have not previously been evaluated in a large cohort to our knowledge. OBJECTIVE: To investigate the clinical features of ocular adnexal DLBCL (OA-DLBCL). DESIGN, SETTING, AND PARTICIPANTS: This retrospective international cooperative study involved 6 eye cancer centers. During 30 years, 106 patients with OA-DLBCL were identified, and 6 were excluded from the study. The median follow-up period was 52 months. MAIN OUTCOMES AND MEASURES: Overall survival, disease-specific survival (DSS), and progression-free survival were the primary end points. RESULTS: One hundred patients with OA-DLBCL were included in the study (median age, 70 years), of whom 54 (54.0%) were female. The following 3 groups of patients with lymphoma could be identified: primary OA-DLBCL (57.0%), OA-DLBCL and concurrent systemic lymphoma (29.0%), and ocular adnexal lymphoma relapse of previous systemic lymphoma (14.0%). Of 57 patients with primary OA-DLBCL, 53 (93.0%) had Ann Arbor stage IE disease, and 4 (7.0%) had Ann Arbor stage IIE disease. According to the TNM staging system, 43 of 57 (75.4%) had T2 tumors. Among all patients, the most frequent treatments were external beam radiation therapy with or without surgery (31.0%) and rituximab-cyclophosphamide, hydroxydaunorubicin, vincristine sulfate, prednisone (CHOP) or rituximab-CHOP-like chemotherapy with or without external beam radiation therapy (21.0%). The 5-year overall survival among the entire cohort was 36.0% (median, 3.5 years; 95% CI, 2.5-4.5 years). Relapse occurred in 43.9% (25 of 57) of patients with primary OA-DLBCL. Increasing T category of the TNM staging system was predictive of DSS (P = .04) in primary OA-DLBCL, whereas the Ann Arbor staging system was not. However, when taking all 100 patients into account, Ann Arbor stage was able to predict DSS (P = .01). Women had a longer median DSS than men (9.8 years; 95% CI, 1.9-17.7 years vs 3.3 years; 95% CI, 1.6-5.0; P = .03). CONCLUSIONS AND RELEVANCE: Most patients with primary OA-DLBCL were seen with Ann Arbor stage IE and TNM T2 disease. The 5-year overall survival was between 2.5 and 4.5 years, which is the 95% CI around the median of 3.5 years in this cohort. Increasing T category appears to be associated with decreased DSS among patients with primary OA-DLBCL. When taking all patients into account, sex and Ann Arbor stage also seem to be DSS predictors.

Follicular lymphoma of the ocular adnexal region: a nation-based study.

PURPOSE: To characterize the clinicopathological features of follicular lymphoma of the ocular adnexal region. METHODS: Retrospective nation-based study of Danish patients with ocular adnexal follicular lymphoma from January 1st 1980 through December 31st 2009. RESULTS: Twenty-four patients with ocular adnexal follicular lymphoma were identified. Fourteen (58%) of the patients were females. The median age was 63 years (range: 42-96 years). Eleven (46%) of the patients had primary ocular adnexal lymphoma, seven (29%) had an ocular adnexal lesion in conjunction with a concurrent systemic lymphoma and six patients (25%) presented with an ocular adnexal relapse. The most frequently affected sites were the lacrimal gland (38%) and the orbit (33%). Thirteen patients (54%) presented with Ann Arbor stage IE lymphoma, four (17%) had stage IIE, two patients (8%) stage IIIE, and five patients (21%) had stage IV lymphoma. Radiotherapy was primarily used in patients with primary lymphoma and those with a stage IE/IIE relapse (82%), while stage IIIE/IV lymphomas most frequently received alkylating chemotherapy (67%). Complete remission was observed in 19 of the patients (79%), but of these 11(58%) had a relapse. The 10-year overall survival for the entire cohort was 59%. The translocation t(14;18) was detected in 16 patients (16/24, 76%). Recurrence was only observed in patients with the t(14;18) (p=0.05, log-rank). CONCLUSIONS: Ocular adnexal follicular lymphoma is more commonly found in elderly female patients. The lacrimal gland is relatively frequently involved. Radiotherapy is the treatment of choice for localized ocular adnexal follicular lymphoma providing a favourable prognosis for majority of patients.

Genetic analysis of an orbital metastasis from a primary hepatic neuroendocrine carcinoma.

A 71-year-old female with a known history of primary hepatic neuroendocrine carcinoma, presented with a visual defect, proptosis and restricted eye movements of the right eye. Biopsies from the orbit and from the primary hepatic neuroendocrine carcinoma showed similar morphological and immunohistochemical features, and high-resolution, array-based comparative genomic hybridization demonstrated loss of one copy each of chromosomes 3 and 18, and gain of 1q both in the primary hepatic neuroendocrine carcinoma and in the orbital tumour. The orbital mass was diagnosed as a metastasis from the primary hepatic neuroendocrine carcinoma. Primary hepatic neuroendocrine tumours are extremely rare, and the orbit is an extremely rare location for a neuroendocrine carcinoma metastasis. This is the first reported case of an orbital metastasis with origin from a primary hepatic neuroendocrine carcinoma.