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We report the case of a 3-year-old girl who presented with an elevated, darkly colored, subconjunctival lesion found to be a ciliary body cyst with extrascleral extension. The patient was treated with excision of bulbar conjunctiva, sclera, and the ciliary body cystic lesion. The defect was repaired with a scleral patch graft. The patient had a small recurrent cyst after 15 months of postsurgical follow-up, and the procedure was repeated. There was no recurrence at follow-up 1 year after the second surgery.

To investigate whether MYD88 L265P mutation, which is frequently present in vitreoretinal lymphoma, can be detected in aqueous humor, a specimen that can be obtained in a clinic setting, potentially mitigating the need for more invasive vitrectomy procedures, and whether this approach can be used to monitor treatment response.Observational case series.Patients who were diagnosed with biopsy-confirmed or clinically diagnosed vitreoretinal lymphoma or biopsy-confirmed vitritis.We evaluated aqueous humor-derived (AHD) MYD88 L265P mutation during vitreous biopsy or at the initial presentation in the clinic if vitreous biopsy was not feasible. Demographic or clinical features of patients were retrospectively reviewed. Aqueous humor-derived MYD88 L265P mutation was re-evaluated after patients completed a course of intravitreal methotrexate and rituximab injection therapy. The NM_002468.4: c.794TC (p.L265P) mutation in the MYD88 gene was evaluated in AHD cellular and cell-free DNA using allele-specific polymerase chain reaction.Detection of AHD MYD88 L265P mutation at the initial diagnosis and to monitor the treatment response.Aqueous humor from 18 eyes of 14 patients with biopsy-confirmed or clinically diagnosed vitreoretinal lymphoma and 3 eyes of 3 patients with biopsy-confirmed vitritis were evaluated. Aqueous humor-derived MYD88 L265P mutation was detected in cell-based and cell-free DNA from 15 (83%) of 18 eyes with biopsy-confirmed or clinically diagnosed vitreoretinal lymphoma but not identified in any of the 3 eyes with vitritis. The mutation was less readily detectable in cellular DNA (10 of 18) compared with cell-free DNA (15 of 18). Furthermore, aqueous sampling after intravitreal methotrexate and rituximab injection therapy revealed absence of this mutation after complete response in 7 eyes. The mutation was detected in 1 eye that developed recurrence in a posttreatment window of 6 months. After a mean of follow-up of 9 months, there was no clinical evidence of vitreoretinal lymphoma recurrence in the 7 eyes with no detectable AHD MYD88 L265P mutation.This investigational study suggests that AHD MYD88 L265P can be detected in eyes with lymphoma and may thus serve as a surrogate, less invasive biopsy in the diagnosis and follow-up of vitreoretinal lymphoma, particularly when cell-free DNA is evaluated.

Intralesional rituximab for low-grade conjunctival lymphoma provided complete response in 11(73%) eyes and partial response in 4(27%) eyes after 37-month(range,6-84) mean follow-up. Side effects were periocular swelling in 1 and allergic reaction in 2 patients.

A 65-year-old male presented with worsening periorbital pain, edema, and erythema refractory to outpatient oral antibiotics. Ophthalmologic evaluation revealed right-sided no light perception visua...

Background Basal cell carcinoma (BCC) is a common skin cancer often curable by excision; however, for patients with BCC around the eye, excision places visual organs and function at risk. In this article, we test the hypothesis that use of the hedgehog inhibitor vismodegib will improve vision‐related outcomes in patients with orbital and extensive periocular BCC (opBCC). Materials and Methods In this open‐label, nonrandomized phase IV trial, we enrolled patients with globe‐ and lacrimal drainage system–threatening opBCC. To assess visual function in the context of invasive periorbital and lacrimal disease, we used a novel Visual Assessment Weighted Score (VAWS) in addition to standard ophthalmic exams. Primary endpoint was VAWS with a score of 21/50 (or greater) considered successful, signifying globe preservation. Tumor response was evaluated using RECIST v1.1. Surgical specimens were examined histologically by dermatopathologists. Results In 34 patients with opBCC, mean VAWS was 44/50 at baseline, 46/50 at 3 months, and 47/50 at 12 months or postsurgery. In total, 100% of patients maintained successful VAWS outcome at study endpoint. Compared with baseline, 3% (95% confidence interval [CI], 0.1–15.3) experienced major score decline (5+ points), 14.7% (95% CI, 5 to 31.1) experienced a minor decline (2–4 points), and 79.4% experienced a stable or improved score (95% CI, 62.1–91.3). A total of 56% (19) of patients demonstrated complete tumor regression by physical examination, and 47% (16) had complete regression by MRI/CT. A total of 79.4% (27) of patients underwent surgery, of which 67% (18) had no histologic evidence of disease, 22% (6) had residual disease with clear margins, and 11% (3) had residual disease extending to margins. Conclusion Vismodegib treatment, primary or neoadjuvant, preserves globe and visual function in patients with opBCC. Clinical trail identification number.NCT02436408. Implications for Practice Use of the antihedgehog inhibitor vismodegib resulted in preservation of end‐organ function, specifically with regard to preservation of the eye and lacrimal apparatus when treating extensive periocular basal cell carcinoma. Vismodegib as a neoadjuvant also maximized clinical benefit while minimizing toxic side effects. This is the first prospective clinical trial to demonstrate efficacy of neoadjuvant antihedgehog therapy for locally advanced periocular basal cell carcinoma, and the first such trial to demonstrate end‐organ preservation., This article reports the results of a prospective clinical trial of vismodegib for patients with basal cell carcinoma occurring in the orbital and periocular regions to assess whether such treatment helps to preserve visual organs and function.

To report long-term outcomes of systemic rituximab therapy for idiopathic orbital inflammation (IOI) as both primary and salvage therapy and to review the English literature.A retrospective review of four consecutive biopsy-proven IOI cases managed with systemic rituximab including demographics, management, and outcomes, and review of English literature, were performed. Primary outcome measures included resolution of symptoms, recurrence, and length of follow up.Of four cases, systemic rituximab was the first-line therapy in two cases and salvage therapy in two cases. The mean age of the patients was 62 years (range, 50-68 years). The orbit was involved in three cases and extraocular muscle in one case. Systemic rituximab (1 g weekly for 4 weeks) was given for one session in three patients and for 12 sessions in 1 patient. All four patients responded with the resolution of all symptoms without recurrence after at least 5 years of follow up. Review of the literature showed systemic rituximab had provided clinical improvement at shorter follow up in 14 of 15 cases when used as a salvage therapy.Systemic rituximab therapy seems to be an effective therapy for IOI as salvage or first-line therapy with long-term clinical durability.

Importance Understanding whether statewide legislation, such as the Michigan Opioid Laws, is associated with reduction in postoperative opioid prescriptions is informative in guiding future legislation. Objective To identify changes in opioid prescribing patterns for oculoplastic and orbital procedures associated with the enactment of the Michigan Opioid Laws in 2017 and 2018. Design, Setting, and Participants This cross-sectional study included 3781 patients who underwent any of 10 common oculoplastic and orbital procedures between June 1, 2016, and November 30, 2019, at a tertiary care institution. Exposures From 2017 to 2018, Michigan enacted a series of laws to address the state's worsening opioid epidemic. Two major components of this legislation enacted on June 1, 2018, required prescribers to review a report of patients' opioid use history and obtain signed consent after educating patients on the use and disposal of opioids prior to prescribing. Main Outcomes and Measures Demographic information, type of surgery, type and amount of opioid prescriptions, and morphine milligram equivalent (MME) were analyzed. MME was calculated as the product of dose, quantity, and opioid-specific conversion factor for each prescription. Linear interpolation spline regression was used to evaluate the association of prescription MME with time. Results Of 3781 patients, 1614 (42.7%) were male. The mean (SD) age at the time of surgery was 63.3 (16.6) years. Of 2026 patients undergoing surgery before June 1, 2018, 1782 (88.0%) were prescribed postoperative opioids; of 1755 patients undergoing surgery after June 1, 2018, 878 (50.0%) were prescribed postoperative opioids (P

Purpose To evaluate the results of permanent medial tarsorrhaphy and to describe the surgical technique. Methods Medial tarsorrhaphy was performed on 30 eyelids with symptomatic exposure keratopathy secondary to eyelid malposition. Observational, retrospective review of preoperative and postoperative examination findings was performed. Results Average age of the cohort was 66 years (31-91). Medial tarsorrhaphy was performed to correct eyelid retraction (100%), exposure keratopathy (80%), lagophthalmos (57%), and ectropion (17%) in patients with cranial nerve VII palsy (47%), Graves eye disease (13%), eczema (7%), floppy eyelid syndrome (7%), after Mohs reconstruction (7%), orbital myositis (3%), and neurofibromatosis (3%). Seventy-three percent (73%) of patients had an average of 3 surgeries (N = 22, standard deviation = 1.12, range = 2-7) before undergoing medial tarsorrhaphy. Medial tarsorrhaphy was performed in combination with another procedure in 53% of cases. Palpebral fissure decreased postoperatively an average of 1.1 mm (N = 20; p = 0.005), inferior scleral show decreased 0.72 mm (N = 22; p = 0.03), lagophthalmos decreased 0.4 mm (N = 15; p = 0.27), and superficial punctate keratopathy improved by 61% (N = 27; p = 0.009). Ectropion completely resolved in 4 of 10 patients (40%). Seven patients (23%) required additional surgery following tarsorrhaphy an average of 8 months later (range = 2-16). In 1 patient (3%), a tarsorrhaphy opened prematurely, and 1 patient (3%) requested partial opening of the tarsorrhaphy. Average duration of follow up was 13 months (N = 30, standard deviation = 14.97, range = 0.2-45.7). Conclusions Medial tarsorrhaphy is a safe and effective primary or salvage technique to address complex causes of eyelid retraction, lagophthalmos, ectropion, and exposure keratopathy.

Immune checkpoint inhibitors were effective and well tolerated in advanced conjunctival squamous cell carcinoma with orbital extension. Of five tumors, four with high mutation burden showed complete and durable response after a mean follow-up of 6 months.

Anti-VEGF treatment of diabetic macular edema (DME) complicating diabetic retinopathy (DR) has greatly improved structural and visual outcomes for patients with diabetes mellitus. However, up to 50% of patients are either nonresponsive or refractory to anti-VEGF treatment (no improvement in BCVA or central macular thickness (CMT)). It is believed that factors such as mitochondrial structural and functional damage, due to oxidative stress, are partially responsible for this lack of improvement. Flavoprotein fluorescence (FPF) has been shown to be a sensitive marker of mitochondrial function and has been found to correlate with the degree of diabetic retinopathy. FPF may also provide additional information regarding therapeutic response of patients receiving anti-VEGF treatment for DME. Eight patients with DR and DME with clinically significant DME (CSDME) who underwent anti-VEGF (bevacizumab) treatment were imaged before injection and at follow-up visit using FPF in addition to standard color fundus photography and OCT CMT. A strong correlation r=0.98 (p=0.000015) between the FPF decrease and the BCVA improvement was observed; BCVA improved as FPF values decreased. Notably, in the same patients, the correlation between OCT CMT decrease and BCVA improvement (r=0.688) was not found to be significant (p=0.13). These findings suggest that FPF can detect improvement in metabolic function preceding structural improvement and even with small changes in edema. Additionally, FPF may be supplementary to current diagnostic methods for earlier detection of therapeutic response to anti-VEGF treatment in patients with DME.

CD40L signaling occurs in several diseases with inflammatory components, including ocular and retinal diseases. However, it has never been evaluated as a pathogenic mechanism in age-related macular degeneration (AMD) or as an inducer of inflammasome formation in any cell type. mRNA and protein levels of CD40, IL-1β, NALP1, NALP3, caspase-1, and caspase-5 were determined by RT-PCR, qPCR, and Western blot. CD40L receptor (CD40, α5β1, and CD11b) expression was determined by Western and immunofluorescent staining. IL-1β, IL-18, and MCP-1 secretions were determined by ELISA. NALP1 and NALP3 inflammasome formation were determined by Co-IP. Experiments were conducted on primary human retinal pigment epithelial (hRPE) cells from four different donors. Human umbilical vein endothelial (HUVEC) and monocytic leukemia (THP-1) cells demonstrated the general applicability of our findings. In hRPE cells, CD40L-induced NALP1 and NALP3 inflammasome activation, cleavage of caspase-1 and caspase-5, and IL-1β and IL-18 secretion. Interestingly, neutralizing CD11b and α5β1 antibodies, but not CD40, reduced CD40L-induced IL-1β secretion in hRPE cells. Similarly, CD40L treatment also induced HUVEC and THP-1 cells to secret IL-1β through CD11b and α5β1. Additionally, the CD40L-induced IL-1β secretion acted in an autocrine/paracrine manner to feed back and induce hRPE cells to secrete MCP-1. This study is the first to show that CD40L induces inflammasome activation in any cell type, including hRPE cells, and that this induction is through CD11b and α5β1 cell-surface receptors. These mechanisms likely play an important role in many retinal and non-retinal diseases and provide compelling drug targets that may help reduce pro-inflammatory processes.

A 12-year-old boy and 63-year-old woman were incidentally found to have a solitary, well-defined, raised, ovoid lesion involving the inferomedial palpebral conjunctiva. Both lesions were separate from the lacrimal caruncle with normal conjunctiva surrounding the lesions. Excisional biopsies were consistent with caruncular tissue. In the English literature, supernumerary lacrimal caruncle has only been previously described in adults despite the congenital nature of the lesion.

Microphthalmia is defined by a globe axial length greater than or equal to 2 standard deviations below the age-adjusted mean and can occur as part of a broader syndrome. The presence of a colobomatous cyst with microphthalmia signifies failure of the embryonic neuroectodermal fissure to close appropriately during development of the globe, creating a protuberant globular appendage that inhibits normal growth and development of the eye itself. Cystic reaccumulation of fluid is common after aspiration or surgical removal. Here, the authors describe a case of a young boy with a colobomatous cyst who underwent eyelid-sparing orbital exenteration followed by reconstruction with absorbable gelatin sponge (Gelfoam, Pfizer, Inc.) and the chemotherapeutic agent bleomycin to promote scarring, achieving the equivalent of a biointegrated implant and facilitating satisfactory placement of an ocular prosthesis. A 2-year follow-up MRI revealed adequate volume in the posterior orbit.

BACKGROUND AND OBJECTIVE: To describe the ocular toxicity of intravitreal carboplatin and etoposide phosphate (VP16P) in Dutch-Belted rabbits. MATERIALS AND METHODS: Twenty-two adult male Dutch-Belted rabbits (Cohort 1) each received a single, bilateral intravitreal injection (0.05 mL). For Cohort 1, safety was assessed via electroretinograms (ERGs) and ocular examination. Of nine total groups in Cohort 1, the first five received the following single agents: Group 1: normal saline; Group 2: VP16P 75 µg; Group 3: VP16P 100 µg; Group 4: carboplatin 4 µg; and Group 5: carboplatin 8 µg. Groups 6 through 9 received the following combination of carboplatin/ VP16P, respectively: Group 6: 8 µg/75 µg, Group 7: 8 µg/50 µg, Group 8: 4 µg/50 µg, and Group 9: 2 µg/25 µg. Cohort 2 consisted of 15 Dutch-Belted rabbits in seven groups (Groups 10 through 16), each receiving a single, bilateral intravitreal injection. For Cohort 2, safety was assessed via histopathology. RESULTS: Groups 2 through 8 demonstrated a statistically significant decrease (relative to Group 1) in at least one ERG waveform amplitude obtained 4 weeks postinjection ( P < .05). Group 9 (carbo 2 µg/VP16P 25 µg) did not manifest ERG toxicity. Fundoscopic toxicity consisted of slight-to-moderate attenuation of vessels in rabbits receiving doses above carbo 4 µg/VP16P 50 µg. Histopathologic retinal toxicity (Cohort 2) was dose-dependent, ranging from full-thickness atrophy in rabbits receiving the highest dose to normal in rabbits receiving carbo 2 µg/VP16P 25 µg. CONCLUSIONS: Combined carboplatin and VP16P may be compatible for intravitreal injection therapy, and a single dose of 2 µg/25 µg appears to be safe in a rabbit model. These agents may be a safer alternative to intravitreal melphalan (Alkeran; GlaxoSmithKline, Brentford, United Kingdom) for the treatment of vitreous seeds in retinoblastoma. [ Ophthalmic Surg Lasers Imaging Retina . 2017;48:151–159.]

PURPOSE The aim of this study was to evaluate expression patterns of known lymphangiogenic growth factors and chemokines in conjunctival melanoma, and to describe patterns of lymphatic vessel growth in these tumors. METHODS This was a retrospective chart review comprising 5 participants (6 tumor specimens) and the main outcome measures were expression of growth factors, chemokines, and their receptors known to be important in tumor lymphangiogenesis as well as patterns of lymphatic vessel growth on immunohistochemical sections. RESULTS Tumor cells in all specimens expressed lymphangiogenic growth factors VEGFC, VEGFD, and their receptor VEGFR3. Chemotactic factors CXCL12 and CCL21 and their receptors, CXCR4 and CCL21, were also expressed in tumor cells and lymphatic endothelial cells. Staining was most intense for these proteins at the invasive tumor edge, suggesting increased lymphangiogenic activity at this location. In addition, lymphatic vessels clustered near the invasive edge of the tumors. CONCLUSIONS VEGFC, VEGFD, and VEGR3 are diffusely expressed by conjunctival melanoma cells, most intensely at the invasive tumor edge. CXCL12, CXCR4, CCL21, and CCR7 were also most intensely expressed at the invasive edge, where the highest density of lymphatic vessels was also observed. These expression patterns suggest that these mediators of tumor-associated lymphangiogenesis warrant further investigation as potential therapeutic targets in conjunctival melanoma.

Thyroid eye disease (TED) usually has mild manifestations in pediatric patients, and orbital decompression is rarely necessarily. The authors present the clinical course of 3 pediatric patients age 16 or younger at the time of decompression surgery with severe orbitopathy. Case 1 is a 9-year-old prepubertal Asian-American female with Graves' disease and TED who underwent balanced decompression for compressive optic neuropathy. Case 2 is a 14-year-old white female with Graves' disease and TED who underwent balanced decompression for compressive optic neuropathy, stretch optic neuropathy, and globe subluxation. Case 3 is a 14-year-old African-American male with unilateral euthyroid TED who underwent staged right-sided lateral, medial, and floor decompressions for asymmetric proptosis. All cases also had disfiguring proptosis and exposure keratopathy, and in all cases, surgery successfully ameliorated the indications. Children, both pre- and post-pubertal, can rarely manifest visually threatening severe orbitopathy due to TED. This represents the first reports of thyroid-related optic neuropathy and globe subluxation in pediatric patients. Further studies examining the mechanism responsible for the disparities in pediatric and adult TED are warranted.

Purpose Evaluate the effectiveness of vismodegib in the management of basal cell carcinoma with orbital extension and/or extensive periocular involvement. Methods Retrospective chart review of 6 consecutive patients with biopsy-proven orbital basal cell carcinoma and 2 additional patients with extensive periocular basal cell carcinoma who were treated with oral vismodegib (150 mg/day) was performed. Results Basal cell carcinoma extended in the orbit in 6 of 8 patients (involving orbital bones in 1 patient), and 2 of 8 patients had extensive periocular involvement (1 with basal cell nevus syndrome). Vismodegib therapy was the only treatment in 6 patients, off-label neoadjuvant in 1 patient, and adjuvant treatment in 1 patient. Orbital tumors in all 4 patients who received vismodegib as sole treatment showed partial response with a mean 83% shrinkage in tumor size after a median of 7 months of therapy. In the 2 patients receiving vismodegib as neoadjuvant or adjuvant therapies, there was complete response after a median of 7 months of therapy and no evidence of clinical recurrence after discontinuing therapy for a median of 15 months. The 2 patients with extensive periocular involvement experienced complete clinical response after a median 14 months of treatment. During treatment, the most common side effects were muscle spasm (75%) followed by alopecia (50%), dysgeusia (25%), dysosmia, and episodes of diarrhea and constipation (13%). Conclusions Basal cell carcinoma with orbital extension and extensive periocular involvement responds to vismodegib therapy. The long-term prognosis remains unknown, and additional prospective studies are indicated.

ObjectiveTo investigate the inflammatory response in giant cell arteritis (GCA) by characterising the DNA methylation pattern within the temporal artery microenvironment.MethodsTwelve patients with non-equivocal histological evidence for GCA and 12 age-matched, sex-matched and ethnicity-matched controls with normal biopsies were studied. DNA was extracted from the affected portions of temporal artery tissue in patients with GCA and from histologically confirmed normal arteries in controls. Genome-wide DNA methylation status was evaluated using the Illumina Infinium HumanMethylation450 BeadChip Array. Differentially methylated loci between affected and unaffected arterial tissues were identified, and subsequent bioinformatic analysis performed. Immunohistochemistry was used to examine tissue expression patterns in temporal artery biopsies.ResultsWe identified 1555 hypomethylated CG sites (853 genes) in affected temporal artery tissue from patients with GCA compared with normal controls. Gene ontology enrichment analysis of hypomethylated genes revealed significant representation in T cell activation and differentiation pathways, including both TH1 and TH17 signatures. Our DNA methylation data suggest a role for increased activity of the calcineurin/nuclear factor of activated T cells (NFAT) signalling pathway in GCA, confirmed by immunohistochemistry showing increased expression and nuclear localisation of NFAT1. NFAT signalling downstream targets such as interleukin (IL)-21/IL-21R and CD40L were overexpressed in GCA-affected arteries. Further, proinflammatory genes including TNF, LTA, LTB, CCR7, RUNX3, CD6, CD40LG, IL2, IL6, NLRP1, IL1B, IL18, IL21, IL23R and IFNG were hypomethylated in the cellular milieu of GCA arteries.ConclusionsWe characterised the inflammatory response in GCA-affected arteries using ‘epigenetic immunophenotyping’ and identified molecules and pathways relevant to disease pathogenesis in GCA.

PRESENTATION A 20-year-old woman presented with a 4-day history of left upper eyelid swelling with erythema and tenderness (Figure 1). Two months prior to presentation, she had a similar episode on the left side, which was diagnosed at an outside facility as a chalazion with associated preseptal cellulitis. Her symptoms resolved with 4 days of oral cephalexin. One month later, she developed similar symptoms on the right side. She was again diagnosed with preseptal cellulitis in the setting of a chalazion, and her symptoms resolved with 7 days of oral cephalexin. Her review of systems was positive for 3-4 years of intermittent joint swelling and pain. Initially, small joints, but recently also medium joints, were involved. The pain and swelling would occur in 1-2 joints for 1-2 weeks and then shift to another 1-2 joints. In addition, she noticed several enlarged cervical and axillary lymph nodes for the past 2 years. She also had dry mouth in the morning, but no significant dry eye symptoms. She noted no fever, chills, night sweats, or weight loss, but had chronic fatigue for 2 months. She also had mild chronic facial erythema that did not worsen with sun exposure. Her family history was notable for her mother having been affected by an unspecified connective tissue disease. On ophthalmologic examination, her visual acuity was 20/20 in both eyes, with normal color vision. Her pupils were normal, with no relative afferent pupillary defect. Her intraocular pressure was normal. She was orthophoric and had no subjective double vision. Right extraocular movements were full, but her left eye showed mildly limited abduction and supraduction. Her confrontation visual fields

The authors present a unique case of bilateral isolated choroidal melanocytosis in an annular pattern that, to our knowledge, has not previously been described. A 44-year-old asymptomatic American Indian woman presented with bilateral choroidal hyperpigmentation in an annular pattern for 12 clock hours around the peripheral retina. No other uveal, scleral, or cutaneous hyperpigmentation was observed. Optical coherence tomography did not demonstrate choroidal thickening or subretinal fluid. The diagnosis of bilateral isolated choroidal melanocytosis was made. Long-term follow-up of this patient and other cases described in the literature is necessary to determine the malignant potential of these lesions. [ Ophthalmic Surg Lasers Imaging Retina . 2019;50:e74–e76.]

Importance Ocular sarcoidosis may be the primary and only clinical manifestation of sarcoidosis, and irreversible loss of visual acuity may occur from delayed treatment. Thus, early diagnosis is imperative to preserve visual acuity. Establishing the diagnosis of sarcoidosis in cases manifesting only in the eye may require a diagnostic biopsy, which may prove challenging in the absence of available ocular surface, lacrimal gland, and systemic tissue for biopsy. Objective To describe diffuse or segmental ciliary body mass as a clinical sign and tissue source for biopsy in the diagnosis of ocular sarcoidosis. Design, setting, and participants This case series captures 3 cases from a university-based ocular oncology and uveitis practice. All 3 patients presented with uveitis and a diffuse or segmental ciliary body mass, which was identified via ultrasonographic biomicroscopy. Main outcomes and measures Clinical, ancillary, and histopathological ocular findings in the 3 patients. Results The patients were a 52-year-old white woman, a 42-year-old African American man, and an 81-year-old white man. Two individuals had unilateral involvement, and 1 had bilateral involvement. All 3 individuals presented with uveitis. Diffuse, circumferential ciliary body masses were observed in 2 patients. A localized, nodular ciliary body mass on the temporal quadrant with superior and inferior extensions was observed in 1 patient. Moderate to high internal reflectivity was observed on ultrasonographic biomicroscopy in all 3 individuals. Biopsies of the ciliary body masses were diagnosed as sarcoidosis in all 3 patients. Conclusions and relevance These findings support that diffuse or segmental ciliary body mass may serve as a clinical sign and tissue source for biopsy in the diagnosis of ocular sarcoidosis, although the frequency of this cannot be determined from 3 cases. To our knowledge, such cases all demonstrate a uveitic component; whether a ciliary body mass caused by sarcoidosis can occur in the absence of uveitis remains unknown.

PURPOSE To determine surgical outcomes after transcranial decompression of the superior orbit in patients with progressive compressive optic neuropathy (CON) secondary to Graves' orbitopathy (GO) who had previously been treated with 3-wall decompression. METHODS Approval from the West Virginia University Institution Review Board was obtained. A retrospective review of 4 patients with GO who received bilateral transcranial decompression of the orbits for progressive compressive optic neuropathy after bilateral maximal extracranial 3-wall decompression was performed. The patients were treated by the Multidisciplinary Orbit and Skull Base Services at West Virginia University and the University of Michigan. RESULTS Bilateral transcranial decompression of the orbit for GO was performed on 8 orbits in 4 patients. All 8 orbits had radiographic evidence of compression of the orbital apex, and all patients had been treated with steroids, orbital radiation, and bilateral 3-wall decompression. Preoperative vision ranged from 20/25 to 20/100, which improved to 20/25 or better in all eyes. The visual field mean deviation improved from a mean of -13.05 to -1.67 dB. Hertel measurements improved from a mean of 19.25 to 15.25 mm. Extraocular motility was essentially unchanged. Two patients were noted to have asymptomatic ocular pulsations. There were no other complications, and all patients remained stable during a follow-up period of 5 years (range 2-8 years). CONCLUSIONS Transcranial decompression is an effective and safe method of salvaging vision when standard treatments fail. This is only the second report of transcranial decompression for refractory compressive optic neuropathy after decompression from a standard approach.

IMPORTANCE: Greater understanding of molecular features of conjunctival melanoma (CM) may improve its clinical management. OBJECTIVE: To evaluate molecular features of CM and application of this information into clinical care. DESIGN, SETTING, AND PARTICIPANTS: In a prospective case series of CM with integrative exome and transcriptome analysis, 8 patients at an academic ocular oncology setting were evaluated. The study was conducted from November 2015 to March 2018. INTERVENTIONS/EXPOSURES: Integrative exome and transcriptome analysis of CMs and clinical management of a patient’s care by using this information. MAIN OUTCOMES AND MEASURES: Molecular characterization of CM and its potential clinical application. RESULTS: In the 8 patients (4 men) included in analysis, 4 subgroups of CM were observed, including the BRAF V600E mutation in 1 tumor, NRAS Q61R mutation in 3 tumors, NF1 mutations (Q1188X, R440X, or M1215K+ S15fs) in 3 tumors, and triple-wild type (triple-WT) in 1 tumor. The triple-WT case had CCND1 amplification and mutation in the CIC gene (Q1508X). Five tumors, including the triple-WT, also harbored mutations in MAPK genes. In addition to the genes linked to mitogen-activated protein kinase and phosphoinositol 3-kinase pathways, those involved in cell cycle and/or survival, ubiquitin-mediated protein degradation, and chromatin remodeling/epigenetic regulation (ATRX being the most frequently mutated: noted in 5 tumors) may play an important role. Other frequently mutated genes included PREX2 (n = 3), APOB (n = 4), and RYR1/2 (n = 4), although their relevance remains to be determined. The mutation burden ranged from 1.1 to 15.6 mutations per megabase (Mut/Mb) and was 3.3 Mut/Mb or less in 3 tumors and more than 10 Mut/Mb in 2 tumors. A patient with a large tumor and BRAF V600E mutation was treated with combined systemic BRAF (dabrafenib) and MEK (trametinib) inhibitors. After 3 months of therapy, her CM responded substantially and the residual tumor was removed by local surgical excision. CONCLUSIONS AND RELEVANCE: The NRAS Q61R and NF1 mutations were more common than the BRAF V600E mutation in this series. Although small tumors (where incisional biopsy is not indicated) are treated with surgical excision regardless of mutational profile, in large tumors carrying the BRAF V600E mutation, neoadjuvant therapy with combined systemic BRAF and MEK inhibitors followed by local excision may be used as an alternative to exenteration. Integrative omics analysis of CM may be informative and guide clinical management and treatment in selected cases.

Purpose Uveal lymphomas are indolent, frequently choroid-involving neoplasms that are mainly CD20-positive B-cell extranodal marginal zone lymphoma. Irreversible visual loss may occur from retinal detachment and/or glaucoma among untreated symptomatic patients, or from radiation-induced changes secondary to external beam radiotherapy. To avoid radiation-induced complications, we used systemic rituximab monotherapy as primary treatment, and present two cases to show its long-term effectiveness for symptomatic primary uveal lymphoma. Observations Two elderly men who presented with painless blurred vision were clinically diagnosed with symptomatic primary uveal lymphoma, which were biopsy-confirmed to be marginal zone lymphoma. Both patients with symptomatic, primary marginal zone uveal lymphoma that appeared as multiple yellow, nummular choroidal infiltrates, had complete ocular remission after three and one cycles of systemic rituximab monotherapy (375mg/m2 infused intravenously once weekly for four consecutive weeks), with disappearance of the lesions and improvement of visual acuity. Both patients tolerated systemic monotherapy well without any adverse systemic or ocular effects. There was no local ocular recurrence at 29 and 39 months after the last treatment. Conclusions and Importance: Systemic rituximab monotherapy induced complete ocular remission and improved visual acuity, without adverse effects, and without local ocular recurrence of uveal lymphoma 29-39 months following the last treatment. To our knowledge, this is the first manuscript to show long-term effectiveness of systemic rituximab monotherapy as the primary treatment for symptomatic primary uveal lymphoma. Long-term follow-up of this indolent neoplasm is still imperative to monitor its ocular and systemic course.

To investigate the practice patterns of office-based counseling on the importance of protective eyeglasses in monocular patients and to offer our counseling recommendations.In this cross-sectional study, data were collected in the form of surveys. Surveys were administered at an oculoplastic ophthalmology clinic in Michigan. Inclusion criteria included adults with vision of 20/400 or worse in only 1 eye. Survey questions were focused on whether patients with monocular vision recall being previously counseled by their primary ophthalmologist about wearing eye protection.A total of 60 surveys were completed. The average age was 62.2 years old (range: 23-90 years old). Of the completed surveys, 56.7% (34/60) did not recall receiving education about wearing protective glasses over their better seeing eye, while 35.0% (21/60) recalled having received education from their referring ophthalmologist about eye protection, and 8.3% (5/60) were uncertain about receiving eye protection counseling. Twenty (33.3%) patients reported the reason for decreased vision. Of those, 35% (7/20) of patients reported monocular vision resulting from trauma, while 65% (13/20) reported vision loss due to other reasons. There was no significant difference in recall of receiving counseling about the importance of eye protection between the 2 groups (p = 0.74).The results of this study highlight the current counseling short-comings, as more than half (56.7%) of patients surveyed did not recall being counseled on the importance of protecting their better seeing-eye, or ways of doing so. More counseling on protective eyewear needs to be incorporated into the preferred practice pattern for care of patients with monocular visual impairment because these patients are vulnerable to the devastating consequences of complete blindness as a result of an injury to their functioning eye.

A 2-month-old boy diagnosed with a mosaic chromosome 18q partial deletion syndrome was referred for bilateral cloudy corneas. The abnormal metaphases had a terminal deletion of the long arm of chromosome 18 as clonal abnormality. The cytogenetics findings were 46,XY, del (18)(q21.2)[12]/46,XY[20]. Ocular findings included bilateral microcornea with dense opacification and unilateral iris and chorioretinal coloboma. Penetrating keratoplasty (PK) was performed on both eyes. Histopathology of the host corneal button showed complete loss of Bowman’s layer, hyperkeratosis of the epithelium, stromal neovascularization, and leukocyte infiltration. Descemet’s membrane and endothelium were irregular in both specimens. CD45 stain for leukocytes confirmed perivascular and epithelial leukocytes infiltration. Mosaic chromosome 18q deletion syndrome is a rare genetic abnormality with a variable phenotype – including ocular findings – and hence, warrants an ophthalmic evaluation and genetic counseling.

The authors describe a 39-year-old woman treated with fingolimod for relapsing-remitting multiple sclerosis for 2 years who then developed a bilateral conjunctival mucosa-associated lymphoid tissue lymphoma. Fingolimod treatment for multiple sclerosis has been associated with lymphoma in 3 previously reported cases. This is the first case of ocular adnexal lymphoma presumed to be due to fingolimod. Given that ophthalmologists regularly monitor many patients on fingolimod for fingolimod-associated macular edema and ophthalmic manifestations of multiple sclerosis, the authors hope to alert physicians of the possibility of ocular adnexal lymphoma in these patients.

BACKGROUND AND OBJECTIVE: Oxidative stress and mitochondrial dysfunction are implicated in the pathogenesis of age-related macular degeneration (AMD). Because increased flavoprotein fluorescence (FPF) is indicative of mitochondrial dysfunction, the authors attempted to detect mitochondrial dysfunction in eyes with AMD using FPF. PATIENTS AND METHODS: Six nonexudative eyes with AMD, including three with geographic atrophy (GA), and age-matched control eyes were imaged with a FPF device. Qualitative and quantitative analyses were conducted on the FPF images. RESULTS: Five eyes with AMD, including all three eyes with GA, showed qualitative and/or quantitative FPF heterogeneity that was not present in control eyes. Mean FPF average intensities of eyes with AMD with ( P = .044) and without ( P = .00060) GA were significantly greater than those of control eyes. The standard deviations of FPF images were greater in eyes with AMD ( P = .020). CONCLUSION: In this small cluster of patients with AMD, retinal FPF is increased, suggesting elevated mitochondrial dysfunction. FPF heterogeneity indicates that an increased variability in mitochondrial dysfunction seems to be present in eyes with advanced disease.

Purpose To determine intraobserver and interobserver reliability of 3 clinical techniques for measuring ocular ductions in patients with thyroid eye disease and to compare these with an established method using a Goldmann perimeter. Our secondary goals were to compare the clinical methods for test duration, ease of learning and performance, and whether these differed between novices and experts. Design Multicenter, prospective, comparative trial. Participants We recruited 38 patients with thyroid orbitopathy and reduced ocular motility from 7 academic centers. Methods At each center, 2 novices and 2 experts measured the ocular ductions of each eye of each patient in 4 directions (0°, 90°, 180°, and 270°) using 3 techniques (best guess [BG], light reflex [LR], and a ruler measuring [RU] technique). Test duration and clinicians' feedback were recorded. A subjective and objective measurement for ocular ductions using a Goldmann perimeter was performed for each subject by a trained technician. The 3 clinical measurements and the perimetry measurements were performed twice, separated by ≥1 hour. Main Outcome Measures We measured the intraobserver and interobserver reliability of the 3 clinical techniques and intraobserver reliability of Goldmann perimeter. Clinical testing reliability was compared between experts and novices. We also examined test duration and clinician feedback. Results The LR technique had significantly better intraobserver and interobserver repeatability compared with the BG or RU clinical measurements and statistically was equivalent to the gold-standard perimetric technique. Reliability was constant regardless of the amount of restriction in ocular movement. There was no difference between reliability values for experts and novices. The LR and BG techniques were significantly faster than the RU or perimetry techniques and were considered easiest to learn and perform, but clinicians had most confidence in the LR technique results. Conclusions The LR technique for measuring ocular ductions in thyroid orbitopathy is more reliable than other clinical techniques and as reliable as the established technique using the perimeter. However, unlike the latter method, it is easier to learn and perform by both novices and experts, is significantly faster, and can be performed by the clinician without machinery or a trained technician. Financial Disclosure(s) The authors have no proprietary or commercial interest in any of the materials discussed in this article.

To determine the ocular toxicity of intravitreally injected daptomycin, a novel antibiotic for treatment of vancomycin-resistant organisms, and its efficacy in treating intraocular infection with coagulase-negative Staphylococcus epidermidis.Four doses of intravitreal daptomycin were injected (75, 188, 375, and 750 μg) into 1 eye of Dutch belted rabbits (n = 3 per dose). Clinical examination, electroretinography, and histologic analysis were performed preinjection and 2 weeks after injection and compared with the fellow eye that received only intravitreal balanced salt solution. Experimental S epidermidis endophthalmitis was induced in Dutch belted rabbits (n = 24), and the ability of 200 μg of intravitreal daptomycin to result in culture-negative vitreous samples was measured at 24 hours and 48 hours.Seventy-five micrograms and 188 μg of daptomycin demonstrated acceptable safety profiles when injected intravitreally in Dutch belted rabbits. There was a dose-dependent increase in cataract formation, electroretinogram suppression, and photoreceptor damage with higher doses. Two hundred micrograms of intravitreal daptomycin resulted in near-complete vitreous sterilization 24 hours after treatment. Vitreous sterilization was complete by 48 hours.A dose of 200 μg of intravitreal daptomycin appears to be safe and efficacious in a rabbit model of bacterial endophthalmitis. Future investigations should focus on daptomycin as a therapeutic option for treating intraocular infection caused by vancomycin-resistant organisms.

Purpose: To compare the efficacy of lateral orbital decompression with medial orbital decompression for the treatment of compressive optic neuropathy (CON) caused by thyroid eye disease (TED). Methods: A retrospective review of all patients undergoing orbital decompression for TED-associated CON between 2003 and 2008 was conducted. Clinical outcome measures included visual acuity, mean deviation on Humphrey visual field, Ishihara color plate testing, afferent pupillary defect, and Hertel exophthalmometry. A composite CON score was also calculated for each patient based on the 3 visual outcome measures, with a higher CON score reflecting greater disease severity. Results: Twenty-eight eyes of 17 patients were included in the study. Ten orbits underwent lateral wall decompression, and 18 orbits underwent medial decompression. Both groups showed a significant postoperative improvement in visual acuity, Humphrey visual field testing, and color testing at 3 months following the initial surgery. The composite CON score improved 9.04 ± 9.97 points after lateral decompression (p = 0.02) and 9.03 ± 10.84 points after medial decompression (p = 0.003). There was no significant difference in the degree of improvement in any of the visual outcome measures between the lateral and medial groups. There was a statistically significant difference in the amount of proptosis reduction resulting from lateral decompression compared with medial decompression (6.3 versus 3.1 mm, respectively, p Conclusions: Lateral orbital decompression and medial orbital decompression are both efficacious for the treatment of TED-associated CON. Lateral decompression also results in a greater proptosis reduction than medial decompression.

Molecular biologic studies have elucidated the roles of specific and innate immune responses in the pathogenesis of HSV keratitis. Recent evidence suggests that interference with innate immune mechanisms may reduce the severity of HSV keratitis and its complications. The agents targeting innate immune responses are particularly amenable to translational therapy for patients at risk of complications of HSV keratitis and poor corneal transplant outcomes. Histopathologic evidence of neovascularization or inflammation in tissue removed at the time of corneal transplantation predicts patients who are at risk for allograft rejection or failure. Such patients are prime candidates for close monitoring and intensive therapy. Newer imaging techniques, such as clinical confocal biomicroscopy, might be useful in identifying neovascularization and inflammation that place patients at high risk for poor allograft outcomes prior to corneal transplantation.

Purpose: To evaluate the efficacy of ultrasonic bone removal during lateral orbital decompression for thyroid eye disease. Methods: Retrospective, comparative, interventional case series of lateral orbital decompressions performed by the senior author for thyroid eye disease between July 2005 and July 2008. Patients were excluded if they had other coexisting orbital conditions or concurrent decompression of other orbital walls. Primary outcome measures included visual acuity, proptosis, lagophthalmos, eyelid retraction, and exposure keratopathy. Results: Thirty-six consecutive lateral orbital decompressions performed by the senior author were reviewed. The Sonopet Omni ultrasonic surgical aspirator was used to remove the lateral wall in 18 cases, and a high-speed drill with a cutting burr was used in the other 18 cases. There was no significant difference between the groups in postoperative visual acuity, proptosis reduction, lagophthalmos, eyelid retraction, exposure keratopathy, or surgical complications. The average reduction in proptosis was 3.9 mm (range, 1–6.5 mm) in the Sonopet group and 4.0 mm (range, 1–6 mm) in the drill group (p = 0.86). In our series, the average surgical case time was slightly shorter in the Sonopet group than in the drill group (104 vs. 118 minutes, p = 0.032). Conclusions: Ultrasonic bone removal is a safe and effective alternative to high-speed burring during lateral orbital decompression for thyroid eye disease.

Purpose:To test whether eyes with central serous retinopathy have elevated retinal flavoprotein fluorescence (FPF) using a novel clinical imaging method.Methods:Three male patients with unilateral central serous retinopathy were examined for FPF at 535 nm induced by 1-msec flashes of 467 nm light. F

Objective To identify whether histopathologic and immunoassay biomarkers of inflammation are predictive for allograft rejection after penetrating keratoplasty (PKP) for herpes simplex virus (HSV) keratitis. Design Retrospective, interventional case series with prospective component of pathologic evaluation of frozen tissue. Participants Sixty-two consecutive patients with HSV keratitis who underwent PKP. Methods A chart review and histopathologic examination of the excised host corneal button was performed to identify associations between clinical data and histopathologic presence of inflammation. Enzyme-linked immunosorbent assay for interleukin (IL)-8 and monocyte chemotactic protein-1 (MCP-1) chemokines and immunohistochemical staining for human leukocyte antigen (HLA)-DR and intercellular adhesion molecule-1 (ICAM-1) antigens was also performed in inflamed and noninflamed specimens. Main Outcome Measures To determine whether the presence of subclinical inflammation at the time of PKP predicts allograft rejection. Results Although 81% of patients had clinically quiescent disease, histopathology revealed that 74% had active corneal inflammation, a finding that was associated with the presence of clinical neovascularization ( P = 0.01). Allograft rejections were experienced by 34% of the patients in this cohort. The histopathologic presence of inflammation was a risk factor for allograft rejection ( P = 0.02). Corneal specimens demonstrating inflammation had significantly increased IL-8 ( P = 0.0005) and MCP-1 ( P = 0.003) levels, and greater immunoreactivity for HLA-DR and ICAM-1 when compared with specimens without inflammation. Treatment with IL-10 ex vivo significantly inhibited IL-8 ( P = 0.006), and MCP-1 ( P = 0.01) chemokines, and qualitatively substantially reduced HLA-DR, but not ICAM-1, expression. Conclusions Histopathologic inflammation is a risk factor for corneal allograft rejection. Financial Disclosure(s) The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Low-level, steady electric fields of 6-10 voltskm stimulated directional orientation and translo- cation of cultured human retinal pigment epithelial cells. The orientative movements (galvanotropism) consisted of somatic elongation of the cells into spindle shapes, fol- lowed by pivotal alignment orthogonal to the field. The anodal edges of the cells underwent retraction of their plasmalemmal extensions, while the cathode edges and the longitudinal ends developed lamellipodia and ruf- fled membranes. These tropic movements were followed by a translocational movement (galvanotaxis) of the cells towards the cathode. Staining of these migrating cells for actin showed the accumulation of stress fibers at the leading (cathodal) edge, as well as at the longitudinal ends of the elongated somata. These results suggest that endogenous, biologically-generated electric fields (eg., injury currents) may play a role in the guidance and mi- gration of retinal pigment epithelial cells after retinal in- Directional shape changes and movements during cell migration are controlled by several extrinsic factors, such as contact inhibition, chemotaxis, haptotaxis, and contact guidance (Trinkaus 1982). In this study, we investigate yet another possible factor that may play a role in controlling cell mi- gration, namely electric (E) fields. The influence of physiological E-fields on the modulation of direc

A 41-year-old female with Sjogren syndrome presented with a 5-month history of bilateral upper eyelid swelling. Incisional biopsy of the left lacrimal gland revealed mucosa-associated lymphoid tissue lymphoma. Due to bilateral severe dry eyes, the patient declined external beam radiotherapy and systemic rituximab was initiated. The patient responded well to intravenous rituximab and the follow-up CT revealed decrease in size of both lacrimal glands. Eleven months after systemic rituximab, the patient developed bilateral lacrimal gland recurrence. The patient declined external beam radiotherapy. Intralesional rituximab (50 mg/1 ml) was injected into the left lacrimal gland, followed by injection in the right lacrimal gland 7 months later. Twenty-three months follow-up after the injection into the right lacrimal gland, there was significant decrease in size of bilateral lacrimal glands and subjective improvement of dry eye symptoms. This case highlights the intralesional rituximab as an alternative therapy for recurrent orbital mucosa-associated lymphoid tissue lymphoma in selected cases.

Reactive oxygen species (ROS) generated during inflammation are believed to play critical roles in various ocular diseases. However, the underlying mechanisms remain poorly understood. We investigated if pro-inflammatory cytokines, tumor necrosis factor (TNF)-alpha, interleukin-1 beta (IL-1 beta), and interferon-gamma (IFN-gamma), induce ROS in human retinal pigment epithelial (RPE) cells. TNF-alpha, IL-1 beta and IFN-gamma increased both intracellular and extracellular ROS production in a time- and dose-dependent manner. Thenoyltrifluoroacetone (TTFA), an inhibitor of mitochondrial respiratory chain, blocked TNF-alpha- and IFN-gamma-, but not IL-1 beta-induced ROS, whereas other two mitochondrial respiratory chain inhibitors, rotenone and antimycin A, had no effect. NADPH oxidase inhibitor (diphenylene iodinium) abolished the ROS production induced by IL-1 beta or IFN-gamma, but not by TNF-alpha, whereas 6-aminonicotinamide (6AN), an inhibitor of the hexose monophosphate shunt (HMS), had no significant effects on the ROS induced by all three cytokines. ROS scavengers, pyrrolidinedithiocarbamate (PDTC) and N-acetyl-cysteine (NAC), reduced the levels of ROS induced by TNF-alpha, IL-1 beta and IFN-gamma (P

PURPOSE To assess the efficacy of a comprehensive technique for correction of severe punctal and medial lower eyelid ectropion and lower eyelid retraction associated with medial canthal ligament (MCL) laxity. METHODS A comprehensive technique that plicates the anterior and posterior crura of the MCL was performed on 8 eyelids of 6 patients with punctal ectropion and MCL laxity. Preoperative and postoperative symptoms, punctal ectropion, medial lower eyelid ectropion, lower eyelid retraction, lagophthalmos, and exposure keratopathy were evaluated. RESULTS At an average of 13 months (range, 8-17 months), preoperative symptoms of epiphora and discomfort improved or resolved in all eyes. Punctal ectropion improved in all eyes and completely resolved in 75% of eyes. Medial lower eyelid ectropion was corrected in all eyes, when present. Lower eyelid retraction, lagophthalmos, and exposure keratopathy improved in all eyes. In 1 case, edema of the caruncle and semilunar fold persisted for 6 months. CONCLUSIONS Combined anterior and transcaruncular MCL plication is an effective and safe procedure for addressing severe punctal and medial lower eyelid ectropion that accompanies MCL laxity and is difficult to correct by other methods. This procedure provides stable, 3-dimensional support to the medial lower eyelid and punctum.

Purpose To report clinical and histopathologic features and biologic behavior of orbital myxomas and angiomyxomas. Design Noncomparative retrospective case series. Participants Patients with histopathologic diagnoses of orbital myxoma or angiomyxoma. Methods Clinical metadata and features were obtained from the medical record. Neoplasms were studied by routine histopathology, special stains, and immunohistochemistry. Main Outcome Measures Final diagnosis, based on histopathology, special stains, and immunohistochemistry, and clinical course from analysis of metadata and clinical features. Results Three myxomas and 3 angiomyxomas were identified in 5 males and 1 female. Median age at presentation was 56 years (range, 4–69), with a follow-up ranging from 6 months to 8 years. Two angiomyxomas occurred in children ages 4 and 7 years whose tumors were locally aggressive and recurred. Recurrence also complicated one case of myxoma after incomplete excision. Pathologically, the tumors were poorly circumscribed. Histopathology showed them to be hypocellular, containing stellate and spindled cells in an abundant, loose, myxoid stroma rich in hyaluronic acid. Small blood vessels were rare in myxomas but abundant in angiomyxomas. Tumor cells were frequently immunoreactive for vimentin, CD34, and factor XIIIa. Conclusions Myxomas rarely involve orbital tissue, and no angiomyxomas of the region have been previously reported. Angiomyxomas in children may be aggressive. Vascularity and bone involvement appear to be important prognostic features for recurrence. Complete resection with a margin of healthy tissue appears to be the treatment of choice. Tumor cell immunopositivity for vimentin, CD34, and factor XIIIa may assist in the histopathologic diagnosis.

VEGF secretion by the human retinal pigment epithelium (hRPE) plays an important role in retinal and choroidal neovascularization. In this study, transforming growth factor-beta2 (TGF-beta2)-induced vascular endothelial growth factor (VEGF) gene expression was investigated in hRPE cells. Treatment of hRPE cells with TGF-beta2 for 24 and 48h as compared to 8h resulted in markedly increased VEGF secretion by fivefold and nine-fold, respectively. Induced VEGF mRNA peaked within 3h of stimulation and remained above the basal at 36h. Stimulation of VEGF expression by TGF-beta2 was blocked by cycloheximide, suggesting that de novo protein synthesis is required. Induced VEGF production was strongly inhibited by anti-inflammatory agents, dexamethasone and cyclosporin A. Despite of the weak stimulation of VEGF expression by TNF-alpha or bFGF alone, co-administration of either of these two cytokines synergized the effect of TGF-beta2 on VEGF mRNA expression and protein production. Quantitative RT-PCR revealed that the synergy was predominantly at the level of VEGF transcription. Moreover, TGF-beta2-induced RPE VEGF secretion was significantly reduced by inhibitors of mitogen-activated protein (MAP) kinase (MEK) (U0126), p38 (SB202190), c-Jun NH2-terminal kinase (JNK), Sp600125, protein tyrosine kinase (PTK) (Genistein), and phosphatidylinositol 3-kinase (PI3K) (Ly294002). Induced VEGF expression was completely abrogated by inhibitors of protein kinase C (PKC) (Ro318220), nuclear factor-kappaB (NF-kappaB) [caffeic acid phenethyl ester (CAPE)], and reactive oxygen species (ROS) [N-acetyl-cysteine (Nac) and diphenyleneiodonium (DPI)]. These results suggest that MEK, p38, JNK, PI3K, and NF-kappaB as well as multiple essential signaling intermediates, including PKC, PTK and ROS, are involved in hRPE VEGF up regulation by TGF-beta2.

Objective To illustrate the role of clinically necessary aggressive subcutaneous debridement with limited excision of necrotic skin in treating necrotizing faciitis, while demonstrating the histopathologic basis of orbital spread and blindness complicating this disorder. Design Observational retrospective case series. Participants Seven consecutive patients cared for by the Eye Plastic and Orbital Surgery Services at the University of Michigan and University of Iowa. Methods Retrospective review of ocular findings, systemic features, management, outcome, and histopathology of debrided tissue from 7 patients with periocular necrotizing fasciitis. Main Outcome Measures Patient survival and morbidity. Results Bilateral involvement was present in 6 of the 7 patients. Five patients suffered ophthalmic or central retinal artery occlusion with loss of vision. All patients underwent extensive debridement of subcutaneous tissue with sparing of overlying nonnecrotic skin and intensive systemic antibiotic therapy. Four patients required unilateral exenteration. After a mean follow-up of 38 months, 6 patients were alive; 1 died perioperatively due to septic shock. Histopathology, not previously described, showed inflammation to spread preferentially along eyelid fibrofatty–fascial tissue planes into the orbit and along orbital fibrous septae, leading to intense perivascular inflammation, thrombosis, and ocular infarction. Conclusions Necrotizing fasciitis is a potentially fatal disease that often causes blindness when affecting the periocular region. To reduce morbidity and mortality in severe infections, prompt subcutaneous debridement and limited resection of necrotic skin are usually necessary.