Ophthalmic manifestations and management considerations for emerging chemical threats.

Chemical agents have been utilized for centuries in warfare and pose a health threat to civilians and military personnel during armed conflict. Despite treaties and regulations against their use, chemical agent exposure remains a threat and measures to understand their effects and countermeasures for systemic and organ-specific health are needed. Many of these agents have ocular complications, both acute and chronic. This mini-review focuses on key chemical agents including vesicants (mustards, lewisite), nerve agents (sarin, VX), knockdown gasses (hydrogen cyanide), and caustics (hydrofluoric acid). Their ophthalmic manifestations and appropriate treatment are emphasized. Acute interventions include removal of the source and meticulous decontamination, as well as normalization of pH to 7.2-7.4 if alteration of the ocular pH is observed. Besides vigorous lavage, acute therapies may include topical corticosteroids and non-steroid anti-inflammatory therapies. Appropriate personal protective equipment (PPE) and strict donning and doffing protocols to avoid healthcare provider exposure are also paramount in the acute setting. For more severe disease, corneal transplantation, amniotic membrane graft, and limbal stem cell transplantation may be needed. Orbital surgery may be required in patients in whom cicatricial changes of the ocular surface have developed, leading to eyelid malposition. Multidisciplinary care teams are often required to handle the full spectrum of findings and consequences associated with emerging chemical threats.

Visual acuity and vision-related quality of life outcomes following cataract surgery in Ebola virus disease survivors.

Objectives: The objectives of this study were to assess relationships between vision-related quality of life (QoL) and visual acuity (VA) in Ebola virus disease (EVD) survivors after cataract surgery in the Ebola Viral Persistence in Ocular Tissues and Fluids (EVICT) Study. Materials and Methods: EVD survivors with undetectable Ebola virus (EBOV) ribonucleic acid in their aqueous humour were eligible to receive manual small-incision cataract surgery (MSICS). Among those that received surgery, assessments of VA and vision-related QoL were assessed pre-and post-cataract surgery. VA was converted from units on a tumbling 'E' chart to the logarithm of the minimal angle of resolution VA (logMAR VA). Vision-related QoL was assessed using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25). Linear regression was used to evaluate the associations between VA and vision-related QoL. P = 0.05 was considered statistically significant for all analyses. Results: Thirty-four EVD survivors underwent cataract surgery in the EVICT study. Before MSICS, the mean logMAR VA was 2.24 (standard deviation [SD]: 0.98), and the mean NEI-VFQ-25 composite score was 54 (SD: 15); however, there was no significant association between the pre-surgery measurements (average difference in VA/10 unit increase in NEI-VFQ-25: -0.04, 95% confidence interval (CI): -0.33-0.26, P = 0.80). There was a significant improvement in logMAR VA after MSICS (mean: 1.6, P < 0.001), but there was no significant change in the NEI-VFQ-25 composite (-0.87, 95% (CI): -10.32-8.59, P = 0.85). None of the subscales showed significant improvements (P > 0.12 for all); however, the magnitude of the mean change for distance activities (6.65), near activities (6.76), general vision (-7.69), social functioning (-9.13) and colour vision (13.33) met the criteria for a clinically meaningful difference (4-6). In the subset with paired measurements (n = 16), there were no significant association changes in logMAR VA and NEI VFQ-25 composite scores (P > 0.12 for all). Conclusion: Following cataract surgery, VA in EVD survivors improved, but these improvements were not reflected in NEI VFQ-25 composite scores or specific subscales; however, the small sample size limits generalizability absent more research. Differences in sociocultural context and activities that affect the QoL in resource-limited areas may contribute to the limitations seen with NEI VFQ-25. In addition, better eye dominance could contribute to any lack of association as NEI VFQ-25 evaluates vision as a whole. Further, assessment of factors contributing to improved QoL may help to define the impact of vision health in varied environments.

Implementation of the Ebola Virus Persistence in Ocular Tissues and Fluids (EVICT) study: Lessons learned for vision health systems strengthening in Sierra Leone.

BACKGROUND: Following the West African Ebola virus disease (EVD) outbreak of 2013-2016 and more recent EVD outbreaks in the Democratic Republic of Congo, thousands of EVD survivors are at-risk for sequelae including uveitis, which can lead to unremitting inflammation and vision loss from cataract. Because of the known risk of Ebola virus persistence in ocular fluid and the need to provide vision-restorative, safe cataract surgery, the Ebola Virus Persistence in Ocular Tissues and Fluids (EVICT) Study was implemented in Sierra Leone. During implementation of this multi-national study, challenges included regulatory approvals, mobilization, community engagement, infection prevention and control, and collaboration between multiple disciplines. In this report, we address the multifacted approach to address these challenges and the impact of implementation science research to address an urgent clinical subspecialty need in an outbreak setting. METHODOLOGY/PRINCIPAL FINDINGS: Given the patient care need to develop a protocol to evaluate ocular fluid for Ebola virus RNA persistence prior to cataract surgery, as well as protocols to provide reassurance to ophthalmologists caring for EVD survivors with cataracts, the EVICT study was designed and implemented through the work of the Ministry of Health, Sierra Leone National Eye Programme, and international partnerships. The EVICT study showed that all 50 patients who underwent ocular fluid sampling at 19 and 34 months, respectively, tested negative for Ebola virus RNA. Thirty-four patients underwent successful cataract surgery with visual acuity improvement. Here we describe the methodology for study implementation, challenges encountered, and key issues that impacted EVD vision care in the immediate aftermath of the EVD outbreak. Key aspects of the EVICT study included defining the pertinent questions and clinical need, partnership alignment with key stakeholders, community engagement with EVD survivor associations, in-country and international regulatory approvals, study site design for infection prevention and control, and thorough plans for EVD survivor follow-up care and monitoring. Challenges encountered included patient mobilization owing to transportation routes and distance of patients in rural districts. Strong in-country partnerships and multiple international organizations overcame these challenges so that lessons learned could be applied for future EVD outbreaks in West and Central Africa including EVD outbreaks that are ongoing in Guinea and Democratic Republic of Congo. CONCLUSIONS/SIGNIFICANCE: The EVICT Study showed that cataract surgery with a protocol-driven approach was safe and vision-restorative for EVD survivors, which provided guidance for EVD ophthalmic surgical care. Ophthalmologic care remains a key aspect of the public health response for EVD outbreaks but requires a meticulous, yet partnered approach with international and local in-country partners. Future efforts may build on this framework for clinical care and to improve our understanding of ophthalmic sequelae, develop treatment paradigms for EVD survivors, and strengthen vision health systems in resource-limited settings.

Efficacy and Safety Outcomes of Cataract Surgery in Survivors of Ebola Virus Disease: 12-Month Results From the PREVAIL VII Study.

Purpose: In survivors of Ebola virus disease (EVD), intraocular viral persistence raises questions about the timing and safety of cataract surgery. To the best of our knowledge, this is the first controlled study evaluating Ebola virus persistence and cataract surgery safety and outcomes in EVD survivors. Methods: Seropositive EVD survivors and seronegative controls with vision worse than 20/40 from cataract and without active intraocular inflammation were enrolled. Aqueous humor from survivors was tested with reverse transcription-polymerase chain reaction for Ebola viral RNA. Participants underwent manual small-incision cataract surgery and 1 year of follow-up examinations. Results: Twenty-two eyes of 22 survivors and 12 eyes of eight controls underwent cataract surgery. All of the aqueous samples tested negative for Ebola viral RNA. Median visual acuity improved from 20/200 at baseline to 20/25 at 1 year in survivors and from count fingers to 20/50 in controls (overall, P < 0.001; between groups, P = 0.07). After a 1-month course of topical corticosteroids, 55% of survivors and 67% of controls demonstrated at least 1+ anterior chamber cell. Twelve months after surgery, optical coherence tomography revealed a median increase in macular central subfield thickness of 42 µm compared with baseline (overall, P = 0.029; between groups, P = 0.995). Conclusions: EVD survivors and controls demonstrated significant visual improvement from cataract surgery. The persistence of intraocular inflammation highlights the importance of follow-up. The absence of detectable intraocular Ebola viral RNA provides guidance regarding the safety of eye surgery in Ebola survivors. Translational Relevance: These findings demonstrate the safety and efficacy of cataract surgery in Ebola survivors and will inform ocular surgery guidelines in this population.

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.

Pathological Features and Clinical Course in Patients With Recurrent or Malignant Orbital Solitary Fibrous Tumor/Hemangiopericytoma.

PURPOSE: A risk assessment score for metastasis based on age, tumor size, and mitotic figures has been suggested for nonorbital solitary fibrous tumor (SFT)/hemangiopericytoma. The authors herein examine the clinicopathological features of recurrent and metastatic orbital SFT and evaluate the existing risk assessment score for orbital SFT. METHODS: The American Society of Ophthalmic Plastic and Reconstructive Surgery Oncology Database was queried for patients with recurrent or malignant orbital hemangiopericytoma/SFT. The medical records were reviewed for clinical and pathologic findings, treatments, and outcomes. RESULTS: Eight patients from 3 institutions were identified with recurrent orbital hemangiopericytoma/SFT. Median age at diagnosis was 59 years, and 4 patients were women. The mean size of tumor was 2.1 ± 1.1 cm. All patients were initially treated with surgery and experienced local recurrence after a median of 4 (range 0.5-10) years. Five patients were treated with orbital radiation. Two patients also developed distant metastases and eventually died of their disease. Median Ki-67 was 5% (range 1-65%) and 5 mitotic figures/10 high-power fields (range 2-30). The previously described risk stratification model for nonorbital SFT did not correlate with the propensity to develop metastases in this cohort; however, both patients with distant metastasis had > 4 mitotic figures /10 high-power fields. CONCLUSIONS: In this cohort of recurrent orbital hemangiopericytoma/SFT, median time to recurrence was 4 years underscoring the importance of careful continued follow-up. The current risk stratification models have limited use for orbital lesions, mostly due to the fact that orbital SFTs are smaller than even the smallest size criteria in this risk assessment model.

Ebola Virus Persistence in Ocular Tissues and Fluids (EVICT) Study: Reverse Transcription-Polymerase Chain Reaction and Cataract Surgery Outcomes of Ebola Survivors in Sierra Leone.

BACKGROUND: Ebola virus disease (EVD) survivors are at risk for uveitis during convalescence. Vision loss has been observed following uveitis due to cataracts. Since Ebola virus (EBOV) may persist in the ocular fluid of EVD survivors for an unknown duration, there are questions about the safety and feasibility of vision restorative cataract surgery in EVD survivors. METHODS: We conducted a cross-sectional study of EVD survivors anticipating cataract surgery and patients with active uveitis to evaluate EBOV RNA persistence in ocular fluid, as well as vision outcomes post cataract surgery. Patients with aqueous humor that tested negative for EBOV RNA were eligible to proceed with manual small incision cataract surgery (MSICS). FINDINGS: We screened 137 EVD survivors from June 2016 - August 2017 for enrolment. We enrolled 50 EVD survivors; 46 with visually significant cataract, 1 with a subluxated lens, 2 with active uveitis and 1 with a blind painful eye due to uveitis. The median age was 24.0years (IQR 17-35) and 35 patients (70%) were female. The median logMAR visual acuity (VA) was 3.0 (Snellen VA Hand motions; Interquartile Range, IQR: 1.2-3.0, Snellen VA 20/320 - Hand motions). All patients tested negative for EBOV RNA by RT-PCR in aqueous humor/vitreous fluid and conjunctiva at a median of 19months (IQR 18-20) from EVD diagnosis in Phase 1 of ocular fluid sampling and 34months (IQR 32-36) from EVD diagnosis in Phase 2 of ocular fluid sampling. Thirty-four patients underwent MSICS, with a preoperative median VA improvement from hand motions to 20/30 at three-month postoperative follow-up (P<0.001). INTERPRETATION: EBOV persistence by RT-PCR was not identified in ocular fluid or conjunctivae of fifty EVD survivors with ocular disease. Cataract surgery can be performed safely with vision restorative outcomes in patients who test negative for EBOV RNA in ocular fluid specimens. These findings impact the thousands of West African EVD survivors at-risk for ocular complications who may also require eye surgery during EVD convalescence.

A 15-year review of secondary and tertiary optic nerve sheath fenestration for idiopathic intracranial hypertension.

PURPOSE: Optic nerve sheath fenestration (ONSF) is a common surgical option for patients with idiopathic intracranial hypertension (IIH) with vision loss refractory to medical management. Little is known about the visual benefit of repeated ONSF. The authors aimed to assess the efficacy of secondary and tertiary ONSF in patients with IIH. METHODS: A retrospective chart review was performed on all patients with repeat ONSF for IIH at Emory University from 1999 to 2016. Primary outcome measures included visual acuity, optic nerve head findings, and visual field results. RESULTS: A total of nine eyes in seven patients (five females and two males) with repeat ONSF were identified. Two of the seven patients had repeat ONSF in both eyes, while the remaining five patients had only one eye repeated. Five of seven patients (five eyes) improved or remained stable after the secondary ONSF. Two patients (three eyes) continued to worsen despite the secondary fenestration surgery and underwent tertiary ONSF at an average of 13.2 months (SD 5.5 months) after the failed secondary ONSF. Both patients that underwent the tertiary fenestration showed improvement. Six of the patients had either improvement or stability in their clinical findings at their last documented follow-up, but one continued to worsen despite intervention. CONCLUSIONS: This study suggests that secondary and tertiary nerve sheath fenestration is a viable management option for patients with progressive vision loss from IIH. Repeat ONSFs do not appear to have increased complication or failure rates compared to prior documented studies regarding primary fenestrations.

Dilated Superior Ophthalmic Vein: Clinical and Radiographic Features of 113 Cases.

PURPOSE: Dilated superior ophthalmic vein (SOV) is an uncommon radiographic finding. The authors review the presentation, etiology, radiography, and visual implications of 113 patients with dilated SOV. METHODS: An observational case series and multicenter retrospective chart review were conducted. There were 113 patients with a dilated SOV. Outcome measures included patient demographics, clinical features, radiographic findings, diagnosis, and treatment, and treatment outcomes were assessed. RESULTS: Cases included 75 women (66%) and 38 men (34%) with a mean age of 49 ± 24 years (range, 0.4-90 years). Diagnoses fell under 6 categories: vascular malformation (n = 92, 81%), venous thrombosis (n = 11, 10%), inflammatory (n = 6, 5%), traumatic hemorrhage (n = 2, 2%), lymphoproliferative (n = 1, 1%), and infectious (n = 1, 1%). Imaging modalities utilized included MRI (n = 98, 87%), digital subtraction angiography (n = 77, 68%), CT (n = 29, 26%), and ultrasonography (n = 4, 4%). Disease status at last follow up included no evidence of disease (n = 57, 50%), alive with persistent disease (n = 53, 47%), and expired from disease (n = 3, 3%). Treatment and management was tailored to the underlying disease process with a mean follow up of 18 months (range, 1 day to 180 months). Visual impairment observed at presentation and last follow up across all cases was 26% and 22%, respectively. CONCLUSION: Dilated SOV is a rare radiographic finding resulting from a wide spectrum of etiologies with clinical implications ranging from benign to sight- and life-threatening. Dilated SOV is most often found with dural-cavernous fistula or carotid-cavernous fistula, orbital or facial arteriovenous malformation, and venous thrombosis. Recognition of this finding and management of the underlying condition is critical.

Gene Expression Profiling and Heterogeneity of Nonspecific Orbital Inflammation Affecting the Lacrimal Gland.

Importance: Although a variety of well-characterized diseases, such as sarcoidosis and granulomatosis with polyangiitis, affect the lacrimal gland, many patients with dacryoadenitis are diagnosed as having nonspecific orbital inflammation (NSOI) on the basis of histology and systemic disease evaluation. The ability to further classify the disease in these patients should facilitate selection of effective therapies. Objective: To test the a priori hypothesis that gene expression profiles would complement clinical and histopathologic evaluations in identifying well-characterized diseases and in subdividing NSOI into clinically relevant groups. Design, Setting, and Participants: In this cohort study, gene expression levels in biopsy specimens of inflamed and control lacrimal glands were measured with microarrays. Stained sections of the same biopsy specimens were used for evaluation of histopathology. Tissue samples of patients were obtained from oculoplastic surgeons at 7 international centers representing 4 countries (United States, Saudi Arabia, Canada, and Taiwan). Gene expression analysis was done at Oregon Health & Science University. Participants were 48 patients, including 3 with granulomatosis with polyangiitis, 28 with NSOI, 7 with sarcoidosis, 4 with thyroid eye disease, and 6 healthy controls. The study dates were March 2012 to April 2017. Main Outcomes and Measures: The primary outcome was subdivision of biopsy specimens based on gene expression of a published list of approximately 40 differentially expressed transcripts in blood, lacrimal gland, and orbital adipose tissue from patients with sarcoidosis. Stained sections were evaluated for inflammation (none, mild, moderate, or marked), granulomas, nodules, or fibrosis by 2 independent ocular pathologists masked to the clinical diagnosis. Results: Among 48 patients (mean [SD] age, 41.6 [19.0] years; 32 [67%] female), the mclust algorithm segregated the biopsy specimens into 4 subsets, with the differences illustrated by a heat map and multidimensional scaling plots. Most of the sarcoidosis biopsy specimens were in subset 1, which had the highest granuloma score. Three NSOI biopsy specimens in subset 1 had no apparent granulomas. Thirty-two percent (9 of 28) of the NSOI biopsy specimens could not be distinguished from biopsy specimens of healthy controls in subset 4, while other examples of NSOI tended to group with gene expression resembling granulomatosis with polyangiitis or thyroid eye disease. The 4 subsets could also be partially differentiated by their fibrosis, granulomas, and inflammation pathology scores but not their lymphoid nodule scores. Conclusions and Relevance: Gene expression profiling discloses clear heterogeneity among patients with lacrimal inflammatory disease. Comparison of the expression profiles suggests that a subset of patients with nonspecific dacryoadenitis might have a limited form of sarcoidosis, while other patients with NSOI cannot be distinguished from healthy controls.

Review of periorbital nerve enlargement and biopsy techniques.

Periorbital nerve enlargement commonly indicates perineural invasion of malignancy or inflammatory conditions. This study reviews the role of supraorbital and infraorbital nerve biopsies in patients presenting with radiographic enlargement and to elucidate the surgical technique involved. A retrospective chart review (1997-2014) was performed at a single tertiary center. Patients with radiographic confirmation of enlarged supraorbital/infraorbital nerves that underwent biopsy were included. Charts were reviewed for: patient demographics and history, clinical symptoms and findings, radiographic findings, surgical method, and treatment. Five patients (4 female, 1 male) met inclusion criteria. Average age was 72.4 years (range 36-90). Four patients had history of cutaneous malignancy. All presented with diplopia and/or dysesthesias. Clinical examination confirmed decreased V1 and/or V2 sensation for 4 patients. Imaging revealed enlargement of V1, V2, and/or V3 in all patients. Infraorbital nerve biopsies were performed in 3 patients via transconjunctival fornix-based orbitotomy with subperiosteal dissection along orbital floor followed by unroofing of infraorbital canal. The remaining 2 underwent supraorbital nerve biopsy via sub-brow incision onto superior orbital rim with reflection of periosteum. Biopsies confirmed squamous cell carcinoma(3), mucoepidermoid carcinoma(1), and idiopathic orbital inflammation(1). Three patients initiated treatment in <1 month. One decided to follow-up closer to home, one was lost to follow-up. For patients presenting with enlarged supraorbital/infraorbital nerves, biopsy can rapidly confirm the underlying condition and facilitate early treatment. A sub-brow approach offers direct access to supraorbital nerve while transconjunctival fornix-based anterior orbitotomy with canal unroofing allows access to infraorbital nerve.

Nodular Fasciitis of the Orbit: A Case Report Confirmed by Molecular Cytogenetic Analysis.

Nodular fasciitis is a benign fibroblastic proliferation typically found in the subcutaneous tissue or superficial fascia of the extremities that is often confused for malignancy. These lesions rarely occur on the eyelids and ocular adnexa and are seldom analyzed by ophthalmic pathologists. USP6 gene rearrangement has been recently demonstrated in nodular fasciitis and this rearrangement may lead to the formation of a fusion gene MYH9-USP6 in some cases. Herein, the authors describe a 38-year-old woman with a 6-month history of a progressively enlarging mass beneath her right medial upper eyelid. Histopathologic analysis of the excisional biopsy confirmed classic features of nodular fasciitis. Molecular cytogenetic analysis revealed a rearrangement of the USP6 locus, confirming the diagnosis of benign nodular fasciitis.

Optic nerve lymphoma: report of two cases and review of the literature.

Lymphoma may involve the optic nerve as isolated optic nerve lymphoma or in association with central nervous system (CNS) or systemic lymphoma. We present two biopsy-proven non-Hodgkin lymphomas of the optic nerve and compare our findings with previously reported cases. We discuss the mechanism of metastasis, classification of optic nerve involvement, clinical features, radiologic findings, optic nerve biopsy indications and techniques, histologic features, and treatments. We propose a classification system of optic nerve lymphoma: isolated optic nerve involvement, optic nerve involvement with CNS disease, optic nerve involvement with systemic disease, and optic nerve involvement with primary intraocular lymphoma. Although it is an uncommon cause of infiltrative optic neuropathy, optic nerve metastasis should be considered in patients with a history of lymphoma. The recommended approach to a patient with presumed optic nerve lymphoma includes neuroimaging and cerebrospinal fluid evaluation as part of the initial workup, then judicious use of optic nerve biopsy, depending on the clinical situation.

Reticulohistiocytoma of the orbit.

Reticulohistiocytoma is a rare, benign histiocytic proliferation of the skin or soft tissue. While ocular involvement has been documented in the past, there have been no previously reported cases of reticulohistiocytoma of the orbit. In this report, the authors describe a reticulohistiocytoma of the orbit in a middle-aged woman.

Bilateral lacrimal gland disease: clinical features of 97 cases.

OBJECTIVE: Bilateral lacrimal gland (LG) disease is a unique presentation that can result from varied causes. We reviewed the diagnoses, clinical features, and outcomes of 97 patients with this entity. DESIGN: Case series. PARTICIPANTS: Ninety-seven patients with bilateral LG disease. METHODS: Retrospective review and statistical analysis using analysis of variance and the Fisher exact test. MAIN OUTCOME MEASURES: Patient demographics, clinical features, diagnostic testing, diagnosis, and treatment. RESULTS: Patient age ranging from 8 to 84 years (mean, 46 years). The predominant gender was female (77%), and race included black (49%), white (38%), and Hispanic (12%) patients. Diagnoses fell into 4 categories: inflammatory (n = 51; 53%), structural (n = 20; 21%), lymphoproliferative (n = 19; 20%), and uncommon (n = 7; 7%) entities. The most common diagnoses included idiopathic orbital inflammation (IOI; n = 29; 30%), sarcoidosis (n = 19; 20%), prolapsed LG (n = 15; 15%), lymphoma (n = 11; 11%), lymphoid hyperplasia (n = 8; 8%), and dacryops (n = 5; 5%). Inflammatory conditions were more likely in younger patients (P<0.05) and in those with pain (P<0.001) and mechanical blepharoptosis (P<0.01) at presentation, whereas lymphoma was more common in older patients (P<0.001) without active signs of inflammation at presentation. Black patients were more likely to have sarcoidosis (P<0.01). Laboratory results showed high angiotensin converting enzyme level being significantly more likely in patients with sarcoidosis (P<0.05). However, sensitivity was limited to 45%, with 25% of patients diagnosed with IOI also demonstrating positive results. Corticosteroid therapy was the treatment of choice in 38 cases, corresponding to resolution of symptoms in 29% and improvement in an additional 32%. Overall, chronic underlying disease was found in 71% of patients, among whom 26% achieved a disease-free state, whereas 3% succumbed to their underlying disease. CONCLUSIONS: The cause of bilateral lacrimal gland disease most commonly was inflammatory, followed by structural and lymphoproliferative. Patient characteristics and clinical presentations were key features distinguishing between competing possibilities. Despite local control with corticosteroids or radiotherapy, underlying disease continued in 71% of patients and led to death in 3%.

Viability of full-thickness skin grafts used for correction of cicatricial ectropion of lower eyelid in previously irradiated field in the periocular region.

BACKGROUND: The purpose of this study was to evaluate the viability of skin grafts used for correction of cicatricial ectropion resulting from previous ablative surgery and radiotherapy for head and neck cancer and to report overall outcomes of cicatricial ectropion repair. METHODS: This is a retrospective, noncomparative case series of all consecutive patients with head and neck cancer who had been exposed to high-dose radiation therapy in their periocular region and had surgical correction of their lower eyelid cicatricial ectropion through placement of a full-thickness skin graft and a lower eyelid tightening procedure by the same surgeon. The primary outcome measure was skin graft viability. Secondary outcome measures comprised postoperative complications, the overall outcome of ectropion repair as judged by improvement in symptoms of exposure keratopathy, and dependence on lubricating eye drops and ointments, as well as cosmetic improvement measured through a grading scale based on the degree of inferior scleral show and/or tarsal conjunctival eversion. RESULTS: Twenty-five patients were eligible for the study. Nineteen men and 6 women had a median age of 63 years (range, 20-84 years). All 25 patients had high-dose radiation therapy for their head and neck cancer. All but 1 patient had major cancer ablative surgery performed before radiation therapy. Thirteen of 25 patients also received chemotherapy. There was 100% viability of the skin grafts used for the repair of lower eyelid cicatricial ectropion. There were a few postoperative complications including the need for revision surgery to correct residual ectropion in the lower eyelid in 2 patients, and a third patient required a revision surgery due to upper eyelid retraction and lagophthalmos after harvest of skin graft from the upper eyelid. Improvement was noted in the subjective symptoms in 22 of 25 patients (88%), whereas 17 patients (68%) were noted to have improvement in their clinical findings on slit lamp examination. All 20 patients, for whom good quality photos were available, had improvement in the degree of cicatricial lower eyelid ectropion as measured by the amount of inferior scleral show and tarsal conjunctival eversion, although 11 patients had some residual ectropion. All 20 had either good or excellent results in the appearance of their skin grafts. CONCLUSION: Our findings suggest that full-thickness skin grafts are a nice option for correction of cicatricial lower eyelid ectropion in a previously radiated field; 100% of the grafts survived. The majority of patients had improvement of ocular surface damage and symptoms, with a decreased dependence on topical lubricants. All evaluable patients had improvement in the degree of cicatricial lower eyelid ectropion, although close to one-half of patients had some mild residual ectropion. The majority of patients had excellent appearance of the skin graft.

Association of clinical response and long-term outcome among patients with biopsied orbital pseudotumor receiving modern radiation therapy.

PURPOSE: To retrospectively evaluate institutional outcomes for patients treated with modern radiation therapy (RT) for biopsied orbital pseudotumor (OP). METHODS AND MATERIALS: Twenty patients (26 affected orbits) with OP were treated with RT between January 2002 and December 2011. All patients underwent biopsy with histopathologic exclusion of other disease processes. Sixteen patients (80%) were treated with intensity modulated RT, 3 (15%) with opposed lateral beams, and 1 (5%) with electrons. Median RT dose was 27 Gy (range 25.2-30.6 Gy). Response to RT was evaluated at 4 months post-RT. Partial response (PR) was defined as improvement in orbital symptoms without an increase in steroid dose. Complete response (CR) 1 and CR 2 were defined as complete resolution of orbital symptoms with reduction in steroid dose (CR 1) or complete tapering of steroids (CR 2). The median follow-up period was 18.6 months (range 4-81.6 months). RESULTS: Seventeen patients (85%) demonstrated response to RT, with 7 (35%), 1 (5%), and 9 (45%) achieving a PR, CR 1, and CR 2, respectively. Of the 17 patients who had ≥ PR at 4 months post-RT, 6 (35%) experienced recurrence of symptoms. Age (>46 years vs ≤ 46 years, P=.04) and clinical response to RT (CR 2 vs CR 1/PR, P=.05) were significantly associated with pseudotumor recurrence. Long-term complications were seen in 7 patients (35%), including 4 with cataract formation, 1 with chronic dry eye, 1 with enophthalmos, and 1 with keratopathy. CONCLUSIONS: RT is an effective treatment for improving symptoms and tapering steroids in patients with a biopsy supported diagnosis of OP. Older age and complete response to RT were associated with a significantly reduced probability of symptom recurrence. The observed late complications may be related to RT, chronic use of steroids/immunosuppressants, medical comorbidities, or combination of factors.

Clinical outcomes of radiotherapy as initial local therapy for Graves' ophthalmopathy and predictors of the need for post-radiotherapy decompressive surgery.

BACKGROUND: The optimal initial local treatment for patients with Graves' ophthalmopathy (GO) is not fully characterized. The purpose of this retrospective study is to describe the clinical outcomes of RT as initial local therapy for GO and define predictors of the need for post-RT salvage bony decompressive surgery. METHODS: 91 patients with active GO and without prior surgery were treated with RT as initial local therapy between 01/1999 and 12/2010, with a median follow-up period of 18.3 months (range 3.7 - 142 months). RT dose was 24 Gy in 12 fractions. 44 patients (48.4%) had prior use of steroids, with 31 (34.1%) being on steroids at the initiation of RT. The most common presenting symptoms were diplopia (79%), proptosis (71%) and soft tissue signs (62%). RESULTS: 84 patients (92.3%) experienced stabilization or improvement of GO symptoms. 58 patients (64%) experienced improvement in their symptoms. 19 patients (20.9%) underwent salvage post-RT bony decompressive surgery. Smoking status and total symptom score at 4 months were independent predictors of post-RT bony decompression with odds ratios of 3.23 (95% CI 1.03 - 10.2) and 1.59 (95% CI 1.06 - 2.4), respectively. Persistent objective vision loss at 4 months post-RT was the most important symptom type in predicting salvage decompression. Chronic dry eye occurred in 9 patients (9.9%) and cataracts developed in 4 patients (4.4%). CONCLUSIONS: RT is effective and well tolerated as initial local therapy for active GO, with only 21% of patients requiring decompressive surgery post RT. Most patients experience stabilization or improvement of GO symptoms, but moderate to significant response occurs in the minority of patients. Smoking status and total symptom severity at 4 months, primarily persistent objective vision loss, are the primary determinants of the need for post-RT salvage bony decompression. Patients who smoke or present with predominantly vision loss symptoms should be advised as to their lower likelihood of symptomatic response to RT and their increased likelihood of requiring post-RT decompressive surgery.

Analysis of αv integrin protein expression in human eyelid and periorbital squamous cell carcinomas.

BACKGROUND: Alpha v integrins are receptors for many extracellular matrix (ECM) protein ligands, including latent transforming growth factor betas (TGFßs). Various studies in mice have shown that ablation of genes encoding αv integrin or TGFß signaling pathway components leads to spontaneous squamous cell carcinomas (SCCs) in the conjunctiva and periocular skin. Here, we have analyzed patterns of αv integrin protein expression and TGFß signaling in human eyelid and periorbital SCC samples. METHODS: An anti-αv integrin antibody was used to immunostain 19 eyelid and periorbital SCC samples. Additionally, tissue lysates from resected normal eyelid and SCC samples were analyzed by immunoblotting for αv integrin protein. Tumor sections were also immunostained with an antibody directed against Smad2, an intracellular signaling protein that is phosphorylated by TGFß receptors. RESULTS: Alpha v integrin protein was highly expressed in the invasive and less-differentiated components of human SCCs. Lower levels of αv integrin protein were detected in more differentiated components of tumors, as well as in SCC in situ. Patterns of phosphorylated Smad2 immunoreactivity correlated with levels αv integrin expression. CONCLUSIONS: Alpha v integrin was expressed at robust levels in tumor cells representing less differentiated, more invasive components of SCC; by contrast, well-differentiated cells as well as SCC in situ expressed low levels of αv integrin protein.

Cutaneous melanoma metastatic to the eyelid and periocular skin.

PURPOSE: To report the clinical and histopathologic features in 6 patients with cutaneous melanoma metastatic to the eyelid and periocular skin. METHODS: Clinical records and radiographic features of all consecutive patients treated by the principal investigator between January 2005 and October 2007 with the diagnosis of cutaneous melanoma metastatic to the eyelid and periocular skin. RESULTS: Six patients ranged in age from 26 to 84 years old (median, 55 years). Five patients had their metastatic lesion in the upper eyelid and 1 in the lower eyelid. The mean survival after the diagnosis of melanoma metastatic to the eyelid was 5.3 months. All patients had metastases at other sites detected prior to the diagnosis of the eyelid metastasis. The mean interval from initial primary tumor diagnosis to metastasis to the eyelid was 121 months. In all 6 patients, palliative surgical resection of the metastatic eyelid lesions was carried out. CONCLUSIONS: Melanoma metastatic to the eyelid is not uncommon in advanced stage cutaneous melanoma. Palliative surgical management of these metastatic lesions should be considered to improve the patient's quality of life.