Specific location of ocular adnexal lymphoma and mortality: an international multicentre retrospective study.

AIMS: To examine whether the specific location of ocular adnexal lymphoma (OAL) and the American Joint Committee on Cancer (AJCC) TNM tumour stage are prognostic factors for mortality in the main OAL subtypes. METHODS: Clinical and survival data were retrospectively collected from seven international eye cancer centres. All patients from 1980 to 2017 with histologically verified primary or secondary OAL were included. Cox regression was used to compare the ocular adnexal tumour locations on all-cause mortality and disease-specific mortality. RESULTS: OAL was identified in 1168 patients. The most frequent lymphoma subtypes were extranodal marginal zone B-cell lymphoma (EMZL) (n=688, 59%); follicular lymphoma (FL) (n=150, 13%); diffuse large B-cell lymphoma (DLBCL) (n=131, 11%); and mantle cell lymphoma (MCL) (n=89, 8%). AJCC/TNM tumour-stage (T-stage) was significantly associated with disease-specific mortality in primary ocular adnexal EMZL and increased through T-categories from T1 to T3 disease. No associations between AJCC/TNM T-stage and mortality were found in primary ocular adnexal FL, DLBCL, or MCL. EMZL located in the eyelid had a significantly increased disease-specific mortality compared with orbital and conjunctival EMZL, in both primary EMZL and the full EMZL cohort. In DLBCL, eyelid location had a significantly higher disease-specific mortality compared with an orbital or lacrimal gland location. CONCLUSION: Disease-specific mortality is associated with AJCC/TNM T-stage in primary ocular adnexal EMZL patients. Lymphoma of the eyelid has the highest disease-specific mortality in primary EMZL, and in the full cohort of EMZL and DLBCL patients.

Thyroid Eye Disease.

Thyroid eye disease, although rare, is the most common inflammatory orbital disorder and is associated with autoimmune thyroid dysfunction. It is a progressive disorder with symptoms and signs that may cause significant facial disfigurement, visual disability, but rarely blindness. We will review the diagnostic criteria, immunologic basis, clinical course, and medical and surgical treatments for thyroid eye disease. Recent developments in the use of biologic agents to treat this disorder appear to be changing its progression curve and offer the first specific and preventative therapeutic options.

Lymphoma of the Lacrimal Gland - An International Multicenter Retrospective Study.

PURPOSE: To characterize the clinical features of subtype-specific lacrimal gland lymphoma and their effect on patient survival. DESIGN: Multicenter retrospective interventional case series. METHODS: Patient data were collected from 6 international eye cancer centers from January 1, 1980, through December 31, 2017. All patients with histologically verified primary or secondary lymphoma of the lacrimal gland were included. Primary endpoints were overall survival (OS) and disease-specific survival (DSS). RESULTS: A total of 260 patients with lacrimal gland lymphoma were identified. The median age was 58 years and 52% of patients were men. Non-Hodgkin B-cell lymphomas constituted 99% (n = 258) and T-cell lymphomas constituted 1% (n = 2). The most frequent lymphoma subtypes were extranodal marginal zone B-cell lymphoma (EMZL) (n = 177, 68%), follicular lymphoma (FL) (n = 26, 10%), diffuse large B-cell lymphoma (DLBCL) (n = 25, 10%), and mantle cell lymphoma (MCL) (n = 17, 7%). Low-grade lymphomas (EMZL and FL) were most commonly treated with external beam radiotherapy (EBRT), whereas high-grade lymphomas (DLBCL and MCL) were treated with chemotherapy in combination with rituximab and/or EBRT. The prognosis was relatively good with a 5-year OS and DSS of 73.8% and 87.5%, respectively. Lymphoma subtype was a statistically significant predictor for DSS, with EMZL (5-year DSS: 93.4%) having the best prognosis and DLBCL (5-year DSS: 52.6%) having the poorest. CONCLUSIONS: This is the largest reported collection of data of subtype-specific lacrimal gland lymphoma. The subtype distribution of lacrimal gland lymphoma resembles that of the ocular adnexa. Prognosis is good and the histologic subtype is a significant predictor for disease-specific survival.

Immunotherapy With Programmed Cell Death 1 Inhibitors for 5 Patients With Conjunctival Melanoma.

Importance: Conjunctival melanoma has the potential for regional lymphatic and distant metastasis. There is an urgent need for effective treatment for patients with metastatic or locally advanced conjunctival melanoma. Objective: To describe the use of immune checkpoint inhibitors for the treatment of conjunctival melanoma in 5 adult patients. Design, Setting, and Participants: A retrospective review was conducted of the medical records of 5 patients with conjunctival melanoma who were treated with immune checkpoint inhibitors from March 6, 2013, to July 7, 2017. Main Outcomes and Measures: Response to treatment and disease-free survival. Results: Of the 5 patients (4 women and 1 man) with metastatic conjunctival melanoma, 4 were treated with a programmed cell death 1 (PD-1) inhibitor, nivolumab, and had a complete response to treatment with no evidence of disease at 1, 7, 9, and 36 months after completing treatment. One patient with metastatic conjunctival melanoma was treated with another PD-1 inhibitor, pembrolizumab, and had stable metastases during the first 6 months of treatment. Later disease progression resulted in treatment cessation after 11 months and switching to another therapy. Two patients treated with nivolumab developed autoimmune colitis that necessitated stopping the immunotherapy; these patients subsequently were managed with systemic corticosteroids or infliximab. Conclusions and Relevance: This case series report suggests that anti-PD-1 therapy can be used to treat metastatic conjunctival melanoma. Longer follow-up is needed to determine the long-term disease-free survival. Future studies might assess the potential for immune checkpoint inhibitors to obviate the need for orbital exenteration in selected patients with locally advanced disease.

Radiographic Course of Medically Managed Pediatric Orbital Subperiosteal Abscesses.

PURPOSE: To describe the natural radiographic course of subperiosteal orbital abscesses that were managed medically in pediatric patients. METHODS: A retrospective case review was undertaken at Children's Mercy Hospitals and Clinics of Kansas City, Missouri. All patients admitted to the hospital and diagnosed as having orbital cellulitis or subperiosteal abscess from 2008 to 2017 were included in the study. Of the 418 patients identified, 15 patients had repeat imaging and did not undergo surgery prior to the second scan. The initial size of the empyema, size of the empyema on repeat imaging, and clinical course were recorded for each patient. RESULTS: The size of the empyemas increased 240% on average in the first 2 to 3 days. Imaging up to 11 days after the diagnosis showed that 9 cases persisted; meanwhile, 4 cases had radiographic resolution, with the earliest by 21 days. Two cases recurred months later. The largest increase in size was 500% over 3 days, but the initial empyema was only 0.3 cm3. CONCLUSIONS: This review describes the natural history of radiographically reimaged subperiosteal empyema. Empyema size will increase for a few days prior to a gradual resolution in 1 to 3 weeks. An ultimate resolution of radiographic evidence of an empyema takes up to 21 days. This information will help guide clinical management and decision making in caring for patients with pediatric orbital cellulitis with subperiosteal empyema. [J Pediatr Ophthalmol Strabismus. 2018;55(6):387-392.].

Thermal imaging of corneal transplant rejection.

PURPOSE: Corneal transplant rejection is one of the most frequent complications, with a reported incidence of 16-30%. In our current research, we investigated the use of infrared thermography to detect ocular surface temperature. We also looked at a case of corneal transplant rejection and this case had an elevated ocular surface temperature when compared to the contralateral eye and other eyes without corneal transplant rejection. METHODS: Twenty-three eyes of twelve patients would serve as control to one eye with clinically evident corneal transplant graft rejection. A Flir T400 320 × 240 pixel, digital thermal camera was used to take a digital photograph and an infrared photograph of each eye. The images were analyzed with the Flir web viewer. RESULTS: We present here a case of corneal transplant rejection documented with both slit lamp photos as well as infrared and corneal surface photos. The studied patient's unaffected eye, and the control group's trends did indeed bring the expected results and proved thermal imagery in this particular field a viable examination method. CONCLUSIONS: We feel that ocular thermography is a useful adjunctive diagnostic tool and that it may be useful to monitor routine corneal transplant patients. Further research into the temperature changes of corneal transplant patients is needed and may allow for earlier intervention for graft rejection.

Lacrimal intubation during dacryocystorhinostomy utilizing the STENTube.

The traditional use of the Crawford tube for lacrimal intubation during dacryocystorhinostomy (DCR) carries several drawbacks. We describe the use of the STENTube for DCR intubation and detail its advantages. Retrospective, noncomparative, interventional case series; 313 patients with nasolacrimal duct obstruction (NLDO) underwent 339 DCRs (216 external, 123 endonasal) with the STENTube from January 2007 - June 2013 by 5 surgeons (RS, QN, TS, SB, TN) across 3 institutions (SUNY Downstate Medical Center, Texas Oculoplastics Consultants, and Moorfields Eye Hospital). Study outcome measures included patient demographics, surgical complications, and epiphora improvement/resolution. 206 (66%) females and 107 (34%) males had a mean age of 63 years (range 2-94 years). Distribution of diagnoses included: 314 complete idiopathic acquired NLDO, 20 partial idiopathic acquired NLDO, and 5 congenital complete NLDO. 316 (93%) were primary DCRs and 23 (7%) were revisions. Epiphora improved in 312 (92%) cases with 294 (86%) experiencing resolution with patent lacrimal irrigation at a mean last follow-up of 9.4 months. Twenty-eight (8%) patients experienced surgical complications with 16 (5%) experiencing tube prolapse, and 20 (6%) requiring re-operation. The STENTube represents a simple method for lacrimal intubation during external or endonasal DCR at a comparable cost to the Crawford tube. It allows for low prolapse rates without the need for additional endonasal fixation procedures, resulting in a simple and comfortable post-operative extraction without risk of lacrimal trauma. The STENTube is our preferred intubation technique during DCR, and should be considered by oculofacial surgeons performing DCR with intubation.

Mutational landscape of lacrimal gland carcinomas and implications for treatment.

BACKGROUND: Lacrimal gland carcinomas are rare. Identification of molecular abnormalities underlying lacrimal gland carcinogenesis is critical to the development of new targeted therapies for lacrimal gland carcinomas. The purpose of our study was to look for mutations that can be targeted as new treatments for lacrimal gland carcinomas. METHODS: Genomic DNA from patients with lacrimal gland epithelial neoplasms was analyzed. The Sequenom matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass ARRAY platform was used to profile 168 common oncogenic point mutations in 40 genes. Mutation frequency was assessed overall and by histologic diagnosis. These genetic mutations were then correlated with clinical outcomes in the patients. RESULTS: The study included 14 men and 10 women with a median age of 45 years (range, 17-75 years). The histologic diagnoses were as follows: adenoid cystic carcinoma (n = 16), low-grade carcinoma ex pleomorphic adenoma (n = 2), high-grade carcinoma ex pleomorphic adenoma (n = 2), squamous carcinoma (n = 1), and pleomorphic adenoma (n = 3). Analysis revealed 18 oncogenic mutations in 13 patients: KRAS mutations in 10 patients (46%), NRAS mutations in 2 patients (8%), MET mutations in 3 patients (13%), PIK3CA mutation in 1 patient (4%), and BRAF mutation in no patients. About half of the patients with adenoid cystic carcinoma had oncogenic mutations (7 of 16; 44%). Of the 16 patients with adenoid cystic carcinoma, 5 had KRAS mutations, 1 had MET mutations, and 1 had an NRAS mutation. CONCLUSION: KRAS, NRAS, and MET mutations are frequent in epithelial neoplasms of the lacrimal gland, with the highest rate of mutations found in adenoid cystic carcinoma. Therapies targeting these genes may be effective treatments for lacrimal gland carcinomas. © 2015 Wiley Periodicals, Head Neck 38: E-E, 2016.

Treatment Challenges with Benign Bone Tumors of the Orbit.

Benign mesenchymal tumors of the craniofacial complex present unique challenges for orbital surgeons because of their potential for orbital compartment syndrome, ocular morbidity, and facial disfigurement and because definitive surgical management may be associated with significant morbidity. While the precise classification of such lesions depends on radiologic as well as histologic evaluations and remains controversial, benign tumors involving the bony walls of the orbit share features of bony expansion, facial deformity, and the potential to cause significant orbital and ophthalmic morbidity. We herein present 2 cases of benign mesenchymal tumors with bony involvement in the orbitofacial region (1 juvenile ossifying fibroma and 1 central giant cell granuloma) and review the current management of similar benign fibro-osseous and reactive bone lesions of the orbit. These rare entities presented share common orbital and ophthalmic manifestations and remain without any effective definitive treatment options.

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.

Ophthalmic complications of targeted cancer therapy and recently recognized ophthalmic complications of traditional chemotherapy.

As our understanding of cancer pathophysiology has increased, so have the number of targeted therapeutic agents available. By targeting specific molecules involved in tumorigenesis, targeted therapeutic agents offer the potential for significant efficacy against tumor cells while minimizing the adverse effects. We highlight the recently recognized ophthalmic complications of targeted cancer therapy, as well as recently recognized complications of traditional chemotherapeutic agents.

Merkel cell carcinoma of the eyelid and periocular region.

Merkel cell carcinoma (MCC) in the eyelid and periocular region can be treated surgically, in most cases, with preservation of the eye and reasonable visual function. Adjuvant radiation therapy, sentinel lymph node biopsy, and chemotherapy should be considered for MCC of the eyelid and periocular region, especially for larger tumors that are T2b or more advanced and lesions that present with regional nodal or distant metastasis.

Correlation of American Joint Committee on Cancer T category for eyelid carcinoma with outcomes in patients with periocular Merkel cell carcinoma.

PURPOSE: Merkel cell carcinoma is a rare but potentially deadly cancer of the eyelid. To date, no studies have reported on clinical parameters at initial presentation of the eyelid tumor that may correlate with disease-free survival (DFS). The purpose of this study was to determine whether the American Joint Committee on Cancer (AJCC) T category for eyelid carcinoma correlates with metastasis and DFS in patients with Merkel cell carcinoma of the periocular region. METHODS: This is a retrospective cohort study from a tertiary referral cancer center. All consecutive patients treated for eyelid or periocular Merkel cell carcinoma between November 1, 1998, and November 1, 2012, were reviewed. The main outcome measures included AJCC T category for eyelid carcinoma and Merkel cell carcinoma at presentation, nodal metastasis at presentation, metastasis during follow up, and DFS. RESULTS: The study included 18 patients, 7 men and 11 women, with median age of 68.5 years. The AJCC T categories for both eyelid carcinoma and Merkel cell carcinoma were significantly correlated with DFS. Using the T categories for eyelid carcinoma, when TX and T2a were grouped into a single category and T2b and T3a into another category, the estimated DFS rate at 3 years was 100% for patients with TX or T2a lesions and 57% for patients with T2b or T3a lesions (p=0.0298). Four patients (22%) had lymph node metastasis at presentation. Presence of lymph node metastasis at presentation was the strongest single predictor of shorter DFS and an increased risk of metastasis during follow up (p=0.0222). CONCLUSIONS: The AJCC eyelid carcinoma T at presentation correlates with DFS in patients with Merkel cell carcinoma of the periocular region. The DFS rate at 3 years was significantly worse for patients with T2b or more extensive tumors by eyelid carcinoma T category. Presence of lymph node metastasis at presentation was predictive of shorter DFS and an increased risk of metastasis during follow up.

Ocular adnexal lymphoma: validation of American Joint Committee on Cancer seventh edition staging guidelines.

BACKGROUND/AIMS: To validate the prognostic significance of the American Joint Committee on Cancer (AJCC) seventh edition staging criteria for ocular adnexal lymphoma (OAL) of all histologic subtypes. METHODS: Retrospective review of clinical records for all consecutive patients with OAL treated from November 1998 to December 2012. RESULTS: 130 patients were evaluated, 82 with primary and 34 with secondary OAL. Fourteen patients were excluded due to incomplete records. 71 women (61.2%) and 45 men (38.8%) had a median age of 61.5 years. Patients were followed for a median of 32.5 months. Treatment varied, in part, related to lymphoma histologic subtype. Overall, there were 17 recurrences (8 local and 9 distant) in patients with primary OAL. For primary OAL, the 5-year disease-free survival (DFS) and overall survival (OS) rates were 55.9% and 85.8%, respectively. For primary OAL, while there was a trend towards decreased 5-year DFS for more aggressive subtypes, this was not statistically significant. More advanced Ann Arbor stage was associated with decreased 5-year DFS; however, this trend was not statistically significant. However, increased AJCC seventh edition T category was associated with decreased 5-year DFS (T1=67.8%, T2=59.2%, T3=28.6%, T4=33.3%; p=0.025). CONCLUSION: AJCC seventh edition T category was predictive of DFS in patients with OAL.

Primary orbital melanoma in association with cellular blue nevus.

PURPOSE: To describe 3 cases of primary orbital melanoma associated with either known or subsequently discovered cellular blue nevus. METHODS: The clinical records and surgical specimens of 3 patients who underwent orbital exenteration for primary orbital melanoma and who had a cellular blue nevus diagnosed before or after detection of the melanoma were retrospectively reviewed. RESULTS: All 3 patients presented with signs and symptoms of an orbital mass. Subsequent biopsy revealed invasive melanoma. One patient had a known history of congenital cellular blue nevus of the eyelid from which the orbital melanoma originated. The other 2 patients had no known history of cutaneous pigmentation or blue nevus. In these 2 patients, the cellular blue nevus was detected on pathologic review of the orbital exenteration specimen (1 patient) or surgical biopsy specimen (1 patient). All 3 patients underwent total body positron emission tomography/computed tomography, and in all 3 results were negative for other sites of disease involvement. In the 2 patients without a previously known nevus a total body skin check was negative for other primary melanoma lesions. All 3 patients underwent orbital exenteration followed by postoperative radiation therapy. CONCLUSIONS: Thorough evaluation of biopsy specimens of "primary" orbital melanoma is warranted to ensure identification of any associated blue nevus because blue nevi are precursor lesions for orbital melanoma, and the presence of a blue nevus would support a primary orbital melanoma rather than a metastatic lesion. Patients with a known blue nevus of the periocular skin and ocular adnexa should be monitored closely for signs of malignant transformation.

Small-incision, sutureless repair of subconjunctival fat prolapse.

PURPOSE: To present a new, small-incision, sutureless surgical technique for the repair of subconjunctival fat prolapse. METHODS: This is a retrospective interventional case series. Four eyes of 3 patients who presented with prolapsed subconjunctival fat were surgically repaired using a small-incision, sutureless technique with fibrin glue. No prolapsed subconjunctival fat was excised. RESULTS: The surgical treatment of prolapsed subconjunctival fat using a small-incision, sutureless technique with fibrin glue was successful in all 4 eyes. There have been no cases of recurrence of the prolapsed subconjunctival fat with a mean follow up of 31 months. CONCLUSIONS: Small-incision, sutureless repositioning of subconjunctival fat using fibrin glue is an effective new surgical technique for the management of prolapsed subconjunctival fat.