Carcinoid Tumors of the Orbit and Ocular Adnexa.

PURPOSE: Well-differentiated neuroendocrine or carcinoid tumors are found most commonly in the gastrointestinal tract. When metastatic to the orbit, they tend to have a propensity for the extraocular muscles. The purpose of this study was to better understand the diversity in presentation of orbital carcinoid disease and to determine predictors for survival. METHODS: In this observational cross-sectional cohort study, data from 8 tertiary orbital practices were compiled. Demographic, clinical, pathologic, American Joint Committee on Cancer stage and grade, imaging, and management data were extracted for all the patients. Descriptive statistics were calculated. Subgroups were compared utilizing analysis of variance analyses and Kaplan-Meier curves. Time to progression and disease-specific and overall mortality were calculated. Comparisons were performed for the following a priori pairs: unknown versus known primary tumor, single versus multiple extraocular muscle involvement, unilateral versus bilateral orbital disease, extraocular muscle versus other orbital involvement, and excisional versus incisional surgery. RESULTS: A total of 28 patients with carcinoid tumors of the orbit were identified. Of these, 57.1% of patients were female, the mean age at diagnosis of the primary tumor was 58.8 years and the mean age at diagnosis of orbital disease was 62.6 years. At primary presentation, all patients were American Joint Committee on Cancer stage III or IV and 21.4% demonstrated carcinoid syndrome. Muscle involvement was noted in 78.6% of patients, and of these, 72% were noted to have single muscle disease. Eight patients had no primary tumor identified; 3 of these 8 demonstrated disseminated disease at the time of diagnosis. The overall 5-year survival rate was 81.8% from diagnosis of primary tumor and 50% from diagnosis of orbital disease. Subgroup analysis revealed that patients with unilateral orbital disease when compared with bilateral orbital disease had a longer progression-free survival and time to death from all causes (p = 0.025). Patients with disease localized to the orbit at presentation had longer time to death than those with disseminated disease. Treatment with surgery, radiation, or octreotide did not appear to affect survival. Patients managed with systemic chemotherapy had a shorter time of survival than the rest of the group. All other subgroup comparisons were not found to be statistically significant. CONCLUSIONS: Neuroendocrine tumors of the orbit represent a wide spectrum of disease, with some cases being part of disseminated disease, while others being localized presentations. This heterogeneity may be responsible for the slightly higher overall survival in these patients than others with metastatic carcinoid tumors in other locations.

Validity and Acceptance of Color Vision Testing on Smartphones.

BACKGROUND: Ishihara color plates (ICP) are the most commonly used color vision test (CVT) worldwide. With the advent of new technologies, attempts have been made to streamline the process of CVT. As hardware and software evolve, smartphone-based testing modalities may aid ophthalmologists in performing more efficient ophthalmic examinations. We assess the validity of smartphone color vision testing (CVT) by comparing results using the Eye Handbook (EHB) CVT application with standard Ishihara color plates (ICP). METHODS: Prospective case-control study of subjects 18 years and older with visual acuity of 20/100 or better at 14 inches. The study group included patients with any ocular pathology. The color vision deficient (CVD) group was patients who failed more than 2 plates. The control group had no known ocular pathology. CVT was performed with both ICP and EHB under standardized background illuminance. Eleven plates were tested with each modality. Validity of EHB CVT and acceptance of EHB CVT were analyzed. Statistical analyses were performed using Bland-Altman plot with limits of agreement (LOA) at the 95th percentile of differences in score, independent samples t tests with 95% confidence interval (CI), and Pearson χ tests. RESULTS: The Bland-Altman plot showed agreement between correct number of plates in EHB and ICP for the study subjects (bias, -0.25; LOA, -1.92 to 1.42). Agreement was also observed between the correct number of plates in EHB and ICP for the controls (bias, -0.01; LOA, -0.61 to 0.59) and CVD (bias, -0.50; LOA, -4.64 to 3.64) subjects. The sensitivity of EHB was 0.92 (95% CI 0.76-1.07) and the specificity of EHB was 1.00 (95% CI 1.00-1.00). Fifty-nine percent preferred EHB, 12% preferred ICP, and 29% had no preference. CONCLUSIONS: In healthy controls and patients with ocular pathology, there was an agreement of CVT results comparing EHB with ICP. Overall, the majority preferred EHB to ICP. These findings demonstrate that further testing is required to understand and improve the validity of smartphone CVT in subjects with ocular pathology.

Clinical Presentation and Anatomical Location of Orbital Plasmacytomas.

PURPOSE: To evaluate the clinical and anatomical location of orbital plasmacytomas and assess local control following therapy. METHODS: The American Society of Ophthalmic Plastic and Reconstructive Surgery Oncology Database was queried to identify patients diagnosed with orbital plasmacytoma. These patients' records were reviewed for demographic characteristics, clinical and radiologic findings, treatments, and outcomes. RESULTS: Thirty patients from 4 institutions (24 from MD Anderson Cancer Center, 3 from SUNY Downstate Medical Center, 2 from University of California, Los Angeles, and 1 from Oregon Health and Science University) were identified. Eighteen patients (60%) were diagnosed with multiple myeloma (MM) before and 11 (37%) were diagnosed with MM immediately after orbital plasmacytoma. Based on imaging, 4 distinct anatomical patterns were identified: 1) bony plasmacytoma affecting the superotemporal orbit, epidural space, and temporal fossa (15 patients; 50%); 2) discrete orbital plasmacytoma (7 patients; 23%); 3) infiltrative plasmacytoma either originating from a sinus (4 patients; 13%); or 4) originating from the orbital floor and infiltrating facial soft tissue (4 patients; 13%). Of the 29 patients with available treatment data, 2 had radiation only, 3 had chemotherapy only, 6 had chemoradiation, and 18 had stem cell transplant following chemoradiation (n = 17) or only chemotherapy (n = 1). Following treatment, 10 patients achieved complete and 11 achieved partial responses. CONCLUSION: Orbital plasmacytomas were found exclusively in patients with MM diagnosed before or immediately after orbital plasmacytoma. Plasmacytomas can have 4 distinct anatomical patterns of origin. Following treatment, all patients had good to excellent local control of their orbital lesions.

Orbitofacial Metastatic Basal Cell Carcinoma: Report of 10 Cases.

PURPOSE: To explore the clinical features, management, and prognosis of metastatic basal cell carcinoma originating in the orbitofacial region. METHODS: Ten cases of orbitofacial metastatic basal cell carcinoma were identified by searching databases at 2 institutions from 1995 to 2015. A retrospective chart review was performed. Main outcome measures included patient demographics, lesion size, location of metastases, histologic subtype, recurrence rate, time between primary tumor diagnosis and metastasis, perineural invasion, treatment modalities, and survival from time of metastasis. RESULTS: The median tumor size at largest dimension was 3.3 cm (range, 1.9-11.5 cm), and 6 of 10 patients had at least 1 local recurrence before metastasis (range, 0-2 recurrences). The most common sites of metastasis included the ipsilateral parotid gland (n = 6) and cervical lymph nodes (n = 5). Histologic subtypes included infiltrative (n = 5), basosquamous (n = 2), nodular (n = 1), and mixed (n = 1). The median time from primary tumor diagnosis to metastasis was 7.5 years (range, 0-13). The median survival time from diagnosis of metastasis to last documented encounter or death was 5.3 years (range, 7 months-22.8 years). Treatment regimens included surgical excision, radiotherapy, and hedgehog inhibitors. CONCLUSIONS: Based on our findings, the following features may be markers of high risk orbitofacial basal cell carcinoma: 1) increasing tumor size, 2) local recurrence of the primary tumor, 3) aggressive histologic subtype, and 4) perineural invasion. Screening should include close observation of the primary site and tissues in the distribution of regional lymphatics, particularly the parotid gland and cervical lymph nodes.

Rates of Positive Findings on Positron Emission Tomography and Bone Marrow Biopsy in Patients With Ocular Adnexal Lymphoma.

PURPOSE: The aim of this study was to determine rates of positive findings on positron emission tomography (PET) and bone marrow biopsy performed during staging workup for ocular adnexal lymphoma (OAL). METHODS: A retrospective review of OAL patients was conducted. Demographics, primary versus secondary OAL, histologic subtype, and findings on PET and bone marrow biopsy performed as part of the initial staging workup for OAL were recorded. RESULTS: The study included 119 patients with OAL. There were 85 primary and 34 secondary OALs. The main histologic subtypes of lymphoma were mucosa-associated lymphoid tissue (n = 61), follicular (n = 26), diffuse large B-cell (n = 17), and mantle cell (n = 10). Positive PET findings were seen in 42 of 68 patients (62%) with primary OAL and 19 of 24 (79%) with secondary OAL. Positive PET findings were seen in 24 of 47 patients (51%) with mucosa-associated lymphoid tissue, 13 of 17 (76%) with follicular, 14 of 15 (93%) with diffuse large B-cell, and 9 of 10 (90%) with mantle cell lymphoma. Positive findings on bone marrow biopsy were seen in 7 of 59 patients (12%) with mucosa-associated lymphoid tissue, 4 of 23 (17%) with follicular, 1 of 17 (6%) with diffuse large B-cell, and 2 of 9 (22%) with mantle cell lymphoma. CONCLUSIONS: Our findings suggest that a significant proportion of patients with primary and secondary OAL have positive findings on PET and bone marrow biopsy at initial diagnosis, suggesting a reasonable yield for these tests as part of the initial staging workup in patients with a new diagnosis of OAL.

Evaluating the growth of eyelid lesions: comparison of clinical evaluation and a software-based model.

PURPOSE: To evaluate the accuracy of clinicians in evaluating the growth of eyelid lesions and to compare the measurements of experienced ophthalmologists to a novel computerized measurement method. DESIGN: Prospective, single center, observational study. METHODS: Six experienced ophthalmologists were asked to measure 3 simulated eyelid lesions using a slit lamp. These lesions were then enlarged, and the same examiners were asked to measure the enlarged lesions without prompting that the lesions had changed. Slit lamp photography of the original lesions and enlarged lesions were analyzed using freely available software from the National Institutes of Health. The results of clinician measurements were compared to the software-generated data. RESULTS: Clinician data regarding the growth of the lesions were as follows: -40.9 to +76.8% for lesion 1, +29.3 to +134.4% for lesion 2, and +148.5 to +1169.2% for lesion 3. Software-based measurements were as follows: +53.6, +100.7, and +182.2% for lesions 1, 2, and 3, respectively. CONCLUSIONS: Monitoring growth of eyelid lesions in clinical practice can be challenging. We propose that using computerized software to analyze surface area of concerning eyelid lesions may provide a significant advantage over current clinical practices.

Epithelial, non-melanocytic and melanocytic proliferations of the ocular surface.

Ocular surface tumors are commonly encountered by ophthalmologists and ophthalmic pathologists. These tumors have varied clinical manifestations. In this article, we discuss the most commonly encountered non-melanocytic and melanocytic ocular surface tumors, with emphasis on their common clinical features, morphologic patterns, and prognostic factors.

Eyelid fistula caused by a scleral buckle.

Complications of scleral buckle procedures for retinal detachments are rather uncommon yet may result in a broad scope of problems. The authors report a case of a chronic eyelid fistula caused by a scleral buckle. The patient was an 81-year-old woman who presented with a nonhealing left upper eyelid wound that was repeatedly misdiagnosed as a chalazion, but diagnostic workup revealed an extruded scleral buckle to be the cause. The patient was treated surgically with removal of the scleral buckle and full-thickness fistula repair and her wound healed well. A scleral buckle can erode through conjunctiva and the full thickness of an eyelid, causing an eyelid fistula and necessitate removal of the buckle.

Association of Exercise and Swimming Goggles With Modulation of Cerebro-ocular Hemodynamics and Pressures in a Model of Spaceflight-Associated Neuro-ocular Syndrome.

Importance: Astronauts on International Space Station missions demonstrate adverse neuro-ocular changes. Reversing a negative translaminar pressure gradient (TLPG) by modulating cerebral blood flow, decreasing intracranial pressure, or increasing intraocular pressure (IOP) has been proposed as potential intervention for spaceflight-associated neuro-ocular syndrome (SANS). Objective: To examine whether exercise (resistance, moderate-intensity aerobic, and high-intensity aerobic) or artificially increasing IOP is associated with modulated cerebro-ocular hemodynamic and pressure changes during head-down tilt (HDT), an analogue of spaceflight, in healthy adults. Design, Setting, and Participants: A single-center investigation was conducted at Johnson Space Center, Houston, Texas, from January 1, 2014, to December 31, 2016, in 20 healthy men. Exposure: On 3 separate days, participants rested supine, were tilted to -15° HDT, and then completed 1 of 3 experimental exercise conditions (moderate-intensity aerobic, resistance, or high-intensity interval aerobic). A subset of 10 participants wore swimming goggles on all days. Main Outcomes and Measures: Applanation rebound tonometry was used to noninvasively assess IOP, and compression sonography was used to assess internal jugular venous pressure (IJVP). Estimated TLPG was calculated as the difference between IOP and IJVP. Cerebral inflow and outflow were measured in extracranial arteries using color-coded duplex ultrasonography. Results: Twenty men participated in the study (mean [SD] age, 36 [9] years). Compared with supine IOP (mean [SD], 19.3 [3.7] mm Hg), IJVP (mean [SD], 21.4 [6.0] mm Hg), and estimated TLPG (mean [SD], -2.1 [7.0] mm Hg), -15° HDT was associated with increased IOP (mean difference, 2.3 mm Hg; 95% CI, 1.4-3.3 mm Hg; P < .001) and IJVP (mean difference, 10.5 mm Hg; 95% CI, 8.9-12.2 mm Hg; P < .001) and with decreased TLPG (mean difference, -8.2 mm Hg; 95% CI, -10.1 to -6.3 mm Hg; P < .001). Exercise (regardless of modality) at -15° HDT was associated with decreased IOP (mean difference, -1.6 mm Hg; 95% CI, -2.6 to -0.6 mm Hg; P = .002) and TLPG (mean difference, -3.5 mm Hg; 95% CI, -6.2 to -0.7 mm Hg; P = .01) compared with rest. Both IOP (mean difference, 2.9 mm Hg; 95% CI, 0.7-5.1 mm Hg; P = .01) and TLPG (mean difference, 5.1 mm Hg; 95% CI, 0.8-9.4 mm Hg; P = .02) were higher in participants who wore swimming goggles compared with those not wearing goggles. Conclusions and Relevance: In this study, exercise was associated with decreased IOP and estimated translaminar pressure gradient in a spaceflight analogue of HDT. The addition of swimming goggles was associated with increased IOP and TLPG in HDT. Further evaluation in spaceflight may be warranted to determine whether modestly increasing IOP is an effective SANS countermeasure.

Sentinel lymph node biopsy for ocular adnexal melanoma.

BACKGROUND: We sought to update our prior report of findings on sentinel lymph node biopsy (SLNB) and predictors of a positive SLN in patients with conjunctival or eyelid melanoma. METHODS: We reviewed the records of all patients with ocular adnexal melanoma who underwent SLNB at one institution during 2000-2015. We determined rates of positive and false-negative findings on SLNB, primary tumour features correlated with positive findings and rate of nodal recurrence (false-negative event) after negative findings. RESULTS: The study included 51 patients, 31 with conjunctival and 20 with eyelid melanoma. These patients include 30 patients who underwent SLNB during 2000-2008, described in our previous report, and 21 additional patients who underwent SLNB during 2008-2015. There were 30 women and 21 men with median age at SLNB of 62 years (range, 24-83). The nodal basins most commonly sampled were intraparotid (27 patients) and level II (14 patients). Ten patients had positive SLNB findings. Compared to tumours with negative findings, tumours with positive findings had greater median thickness (3.5 mm versus 2.2 mm, p = 0.04), greater median number of mitotic figures (6 versus 2, p = 0.03) and greater incidence of ulceration (80% versus 26%, p = 0.003). Perineural and vascular invasion were not significantly associated with positive findings. There were three false-negative events. Three patients (6%) had temporary marginal mandibular weakness which resolved spontaneously. CONCLUSION: SLNB in patients with ocular adnexal melanoma is safe and identifies nodal micrometastasis in approximately 20% of cases. Histologic features associated with a positive SLN included greater tumour thickness, greater number of mitotic figures and ulceration.

Infraorbital Dark Circles: A Review of the Pathogenesis, Evaluation and Treatment.

Infraorbital dark circles represent a common and multifactorial challenge in the world of aesthetic medicine and are the result of a variety of factors including deep facial anatomy, soft tissue changes, as well as contributions from the skin. A variety of treatment options exist, and a customised management strategy can be developed for the particular anatomic changes present. A literature search using MEDLINE and non-MEDLINE sources was performed utilising keywords including: 'Dark circles' 'infraorbital dark circles', 'infraorbital pigment', 'under-eye circles' and 'lower eyelid bags'. A comprehensive review of the literature was performed and the data were assimilated with evidence from our practice. This review provides a detailed discussion of the aetiology, pathogenesis, evaluation and management of infraorbital dark circles. An understanding of the deep and superficial anatomy is crucial to the management of this complex entity. The armamentarium for treatment includes minimally invasive interventions such as makeup and cosmeceuticals, a variety of laser and chemical treatments, fillers and fat transfer, as well as more invasive surgical manoeuvres.

Prevalence and Severity of Ocular Surface Neoplasia in African Nations and Need for Early Interventions.

Ocular surface squamous neoplasia (OSSN) is a common ocular surface tumor with an increased incidence in African countries (3.4 and 3.0 cases/year/100,000). Despite its potential for vision loss and death, OSSN remains largely neglected by both eye and HIV care programs in Africa. The purpose of this review is to identify the barriers to timely diagnosis and early interventions for OSSN in Africa. PubMed searches were conducted targeting previous use of topical chemotherapy (interferon alpha 2b, Mitomycin-C, 5-Fluorouracil) and Human papillomavirus (HPV) vaccination in Africa. We found that OSSN is a significant vision and life-threatening health problem in Africa leading to significant loss of vision, as well as facial disfigurement and social stigma. We did not find any reports on the use of topical interferon, Mitomycin-C or HPV vaccination for OSSN in Africa. One report on the use of topical 5-FU for OSSN in Africa was found. Common barriers to early detection and management of OSSN in Africa include lack of sufficient laboratory infrastructure, lack of trained healthcare personnel, lack of compliance with follow-up visits, cost of topical chemotherapies, and cultural preferences for traditional medicines. In conclusion, OSSN is a significant vision and life-threatening health problem in Africa. There is not much literature on prevention or treatment options for early stages of OSSN in Africa. The use of topical chemotherapy as early interventions and judicious use of smart phone Apps to help with remote diagnosis of early OSSN should be further explored.

Hedgehog Pathway Inhibition for Locally Advanced Periocular Basal Cell Carcinoma and Basal Cell Nevus Syndrome.

PURPOSE: To review our experience treating patients with the Hedgehog pathway inhibitor, vismodegib, in patients with orbital or periocular locally advanced or metastatic basal cell carcinoma (BCC) or basal cell nevus syndrome. DESIGN: Retrospective interventional case series. METHODS: We reviewed all patients with locally advanced or metastatic orbital or periocular BCC or basal cell nevus syndrome treated with the Hedgehog pathway inhibitor, vismodegib, at a comprehensive cancer center from 2009 through 2015. Reviewed data included age; sex; American Joint Commission on Cancer tumor, node, metastasis staging system designation; type and grade of drug-related side effects; response to treatment; duration of follow-up, and status at last follow-up. RESULTS: The study included 10 white men and 2 white women; the median age was 64.5 years. Ten patients had locally advanced BCC; 2 had basal cell nevus syndrome. Among the patients with locally advanced BCC, 5 had T3bN0M0 disease at presentation; 1 each had T3aN0M0, T3bN1M0, T2N1M1, T4N1M1, and T4N2cM1 disease. Overall, 3 patients had a complete response, 6 had a partial response, and 3 had stable disease at last follow-up. Two patients developed progressive disease after a complete response for 38 months and stable disease for 16 months, respectively. All patients developed grade I drug-related adverse effects, most commonly muscle spasms (12 patients), weight loss (10), dysgeusia (9), alopecia (9), decreased appetite (5), and fatigue (4). Five patients developed grade II adverse effects. At last follow-up, none of the 5 patients presenting with T3bN0M0, nor the patient with T3bN1M0 disease, had required orbital exenteration. CONCLUSION: Hedgehog pathway inhibition produces a significant clinical response in most patients with locally advanced or metastatic orbital or periocular BCC or basal cell nevus syndrome and can obviate orbital exenteration in some patients. Drug-related adverse effects are manageable in most patients.

Dry eye syndrome due to botulinum toxin type-A injection: guideline for prevention.

Dry eye syndrome is a potential complication of botulinum toxin type-A injection (BTX-A) into the lateral canthal rhytids (crow's feet). The early manifestations of this syndrome are subtle and are rarely reported to the treating physician. A guideline for early detection of dry-eye state is proposed, in order to avoid more troublesome adverse effects that may develop with repeated injections of BTX-A into the crow's feet region. If suspected early, clinical manifestations remain minor and are reversible. However, delayed diagnosis may lead to troublesome and persistent symptoms. A novel and practical grading scale of lower eyelid snap-back and distraction tests is offered that helps in documenting patient's clinical progress and in deciding when BTX-A injections should be delayed or discontinued.